Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma

PubMed Central

Ambrosio, Maria R.; Rocca, Bruno J.; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T.; Tripodi, Sergio A.; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

Technetium-99m mercaptoacetyltriglycine clearance: reference values for infants and children.

PubMed

Schofer, O; König, G; Bartels, U; Bockisch, A; Piepenburg, R; Beetz, R; Meyer, G; Hahn, K

1995-11-01

Six hundred and thirty-nine clearance studies performed in children aged 7 days to 19 years utilizing technetium-99m mercaptoacetyltriglycine (MAG 3) were retrospectively analysed. Standardized conditions for the investigation included: parenteral hydration (60 ml/hxm2 body surface) in addition to normal oral fluid intake, weight-related dose of 99mTc-MAG 3 (1 MBq/kg body weight, minimum 15 MBq) and calculation of clearance according to Bubeck et al. Of the 513 children, 169 included in this analysis could be classified as "normal" with regard to their renal function. Normal kidney function was judged by the following criteria: normal GFR for age, normal tubular function (absence of proteinuria and glucosuria), normal renal parenchyma (on ultrasonography, MAG 3 scan and intravenous pyelography), absence of significant obstruction and gross reflux (>grade I), no single kidney and no difference in split renal function >20%. Results showed increasing MAG 3 clearance values for infants during the first months of life, reaching the normal range for older children and adults between 7 and 12 months.

Feasibility of Repairing Glomerular Basement Membrane Defects in Alport Syndrome

PubMed Central

Lin, Xiaobo; Suh, Jung Hee; Go, Gloriosa

2014-01-01

Alport syndrome is a hereditary glomerular disease that leads to kidney failure. It is caused by mutations affecting one of three chains of the collagen α3α4α5(IV) heterotrimer, which forms the major collagen IV network of the glomerular basement membrane (GBM). In the absence of the α3α4α5(IV) network, the α1α1α2(IV) network substitutes, but it is insufficient to maintain normal kidney function. Inhibition of angiotensin-converting enzyme slows progression to kidney failure in patients with Alport syndrome but is not a cure. Restoration of the normal collagen α3α4α5(IV) network in the GBM, by either cell- or gene-based therapy, is an attractive and logical approach toward a cure, but whether or not the abnormal GBM can be repaired once it has formed and is functioning is unknown. Using a mouse model of Alport syndrome and an inducible transgene system, we found that secretion of α3α4α5(IV) heterotrimers by podocytes into a preformed, abnormal, filtering Alport GBM is effective at restoring the missing collagen IV network, slowing kidney disease progression, and extending life span. This proof-of-principle study demonstrates the plasticity of the mature GBM and validates the pursuit of therapeutic approaches aimed at normalizing the GBM to prolong kidney function. PMID:24262794

Feasibility of repairing glomerular basement membrane defects in Alport syndrome.

PubMed

Lin, Xiaobo; Suh, Jung Hee; Go, Gloriosa; Miner, Jeffrey H

2014-04-01

Alport syndrome is a hereditary glomerular disease that leads to kidney failure. It is caused by mutations affecting one of three chains of the collagen α3α4α5(IV) heterotrimer, which forms the major collagen IV network of the glomerular basement membrane (GBM). In the absence of the α3α4α5(IV) network, the α1α1α2(IV) network substitutes, but it is insufficient to maintain normal kidney function. Inhibition of angiotensin-converting enzyme slows progression to kidney failure in patients with Alport syndrome but is not a cure. Restoration of the normal collagen α3α4α5(IV) network in the GBM, by either cell- or gene-based therapy, is an attractive and logical approach toward a cure, but whether or not the abnormal GBM can be repaired once it has formed and is functioning is unknown. Using a mouse model of Alport syndrome and an inducible transgene system, we found that secretion of α3α4α5(IV) heterotrimers by podocytes into a preformed, abnormal, filtering Alport GBM is effective at restoring the missing collagen IV network, slowing kidney disease progression, and extending life span. This proof-of-principle study demonstrates the plasticity of the mature GBM and validates the pursuit of therapeutic approaches aimed at normalizing the GBM to prolong kidney function.

Successful Surgical Treatment of Anuria Caused by Renal Artery Occlusion

PubMed Central

Flye, M. Wayne; Anderson, Robert w.; Fish, Jay C.; Silver, Donald

1982-01-01

Anuria resulting from obstruction of the renal arteries to both Kidneys or to a solitary kidney is unusual. The tolerance of the kidney to this ischemia is largely dependent upon the presence of collaterals, stimulated by pre-existing arterial disease. Our experience with six patients with anuria caused by renal artery occlusion supports the role of revascularization in the recovery of significant renal function. Four of these patients had hypertension, impaired renal function, and the existence of collateral circulation to an ischemic kidney, prior to occlusion, while two patients had normal renal function (serum creatinine = 0.5 and 0.9 mg/dl) before occlusion. The intervals of anuria for the two previously normal kidneys were six hours and five days, and 2 to 14 days in the four patients with vascular disease. Isotope scanning suggested renal artery occlusion in two patients, but arteriograms confirmed the diagnosis in all six. A thrombectomy restored blood flow through the two previously normal renal arteries. Grafts from the aorta or celiax axis were used for three patients and the splenic artery was used for the sixth patient. Urine flow began during or soon after operation in all patients. Dialysis was necessary for 30 and 45 days in the two patients with normal kidneys, but in only one of the four patients with previous disease (for ten days). Serum creatinine decreased to <2.0 mg/dl after operation, except in the man with a solitary kidney, who five years later has a creatinine of 3 mg/dl. All four patients with previous arterial disease died from cardiac failure within 1 to 30 months after operation. Therefore, anuria of acute onset should be evaluated by renal scan and arteriogram to detect those patients with proximal renal artery occlusion in preparation for revascularization. ImagesFig. 2a.Fig. 2b.Fig. 3.Fig. 4a.Fig. 4b.Fig. 5.Fig. 6a.Fig. 6b. PMID:7059245

Role of AMP-activated protein kinase in kidney tubular transport, metabolism, and disease.

PubMed

Rajani, Roshan; Pastor-Soler, Nuria M; Hallows, Kenneth R

2017-09-01

AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins. These new studies have focused on the role of AMPK in the kidney in the setting of various diseases such as diabetes, which include evaluation of the effects of the hyperglycemic state on podocyte and tubular cell function. Other recent studies have investigated how reduced kidney mass, polycystic kidney disease (PKD), and fibrosis affect AMPK activation status. A general theme of several conditions that lead to chronic kidney disease (CKD) is that AMPK activity is abnormally suppressed relative to that in normal kidneys. Thus, the idea that AMPK activation may be a therapeutic strategy to slow down the progression of CKD has emerged. In addition to drugs such as metformin and 5-aminoimidazole-4-carboxamide ribonucleotide that are classically used as AMPK activators, recent studies have identified the therapeutic potential of other compounds that function at least partly as AMPK activators, such as salicylates, statins, berberine, and resveratrol, in preventing the progression of CKD. AMPK in the kidney plays a unique role at the crossroads of energy metabolism, ion and water transport, inflammation, and stress. Its potential role in modulating recovery from vs. progression of acute and chronic kidney injury has been the topic of recent research findings. The continued study of AMPK in kidney physiology and disease has improved our understanding of these physiological and pathological processes and offers great hope for therapeutic avenues for the increasing population at risk to develop kidney failure.

Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

PubMed

Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

2009-10-01

The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

Preoperative Renal Volume: A Surrogate Measure for Radical Nephrectomy-Induced Chronic Kidney Disease.

PubMed

Wu, Fiona Mei Wen; Tay, Melissa Hui Wen; Tai, Bee Choo; Chen, Zhaojin; Tan, Lincoln; Goh, Benjamin Yen Seow; Raman, Lata; Tiong, Ho Yee

2015-12-01

Surgically induced chronic kidney disease (CKD) has been found to have less impact on survival as well as function when compared to medical causes for CKD. The aim of this study is to evaluate whether preoperative remaining kidney volume correlates with renal function after nephrectomy, which represents an individual's renal reserve before surgically induced CKD. A retrospective review of 75 consecutive patients (29.3% females) who underwent radical nephrectomy (RN) (2000-2010) was performed. Normal side kidney parenchyma, excluding renal vessels and central sinus fat, was manually outlined in each transverse slice of CT image and multiplied by slice thickness to calculate volume. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. CKD is defined as eGFR < 60 mL/min/1.73 m(2). Mean preoperative normal kidney parenchymal volume (mean age 55 [SD 13] years) is 150.7 (SD 36.4) mL. Over median follow-up of 36 months postsurgery, progression to CKD occurred in 42.6% (n = 32) of patients. On multivariable analysis, preoperative eGFR and preoperative renal volume <144 mL are independent predictors for postoperative CKD. On Kaplan-Meier analysis, median time to reach CKD postnephrectomy is 12.7 (range 0.03-43.66) months for renal volume <144 mL but not achieved if renal volume is >144 mL. Normal kidney parenchymal volume and preoperative eGFR are independent predictive factors for postoperative CKD after RN and may represent renal reserve for both surgically and medically induced CKD, respectively. Preoperative remaining kidney volume may be an adjunct representation of renal reserve postsurgery and predict later renal function decline due to perioperative loss of nephrons.

Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.

Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less

Conditional ablation of glycogen synthase kinase 3β in postnatal mouse kidney.

PubMed

Ge, Yan; Si, Jin; Tian, Li; Zhuang, Shougang; Dworkin, Lance D; Gong, Rujun

2011-01-01

Glycogen synthase kinase (GSK)3 is a ubiquitously expressed serine/threonine kinase existing in two isoforms, namely GSK3α and GSK3β. Aside from the long-recognized role in insulin signal transduction and glycogen biosynthesis, GSK3β has been recently coined as a master control molecule in nuclear factor-κB activation and inflammatory kidney injury. Nevertheless, previous studies are less conclusive because they relied greatly on small molecule inhibitors, which lack selectivity and barely distinguish between the GSK3 isoforms. In addition, early embryonic lethality after global knockout of GSK3β precludes interrogation of the biological role of GSK3β in the adult kidney. To circumvent these issues, the Cre/loxP system was used to generate a conditional knockout mouse model in which the GSK3β gene was specifically deleted in kidney cortical tubules at postnatal mature stage. Kidney-specific ablation of GSK3β resulted in a phenotype no different from control littermates. Knockout mice (KO) were viable and exhibited normal development and normal kidney physiology in terms of kidney function, urine albumin excretion, and urine-concentrating ability. It is noteworthy that apart from normal glomerular and tubulointerstitial morphology, the kidneys from KO demonstrated more glycogen accumulation in the renal cortical tubules as assessed by both periodic acid-Schiff staining for light microscopy and direct biochemical assay, consistent with an elevated glycogen synthetic activity as evidenced by diminished inhibitory phosphorylation of glycogen synthase that occurred subsequent to GSK3β ablation. This finding was further validated by electron microscopic observations of increased deposition of glycogen particles in the renal tubules of KO, suggesting that GSK3α could not fully compensate for the loss of GSK3β in regulating glycogen metabolism in the kidney. Collectively, our study suggests that kidney-specific ablation of GSK3β barely affects kidney function and histology under normal circumstances. Extended examinations of these KO under diseased conditions are merited to understand the role of GSK3β in renal pathophysiology.

Case Report: First Reported Combined Heart-Liver Transplant in a Patient With a Congenital Solitary Kidney.

PubMed

Hanna, R M; Kamgar, M; Hasnain, H; Khorsan, R; Nsair, A; Kaldas, F; Baas, A; Bunnapradist, S; Wilson, J M

2018-04-01

We report a case of successful combined heart liver transplant in a patient with a congenital solitary kidney. The patient had normal renal function before combined heart-liver transplantation and developed acute kidney injury requiring slow continuous dialysis and subsequent intermittent dialysis for almost 8 weeks post transplantation. Her renal function recovered and she remains off dialysis now 7 months post transplantation. She only currently has mild chronic renal insufficiency. We believe this is the first reported case of successful heart liver transplant in a patient with a congenital solitary kidney. Published by Elsevier Inc.

The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis".

PubMed

Bricker, N S; Morrin, P A; Kime, S W

1997-09-01

Clinical and experimental data relating to the functional capacity of the surviving nephrons of the chronically diseased kidney for the most part support the thesis that these nephrons retain their essential functional integrity regardless of the nature of the underlying form of chronic Bright's disease. There are instances in which specific alterations of function correlate with pathologic involvement of a particular site of the nephron but these appear to represent the exceptions, and in general the more advanced the disease becomes, the less evident are the differentiating features. Studies on dogs with unilateral renal disease indicate that the functional capacity of the nephrons of the diseased kidney parallels that of the nephrons of the contralateral normal kidney. These data tend to exclude widespread intrinsic damage to the functioning nephrons by the underlying pathologic processes. From these observations, as well as from certain supporting clinical and experimental observations, it is suggested that the majority of surviving nephrons in the patient with bilateral renal disease similarly are functionally intact. Concepts of the pathologic physiology of the kidney, based on the "intact nephron hypothesis", are presented. Within the framework of this hypothesis it is concluded that (1) the diseased kidney consists of a diminished number of nephrons, most of which retain essentially normal functional abilities; (2) certain of the apparent abnormalities in function in bilateral renal disease may relate to adaptive changes imposed by the decreased nephron population and the attendant derangements in body fluids rather than to structural distortion of nephrons; (3) the over-all flexibility of the diseased kidney decreases as the number of constituent nephrons decreases; but (4) there is an orderly and predictable pattern of excretion for all substances.

A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology.

PubMed

Gianfranca, Cabiddu; Donatella, Spotti; Giuseppe, Gernone; Domenico, Santoro; Gabriella, Moroni; Gina, Gregorini; Franca, Giacchino; Rossella, Attini; Monica, Limardo; Linda, Gammaro; Tullia, Todros; Piccoli, Giorgina Barbara

2018-06-14

Kidney transplantation (KT) is often considered to be the method best able to restore fertility in a woman with chronic kidney disease (CKD). However, pregnancies in KT are not devoid of risks (in particular prematurity, small for gestational age babies, and the hypertensive disorders of pregnancy). An ideal profile of the potential KT mother includes "normal" or "good" kidney function (usually defined as glomerular filtration rate, GFR ≥ 60 ml/min), scant or no proteinuria (usually defined as below 500 mg/dl), normal or well controlled blood pressure (one drug only and no sign of end-organ damage), no recent acute rejection, good compliance and low-dose immunosuppression, without the use of potentially teratogen drugs (mycophenolic acid and m-Tor inhibitors) and an interval of at least 1-2 years after transplantation. In this setting, there is little if any risk of worsening of the kidney function. Less is known about how to manage "non-ideal" situations, such as a pregnancy a short time after KT, or one in the context of hypertension or a failing kidney. The aim of this position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology is to review the literature and discuss what is known about the clinical management of CKD after KT, with particular attention to women who start a pregnancy in non-ideal conditions. While the experience in such cases is limited, the risks of worsening the renal function are probably higher in cases with markedly reduced kidney function, and in the presence of proteinuria. Well-controlled hypertension alone seems less relevant for outcomes, even if its effect is probably multiplicative if combined with low GFR and proteinuria. As in other settings of kidney disease, superimposed preeclampsia (PE) is differently defined and this impairs calculating its real incidence. No specific difference between non-teratogen immunosuppressive drugs has been shown, but calcineurin inhibitors have been associated with foetal growth restriction and low birth weight. The clinical choices in cases at high risk for malformations or kidney function impairment (pregnancies under mycophenolic acid or with severe kidney-function impairment) require merging clinical and ethical approaches in which, beside the mother and child dyad, the grafted kidney is a crucial "third element".

Impact of parenchymal loss on renal function after laparoscopic partial nephrectomy under warm ischemia.

PubMed

Bagheri, Fariborz; Pusztai, Csaba; Farkas, László; Kallidonis, Panagiotis; Buzogány, István; Szabó, Zsuzsanna; Lantos, János; Imre, Marianna; Farkas, Nelli; Szántó, Árpád

2016-12-01

To elucidate the impact of renal parenchymal loss and the ischemic reperfusion injury (RI) on the renal function after laparoscopic partial nephrectomy (LPN) under warm ischemia (WI). Thirty-five patients with a single polar renal mass ≤4 cm and normal contralateral kidney underwent LPN. Transperitoneal LPN with WI using en bloc hilar occlusion was performed. The total differential renal function (T-DRF) using 99m Tc-dimercaptosuccinic acid was evaluated preoperatively and postoperatively over a period of 1 year. A special region of interest (ROI) was selected on the non-tumorous pole of the involved kidney, and was compared with the same ROI in the contralateral kidney. The latter comparison was defined as partial differential renal function (P-DRF). Any postoperative decline in the P-DRF of the operated kidney was attributed to the RI. Subtraction of the P-DRF decline from the T-DRF decline was attributed to the parenchymal loss caused by the resection of the tumor and suturing of the normal parenchyma. The mean WI time was 22 min, and the mean weight of resected specimen was 18 g. The mean postoperative eGFR declined to 87 ml/min/1.73 m 2 from its baseline mean value of 97 ml/min/1.73 m 2 (p value = 0.075). Mean postoperative T-DRF and P-DRF of the operated kidney declined by 7 and 3 %, respectively. After LPN of small renal mass, decline in renal function is primarily attributed to parenchymal loss caused by tumor resection and suturing of the normal parenchyma rather than the RI.

The normal and pathologic renal medulla: a comprehensive overview.

PubMed

López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

2015-04-01

The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

PubMed

Sandilands, Euan A; Cameron, Sharon; Paterson, Frances; Donaldson, Sam; Briody, Lesley; Crowe, Jane; Donnelly, Julie; Thompson, Adrian; Johnston, Neil R; Mackenzie, Ivor; Uren, Neal; Goddard, Jane; Webb, David J; Megson, Ian L; Bateman, Nicholas; Eddleston, Michael

2012-02-03

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

Evaluation of Acute Kidney Injury and Mortality After Intensive Blood Pressure Control in Patients With Intracerebral Hemorrhage.

PubMed

Burgess, L Goodwin; Goyal, Nitin; Jones, G Morgan; Khorchid, Yasser; Kerro, Ali; Chapple, Kristina; Tsivgoulis, Georgios; Alexandrov, Andrei V; Chang, Jason J

2018-04-13

We sought to assess the risk of acute kidney injury (AKI) and mortality associated with intensive systolic blood pressure reduction in acute intracerebral hemorrhage. Patients with acute intracerebral hemorrhage had spontaneous cause and symptom onset within 24 hours. We excluded patients with structural causes, coagulopathy, thrombocytopenia, and preexisting end-stage renal disease. We defined AKI using the Acute Kidney Injury Network criteria. Chronic kidney disease status was included in risk stratification and was defined by Kidney Disease Outcomes Quality Initiative staging. Maximum systolic blood pressure reduction was defined over a 12-hour period and dichotomized using receiver operating characteristic curve analysis. Descriptive statistics were done using independent sample t tests, χ 2 tests, and Mann-Whitney U tests, whereas multivariable logistic regression analysis was used to evaluate for predictors for AKI and mortality. A total of 448 patients with intracerebral hemorrhage met inclusion criteria. Maximum systolic blood pressure reduction was dichotomized to 90 mm Hg and found to increase the risk of AKI in patients with normal renal function (odds ratio, 2.1; 95% confidence interval, 1.19-3.62; P =0.010) and chronic kidney disease (odds ratio, 3.91; 95% confidence interval, 1.26-12.15; P =0.019). The risk of AKI was not significantly different in normal renal function versus chronic kidney disease groups when adjusted for demographics, presentation characteristics, and medications associated with AKI. AKI positively predicted mortality for patients with normal renal function (odds ratio, 2.41; 95% confidence interval, 1.11-5.22; P =0.026) but not for patients with chronic kidney disease (odds ratio, 3.13; 95% confidence interval, 0.65-15.01; P =0.154). These results indicate that intensive systolic blood pressure reduction with a threshold >90 mm Hg in patients with acute intracerebral hemorrhage may be an independent predictor for AKI. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease.

PubMed

Swallow, E A; Aref, M W; Chen, N; Byiringiro, I; Hammond, M A; McCarthy, B P; Territo, P R; Kamocka, M M; Winfree, S; Dunn, K W; Moe, S M; Allen, M R

2018-06-11

This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces. Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities. Bisphosphonates are commonly used in reducing fracture risk in a variety of diseases, yet their use is not recommended in advanced stages of CKD. This study aimed to characterize the accumulation of a single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of reduced kidney function. At 25 weeks of age, FAM-ZOL was administered to normal and CKD rats. Twenty-four hours later, multiple bones were collected and assessed using bulk fluorescence imaging, two-photon imaging, and dynamic histomorphometry. CKD animals had significantly higher levels of FAM-ZOL accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral body or mandible, based on multiple measurement modalities. Although a majority of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD animals, the latter had significantly higher levels of fluorescence per unit bone surface in the proximal tibia. These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone.

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

PubMed

Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai

2006-09-12

To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

First documented case of successful kidney transplantation from a donor with acute renal failure treated with dialysis.

PubMed

Bacak-Kocman, Iva; Peric, Mladen; Kastelan, Zeljko; Kes, Petar; Mesar, Ines; Basic-Jukic, Nikolina

2013-10-01

There is a widening gap between the needs and possibilities of kidney transplantation. In order to solve the problem of organ shortage, the selection criteria for kidney donors have been less stringent over the last years. Favorable outcome of renal transplantation from deceased donors with acute renal failure requiring dialysis may have an important role in expanding the pool of donors. We present the case of two renal transplantations from a polytraumatized 20-years old donor with acute renal failure requiring dialysis. One recipient established good diuresis from the first post-transplant day and did not require hemodialysis. The second recipient had delayed graft function and was treated with 8 hemodialysis sessions. The patient was discharged with good diuresis and normal serum creatinine. After two years of follow-up, both recipients have normal graft function. According to our experience, kidneys from deceased young donors with acute renal failure requiring dialysis may be transplanted, in order to decrease the number of patients on transplantation waiting lists.

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

PubMed

Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu

2008-01-15

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

PubMed

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

PubMed Central

Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

Kidney Function in Obesity-Challenges in Indexing and Estimation.

PubMed

Chang, Alex R; Zafar, Waleed; Grams, Morgan E

2018-01-01

As the prevalence of obesity continues to increase worldwide, an increasing number of people are at risk for kidney disease. Thus, there is a critical need to understand how best to assess kidney function in this population, and several challenges exist. The convention of indexing glomerular filtration rate (GFR) to body surface area (BSA) attempts to normalize exposure to metabolic wastes across populations of differing body size. In obese individuals, this convention results in a significantly lower indexed GFR than unindexed GFR, which has practical implications for drug dosing. Recent data suggest that "unindexing" estimated GFR (multiplying by BSA/1.73 m 2 ) for drug dosing may be acceptable, but pharmocokinetic data to support this practice are lacking. Beyond indexing, biomarkers commonly used for estimating GFR may induce bias. Creatinine is influenced by muscle mass, whereas cystatin C correlates with fat mass, both independent of kidney function. Further research is needed to evaluate the performance of estimating equations and other filtration markers in obesity, and determine whether unindexed GFR might better predict optimal drug dosing and clinical outcomes in patients whose BSA is very different than the conventional normalized value of 1.73 m 2 . Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The Utility of the Remnant Kidney Volume/Body Surface Area Ratio and Tumor Diameter as Predictors of Postoperative Degree of Renal Functional Decline in Patients With Renal Cell Carcinoma Treated by Radical Nephrectomy.

PubMed

Sejima, Takehiro; Yamaguchi, Noriya; Iwamoto, Hideto; Masago, Toshihiko; Morizane, Shuichi; Ono, Koji; Koumi, Tsutomu; Honda, Masashi; Takenaka, Atsushi

2015-08-01

To characterize the preoperative factors affecting renal cell carcinoma patients as predictive of post-radical nephrectomy (RN) mild (M-decline) or severe (S-decline) renal functional decline and to elucidate the histopathologic features of the resected normal kidney cortex, as well as the occurrence of cardiovascular disease (CVD) in both M-decline and S-decline patients. M-decline and S-decline were categorized as a percentage of postoperative estimated glomerular filtration rate decline of <20 and of >40, respectively. The preoperative factors analyzed were patient demographics, comorbidities, and radiographic findings, including remnant kidney status and tumor size. The factors based on postoperative information analyzed were tumor and normal cortex pathology and CVD events. In 175 patient cohort, 21 and 32 cases were categorized as M-decline and S-decline, respectively. Absence of comorbidities, larger remnant kidney volume (RKV)/body surface area (BSA) ratio, and larger tumor diameter were significantly predictive of M-decline, whereas smaller tumor diameter was significantly predictive of S-decline. The global glomerulosclerosis extent in nephrectomized normal cortex of S-decline cases was significantly higher than in other types of cases. No CVD event was observed in M-decline cases. This is the first report to identify the RKV/BSA ratio as a promising predictor of post-RN degree of renal functional decline. Post-RN prevention of life-threatening outcomes according to preoperative and postoperative information, including the degree of post-RN renal functional decline and histopathology of the nephrectomized normal cortex, should be considerable in future urological tasks. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of neuropeptide Y in renal sympathetic vasoconstriction: studies in normal and congestive heart failure rats.

PubMed

DiBona, G F; Sawin, L L

2001-08-01

Sympathetic nerve activity, including that in the kidney, is increased in heart failure with increased plasma concentrations of norepinephrine and the vasoconstrictor cotransmitter neuropeptide Y (NPY). We examined the contribution of NPY to sympathetically mediated alterations in kidney function in normal and heart failure rats. Heart failure rats were created by left coronary ligation and myocardial infarction. In anesthetized normal rats, the NPY Y(1) receptor antagonist, H 409/22, at two doses, had no effect on heart rate, arterial pressure, or renal hemodynamic and excretory function. In conscious severe heart failure rats, high-dose H 409/22 decreased mean arterial pressure by 8 +/- 2 mm Hg but had no effect in normal and mild heart failure rats. During graded frequency renal sympathetic nerve stimulation (0 to 10 Hz), high-dose H 409/22 attenuated the decreases in renal blood flow only at 10 Hz (-36% +/- 5%, P <.05) in normal rats but did so at both 4 (-29% +/- 4%, P <.05) and 10 Hz (-33% +/- 5%, P <.05) in heart failure rats. The glomerular filtration rate, urinary flow rate, and sodium excretion responses to renal sympathetic nerve stimulation were not affected by high-dose H 409/22 in either normal or heart failure rats. NPY does not participate in the regulation of kidney function and arterial pressure in normal conscious or anesthetized rats. When sympathetic nervous system activity is increased, as in heart failure and intense renal sympathetic nerve stimulation, respectively, a small contribution of NPY to maintenance of arterial pressure and to sympathetic renal vasoconstrictor responses may be identified.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geyskes, G.G.; Oei, H.Y.; Puylaert, C.B.

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in themore » time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of /sup 99m/Tc-diethylenetriamine pentaacetic acid uptake and a delay of /sup 131/I-hippurate excretion, while the /sup 131/I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.« less

Urinary Virome Perturbations in Kidney Transplantation.

PubMed

Sigdel, Tara K; Mercer, Neil; Nandoe, Sharvin; Nicora, Carrie D; Burnum-Johnson, Kristin; Qian, Wei-Jun; Sarwal, Minnie M

2018-01-01

The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.

Renal function changes after percutaneous nephrolithotomy in patients with renal calculi with a solitary kidney compared to bilateral kidneys.

PubMed

Shi, Xiaolei; Peng, Yonghan; Li, Ling; Li, Xiao; Wang, Qi; Zhang, Wei; Dong, Hao; Shen, Rong; Lu, Chaoyue; Liu, Min; Gao, Xiaofeng; Sun, Yinghao

2018-05-26

To evaluate renal function changes and risk factors for acute kidney injury (AKI) after percutaneous nephrolithotomy (PCNL) in patients with renal calculi with a solitary kidney (SK) or normal bilateral kidneys (BKs). Between 2012 and 2016, 859 patients undergoing PCNL were retrospectively reviewed at Changhai Hospital. In all, 53 patients with a SK were paired with 53 patients with normal BKs via a propensity score-matched analysis. Data for the following variables were collected: age, sex, body mass index, stone size, distribution, operation time, perioperative outcomes, and complications. The complications were graded according to the modified Clavien-Dindo system. Univariable and multivariable logistic regression models were constructed to evaluate risk factors for predicting AKI. The SK and BKs groups were comparable in terms of age, sex ratio, stone size, stone location distribution, comorbidities, and American Society of Anesthesiologists Physical Status classification. The initial and final stone-free rates were comparable between the SK and BKs groups (initial: 52.83% vs 58.49%, P = 0.696; final: 84.91% vs 92.45%, P = 0.359). There was no difference between the two groups for complications, according to the Clavien-Dindo grades. The estimated glomerular filtration rate (eGFR) increased dramatically after the stone burden was immediately relieved, and during the 6-month follow-up eGFR was lower in the SK group compared with the BKs group. We found a modest improvement in renal function immediately after PCNL in the BKs group, and renal function gain was delayed in the SK group. Through logistic regression analysis, we discovered that a SK, preoperative creatinine and diabetes were independent risk factors for predicting AKI after PCNL. Considering the overall complication rates, PCNL is generally a safe procedure for treating renal calculi amongst patients with a SK or normal BKs. Follow-up renal function analysis showed a modest improvement in patients of both groups. Compared to patients with normal BKs, patients with a SK were more likely to develop AKI after PCNL. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

A Case Report of Successful Kidney Donation After Brain Death Following Nicotine Intoxication.

PubMed

Räsänen, M; Helanterä, I; Kalliomäki, J; Savikko, J; Parry, M; Lempinen, M

Nicotine intoxication is a rare cause of death and can lead to brain death after respiratory arrest and hypoxic-ischemic encephalopathy. To our knowledge, no previous reports regarding organ donation after nicotine intoxication have been described. We present a successful case of kidney donation after brain death caused by subcutaneous nicotine overdose from liquid nicotine from an e-cigarette cartridge in an attempted suicide. Both kidneys were transplanted successfully with immediate graft function, and both recipients were discharged at postoperative day 9 with normal plasma creatinine levels. Graft function has remained excellent in follow-up. This case suggests that kidneys from a donor with fatal nicotine intoxication may be successfully used for kidney transplantation in the absence of other contraindications for donation. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum creatinine levels are significantly influenced by renal size in the normal pediatric population.

PubMed

Di Zazzo, Giacomo; Stringini, Gilda; Matteucci, Maria Chiara; Muraca, Maurizio; Malena, Saverio; Emma, Francesco

2011-01-01

Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children. A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender. When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements. These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship.

Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

PubMed

de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

2015-02-01

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

Simple ectopic kidney in three dogs.

PubMed

Choi, Jiyoung; Lee, Heechun; Lee, Youngwon; Choi, Hojung

2012-10-01

Simple ectopic kidney was diagnosed in three dogs by means of radiography and ultrasonography. A 2-year-old castrated male Schnauzer, a 13-year-old female Schnauzer and a 9-year-old male Jindo were referred with vomiting, hematuria and ocular discharge, respectively. In all three dogs, oval-shaped masses with soft tissue density were observed in the mid to caudal abdomen bilaterally or unilaterally, and kidney silhouettes were not identified at the proper anatomic places on abdominal radiographs. Ultrasonography confirmed the masses were malpositioned kidney. The ectopic kidneys had relatively small size, irregular shape and short ureter but showed normal function on excretory urography.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

PubMed Central

2012-01-01

Background Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. Methods/Design We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. Discussion Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. Trial registration Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18. PMID:22305183

Combined heart-kidney transplantation after total artificial heart insertion.

PubMed

Ruzza, A; Czer, L S C; Ihnken, K A; Sasevich, M; Trento, A; Ramzy, D; Esmailian, F; Moriguchi, J; Kobashigawa, J; Arabia, F

2015-01-01

We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.

PubMed

Eirin, Alfonso; Zhu, Xiang-Yang; Ferguson, Christopher M; Riester, Scott M; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O

2015-01-19

Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Hospitalized hemorrhagic stroke patients with renal insufficiency: clinical characteristics, care patterns, and outcomes.

PubMed

Ovbiagele, Bruce; Schwamm, Lee H; Smith, Eric E; Grau-Sepulveda, Maria V; Saver, Jeffrey L; Bhatt, Deepak L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C

2014-10-01

There is a paucity of information on clinical characteristics, care patterns, and clinical outcomes for hospitalized intracerebral hemorrhage (ICH) patients with chronic kidney disease (CKD). We assessed characteristics, care processes, and in-hospital outcome among ICH patients with CKD in the Get With the Guidelines-Stroke (GWTG-Stroke) program. We analyzed 113,059 ICH patients hospitalized at 1472 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. In-hospital mortality and use of 2 predefined ICH performance measures were examined based on glomerular filtration rate. Renal dysfunction was categorized as a dichotomous (+CKD = estimated glomerular filtration rate <60) or rank ordered variable as CKD (<60), and by clinical stage: (normal [≥90], mild [≥60-<90], moderate [≥30-<60], severe [≥15-<30], and/or kidney failure [<15 or dialysis]). There were 33,219 (29%) ICH patients with CKD. Patients with CKD were more likely to be older, female, and with comorbid conditions such as diabetes. Compared with patients with normal kidney function, those with CKD were slightly less likely to receive deep venous thrombosis (DVT) prophylaxis but similarly received discharge smoking cessation intervention. Inpatient mortality was also higher for those with CKD (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.42-1.52), mild dysfunction (adjusted OR, 1.12; 95% CI, 1.08-1.16), moderate dysfunction (adjusted OR, 1.46; 95% CI, 1.39-1.53), severe dysfunction (adjusted OR, 1.96; 95% CI, 1.81-2.12), and kidney failure (adjusted OR, 2.22; 95% CI, 2.04-2.43) relative to those with normal renal function. Chronic kidney disease is present in nearly a third of patients hospitalized with ICH and is associated with slightly worse care and substantially higher mortality than those with normal renal function. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Serum Neutrophil Gelatinase-Associated Lipocalin and Urinary Kidney Injury Molecule-1 as Potential Biomarkers of Subclinical Nephrotoxicity After Gadolinium-Based and Iodinated-Based Contrast Media Exposure in Pediatric Patients with Normal Kidney Function

PubMed Central

Spasojević-Dimitrijeva, Brankica; Kotur-Stevuljević, Jelena; Đukić, Milan; Paripović, Dušan; Miloševski-Lomić, Gordana; Spasojević-Kalimanovska, Vesna; Pavićević, Polina; Mitrović, Jadranka; Kostić, Mirjana

2017-01-01

Background New renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) show promise in early diagnosis of contrast media induced acute kidney injury (CI-AKI). The purpose of our study was to compare the subclinical nephrotoxicity (a condition without changes in standard renal biomarkers) of gadolinium-based contrast media (Gd-DTPA, gadopentetate dimeglumine) and iodinated-based contrast media (iopromide) in pediatric patients with normal kidney function. Material/Methods The first group (n=58) of patients included in the study were undergoing angiography with iopromide, and the second group (n=65) were undergoing magnetic resonance (MR) angiography/urography with Gd-DTPA administration. The concentrations of NGAL and KIM-1 were measured four times in the urine (pre-contrast, then at four hours, 24 hours, and 48 hours after contrast administration), and serum NGAL was measured at 0 (baseline), 24 hours, and 48 hours after contrast exposure. Results After 24 hours, serum NGAL increase of ≥25% was noticed in 32.6% of the patients in the iopromide group and in 25.45% of the patients in the gadolinium group, with significantly higher average percent of this increase in first group (62.23% vs. 36.44%, p=0.002). In the Gd-DTPA group, we observed a statistically significant increase in urinary KIM-1 24 hours after the procedure. Normalized urinary KIM-1, 24 hours after contrast exposure, was a better predictive factor for CI-AKI than other biomarkers (AUC 0.757, cut off 214 pg/mg, sensitivity 83.3%, specificity 54.2%, p=0.035). Conclusions In children with normal renal function, exposure to iodinated-based and gadolinium-based media might lead to subclinical nephrotoxicity, which could be detected using serum NGAL and urinary KIM-1. PMID:28874655

Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury.

PubMed

Nickolas, Thomas L; O'Rourke, Matthew J; Yang, Jun; Sise, Meghan E; Canetta, Pietro A; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2008-06-03

A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Prospective cohort study. Emergency department of Columbia University Medical Center, New York, New York. 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-beta-d-glucosaminidase (NAG) by enzyme measurement, alpha1-microglobulin and alpha(1)-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 microg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 microg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, alpha1-microglobulin, alpha1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). All patients came from a single center. Few kidney biopsies were performed. A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes.

Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase–Associated Lipocalin for Diagnosing Acute Kidney Injury

PubMed Central

Nickolas, Thomas L.; O’Rourke, Matthew J.; Yang, Jun; Sise, Meghan E.; Canetta, Pietro A.; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2010-01-01

Background A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. Objective To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase–associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Design Prospective cohort study. Setting Emergency department of Columbia University Medical Center, New York, New York. Participants 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Measurements Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-β-D-glucosaminidase (NAG) by enzyme measurement, α1-microglobulin and α1-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Results Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 μg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 μg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, α1-microglobulin, α1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). Limitations All patients came from a single center. Few kidney biopsies were performed. Conclusion A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes. PMID:18519927

Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study.

PubMed

Mocroft, Amanda; Lundgren, Jens D; Ross, Michael; Fux, Christoph A; Reiss, Peter; Moranne, Olivier; Morlat, Philippe; Monforte, Antonella d'Arminio; Kirk, Ole; Ryom, Lene

2016-01-01

Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir. In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored. The Highly Active Antiretroviral Therapy Oversight Committee. Copyright © 2016 Elsevier Ltd. All rights reserved.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus.

PubMed

Li, Jiang; Guo, Qing-Jun; Cai, Jin-Zhen; Pan, Cheng; Shen, Zhong-Yang; Jiang, Wen-Tao

2017-12-07

Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

[Antioxidant properties of cluster rhenium compounds and their effect on erythropoiesis of rats with guerin carcinoma].

PubMed

Voronkova, Y S; Babiy, S O; Ivans'kar, L V; Shtemenko, O V; Shtemenko, N I

2015-01-01

Biochemical characteristics of kidneys, pe- ripheral blood and bone marrow of rats in model of tumor growth under introduction of cisplatin and cis-tetrachlorodi-μ-isobutyratodirhenium(III), cis-Re2(i-C3H7COO)2Cl4 (I) have been investigated. It was shown that introduction of I alone and together with cisplatin led to decrease of biochemical markers of oxidation of lipids and proteins in tissue homogenates of the kidneys, change of enzyme activity in the urea and tissue homogenates of the kidneys, by a decrease of filtration function of kidneys. Introduction of nanoliposomal forms of the rhenium cluster compound led to a practically normal morphological picture of bone marrow and increase of the RBC (by 60%) with normalization of hematocrit counts, and decrease of quantities of destructed RBC (3.2 times) in comparison with the tumor-bearing animals. A tentative scheme of influence of cluster rhenium compound on erythropoiesis through regulation of synthesis of erythropoietin in kidneys has been proposed.

Angiotensin converting enzyme inhibition and the kidney

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.

1988-01-01

Angiotensin II (Ang II) induces a marked reduction in renal blood flow at doses well below those required to induce a pressor response, and as blood flow falls there is a decline in glomerular filtration rate and sodium excretion. This striking sensitivity of the renal blood supply led many workers to consider the possibility that angiotensin functions as a local renal hormone. As angiotensin converting enzyme (ACE) was found in particular abundance in the lung, it seemed reasonable to suspect that most of the conversion occurred there, and that the function of Ang II would be primarily systemic, rather than intrarenal. In this review, I will explore the evidence that has accumulated on these two possibilities, since they have important implications for our current understanding of normal kidney function and derangements of kidney function in disease.

Microgravity

NASA Image and Video Library

1998-01-01

Cells from kidneys lose some of their special features in conventional culture but form spheres replete with specialized cell microvilli (hair) and synthesize hormones that may be clinically useful. Ground-based research studies have demonstrated that both normal and neoplastic cells and tissues recreate many of the characteristics in the NASA bioreactor that they display in vivo. Proximal kidney tubule cells that normally have rich apically oriented microvilli with intercellular clefts in the kidney do not form any of these structures in conventional two-dimensional monolayer culture. However, when normal proximal renal tubule cells are cultured in three-dimensions in the bioreactor, both the microvilli and the intercellular clefts form. This is important because, when the morphology is recreated, the function is more likely also to be rejuvenated. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC).

Tissue grown in NASA Bioreactor

NASA Technical Reports Server (NTRS)

1998-01-01

Cells from kidneys lose some of their special features in conventional culture but form spheres replete with specialized cell microvilli (hair) and synthesize hormones that may be clinically useful. Ground-based research studies have demonstrated that both normal and neoplastic cells and tissues recreate many of the characteristics in the NASA bioreactor that they display in vivo. Proximal kidney tubule cells that normally have rich apically oriented microvilli with intercellular clefts in the kidney do not form any of these structures in conventional two-dimensional monolayer culture. However, when normal proximal renal tubule cells are cultured in three-dimensions in the bioreactor, both the microvilli and the intercellular clefts form. This is important because, when the morphology is recreated, the function is more likely also to be rejuvenated. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC).

Antigravity suit inflation - Kidney function and cardiovascular and hormonal responses in men

NASA Technical Reports Server (NTRS)

Geelen, Ghislaine; Kravik, Stein E.; Hadj-Aissa, Aoumeur; Leftheriotis, Georges; Vincent, Madeleine

1989-01-01

The effect of the lower body positive pressure (LBPP) on kidney function in normal men was investigated in experiments in which the subjects underwent 30 min of sitting and then were subjected to 4.5 h of 70-deg head-up tilt. During the last 3 h of the tilt period, an antigravity suit (60 T legs, 30 T abdomen) was applied. The results showed that LBPP induces a significant increase in effective renal plasma flow and significant changes in the kidney excretory patterns, which were similar to those observed during a water immersion or the early phase of bed rest.

The influence of contrast media on kidney function in patients with stable coronary artery disease.

PubMed

Reuter, Simon Bertram; Harutyunyan, Marina; Mygind, Naja Dam; Jørgensen, Erik; Kastrup, Jens

2014-08-01

To investigate the incidence of contrast media-induced nephropathy (CIN) in patients with stable coronary artery disease (CAD) referred for elective coronary intervention following hydration routines. The reversibility of CIN was followed in a 6 month-period. A total of 447 patients referred for elective coronary intervention due to suspected CAD were included. Blood samples were collected before and 24 h after intervention and medical records were obtained. Patients had no drinking fluid restrictions and were routinely treated with a 1000 ml saline infusion. All patients were invited to a 6-month examination and collection of blood samples. A total of 19 patients (4.3%) developed CIN. CIN patients had a pre-investigation higher estimated glomerular filtration rate (eGRF), lower level of kidney failure and lower creatinine level than non-CIN patients. Kidney function was not normalized in CIN patients 6 months after the intervention. Two patients still met the definition of CIN. With no restriction in fluid intake and supplementary infusion of saline, only a few patients with stable CAD developed early indications of CIN during elective coronary interventions. Kidney function and the amount of contrast media used was not a predictor of CIN development. The induced CIN was not completely normalized in a 6-month follow-up period.

Quantification of single-kidney glomerular filtration rate with electron-beam computed tomography

NASA Astrophysics Data System (ADS)

Lerman, Lilach O.; Ritman, Erik L.; Pelaez, Laura I.; Sheedy, Patrick F., II; Krier, James D.

2000-04-01

The ability to accurately and noninvasively quantify single- kidney GFR could be invaluable for assessment of renal function. We developed a model that enables this measurement with EBCT. To examine the reliability of this method, EBCT renal flow and volume studies after contrast media administration were performed in pigs with unilateral renal artery stenosis (Group 1), controls (Group 2), and simultaneously with inulin clearance (Group 3). Renal flow curves, obtained from the bilateral renal cortex and medulla, depicted transit of the contrast through the vascular and tubular compartments, and were fitted using extended gamma- variate functions. Renal blood flow was calculated as the sum of products of cortical and medullary perfusions and volumes. Normalized GFR (mL/min/cc) was calculated using the rate (maximal slope) of proximal tubular contrast accumulation, and EBCT-GFR as normalized GFR* cortical volume. In Group 1, the decreased GFR of the stenotic kidney correlated well with its decreased volume and RBF, and with the degree of stenosis (r equals -0.99). In Group 3, EBCT-GFR correlated well with inulin clearance (slope 1.1, r equals 0.81). This novel approach can be very useful for quantification of concurrent regional hemodynamics and function in the intact kidneys, in a manner potentially applicable to humans.

Effects of kidney or kidney-pancreas transplantation on plasma pentosidine.

PubMed

Hricik, D E; Schulak, J A; Sell, D R; Fogarty, J F; Monnier, V M

1993-02-01

Tissue and plasma concentrations of pentose-derived glycation end-products ("pentosidine") are elevated in diabetic patients with normal renal function and in both diabetic and nondiabetic patients with end-stage renal disease. To determine the effects of correcting hyperglycemia and/or renal failure on the accumulation of pentosidine, we used reverse phase and ion exchange high performance liquid chromatography to measure this advanced glycation end-product in plasma proteins of diabetic and nondiabetic transplant recipients at various time intervals after kidney-pancreas or kidney transplantation. Changes in plasma pentosidine levels after transplantation were compared to changes in simultaneously obtained glycohemoglobin levels. Both kidney and kidney-pancreas transplantation were accompanied by a dramatic, but incomplete, reduction of plasma pentosidine concentrations within three months of transplantation. Kidney-pancreas transplantation resulted in normal glycohemoglobin levels within three months but offered no advantage over kidney transplantation alone in the partial correction of plasma pentosidine levels. There was no correlation between posttransplant plasma pentosidine and glycohemoglobin levels in either diabetic or nondiabetic transplant recipients. We conclude that renal failure is the major factor accounting for the accumulation of pentosidine in both diabetic and nondiabetic patients with end-stage renal disease. Restoration of euglycemia after kidney-pancreas transplantation provides no additional benefit in reducing plasma pentosidine levels to that achieved by correction of renal failure after kidney transplantation alone.

The gut-kidney axis in chronic renal failure: A new potential target for therapy.

PubMed

Khoury, Tawfik; Tzukert, Keren; Abel, Roy; Abu Rmeileh, Ayman; Levi, Ronen; Ilan, Yaron

2017-07-01

Evidence is accumulating to consider the gut microbiome as a central player in the gut-kidney axis. Microbiome products, such as advanced glycation end products, phenols, and indoles, are absorbed into the circulation but are cleared by normal-functioning kidneys. These products then become toxic and contribute to the uremic load and to the progression of chronic kidney failure. In this review, we discuss the gut-kidney interaction under the state of chronic kidney failure as well as the potential mechanisms by which a change in the gut flora (termed gut dysbiosis) in chronic kidney disease (CKD) exacerbates uremia and leads to further progression of CKD and inflammation. Finally, the potential therapeutic interventions to target the gut microbiome in CKD are discussed. © 2016 International Society for Hemodialysis.

An unusual case of acute kidney injury due to vancomycin lessons learnt from reliance on eGFR.

PubMed

Barraclough, Katherine; Harris, Marianne; Montessori, Val; Levin, Adeera

2007-08-01

We present a case of renal impairment in an emaciated HIV-infected male that initially went unrecognized because of reliance on serum creatinine and estimated glomerular filtration rate (eGFR). Inaccurate vancomycin dosing led to toxic drug levels (66 mg/l), associated with acute and severe worsening of kidney function. This occurred in the context of escalating doses of vancomycin given in the presence of changing kidney function, albeit kidney function that always remained well within the normal range (serum creatinine 29 - 42 mumol/l). In the absence of other plausible explanations, a presumptive diagnosis of vancomycin nephrotoxicity was made. Given the rarity of this diagnosis in the current era, we discuss the pathophysiology of vancomycin nephrotoxicity. We also explore the potential reasons for inaccuracy of GFR prediction equations in the HIV population, and discuss the potential pitfalls associated with application of eGFR or even serum creatinine without appropriate understanding of their limitations. We believe our case highlights a number of important teaching points: Vancomycin nephrotoxitiy is rare but can occur in the setting of kidney dysfunction. Current assessment of kidney function using creatinine and eGFR requires awareness of the clinical caveats in which these measures may be misleading. Acute changes in kidney function, irrespective of the test used, should be contextualized to the individual situation. Persons with HIV and low muscle mass constitute a specific subgroup in whom assessment of kidney function may be problematic using creatinine. We support ongoing efforts to develop or refine equations for specific unique and easily identifiable populations.

How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology

PubMed Central

Williamson, Lydia; New, David

2014-01-01

Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. PMID:25239988

How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology.

PubMed

Williamson, Lydia; New, David

2014-09-19

Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. 2014 BMJ Publishing Group Ltd.

First successful combined heart and kidney transplant in Iran: a case report.

PubMed

Ahmadi, Zargham-Hossein; Mirhosseini, Seyed Mohsen; Fakhri, Mohammad; Mozaffary, Amirhossein; Lotfaliany, Mojtaba; Nejatollahi, Seyed Mohammad Reza; Marashi, Seyed-Ali; Behzadnia, Neda; Sharif-Kashani, Babak

2013-08-01

Combined heart and kidney transplant has become an accepted therapy for patients with coexisting heart and kidney failure. This method, compared with single-organ transplant, has a better outcome. Here, we report the first successful combined heart and kidney transplant in Iran. The patient was a 36-year-old man with end-stage renal disease owing to IgA nephropathy, admitted to Masih Daneshvari Hospital in Tehran, Iran for progressive dyspnea and chest pain. In-patient evaluations revealed cardiomyopathy leading to end-stage heart failure. Owing to concurrent heart and kidney end-stage diseases, combined cardiorenal transplant was done. Eight months after his transplant, routine follow-ups have not shown any signs of acute rejection. He is now New York Heart Association functional class I. Both cardiac and renal functions are within normal ranges. Good outcome during follow-up for this case justifies simultaneous heart plus kidney transplants as an alternate treatment for patients with advanced disease of both organs.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

Impact of Momordica charantia extract on kidney function and structure in mice.

PubMed

Mardani, Saeed; Nasri, Hamid; Hajian, Shabnam; Ahmadi, Ali; Kazemi, Reyhane; Rafieian-Kopaei, Mahmoud

2014-01-01

Bitter Melon (BM) is known for its hypoglycemic effect and is commonly used in populations. This study examined the effects and safety of bitter melon fruit in laboratory mice. In this experimental study 70 male mice (25-30 gr) were randomly divided into 7 groups. The mice were injected intraperitoneally with single doses of 0, 100, 500, 1000, 2000 and 4000 mg/kg and multiple doses 500 mg/kg daily for 7 days. The mice were then observed for 72 hours before sacrificing. Immediately kidneys were taken out for histological examinations. Tubular cell vacuolization and flattening as well as hyaline casts, debris and dilatation of tubular lumen were the morphologic lesions which were assessed with scores from 0 to 4, while zero score addressed normal renal tissue. Serum samples were assayed for kidney function (creatinine; Cr and Blood Urea Nitrogen; BUN). Blood and bitter melon antioxidant activities were measured, too. Data were analyzed with Stata software (Stata Corp. 2011. Stata Statistical Software: Release 12. College Station, TX: Stata Corp LP)using ANOVA and Bonferroni tests. All single dose groups showed normal behavior after the dosing and no statistical changes were observed in blood parameters (p>0.05). Histological examinations revealed normal organ structures, however, the group treated for 7 days showed statistically a significant change in BUN (p=0.002) and a borderline significance in Cr (p=0.051). Administration of up to 4000 mg/kg did not have any effect on the mice kidney function and histology, however chronic administration were nephrotoxic. More studies with different dosage regimens are suggested.

Mechanisms of nephroprotective effect of mitochondria-targeted antioxidants under rhabdomyolysis and ischemia/reperfusion.

PubMed

Plotnikov, E Y; Chupyrkina, A A; Jankauskas, S S; Pevzner, I B; Silachev, D N; Skulachev, V P; Zorov, D B

2011-01-01

Oxidative stress-related renal pathologies apparently include rhabdomyolysis and ischemia/reperfusion phenomenon. These two pathologies were chosen for study in order to develop a proper strategy for protection of the kidney. Mitochondria were found to be a key player in these pathologies, being both the source and the target for excessive production of reactive oxygen species (ROS). A mitochondria-targeted compound which is a conjugate of a positively charged rhodamine molecule with plastoquinone (SkQR1) was found to rescue the kidney from the deleterious effect of both pathologies. Intraperitoneal injection of SkQR1 before the onset of pathology not only normalized the level of ROS and lipid peroxidized products in kidney mitochondria but also decreased the level of cytochrome c in the blood, restored normal renal excretory function and significantly lowered mortality among animals having a single kidney exposed to ischemia/reperfusion. The SkQR1-derivative missing plastoquinone (C12R1) possessed some, although limited nephroprotective properties and enhanced animal survival after ischemia/reperfusion. SkQR1 was found to induce some elements of nephroprotective pathways providing ischemic tolerance such as an increase in erythropoietin levels and phosphorylation of glycogen synthase kinase 3β in the kidney. SkQR1 also normalized renal erythropoietin level lowered after kidney ischemia/reperfusion and injection of a well-known nephrotoxic agent gentamicin. Copyright © 2010 Elsevier B.V. All rights reserved.

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

PubMed

Petras, Dimitrios; Koutroutsos, Konstantinos; Kordalis, Athanasios; Tsioufis, Costas; Stefanadis, Christodoulos

2013-08-01

The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

Postrenal acute kidney injury in a patient with unilateral ureteral obstruction caused by urolithiasis: A case report.

PubMed

Kazama, Itsuro; Nakajima, Toshiyuki

2017-10-01

In patients with bilateral ureteral obstruction, the serum creatinine levels are often elevated, sometimes causing postrenal acute kidney injury (AKI). In contrast, those with unilateral ureteral obstruction present normal serum creatinine levels, as long as their contralateral kidneys are preserved intact. However, the unilateral obstruction of the ureter could affect the renal function, as it humorally influences the renal hemodynamics. A 66-year-old man with a past medical history of hypertension and diabetes mellitus came to our outpatient clinic because of right abdominal dullness. Unilateral ureteral obstruction caused by a radio-opaque calculus in the right upper ureter and a secondary renal dysfunction. As oral hydration and the use of calcium antagonists failed to allow the spontaneous stone passage, extracorporeal shock wave lithotripsy (ESWL) was performed. Immediately after the passage of the stone, the number of red blood cells in the urine was dramatically decreased and the serum creatinine level almost returned to the normal range with the significant increase in glomerular filtration rate. Unilateral ureteral obstruction by the calculus, which caused reflex vascular constriction and ureteral spasm in the contralateral kidney, was thought to be responsible for the deteriorating renal function.

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial.

PubMed

Zhu, Ran; Allingstrup, Matilde J; Perner, Anders; Doig, Gordon S

2018-05-15

We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. ICUs of 16 hospitals throughout Australia and New Zealand. Adult critically ill patients expected to remain in the study ICU for longer than 2 days. Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, -7.9%; 95% CI, -15.1 to -0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, -0.6%; 95% CI, -16.2 to 15.2; p = 0.95). In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.

The Genetics and Epigenetics of Kidney Development

PubMed Central

Patel, Sanjeevkumar R.; Dressler, Gregory R.

2013-01-01

The development of the mammalian kidney has been studied at the genetic, biochemical, and cell biological level for more than 40 years. As such, detailed mechanisms governing early patterning, cell lineages, and inductive interactions are well described. How genes interact to specify the renal epithelial cells of the nephrons and how this specification is relevant to maintaining normal renal function is discussed. Implicit in the development of the kidney are epigenetic mechanisms that mark renal cell types and connect certain developmental regulatory factors to chromatin modifications that control gene expression patterns and cellular physiology. In adults, such regulatory factors and their epigenetic pathways may function in regeneration and may be disturbed in disease processes. PMID:24011574

Alport Syndrome

MedlinePlus

... in your genes (mutations) to a protein called collagen. Collagen is important to the normal structure and function of the kidneys. Changes to collagen can also cause problems with the eyes and ...

Four-dimensional MRI of renal function in the developing mouse.

PubMed

Xie, Luke; Subashi, Ergys; Qi, Yi; Knepper, Mark A; Johnson, G Allan

2014-09-01

The major roles of filtration, metabolism and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for the early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (four dimensional) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full three-dimensional image (isotropic resolution, 125 microns) every 7.7 s over a 50-min scan. This time course permitted the demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13 and 17 weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts to segment the four regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM and inner medulla (IM). Local volumes, time-to-peak (TTP) values and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Comparison of the Gene Expression Profiles from Normal and Fgfrl1 Deficient Mouse Kidneys Reveals Downstream Targets of Fgfrl1 Signaling

PubMed Central

Gerber, Simon D.; Amann, Ruth; Wyder, Stefan; Trueb, Beat

2012-01-01

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron. PMID:22432025

Amyloidosis

MedlinePlus

... your tissues as amyloid, interfering with normal function. AA amyloidosis mostly affects your kidneys but occasionally your ... infectious or inflammatory disease increases your risk of AA amyloidosis. Family history. Some types of amyloidosis are ...

Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

PubMed

Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

2010-11-01

A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

PubMed

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

PubMed Central

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

Star fruit toxicity: a cause of both acute kidney injury and chronic kidney disease: a report of two cases.

PubMed

Abeysekera, R A; Wijetunge, S; Nanayakkara, N; Wazil, A W M; Ratnatunga, N V I; Jayalath, T; Medagama, A

2015-12-17

Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits. The first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2-3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis. These cases illustrate the importance of obtaining the patient's detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause.

New approaches in renal microscopy: volumetric imaging and superresolution microscopy.

PubMed

Kim, Alfred H J; Suleiman, Hani; Shaw, Andrey S

2016-05-01

Histologic and electron microscopic analysis of the kidney has provided tremendous insight into structures such as the glomerulus and nephron. Recent advances in imaging, such as deep volumetric approaches and superresolution microscopy, have the capacity to dramatically enhance our current understanding of the structure and function of the kidney. Volumetric imaging can generate images millimeters below the surface of the intact kidney. Superresolution microscopy breaks the diffraction barrier inherent in traditional light microscopy, enabling the visualization of fine structures. Here, we describe new approaches to deep volumetric and superresolution microscopy of the kidney. Rapid advances in lasers, microscopic objectives, and tissue preparation have transformed our ability to deep volumetric image the kidney. Innovations in sample preparation have allowed for superresolution imaging with electron microscopy correlation, providing unprecedented insight into the structures within the glomerulus. Technological advances in imaging have revolutionized our capacity to image both large volumes of tissue and the finest structural details of a cell. These new advances have the potential to provide additional profound observations into the normal and pathologic functions of the kidney.

Embryonic kidney function in a chronic renal failure model in rodents.

PubMed

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

En bloc transplantation of horseshoe kidney in Korea

PubMed Central

Bang, Jun Bae; Lee, Jae Myeong; Oh, Chang-Kwon; Lee, Kyo Won; Park, Jae Berm; Kim, Sung Joo

2017-01-01

Transplantation of the horseshoe kidney can be performed en bloc or split into 2 grafts according to the vascular anomaly and the existence of the urinary collecting system in isthmus. From 2011 to 2014, there were 3 horseshoe kidney transplantations in Korea and transplantations were performed at 2 different centers. The transplantations were carried out successfully for all recipients without complications. All recipients have shown good graft kidney function after transplantation. No severe complication was revealed during follow-up period. We described the surgical technique used in the en bloc method to overcome various vascular anomalies and difficulties in choosing cannulation site and postoperative complications. En bloc transplantation of a horseshoe kidney is a useful strategy for patients with end-stage renal disease, and can provide favorable outcomes compared to the transplantation of a normal kidney. PMID:28289672

Clinical case report: a rare cause of acute kidney failure - tissue is the issue.

PubMed

Heggermont, Ward A; Verhoef, Gregor; Evenepoel, Pieter; Sprangers, Ben; Lerut, Evelyn; Tousseyn, Thomas; Claes, Kathleen

2017-06-01

A patient was admitted to the medical emergency department by his family physician. His complaints were weakness and fatigue for more than one week. Four days before admission, he went to his general practitioner for these complaints and also for painful elbows. His physician prescribed diclofenac and esomeprazole. Upon presentation, he had high systolic/diastolic blood pressure (>180/>90 mm Hg, measured repeatedly), and otherwise normal parameters. He had gained 6.5 kg in body weight. Clinical examination was normal, except for very mild bilateral malleolar edema. Routine blood tests showed a strongly elevated serum creatinine, hyperkalemia, and elevated lactate dehydrogenase. Haptoglobin levels were normal. Urinalysis showed a normal sediment, urine and blood cultures remained sterile. Ophthalmoscopy was completely normal, as was a routine chest X-ray. Renal ultrasound demonstrated kidneys with a diameter of 13 cm. Due to uncontrollable hypertension, our patient was hospitalized at the intensive care department where intravenous nifedipine was started, with good instantaneous control of blood pressure. Because of increasing potassium levels acute hemodialysis was started within 24 h after admission. Differential diagnosis consisted of diclofenac- or esomeprazole-induced interstitial nephritis or rapidly progressive glomerulonephritis. A renal biopsy was performed within 72 h after admission. The kidney biopsy showed an overwhelming inflammatory cell infiltrate consisting of a monoclonal lymphocytic cell population. However, the numerous mitotic figures, polyploidy, and prominent nucleoli present, were indicative of a lymphoma. Additional stainings confirmed a non-Hodgkin diffuse large-cell B-cell lymphoma. Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, and prednisolone) was initiated with very good clinical and biochemical response, yet only mild recovery of kidney function. Occasionally the kidney is involved as an extranodal non-Hodgkin lymphoma (NHL) localization. However, a primary presentation of acute kidney failure due to lymphoma localization is extremely rare. Our case demonstrates that early renal biopsy is indispensable for fast and adequate diagnosis and treatment.

Nephro-protective action of P. santalinus against alcohol-induced biochemical alterations and oxidative damage in rats.

PubMed

Bulle, Saradamma; Reddy, Vaddi Damodara; Hebbani, Ananda Vardhan; Padmavathi, Pannuru; Challa, Chandrasekhar; Puvvada, Pavan Kumar; Repalle, Elisha; Nayakanti, Devanna; Aluganti Narasimhulu, Chandrakala; Nallanchakravarthula, Varadacharyulu

2016-12-01

The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na + /K + -ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Cyclodextrin Protects Podocytes in Diabetic Kidney Disease

PubMed Central

Merscher-Gomez, Sandra; Guzman, Johanna; Pedigo, Christopher E.; Lehto, Markku; Aguillon-Prada, Robier; Mendez, Armando; Lassenius, Mariann I.; Forsblom, Carol; Yoo, TaeHyun; Villarreal, Rodrigo; Maiguel, Dony; Johnson, Kevin; Goldberg, Ronald; Nair, Viji; Randolph, Ann; Kretzler, Matthias; Nelson, Robert G.; Burke, George W.; Groop, Per-Henrik; Fornoni, Alessia

2013-01-01

Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD+) when compared with diabetic patients with normoalbuminuria (DKD−) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes. PMID:23835338

Application of ureterorenoscope and flexible ureterorenoscope lithotripsy in removing calculus from extracorporeal living donor renal graft: a single-center experience.

PubMed

Lin, Chun-Hua; Zhang, Zuo-Fu; Wang, Jiahui; Yu, Lu-Xin; Wang, Wen-Ting; Shi, Lei; Lin, Xiang-Nan

2017-11-01

Here, we reported our clinical application of ureterorenoscope (URS) and flexible URS lithotripsy in stone removal on 10 cases of excised living donor kidney graft. After the extraction of donor kidney by retroperitoneal laparoscopy, the donor graft was perfused with 4 °C HCA solution. Calculus between 2-4 mm were removed intact with lithotomy forceps under direct vision of URS. Larger calculi of >4 mm were fractured with flexible URS combining holmium laser lithotripsy. Fragments of the calculus were extracted with basket extractor and lithotomy forceps. All operations were successful. The operation time was 14-31 min (average 21.2 ± 6.3 min). The kidneys were then transplanted to the recipients using routine procedure. The transplanted kidneys functioned well after transplantation. Gross hematuria resolved 1-4 d after operation (average 2.6 ± 0.9 d). The transplanted kidneys functioned well without early complications such as functional recovery delay and acute graft rejection. The donors and recipients were followed for 12 months. The size of the transplanted kidneys was normal and new stones or urinary obstruction was not seen upon urinary color Doppler ultrasound examination. In conclusion, we believe it is feasible, safe and effective to use URS or flexible URS combining holmium laser lithotripsy on extracorporeal living donor kidney.

Analysis of renal blood flow and renal volume in normal fetuses and in fetuses with a solitary functioning kidney.

PubMed

Hindryckx, An; Raaijmakers, Anke; Levtchenko, Elena; Allegaert, Karel; De Catte, Luc

2017-12-01

To evaluate renal blood flow and renal volume for the prediction of postnatal renal function in fetuses with solitary functioning kidney (SFK). Seventy-four SFK fetuses (unilateral renal agenesis [12], multicystic dysplastic kidney [36], and severe renal dysplasia [26]) were compared with 58 healthy fetuses. Peak systolic velocity (PSV), pulsatility index (PI), and resistance index (RI) of the renal artery (RA) were measured; 2D and 3D (VOCAL) volumes were calculated. Renal length and glomerular filtration rate (GFR) were obtained in SFK children (2 years). Compared with the control group, the PSV RA was significantly lower in nonfunctioning kidneys and significantly higher in SFK. Volume measurements indicated a significantly larger volume of SFK compared with healthy kidneys. All but 4 children had GFR above 70 mL/min/1.73 m 2 , and compensatory hypertrophy was present in 69% at 2 years. PSV RA and SFK volume correlated with postnatal renal hypertrophy. No correlation between prenatal and postnatal SFK volume and GFR at 2 years was demonstrated. Low PSV RA might have a predictive value for diagnosing a nonfunctioning kidney in fetuses with a SFK. We demonstrated a higher PSV RA and larger renal volume in the SFK compared with healthy kidneys. © 2017 John Wiley & Sons, Ltd.

Kidney Transplantation in a Patient Lacking Cytosolic Phospholipase A2 Proves Renal Origins of Urinary PGI-M and TX-M.

PubMed

Mitchell, Jane A; Knowles, Rebecca B; Kirkby, Nicholas S; Reed, Daniel M; Edin, Matthew L; White, William E; Chan, Melissa V; Longhurst, Hilary; Yaqoob, Magdi M; Milne, Ginger L; Zeldin, Darryl C; Warner, Timothy D

2018-02-16

The balance between vascular prostacyclin, which is antithrombotic, and platelet thromboxane A 2 , which is prothrombotic, is fundamental to cardiovascular health. Prostacyclin and thromboxane A 2 are formed after the concerted actions of cPLA 2 α (cytosolic phospholipase A 2 ) and COX (cyclooxygenase). Urinary 2,3-dinor-6-keto-PGF 1α (PGI-M) and 11-dehydro-TXB 2 (TX-M) have been taken as biomarkers of prostacyclin and thromboxane A 2 formation within the circulation and used to explain COX biology and patient phenotypes, despite concerns that urinary PGI-M and TX-M originate in the kidney. We report data from a remarkable patient carrying an extremely rare genetic mutation in cPLA 2 α, causing almost complete loss of prostacyclin and thromboxane A 2 , who was transplanted with a normal kidney resulting in an experimental scenario of whole-body cPLA 2 α knockout, kidney-specific knockin. By studying this patient, we can determine definitively the contribution of the kidney to the productions of PGI-M and TX-M and test their validity as markers of prostacyclin and thromboxane A 2 in the circulation. Metabolites were measured using liquid chromatography-tandem mass spectrometry. Endothelial cells were grown from blood progenitors. Before kidney transplantation, the patient's endothelial cells and platelets released negligible levels of prostacyclin (measured as 6-keto-prostaglandin F 1α ) and thromboxane A 2 (measured as TXB 2 ), respectively. Likewise, the urinary levels of PGI-M and TX-M were very low. After transplantation and the establishment of normal renal function, the levels of PGI-M and TX-M in the patient's urine rose to within normal ranges, whereas endothelial production of prostacyclin and platelet production of thromboxane A 2 remained negligible. These data show that PGI-M and TX-M can be derived exclusively from the kidney without contribution from prostacyclin made by endothelial cells or thromboxane A 2 by platelets in the general circulation. Previous work relying on urinary metabolites of prostacyclin and thromboxane A 2 as markers of whole-body endothelial and platelet function now requires reevaluation. © 2018 The Authors.

Neonatal diabetes mellitus, congenital hypothyroidism, hepatic fibrosis, polycystic kidneys, and congenital glaucoma: a new autosomal recessive syndrome?

PubMed

Taha, Doris; Barbar, Maha; Kanaan, Hassan; Williamson Balfe, John

2003-10-15

We report on two sibs (of 4) with a syndrome of minor facial anomalies, proportionate IUGR, neonatal non-autoimmune diabetes mellitus (NDM), severe congenital hypothyroidism (CH), cholestasis, congenital glaucoma, and polycystic kidneys. Liver disease progressed to hepatic fibrosis. The renal disease was characterized by large kidneys and multiple small cysts with deficient corticomedullary junction differentiation and normal kidney function. The phenotype observed in the two sibs was identical. Although a combination of liver, kidney, and pancreatic involvement has been described in Ivemark syndrome (hepato-renal-pancreatic syndrome), the coexistence of NDM, CH, and glaucoma in both sibs suggests the possibility that this combination of manifestations describes a new autosomal recessive syndrome. Mutation analysis for several candidate genes is warranted. Copyright 2003 Wiley-Liss, Inc.

Lipopolysaccharide effects on the proliferation of NRK52E cells via alternations in gap-junction function.

PubMed

Hei, Ziqing; Zhang, Ailan; Wei, Jing; Gan, Xiaoliang; Wang, Yanling; Luo, Gangjian; Li, Xiaoyun

2012-07-01

Gap junctions regulate proper kidney function by facilitating intercellular communication, vascular conduction, and tubular purinergic signaling. However, no clear relationship has been described between gap-junction function and acute kidney injury induced by the endotoxin lipopolysaccharide (LPS). Normal rat kidney epithelial cells (NRK52E cells) were seeded at high and low densities to promote or impede gap-junction formation, respectively, and establish distinctive levels of intercellular communication in culture. Cells were then challenged with LPS at various concentrations (10-1,000 ng/mL). LPS-induced formation and function of gap junctions were assessed by measuring changes in cell proliferation and colony-forming rates, fluorescent dye transmission to adjacent cells, expression levels of connexin43, and repositioning of confluent cells in response to the gap junction inhibitor oleamide or agonist retinoic acid. The cell proliferation rate and colony-forming rate of high- and low-density NRK52E cells were decreased upon LPS challenge, in a dose-dependent manner. The colony-forming rate of confluent high-density cells was significantly lower than that of low-density cells. Oleamide treatment raised the LPS-induced colony-forming rate of high-density cells, whereas retinoic acid decreased the rate. Neither oleamide nor retinoic acid significantly affected the LPS-induced colony-forming rate of low-density cells. Fluorescence transmission of high-density cells was reduced by LPS challenge, in a dose-dependent manner, but inclusion of retinoic acid increased the LPS-induced transmission of fluorescence. LPS challenge of either high- or low-density NRK52E cells resulted in down-regulated connexin43 expression. Gap-junction function plays an important role in concentration-dependent cytotoxic effect of LPS on normal rat kidney cells in vitro.

Efficacy of oral hydration in the prevention of contrast-induced acute kidney injury in patients undergoing coronary angiography or intervention.

PubMed

Akyuz, Sukru; Karaca, Mehmet; Kemaloglu Oz, Tugba; Altay, Servet; Gungor, Baris; Yaylak, Baris; Yazici, Selcuk; Ozden, Kivilcim; Karakus, Gultekin; Cam, Nese

2014-01-01

Efficacy of intravenous (IV) volume expansion in preventing contrast-induced acute kidney injury (CI-AKI) is well known. However, the role of oral hydration has not been well established. The aim of this work was to evaluate the efficacy of oral hydration in preventing CI-AKI. We prospectively randomized 225 patients undergoing coronary angiography and/or percutaneous coronary intervention in either oral hydration or IV hydration groups. Patients who have at least one of the high-risk factors for developing CI-AKI (advanced age, type 2 diabetes mellitus, anemia, hyperuricemia, a history of cardiac failure or systolic dysfunction) were included in the study. All patients had normal renal function or stage 1-2 chronic kidney disease. Patients in the oral hydration group were encouraged to drink unrestricted amounts of fluids freely whereas isotonic saline infusion was performed by the standard protocol in the IV hydration group. CI-AKI occurred in 8/116 patients (6.9%) in the oral hydration group and 8/109 patients (7.3%) in the IV hydration group (p = 0.89). There was also no statistically significant difference between the two groups when different CI-AKI definitions were taken into account. Oral hydration is as effective as IV hydration in preventing CI-AKI in patients with normal kidney function or stage 1-2 chronic kidney disease, and who also have at least one of the other high-risk factors for developing CI-AKI. © 2014 S. Karger AG, Basel.

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules

PubMed Central

Armour, Eric A.; Carson, Robert P.

2012-01-01

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026

Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.

PubMed

Armour, Eric A; Carson, Robert P; Ess, Kevin C

2012-08-15

Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.

Infundibulopelvic stenosis in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucaya, J.; Enriquez, G.; Delgado, R.

1984-03-01

Of 11,500 children who underwent excretory urography during a 17-year period, three were found to have the rare renal malformation infundibulopelvic stenosis, characterized by caliceal dilatation, infundibular stenosis, and hypoplasia or stenosis of the renal pelvis. The contralateral kidney was absent in two cases and normal in the other. Voiding cystourethrograms were normal in all three. Renal sonography showed a variable degree of caliceal dilatation without associated pelvic dilatation. The diagnosis was confirmed by retrograde ureteropyelography in one case. Two patients were followed for 12 and 18 months, respectively; both remained asymptomatic with normal renal function, and sequential sonographic examinationsmore » of their kidneys have shown no significant changes. The third patient died of an unrelated condition. Infundibulopelvic stenosis has highly characteristic radiographic features, and prognosis is good for most affected patients.« less

Regulation of oxygen utilization by angiotensin II in chronic kidney disease

PubMed Central

Deng, Aihua; Tang, Tong; Singh, Prabhleen; Wang, Chen; Satriano, Joe; Thomson, Scott C; Blantz, Roland C

2010-01-01

Angiotensin II (ANG II) blockade delays progression of chronic kidney disease (CKD) by modifying intrarenal hemodynamics, but the effect on metabolic adaptations has not been examined. Using renal ablation/infarction (A/I) model of CKD in rats at one week, the effects of ANG II blockade by captopril (CAP) and losartan (LOS) on renal O2 consumption (QO2), renal nitric oxide (NO) activity and nitric oxide synthase (NOS) protein expression was examined. A/I kidneys exhibited proteinuria, reduced GFR, renal blood flow (RBF) and NOS-1 protein expression, while QO2 factored by sodium reabsorption (QO2/TNa) was markedly increased. CAP + LOS treatment increased GFR, RBF, and TNa, while QO2 remained unchanged, thus normalizing QO2/TNa. NOS-1 expression was normalized with CAP + LOS, as was proteinuria. Triple antihypertensive therapy administered to control for the blood pressure reduction, and lysine administration to increase GFR and RBF, did not normalize QO2/TNa, suggesting a specific effect of ANG II in elevating QO2/TNa. NOS blockade, to test functional NO activity on QO2 and QO2/TNa, increased QO2 in shams, but not in untreated A/I. The increase in QO2 was restored in CAP + LOS treated A/I. CAP + LOS treatment normalized the increased QO2/TNa and functional NO activity in A/I independent of the blood pressure and GFR effects, providing evidence for an additional mechanism underlying the benefits of ANG II inhibition therapy. PMID:18818681

Renal uptake of radioactive mercury (/sup 197/HgCl/sub 2/): method for testing the functional value of each kidney. Technique--results--and clinical application in urology and nephrology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raynaud, C.

The first three chapters consider measurement of mercury renal uptake by external counting, by quantitative scintigraphy, and by the gamma camera. Some topics discussed in the remaining 14 chapters are as follows: renal depth; phantoms; precautions regarding the liver, spleen, and intestine; stability of /sup 197/HgCl/sub 2/ solutions; use of mercury renal uptake in pediatric and adult urology; indications for mercury renal uptake in renal transplants; and appraisal of the radiological and chemical toxicity of /sup 197/HgCl/sub 2/. It was concluded that mercury renal uptake is an accurate and nontraumatizing method of measuring the functional value of each kidney. Itmore » makes it possible to determine whether a kidney is normal or pathological and to what extent its function is diminished or increased. (HLW)« less

Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney.

PubMed

Akbari, Mohsen; Goodarzi, Nader; Tavafi, Majid

2017-03-01

The functions of the mammalian kidney are closely related to its structure. This suggests that renal function can be completely characterized by accurate knowledge of its quantitative morphological features. The aim of this study was to investigate the histomorphometric features of the kidney using design-based and unbiased stereological methods in the Persian squirrel (Sciurus anomalus), which is the only representative of the Sciuridae family in the Middle East. The left kidneys of five animals were examined. Total volume of the kidney, cortex, and medulla were determined to be 960.75 ± 87.4, 754.31 ± 77.09 and 206.1 ± 16.89 mm 3 , respectively. The glomerular number was 32844.03 ± 1069.19, and the total glomerular volume was estimated to be 36.7 ± 1.45 mm 3 . The volume and length of the proximal convoluted tubule were estimated at 585.67 ± 60.7 mm 3 and 328.8 ± 14.8 m, respectively, with both values being greater than those reported in the rat kidney. The volume and length of the distal convoluted tubule were calculated at 122.34 ± 7.38 mm 3 and 234.4 ± 17.45 m, respectively, which are also greater than those reported in the rat kidney. Despite the comparable body weight, the total number and mean individual volume of glomeruli in the Persian squirrel kidney were greater than those in the rat kidney. Overall, the stereological variables of the kidneys elucidated in this study are exclusive to the Persian squirrel. Our findings, together with future renal physiological data, will contribute to a better understanding of the renal structure-function relationship in the Persian squirrel.

Leukemia kidney infiltration can cause secondary polycythemia by activating hypoxia-inducible factor (HIF) pathway.

PubMed

Osumi, Tomoo; Awazu, Midori; Fujimura, Eriko; Yamazaki, Fumito; Hashiguchi, Akinori; Shimada, Hiroyuki

2013-06-01

Secondary polycythemia with increased production of erythropoietin (EPO) is known to occur in kidney diseases such as hydronephrosis and cystic disease, but the mechanism remains unclear. We report an 18-year-old female with isolated renal relapse of acute lymphoblastic leukemia accompanied by polycythemia. At the relapse, she presented with bilateral nephromegaly, mild renal dysfunction, and erythrocytosis with increased serum EPO levels up to 52.1 mIU/mL (9.1-32.8). Renal biopsy demonstrated diffuse lymphoblastic infiltration. The expression of hypoxia-inducible factor (HIF)-1α, which is undetectable in normal kidney, was observed in the renal tubule epithelium compressed by lymphoblastic cells. These findings suggest that erythrocytosis was caused by renal ischemia due to leukemic infiltration. Polycythemia probably became apparent because of the lack of leukemic involvement of the bone marrow. With chemotherapy, the serum EPO level rapidly decreased to normal range accompanied by the normalization of kidney size and function. Renal leukemic infiltration may enhance EPO production, although not recognized in the majority of cases because of bone marrow involvement. Our case has clarified the mechanism of previously reported polycythemia associated with renal diseases as renal ischemia. Furthermore, we have added renal ischemia resulting from tumor infiltration to the list of causes of secondary polycythemia.

Laparoscopic kidney orthotopic transplant: preclinical study in the pig model.

PubMed

He, B; Musk, G C; Mou, L; Waneck, G L; Delriviere, L

2013-06-01

Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45-50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 μmol/L on day 3; 224.5 μmol/L at week 1; 127 μmol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant. Copyright © 2013 Elsevier Inc. All rights reserved.

Reestablishment of radiographic kidney size in Miniature Schnauzer dogs

PubMed Central

SOHN, Jungmin; YUN, Sookyung; LEE, Jeosoon; CHANG, Dongwoo; CHOI, Mincheol; YOON, Junghee

2016-01-01

Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly. PMID:27594274

Reestablishment of radiographic kidney size in Miniature Schnauzer dogs.

PubMed

Sohn, Jungmin; Yun, Sookyung; Lee, Jeosoon; Chang, Dongwoo; Choi, Mincheol; Yoon, Junghee

2017-01-10

Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly.

Uromodulin: a new biomarker of fetal renal function?

PubMed

Botelho, Thais Emanuelle Faria; Pereira, Alamanda Kfoury; Teixeira, Patrícia Gonçalves; Lage, Eura Martins; Osanan, Gabriel Costa; Silva, Ana Cristina Simões E

2016-12-01

Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

Kidney Stones as an Underrecognized Clinical Sign in Pediatric Cushing Disease.

PubMed

Rahman, Sara H; Papadakis, Georgios Z; Keil, Margaret F; Faucz, Fabio R; Lodish, Maya B; Stratakis, Constantine A

2016-03-01

To investigate the prevalence of kidney stones in a population of children with Cushing disease (CD) and to compare it with the prevalence of kidney stones in healthy children. Clinical and biochemical data from 139 pediatric patients with CD (68 females, 71 males) were analyzed retrospectively. Computed tomography scans were reviewed for kidney stones. Among 139 patients, 27 with CD (19.4%) had either radiographic evidence and/or a history of kidney stones. Those with kidney stones had higher urine free cortisol (P = .008) and transsphenoidal surgery at an older age (P = .007). The average urinary calcium/creatinine ratio was elevated in patients with CD (0.22 ± 0.11). The prevalence of kidney stones was higher in children with CD than in normal children (19.42% vs 1.0%; P < .001). Our results illustrate that kidney stones are an underestimated complication of pediatric CD, especially when compared with the prevalence of nephrolithiasis in the general pediatric population. Long-term consequences for kidney function are not known and need to be studied. Published by Elsevier Inc.

[Long-term outcomes of children treated with continuous renal replacement therapy].

PubMed

Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á

2015-12-01

The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

LDL-oxidation, serum uric acid, kidney function and pulse-wave velocity: Data from the Brisighella Heart Study cohort.

PubMed

Cicero, Arrigo F G; Kuwabara, Masanari; Johnson, Richard; Bove, Marilisa; Fogacci, Federica; Rosticci, Martina; Giovannini, Marina; D'Addato, Sergio; Borghi, Claudio

2018-06-15

Serum uric acid (SUA) and oxidized LDL (oxLDL) may be associated with arterial aging. The aim of our study was to evaluate the relationship between SUA, oxLDL and arterial stiffness in subjects with normal renal function and in patients with mild or moderate renal impairment. From the database of the 2012 Brisighella Heart Study, we compared age-matched adult, non-smoker subjects without cardiovascular disease and with normal renal function (n = 205), subjects with stage II chronic kidney disease (CKD) (n = 118) and subjects with stage III CKD (n = 94). All subjects underwent a determination of the LDL oxidative susceptibility, oxLDL levels, SUA and Pulse Wave Velocity (PWV). By univariate analysis, PWV correlated with a large number of clinical, haemodynamic and metabolic parameters, including estimated glomerular filtration rate (eGFR) in subjects with normal renal function and in those with stage II or III CKD. Stepwise multiple regression analyses showed that in the presence of normal renal function or stage II CKD, the main predictors of PWV were age, systolic blood pressure (SBP), ox-LDL, apolipoprotein B and SUA (p < 0.05), while in the presence of stage III CKD only age, SBP and apolipoprotein B remained significant (p < 0.05). Both ox-LDL and SUA independently predicts PWV only in subjects with normal or mildly reduced renal function, but not in the subjects with more compromised eGFR. This study confirms the complex relationship of SUA with cardiovascular and metabolic disease in the patient with established renal disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Altered microRNA regulation of short chain fatty acid receptors in the hypertensive kidney is normalized with hydrogen sulfide supplementation.

PubMed

Weber, Gregory J; Foster, Jaleyea; Pushpakumar, Sathnur B; Sen, Utpal

2018-06-15

Hypertension affects nearly one third of the adult US population and is a significant risk factor for chronic kidney disease (CKD). An expanding body of recent studies indicates that gut microbiome has crucial roles in regulating physiological processes through, among other mechanisms, one mode of short chain fatty acids (SCFA) and their target receptors. In addition, these SCFA receptors are potential targets of regulation by host miRNAs, however, the mechanisms through which this occurs is not clearly defined. Hydrogen sulfide (H 2 S) is an important gasotransmitter involved in multiple physiological processes and is known to alleviate adverse effects of hypertension such as reducing inflammation in the kidney. To determine the role of host microRNAs in regulating short chain fatty acid receptors in the kidney as well as the gut, C57BL/6J wild-type mice were treated with or without Ang-II and H 2 S donor GYY4137 (GYY) for 4 weeks to assess whether GYY would normalize adverse effects observed in hypertensive mice and whether this was in part due to altered gut microbiome composition. We observed several changes of SCFA receptors, including Olfr78, Gpr41/43 and predicted microRNA regulators in the kidney among the different treatments. Increased expression of inflammatory markers Il6 and Rorc2, along with Tgfβ, were found in the hypertensive kidney. The glomerular filtration rate (GFR) was improved in mice treated with Ang-II + GYY compared with Ang-II only, indicating improved kidney function. The Erysipelotrichia class of bacteria, linked with high fat diets, was enriched in hypertensive animals but reduced with GYY supplementation. These data point towards a role for miRNA regulation of SCFA receptors in hypertensive kidney and are normalized by H 2 S supplementation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Renal cell carcinoma: new insights and challenges for a clinician scientist.

PubMed

Shingarev, Roman; Jaimes, Edgar A

2017-08-01

There is a growing recognition of the complex interplay between renal cell cancer (RCC), kidney function, mechanical reduction of nephron mass, and systemic agents targeting the cancer. Earlier detection of RCC and rising life expectancy of cancer survivors places a greater emphasis on preservation of renal function after cancer resection and during systemic therapy. Unique adverse effects associated with RCC drugs not only help reveal cancer pathophysiology but also expand our knowledge of normal cell signaling and metabolism. In this review, we outline our current understanding of RCC biology and treatment, their bidirectional relationship with kidney function, and unmet research needs in this field. Copyright © 2017 the American Physiological Society.

Apical Plasma Membrane Mispolarization of NaK-ATPase in Polycystic Kidney Disease Epithelia Is Associated with Aberrant Expression of the β2 Isoform

PubMed Central

Wilson, Patricia D.; Devuyst, Olivier; Li, Xiaohong; Gatti, Laura; Falkenstein, Doris; Robinson, Shawn; Fambrough, Douglas; Burrow, Christopher R.

2000-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease of the kidney, characterized by cystic enlargement of renal tubules, aberrant epithelial proliferation, and ion and fluid secretion into the lumen. Previous studies have shown abnormalities in polarization of membrane proteins, including mislocalization of the NaK-ATPase to the apical plasma membranes of cystic epithelia. Apically located NaK-ATPase has previously been shown to be fully functional in vivo and in membrane-grown ADPKD epithelial cells in vitro, where basal-to-apical 22Na transport was inhibited by application of ouabain to the apical membrane compartment. Studies were conducted with polymerase chain reaction-generated specific riboprobes and polyclonal peptide antibodies against human sequences of α1, α3, β1, and β2 subunits of NaK-ATPase. High levels of expression of α1 and β1 messenger RNA were detected in ADPKD and age-matched normal adult kidneys in vivo, whereas β2 messenger RNA was detected only in ADPKD kidneys. Western blot analysis and immunocytochemical studies showed that, in normal adult kidneys, peptide subunit-specific antibodies against α1 and β1 localized to the basolateral membranes of normal renal tubules, predominantly thick ascending limbs of Henle’s loop. In ADPKD kidneys, α1 and β2 subunits were localized to the apical epithelial cell membranes, whereas β1 was distributed throughout the cytoplasm and predominantly in the endoplasmic reticulum, but was not seen associated with cystic epithelial cell membranes or in cell membrane fractions. Polarizing, renal-derived epithelial Madin Darby canine kidney cells, stably expressing normal or N-terminally truncated chicken β1 subunits, showed selective accumulation in the basolateral Madin Darby canine kidney cell surface, whereas c-myc epitope-tagged chicken β2 or human β2 subunits accumulated selectively in the apical cell surface. Similarly, human ADPKD epithelial cell lines, which endogenously expressed α1 and β2 NaK-ATPase subunits, showed colocalization at the apical cell surface and coassociation by immunoprecipitation analysis. These results are consistent with a model in which the additional transcription and translation of the β2 subunit of NaK-ATPase may result in the apical mislocalization of NaK-ATPase in ADPKD cystic epithelia. PMID:10623674

Functional capacity and cryopreservation of fetal rat pancreas in streptozotocin-diabetes. [Effectiveness of transplantation of fetal pancreas for control of diabetes in adult rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, J.; Clark, W.; Molnar, I.G.

1976-01-01

The fetal rat pancreas has a marked capacity for growth and maturation in glucose responsivity after transplantation under the kidney capsules of adult rats. The optimal conditions for function of the organ are a 3-week period of growth in a normal rat before transfer to a diabetic animal. Under these conditions diabetes is completely reversed by one fetal pancreas, and glucose disappearance rate and plasma insulin response to glucose are normal. Shunting of the venous drainage into the liver from fetal pancreases placed beneath the kidney capsule results in a marked improvement in diabetes control, and this technique may provemore » useful in experimental or human applications. Cryopreservation of the fetal pancreas has been successfully accomplished and will serve as a useful adjuvant to this method of reversing experimental diabetes.« less

Glomerular Podocytes Express Type 1 Adenylate Cyclase: Inactivation Results in Susceptibility to Proteinuria

PubMed Central

Xiao, Zhijie; He, Liqun; Takemoto, Minoru; Jalanko, Hannu; Chan, Guy C.; Storm, Daniel R.; Betsholtz, Christer; Tryggvason, Karl; Patrakka, Jaakko

2011-01-01

Background/Aims The organization of actin cytoskeleton in podocyte foot processes plays a critical role in the maintenance of the glomerular filtration barrier. The cAMP pathway is an important regulator of the actin network assembly in cells. However, the role of the cAMP pathway in podocytes is not well understood. Type 1 adenylate cyclase (Adcy1), previously thought to be specific for neuronal tissue, is a member of the family of enzymes that catalyses the formation of cAMP. In this study, we characterized the expression and role of Adcy1 in the kidney. Methods Expression of Adcy1 was studied by RT-PCR, Northern blotting and in situ hybridization. The role of Adcy1 in podocytes was investigated by analyzing Adcy1 knockout mice (Adcy1–/–). Results and Conclusion: Adcy1 is expressed in the kidney specifically by podocytes. In the kidney, Adcy1 does not have a critical role in normal physiological functioning as kidney histology and function are normal in Adcy1–/– mice. However, albumin overload resulted in severe albuminuria in Adcy1–/– mice, whereas wild-type control mice showed only mild albumin leakage to urine. In conclusion, we have identified Adcy1 as a novel podocyte signaling protein that seems to have a role in compensatory physiological processes in the glomerulus. PMID:21196775

Predicting postnatal renal function of prenatally detected posterior urethral valves using fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient determination.

PubMed

Faure, Alice; Panait, Nicoleta; Panuel, Michel; Alessandrini, Pierre; D'Ercole, Claude; Chaumoitre, Kathia; Merrot, Thierry

2017-07-01

The objective of this study was to evaluate the accuracy of fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination to predict postnatal renal function (nadir creatinine at 1 year and eGFR) of men with posterior urethral valves (PUV). Between 2003 and 2014, 11 MRI were performed on fetuses (between 28 and 32 weeks) in whom second trimester sonography suggested severe bilateral urinary tract anomalies, suspected of PUV. The ADC of the 11 fetuses ranged from 1.3 to 2.86 mm 2  s -1 (median = 1.79 mm 2  s -1 , normal range for fetal kidney: 1.1-1.8). Two pregnancies with ADC > 2.6 mm 2  s -1 were interrupted; the autopsy confirmed PUV and Potter syndrome. For the remaining nine babies, the follow-up was 5.4 years (0.8-10). Four children with abnormal ADC (1.8-2.3) had chronic kidney disease. The remaining five cases with normal nadir creatinine and eGFR had normal ADC. One case with unilateral elevated ADC had a poor ipsilateral renal function on dimercaptosuccinic acid scan. Here, it seems that diffusion-weighted magnetic resonance imaging with ADC determination could be useful in accurately evaluating fetal kidneys in PUV and predicting renal function. It may be an additional, non-invasive method when biologic and sonographic findings are inconclusive, especially in the case of oligohydramnios. Further studies are needed to confirm our data. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Effects of water uptake on melamine renal stone formation in mice.

PubMed

Peng, Jiao; Li, Daxu; Chan, Yee Kwan; Chen, Yan; Lamb, Jonathan R; Tam, Paul K H; El-Nezami, Hani

2012-06-01

Melamine-tainted food can induce kidney stones both in humans and animals and in domestic animals, severe cases caused acute kidney failure and death. Although increasing water intake can ameliorate kidney stone formation, its effect on melamine (Mel)-induced kidney stones has not been studied. We have analysed the effect of restricted ingestion of drinking water on melamine stone formation in mice. They were given melamine and cyanuric acid orally and received drinking water either freely or for a restricted time. Kidney stone formation and renal function were monitored. Mice receiving drinking water for a restricted 10-h period initially lost body weight, which returned to normal within 2 days. No other abnormalities were observed. Ingestion of melamine alone failed to induce kidney stones even under conditions of restricted drinking water. In mice treated with melamine together with cyanuric acid for 3 days, no renal stones were formed when the supply of drinking was normal. However, when drinking water was limited, stone formation was observed and accompanied by high levels of serum urea and creatinine. An increase in urine haemoglobin and glucose levels was also found. The administration resulted in up-regulated tissue osteopontin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin messenger RNA expression and macrophage infiltration. Our results indicate the importance of water intake in the formation of melamine-induced renal stone formation in the mouse and provide new information on the mechanisms of melamine stone formation.

Oral hydration for prevention of contrast-induced acute kidney injury in elective radiological procedures: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Cheungpasitporn, Wisit; Thongprayoon, Charat; Brabec, Brady A; Edmonds, Peter J; O'Corragain, Oisin A; Erickson, Stephen B

2014-12-01

The reports on efficacy of oral hydration treatment for the prevention of contrast-induced acute kidney injury (CIAKI) in elective radiological procedures and cardiac catheterization remain controversial. The objective of this meta-analysis was to assess the use of oral hydration regimen for prevention of CIAKI. Comprehensive literature searches for randomized controlled trials (RCTs) of outpatient oral hydration treatment was performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews, and clinicaltrials.gov from inception until July 4(th), 2014. Primary outcome was the incidence of CIAKI. Six prospective RCTs were included in our analysis. Of 513patients undergoing elective procedures with contrast exposures,45 patients (8.8%) had CIAKI. Of 241 patients with oral hydration regimen, 23 (9.5%) developed CIAKI. Of 272 patients with intravenous (IV) fluid regimen, 22 (8.1%) had CIAKI. Study populations in all included studies had relatively normal kidney function to chronic kidney disease (CKD) stage 3. There was no significant increased risk of CIAKI in oral fluid regimen group compared toIV fluid regimen group (RR = 0.94, 95% confidence interval, CI = 0.38-2.31). According to our analysis,there is no evidence that oral fluid regimen is associated with more risk of CIAKI in patients undergoing elective procedures with contrast exposures compared to IV fluid regimen. This finding suggests that the oral fluid regimen might be considered as a possible outpatient treatment option for CIAKI prevention in patients with normal to moderately reduced kidney function.

Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

PubMed

Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

2014-09-05

Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively). On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels. Copyright © 2014 by the American Society of Nephrology.

Effects of green tea tannin on cisplatin-induced nephropathy in LLC-PK1 cells and rats.

PubMed

Yokozawa, T; Nakagawa, T; Lee, K I; Cho, E J; Terasawa, K; Takeuchi, S

1999-11-01

A study was conducted to clarify whether green tea tannin ameliorated cisplatin-induced renal injury in terms of lactate dehydrogenase and malondialdehyde leakage from a renal epithelial cell line, swine-derived LLC-PK1 cells in culture. Green tea tannin was shown to suppress the cytotoxicity of cisplatin, the suppressive effect increasing with the dose of green tea tannin. The effect of cisplatin was then investigated in rats given green tea tannin for 40 days before cisplatin administration and in control rats given no green tea tannin. In control rats, blood, urinary and renal parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, rats given green tea tannin showed decreased blood levels of urea nitrogen and creatinine, and decreased urinary levels of protein and glucose, reflecting less damage to the kidney. In this group, the activity of catalase in the renal tissue was increased, while the level of malondialdehyde was decreased, suggesting the involvement of radicals in the normalizing of kidney function. Based on the evidence available it appeared that green tea tannin eliminated oxidative stress and was beneficial to renal function.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.

Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histologicalmore » follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.« less

Characterization of kidney CD45intCD11bintF4/80+MHCII+CX3CR1+Ly6C- "intermediate mononuclear phagocytic cells".

PubMed

Lee, Sul A; Noel, Sanjeev; Sadasivam, Mohanraj; Allaf, Mohamad E; Pierorazio, Phillip M; Hamad, Abdel R A; Rabb, Hamid

2018-01-01

Kidney immune cells play important roles in pathogenesis of many diseases, including ischemia-reperfusion injury (IRI) and transplant rejection. While studying murine kidney T cells, we serendipitously identified a kidney mononuclear phagocytic cell (MPC) subset characterized by intermediate surface expression of CD45 and CD11b. These CD45intCD11bint MPCs were further identified as F4/80+MHCII+CX3CR1+Ly6C- cells, comprising ~17% of total CD45+ cells in normal mouse kidney (P < 0.01) and virtually absent from all other organs examined except the heart. Systemic clodronate treatment had more significant depletive effect on the CD45intCD11bint population (77.3%±5.9%, P = 0.03) than on CD45highCD11b+ population (14.8%±16.6%, P = 0.49). In addition, CD45intCD11bint MPCs had higher phagocytic function in the normal kidney (35.6%±3.3% vs. 24.1%±2.2%, P = 0.04), but lower phagocytic capacity in post-ischemic kidney (54.9%±1.0% vs. 67.8%±1.9%, P < 0.01) compared to the CD45highCD11b+ population. Moreover, the CD45intCD11bint population had higher intracellular production of the pro-inflammatory tumor necrosis factor (TNF)-α (58.4%±5.2% vs. 27.3%±0.9%, P < 0.001) after lipopolysaccharide (LPS) stimulation and lower production of the anti-inflammatory interleukin (IL)-10 (7.2%±1.3% vs. 14.9%±2.2%, P = 0.02) following kidney IRI, suggesting a functional role under inflammatory conditions. The CD45intCD11bint cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45highCD11b+ cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45intCD11bint MPC subtype in human kidney. We conclude that CD45intCD11bint F4/80+MHCII+CX3CR1+Ly6C-population represent a unique subset of MPCs found in both mouse and human kidneys. Future studies will further characterize their role in kidney health and disease.

Can zero-hour cortical biopsy predict early graft outcomes after living donor renal transplantation?

PubMed

Rathore, Ranjeet Singh; Mehta, Nisarg; Mehta, Sony Bhaskar; Babu, Manas; Bansal, Devesh; Pillai, Biju S; Sam, Mohan P; Krishnamoorthy, Hariharan

2017-11-01

The aim of this study was to identify relevance of subclinical pathological findings in the kidneys of living donors and correlate these with early graft renal function. This was a prospective study on 84 living donor kidney transplant recipients over a period of two years. In all the donors, cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial, and tubule status. The graft function of patients with normal histology was compared with those of abnormal histological findings at one, three, and six months, and one year post-surgery. Most abnormal histological findings were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF, 13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the commonly observed pathological findings in zero-hour biopsies. Only those donors who had histological changes of IF and ATN showed progressive deterioration of renal function at one month, three months, six months, and one year post-transplantation. In donors with other histological changes, no significant effect on graft function was observed. Zero-hour cortical biopsy gave us an idea of the general status of the donor kidney and presence or absence of subclinical pathological lesions. A mild degree of subclinical and pathological findings on zero-hour biopsy did not affect early graft renal function in living donor kidney transplantation. Zero-hour cortical biopsy could also help in discriminating donor-derived lesions from de novo alterations in the kidney that could happen subsequently.

Final Year Nursing Students in Nigeria; How Knowledgeable and Prepared are They to Offer Medical Care to Patients with Chronic Kidney Disease?

PubMed Central

Okwuonu, Chimezie Godswill; Kanu, Hannah Sylvanus; Odigie, Ojeh-Oziegbe

2017-01-01

Background: Nurses play an important role in the management of chronic kidney disease (CKD) patients at primary, secondary, and tertiary levels of care. In other to perform their functions, it is pertinent that they have a good understanding of kidney functions and CKD. We do not know if the current educational curriculum prepares them adequately for this role. Aim: To assess the knowledge level of kidney functions and diseases among final year nursing students in Abia State Nigeria. Materials and Methods: This was a cross sectional study involving final year diploma and Bachelor of nursing (B. Nursing) students who were randomly chosen. Structured, self-administered questionnaire containing 18 items was the tool for data collection. A score of one was given for each correctly answered question on functions of the kidney, symptoms, signs, causes, and complications of CKD. A score of 50% and above was regarded as good knowledge. Results: Two hundred questionnaires were distributed, but 186 were returned (response rate of 93%). Male:female ratio was 1:14.5. One hundred and seventeen (62.9%) knew the correct definition of CKD, but only 69 (37.1%) knew the normal range of glomerular filtration rate. Eighty-one percent had good knowledge of kidney functions while 39 (21%) had good knowledge of CKD. Overall, 42 (22.6%) had good knowledge of kidney functions and CKD. Students who rotated through the dialysis unit during their clinical posting had higher mean knowledge score than others (P = 0.03). There was no significant difference in the mean knowledge scores of the diploma and B. Nursing students (P = 0.76). Conclusion: The majority of the final year students had poor knowledge of CKD. There is need to expand the current teaching curriculum so as to increase the knowledge of these future nurses on the basic concepts of CKD to improve outcomes of patient management. PMID:28300046

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

PubMed

Anuwatmatee, Sahapab; Allison, Matthew A; Shlipak, Michael G; McClelland, Robyn L; Kramer, Holly; Tang, Shudi; Hou, Liming; Rye, Kerry-Anne; Ong, Kwok Leung

2018-05-15

Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year). At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05). Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

RAAS-mediated Redox effects in Chronic Kidney Disease

PubMed Central

Nistala, Ravi; Wei, Yongzhong; Sowers, James R; Whaley-Connell, Adam

2009-01-01

The renin-angiotensin-aldosterone-system (RAAS) is central to the pathogenesis of hypertension, cardiovascular and kidney disease. Emerging evidence support various pathways through which a local renal RAAS can affect kidney function, hypertension, and cardiovascular disease. A prominent mechanism appears to be loss of redox homeostasis and formation of excessive free radicals. Free radicals such as reactive oxygen species (ROS) are necessary in normal physiologic processes including development of nephrons, erythropoeisis and tubular sodium transport. However, loss of redox homeostasis contributes to pro-inflammatory and pro-fibrotic pathways in the kidney that in turn lead to reduced vascular compliance, podocyte pathology and proteinuria. Both blockade of the RAAS and oxidative stress produces salutary effects on hypertension and glomerular filtration barrier injury. Thus, the focus of current research is on understanding the pathophysiology of chronic kidney disease in the context of an elevated RAAS and unbalanced redox mechanisms. PMID:19218092

Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients

PubMed Central

Habib, Samy L

2009-01-01

Background The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell carcinomas. Loss of heterozygosity at the 8-oxoG-DNA glycosylase (OGG1) allele is found in human kidney clear cell carcinoma identifying loss of OGG1 function as a possible contributor to tumorigenesis in the kidney. Tuberin regulates OGG1 through the transcription factor NF-YA in cultured cells. The purpose of this study is to determine the effect of tuberin-deficiency on OGG1 protein and mRNA levels as well as on 8-oxodG levels in kidney tumors from patients with TSC. In addition we evaluated the phophorylation level of downstream targets of mTOR, phospho-S70K, in kidney tumor tissue from TSC patients. Results Kidney angiomyolipoma tissue from TSC patients expresses significant levels of phopho-tuberin and low levels of tuberin compared to control kidney tissue. The increase in tuberin phosphorylation and the decrease tuberin expression are associated with decrease in OGG1 protein and mRNA levels in tumor samples compared to normal kidney samples. The decrease OGG1 expression is also associated with significant decrease in the transcription factor, NF-YA, expression in tumor samples compared to normal tissues. In addition, the levels of 8-oxodG are 4-fold higher in tumors compared to control samples. The significant increase of phospho-tuberin expression is associated with increase phosphorylation of S6K in tumor samples compared to controls. Cyclin D1 expression is also 3-fold higher in increase in the tumor tissues compared to normal kidney tissues. Conclusion These data indicate that tuberin deficiency in angiomyolipoma enhances mTOR activation by phosphorylation of S6K and downregulation of protein and mRNA expression of OGG1 resulted in accumulation of oxidized DNA in patients with TSC. These data suggest that tuberin and OGG1 are important proteins in the pathogenesis of angiomyolipoma in TSC patients. PMID:19265534

Computational analysis of kidney scintigrams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vrincianu, D.; Puscasu, E.; Creanga, D.

The scintigraphic investigation of normal and pathological kidneys was carried out using specialized gamma-camera device from nuclear medicine hospital department. Technetium 90m isotope with gamma radiation emission, coupled with vector molecules for kidney tissues was introduced into the subject body, its dynamics being recorded as data source for kidney clearance capacity. Two representative data series were investigated, corresponding to healthy and pathological organs respectively. The semi-quantitative tests applied for the comparison of the two distinct medical situations were: the shape of probability distribution histogram, the power spectrum, the auto-correlation function and the Lyapunov exponent. While power spectrum led to similarmore » results in both cases, significant differences were revealed by means of distribution probability, Lyapunov exponent and correlation time, recommending these numerical tests as possible complementary tools in clinical diagnosis.« less

Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

PubMed

Glassock, Richard J; Rule, Andrew D

2016-01-01

The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD. © 2016 S. Karger AG, Basel.

Changes in Renal Function and Blood Pressure in Patients with Stone Disease

NASA Astrophysics Data System (ADS)

Worcester, Elaine M.

2007-04-01

Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

Early outcomes of liver transplants in patients receiving organs from hypernatremic donors.

PubMed

Khosravi, Mohammad Bagher; Firoozifar, Mohammad; Ghaffaripour, Sina; Sahmeddini, Mohammad Ali; Eghbal, Mohammad Hossien

2013-12-01

Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival during liver transplants. However, recent studies have found no association between the donor serum sodium and transplant outcome. This study sought to show the negative effect donor hypernatremia has on initial liver allograft function. This is the first study to investigate international normalized ratio and renal factors of patients with normal and those with hypernatremic donor livers. This study was conducted at the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July 2011. Four hundred seven consecutive adult orthotopic liver transplants were performed at the University of Shiraz Medical Center. There were 93 donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group 2). Posttransplant data after 5 days showed that aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and kidney function did not differ between the groups. Hypernatremia is the most important complication after brain death. Previous studies have suggested donor hypernatremia results in a greater incidence of early postoperative graft dysfunction in liver transplant and is considered one of the extended criteria donor. However, in recent years, this hypothesis has been questioned. Our study shows no difference between patients' initial results of liver and kidney functioning with normal and hypernatremic donor livers. This is the first study to investigate international normalized ratio as a fundamental factor in defining early allograft dysfunction and renal factors between patients with normal and hypernatremic donor's livers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H.B.; Blaufox, M.D.

Rats with one kidney clamped (2K1C), both kidneys clamped (2K2C), unilaterally nephrectomized with remaining kidney clamped (1K1C), and normals, were studied using /sup 99m/Tc mercaptoacetyltriglycine ((/sup 99m/Tc)MAG-3) and /sup 131/I orthoiodohippurate ((/sup 131/I)OIH). Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH were performed after constricted rats became hypertensive. Clearances were repeated after i.v. Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH in normals didn't change significantly after Captopril. Clearances of (/sup 99m/Tc)MAG-3 and (/sup 131/I)OIH decreased insignificantly after Captopril in the 2K2C model. in the 2K1C group, normal kidney clearance increased ((/sup 99m/Tc)MAG-3 p less than 0.01 and (/sup 131/I)OIH pmore » less than 0.025) and clamped kidney clearance decreased after inhibition ((/sup 99m/Tc)MAG-3, p less than 0.01, (/sup 131/I)OIH p less than 0.02). Clearances increased in the 1K1C group after Captopril ((/sup 99m/Tc)MAG-3 p less than 0.0025 and (/sup 131/I)OIH, p less than 0.001). The ratio of (/sup 99m/Tc)MAG-3 to (/sup 131/I)OIH before Captopril was 0.81 and 0.84 after Captopril. Changes in renal function after Captopril depend on the model of renovascular hypertension and possibly the dose administered. Technetium-99m MAG-3 clearance parallels (/sup 131/I)orthoiodohippurate in renovascular hypertension.« less

High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

PubMed Central

Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

2011-01-01

Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

Activation of Hypoxia-Inducible Factors Prevents Diabetic Nephropathy

PubMed Central

Nordquist, Lina; Friederich-Persson, Malou; Fasching, Angelica; Liss, Per; Shoji, Kumi; Nangaku, Masaomi; Hansell, Peter

2015-01-01

Hyperglycemia results in increased oxygen consumption and decreased oxygen tension in the kidney. We tested the hypothesis that activation of hypoxia-inducible factors (HIFs) protects against diabetes-induced alterations in oxygen metabolism and kidney function. Experimental groups consisted of control and streptozotocin-induced diabetic rats treated with or without chronic cobalt chloride to activate HIFs. We elucidated the involvement of oxidative stress by studying the effects of acute administration of the superoxide dismutase mimetic tempol. Compared with controls, diabetic rats displayed tissue hypoxia throughout the kidney, glomerular hyperfiltration, increased oxygen consumption, increased total mitochondrial leak respiration, and decreased tubular sodium transport efficiency. Diabetic kidneys showed proteinuria and tubulointerstitial damage. Cobalt chloride activated HIFs, prevented the diabetes-induced alterations in oxygen metabolism, mitochondrial leak respiration, and kidney function, and reduced proteinuria and tubulointerstitial damage. The beneficial effects of tempol were less pronounced after activation of HIFs, indicating improved oxidative stress status. In conclusion, activation of HIFs prevents diabetes-induced alteration in kidney oxygen metabolism by normalizing glomerular filtration, which reduces tubular electrolyte load, preventing mitochondrial leak respiration and improving tubular transport efficiency. These improvements could be related to reduced oxidative stress and account for the reduced proteinuria and tubulointerstitial damage. Thus, pharmacologic activation of the HIF system may prevent development of diabetic nephropathy. PMID:25183809

Clinical course of dengue fever and its impact on renal function in renal transplant recipients and patients with chronic kidney disease.

PubMed

Arun Thomas, E T; George, Jacob; Sruthi, Devi; Vineetha, N S; Gracious, Noble

2018-04-01

Dengue fever is a mosquito-borne viral disease endemic in many tropical and sub-tropical countries. There is only limited data in the literature about dengue fever in renal transplant recipients and patients with chronic kidney disease. This study compares the clinical course of dengue fever and its impact on renal function in renal transplant recipients, patients with chronic kidney disease and patients with normal base line renal function. An observational study was conducted from 1 st May to 31 st July 2017, at a tertiary care centre of South India. A major epidemic of dengue had occurred during the study period. Twelve renal transplant recipients, 22 patients with CKD and 58 patients with normal baseline renal function (control group) admitted with dengue fever were prospectively studied. Nadir WBC count was lowest in renal transplant recipients (2575 + 1187/mm 3 ), [P<0.001]. Renal transplant recipients took more time for normalisation of platelet count (6 + 4.5 days), [P<0.001]. All 22 patients with CKD and 11 of 12 renal transplant recipients had worsening of renal function where as only 17 of 58 patients in the control group had worsening [P<0.001]. Sixteen patients with CKD, one renal transplant recipient and none among control group required hemodialysis [P<0.001]. Dialysis requiring patients had more hemoconcentration (52.5+ 19.9% increase in haemoglobin), [P<0.001]. Seven patients with CKD were dialysis dependent at the end of 2 weeks. Clinical features of dengue fever were different in renal transplant recipients and patients with CKD. Severe worsening of renal function was common in CKD patients. Worsening of renal function in renal transplant recipients was less severe and transient. This article is protected by copyright. All rights reserved.

The importance of total kidney volume in evaluating progression of polycystic kidney disease

PubMed Central

Grantham, Jared J.; Torres, Vicente E.

2017-01-01

The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue. PMID:27694979

Rhabdomyolysis-Associated Acute Kidney Injury With Normal Creatine Phosphokinase.

PubMed

Kamal, Faisal; Snook, Lindsay; Saikumar, Jagannath H

2018-01-01

Rhabdomyolysis is a syndrome characterized by the breakdown of skeletal muscle and leakage of intracellular myocyte contents, such as creatine phosphokinase (CPK) and myoglobin, into the interstitial space and plasma resulting in acute kidney injury (AKI). Elevated CPK of at least 5 times the upper limit of normal is an important diagnostic marker of Rhabdomyolysis. We present a case of rhabdomyolysis with severe AKI with a normal CPK at presentation. A 32-year-old man presented with acute respiratory failure and AKI after an overdose of recreational drugs. Urinalysis at presentation showed trace amounts of blood, identified as rare red blood cells under microscopy. CPK was 156 U/L at presentation. Workup for glomerulonephritis and vasculitis was negative. He was initiated on renal replacement therapy, and a kidney biopsy showed severe acute tubular injury with positive myoglobin casts. Supportive management and renal replacement therapy was provided, and renal function spontaneously improved after a few weeks. This is an uncommon clinical presentation of severe rhabdomyolysis complicated by AKI. This suggests that CPK alone may not be a sensitive marker for rhabdomyolysis-induced AKI in some cases. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo.

PubMed

Mugford, Joshua W; Sipilä, Petra; Kobayashi, Akio; Behringer, Richard R; McMahon, Andrew P

2008-07-15

The mammalian kidney consists of an array of tubules connected to a ductal system that collectively function to control water/salt balance and to remove waste from the organisms' circulatory system. During mammalian embryogenesis, three kidney structures form within the intermediate mesoderm. The two most anterior structures, the pronephros and the mesonephros, are transitory and largely non-functional, while the most posterior, the metanephros, persists as the adult kidney. We have explored the mechanisms underlying regional specific differentiation of the kidney forming mesoderm. Previous studies have shown a requirement for Hox11 paralogs (Hoxa11, Hoxc11 and Hoxd11) in metanephric development. Mice lacking all Hox11 activity fail to form metanephric kidney structures. We demonstrate that the Hox11 paralog expression is restricted in the intermediate mesoderm to the posterior, metanephric level. When Hoxd11 is ectopically activated in the anterior mesonephros, we observe a partial transformation to a metanephric program of development. Anterior Hoxd11(+) cells activate Six2, a transcription factor required for the maintenance of metanephric tubule progenitors. Additionally, Hoxd11(+) mesonephric tubules exhibit an altered morphology and activate several metanephric specific markers normally confined to distal portions of the functional nephron. Collectively, our data support a model where Hox11 paralogs specify a metanephric developmental program in responsive intermediate mesoderm. This program maintains tubule forming progenitors and instructs a metanephric specific pattern of nephron differentiation.

Renal functional reserve and renal hemodynamics in hypertensive patients.

PubMed

Gaipov, Abduzhappar; Solak, Yalcin; Zhampeissov, Nurlan; Dzholdasbekova, Aliya; Popova, Nadezhda; Molnar, Miklos Z; Tuganbekova, Saltanat; Iskandirova, Elmira

2016-10-01

The renal functional reserve (RFR) is the ability of the kidneys to increase renal plasma flow and glomerular filtration rate (GFR) in response to protein intake. It is a measure of functional and anatomic integrity of nephrons. It is not known what relation between RFR and kidney Doppler parameters. We aimed to study the relation between the RFR and renal hemodynamic parameters in hypertensive patients with and without nephropathy who had normal kidney function. Twenty-four hypertensive subjects with nephropathy (HTN-n, n = 10) and hypertension without nephropathy (HTN, n = 14) were included in the study. Control group included 11 healthy subjects. Baseline GFR (GFR1) and GFR after intake of egg protein 1 mg/kg of body weight were determined (GFR2). RFR was calculated by the following formula: (GFR2-GFR1)/GFR1 × 100%. Doppler ultrasonography was performed. Arterial blood pressure (BP), body mass index (BMI), and estimated GFR were also recorded. HTN and HTN-n groups had impaired levels of RFR compared with controls (p < 0.05), significantly decreased value of flow velocity parameters (Vmax, Vmin), and increased RRI compared with controls. There was significant negative correlation of RFR with blood pressure levels (sBP, r = -0.435, p = 0.009; dBP, r = -0.504, p = 0.002), RRI (r = -0.456, p = 0.008), micro albuminuria (MAU, r = -0.366, p = 0.031) and positive correlation with Vmax and Vmin (r = 0.556, p = 0.001 and r = 0.643, respectively, p < 0.001). Linear regression showed that RRI and MAU were independent predictors of decreased RFR. RFR is lower in hypertensive patients despite near-normal level of kidney function and is related to particular level of BP. RRI and MAU were independent predictors of decreased RFR.

Chronic Kidney Disease and Exposure to Nephrotoxic Metals

PubMed Central

Orr, Sarah E.; Bridges, Christy C.

2017-01-01

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of functional nephrons. As injured nephrons become sclerotic and die, the remaining healthy nephrons undergo numerous structural, molecular, and functional changes in an attempt to compensate for the loss of diseased nephrons. These compensatory changes enable the kidney to maintain fluid and solute homeostasis until approximately 75% of nephrons are lost. As CKD continues to progress, glomerular filtration rate decreases, and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may enhance mortality and/or morbidity of an individual. Environmental toxicants of particular concern are arsenic, cadmium, lead, and mercury. Since these metals are present throughout the environment and exposure to one or more of these metals is unavoidable, it is important that the way in which these metals are handled by target organs in normal and disease states is understood completely. PMID:28498320

Inhibition of WISE preserves renal allograft function.

PubMed

Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

2013-01-01

Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

[Acute renal failure due to RAAS-inhibitors combined with dehydration].

PubMed

Scherpbier, Nynke D; de Grauw, Wim J C; Wetzels, Jack F M; Vervoort, Gerald M M

2010-01-01

Two men (61 and 81 years old) with mild impaired kidney function developed acute renal failure due to dehydration combined with the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS). After rehydration, correction of hyperkalaemia and stopping RAAS-inhibition and diuretics, they recovered completely. Many patients using RAAS-inhibitors have impaired renal function. In the case of dehydration due to gastroenteritis or prolonged fever they risk developing acute renal failure. The high risk groups are elderly patients, patients with atherosclerosis or heart failure and those with co-medication of diuretics or NSAIDs. The underlying mechanism is that the normal pathways to protect kidney perfusion in case of hypovolaemia are blocked by the use of RAAS-inhibitors or NSAIDs. In the case of dehydration in patients with chronic kidney disease using RAAS-inhibitors, serum creatinine and potassium levels should be monitored. Temporary discontinuation of RAAS-inhibitors or diuretics is often necessary.

Williams-Beuren syndrome associated with single kidney and nephrocalcinosis: a case report.

PubMed

Abidi, Kamel; Jellouli, Manel; Ben Rabeh, Rania; Hammi, Yousra; Gargah, Tahar

2015-01-01

Williams-Beuren syndrome is a rare neurodevelopmental disorder, characterized by congenital heart defects, abnormal facial features, mental retardation with specific cognitive and behavioral profile, growth hormone deficiency, renal and skeletal anomalies, inguinal hernia, infantile hypercalcaemia. We report a case with Williams-Beuren syndrome associated with a single kidney and nephrocalcinosis complicated by hypercalcaemia. A male infant, aged 20 months presented growth retardation associated with a psychomotor impairment, dysmorphic features and nephrocalcinosis. He had also hypercalciuria and hypercalcemia. Echocardiography was normal. DMSA renal scintigraphy showed a single functioning kidney. The FISH generated one ELN signal in 20 metaphases read and found the presence of ELN deletion, with compatible Williams-Beuren syndrome.

Gap junctions favor normal rat kidney epithelial cell adaptation to chronic hypertonicity.

PubMed

Desforges, Bénédicte; Savarin, Philippe; Bounedjah, Ouissame; Delga, Stéphanie; Hamon, Loïc; Curmi, Patrick A; Pastré, David

2011-09-01

Upon hypertonic stress most often resulting from high salinity, cells need to balance their osmotic pressure by accumulating neutral osmolytes called compatible osmolytes like betaine, myo-inositol, and taurine. However, the massive uptake of compatible osmolytes is a slow process compared with other defense mechanisms related to oxidative or heat stress. This is especially critical for cycling cells as they have to double their volume while keeping a hospitable intracellular environment for the molecular machineries. Here we propose that clustered cells can accelerate the supply of compatible osmolytes to cycling cells via the transit, mediated by gap junctions, of compatible osmolytes from arrested to cycling cells. Both experimental results in epithelial normal rat kidney cells and theoretical estimations show that gap junctions indeed play a key role in cell adaptation to chronic hypertonicity. These results can provide basis for a better understanding of the functions of gap junctions in osmoregulation not only for the kidney but also for many other epithelia. In addition to this, we suggest that cancer cells that do not communicate via gap junctions poorly cope with hypertonic environments thus explaining the rare occurrence of cancer coming from the kidney medulla.

Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis.

PubMed

Humphreys, Benjamin D; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Movahedi Naini, Said; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P; Kuchroo, Vijay K; Bonventre, Joseph V

2013-09-01

Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.

Use of daptomycin in the treatment of vancomycin-resistant enterococcal urinary tract infections: a short case series.

PubMed

Ramaswamy, Divya Pradeep; Amodio-Groton, Maria; Scholand, Stephen J

2013-07-16

Vancomycin-resistant enterococci are a leading cause of hospital-acquired urinary tract infection and a growing concern for the clinician. The aim of this study was to evaluate the effectiveness of daptomycin in the treatment of patients with vancomycin-resistant enterococcal urinary tract infection treated in our 200-bed community-based institution. Patients with confirmed symptomatic vancomycin-resistant enterococcal urinary tract infection identified by infectious disease consultation between January 1, 2007, and December 8, 2009, vancomycin-resistant enterococci-positive urine culture, and urinary symptoms and/or pyuria on urinalysis, and treated with daptomycin, were included in this case series. Daptomycin was generally administered at a planned dosage regimen of ≥ 5 mg/kg every 24 hours in patients with normal to moderately impaired kidney function or every 48 hours in patients with severe kidney disease. Microbiologic cure was defined as eradication of vancomycin-resistant enterococci in urine cultures taken after the completion of daptomycin treatment. Clinical cure was defined by symptom resolution, as assessed by the infectious disease clinician caring for the patient. Included in this case series are 10 patients who received daptomycin for confirmed vancomycin-resistant enterococcal urinary tract infection. Patients had a history of extensive hospital stays. Chart review revealed that all levels of kidney function (3, 2, 3, and 2 patients with kidney disease classified as normal, mild, moderate, and severe/kidney failure, respectively) were represented in the sample and that patients with (n = 5) or without (n = 5) previous urinary tract infection and with (n = 3) or without (n = 7) Foley catheters were included. Treatment with daptomycin achieved clinical cure and vancomycin-resistant enterococcal eradication in all cases in this series. Treatment with daptomycin was well tolerated and effective in all patients in this series, regardless of renal function, history of urinary tract infection, or Foley catheter use. This study adds to emerging clinical evidence that daptomycin is a valuable treatment for vancomycin-resistant enterococcal urinary tract infection.

Angiotensin II Type 1 Receptor-Associated Protein Regulates Kidney Aging and Lifespan Independent of Angiotensin.

PubMed

Uneda, Kazushi; Wakui, Hiromichi; Maeda, Akinobu; Azushima, Kengo; Kobayashi, Ryu; Haku, Sona; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Matsuda, Miyuki; Ohsawa, Masato; Minegishi, Shintaro; Ishigami, Tomoaki; Toya, Yoshiyuki; Atobe, Yoshitoshi; Yamashita, Akio; Umemura, Satoshi; Tamura, Kouichi

2017-07-27

The kidney is easily affected by aging-associated changes, including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Particularly, renal tubulointerstitial fibrosis is a final common pathway in most forms of progressive renal disease. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP), which was originally identified as a molecule that binds to AT1R, is highly expressed in the kidney. Previously, we have shown that ATRAP suppresses hyperactivation of AT1R signaling, but does not affect physiological AT1R signaling. We hypothesized that ATRAP has a novel functional role in the physiological age-degenerative process, independent of modulation of AT1R signaling. ATRAP-knockout mice were used to study the functional involvement of ATRAP in the aging. ATRAP-knockout mice exhibit a normal age-associated appearance without any evident alterations in physiological parameters, including blood pressure and cardiovascular and metabolic phenotypes. However, in ATRAP-knockout mice compared with wild-type mice, the following takes place: (1) age-associated renal function decline and tubulointerstitial fibrosis are more enhanced; (2) renal tubular mitochondrial abnormalities and subsequent increases in the production of reactive oxygen species are more advanced; and (3) life span is 18.4% shorter (median life span, 100.4 versus 123.1 weeks). As a key mechanism, age-related pathological changes in the kidney of ATRAP-knockout mice correlated with decreased expression of the prosurvival gene, Sirtuin1 . On the other hand, chronic angiotensin II infusion did not affect renal sirtuin1 expression in wild-type mice. These results indicate that ATRAP plays an important role in inhibiting kidney aging, possibly through sirtuin1-mediated mechanism independent of blocking AT1R signaling, and further protecting normal life span. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury.

PubMed

Sawhney, Simon; Marks, Angharad; Fluck, Nick; Levin, Adeera; McLernon, David; Prescott, Gordon; Black, Corri

2017-08-01

The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4 (4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs no AKI) was greatest among those with higher post-discharge eGFRs with multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68-1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30, respectively. The excess risk after AKI persisted over ten years of study, irrespective of AKI severity, or post-episode proteinuria. Thus, even if post-discharge kidney function returns to normal, hospital admission with AKI is associated with increased renal progression that persists for up to ten years. Follow-up plans should avoid false reassurance when eGFR after AKI returns to normal. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Oral Hydration for Prevention of Contrast-Induced Acute Kidney Injury in Elective Radiological Procedures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Cheungpasitporn, Wisit; Thongprayoon, Charat; Brabec, Brady A.; Edmonds, Peter J.; O'Corragain, Oisin A.; Erickson, Stephen B.

2014-01-01

Background: The reports on efficacy of oral hydration treatment for the prevention of contrast-induced acute kidney injury (CIAKI) in elective radiological procedures and cardiac catheterization remain controversial. Aims: The objective of this meta-analysis was to assess the use of oral hydration regimen for prevention of CIAKI. Materials and Methods: Comprehensive literature searches for randomized controlled trials (RCTs) of outpatient oral hydration treatment was performed using MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials Systematic Reviews, and clinicaltrials.gov from inception until July 4th, 2014. Primary outcome was the incidence of CIAKI. Results: Six prospective RCTs were included in our analysis. Of 513patients undergoing elective procedures with contrast exposures,45 patients (8.8%) had CIAKI. Of 241 patients with oral hydration regimen, 23 (9.5%) developed CIAKI. Of 272 patients with intravenous (IV) fluid regimen, 22 (8.1%) had CIAKI. Study populations in all included studies had relatively normal kidney function to chronic kidney disease (CKD) stage 3. There was no significant increased risk of CIAKI in oral fluid regimen group compared toIV fluid regimen group (RR = 0.94, 95% confidence interval, CI = 0.38-2.31). Conclusions: According to our analysis,there is no evidence that oral fluid regimen is associated with more risk of CIAKI in patients undergoing elective procedures with contrast exposures compared to IV fluid regimen. This finding suggests that the oral fluid regimen might be considered as a possible outpatient treatment option for CIAKI prevention in patients with normal to moderately reduced kidney function. PMID:25599049

Small renal size in newborns with spina bifida: possible causes.

PubMed

Montaldo, Paolo; Montaldo, Luisa; Iossa, Azzurra Concetta; Cennamo, Marina; Caredda, Elisabetta; Del Gado, Roberto

2014-02-01

Previous studies reported that children with neural tube defects, but without any history of intrinsic renal diseases, have small kidneys when compared with age-matched standard renal growth. The aim of this study was to investigate the possible causes of small renal size in children with spina bifida by comparing growth hormone deficiency, physical limitations and hyperhomocysteinemia. The sample included 187 newborns with spina bifida. Renal sizes in the patients were assessed by using maximum measurement of renal length and the measurements were compared by using the Sutherland monogram. According to the results, the sample was divided into two groups--a group of 120 patients with small kidneys (under the third percentile) and a control group of 67 newborns with normal kidney size. Plasma total homocysteine was investigated in mothers and in their children. Serum insulin-like growth factor-1 (IGF-1) levels were measured. Serum IGF-1 levels were normal in both groups. Children and mothers with homocysteine levels >10 μmol/l were more than twice as likely to have small kidneys and to give to birth children with small kidneys, respectively, compared with newborns and mothers with homocysteine levels <10 μmol/l. An inverse correlation was also found between the homocysteine levels of mothers and kidney sizes of children (r = - 0.6109 P ≤ 0.01). It is highly important for mothers with hyperhomocysteinemia to be educated about benefits of folate supplementation in order to reduce the risk of small renal size and lower renal function in children.

Changes in serum cystatin C, creatinine, and C-reactive protein after cardiopulmonary bypass in patients with normal preoperative kidney function.

PubMed

Svensson, Anders S; Kvitting, John-Peder Escobar; Kovesdy, Csaba P; Cederholm, Ingemar; Szabó, Zoltán

2016-06-01

The use of cardiopulmonary bypass (CPB) can cause changes in serum creatinine and cystatin C independent of glomerular filtration rate. We aimed to quantify the temporal changes of these biomarkers and C-reactive protein (CRP) after CPB. This was a prospective study at an academic medical centre between April and October 2013. We compared postoperative changes in serum creatinine and cystatin C in 38 patients with normal preoperative kidney function who underwent cardiac surgery using CPB and did not develop perioperative acute kidney injury (AKI). The effect of inflammation on intra-individual changes was examined in mixed effects regressions, using measurements of pre- and postoperative CRP. Both serum creatinine (79.9 ± 22.7 vs. 92.6 ± 21.4 µmol/L, P = 0.001) and cystatin C (1.16 ± 0.39 vs. 1.33 ± 0.37 mg/L, P = 0.012) decreased significantly in the first 8 h postoperatively compared to preoperatively, as a result of haemodilution. Thereafter serum creatinine returned to preoperative levels, whereas serum cystatin C continued to rise and was significantly elevated at 72 h post-CPB compared to preoperative levels (1.53 ± 0.48 vs. 1.33 ± 0.37 mg/L, P = 0.003). CRP levels increased significantly post-CPB and were significantly associated with increases in both serum creatinine and cystatin C. Serum creatinine and cystatin C appear not to be interchangeable biomarkers during and immediately after CPB. Processes unrelated to kidney function such as acute inflammation have a significant effect on post-CPB changes in these biomarkers, and may result in significant increases in serum cystatin C that could erroneously be interpreted as AKI. © 2015 Asian Pacific Society of Nephrology.

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.

PubMed

Hinder, Lucy M; Park, Meeyoung; Rumora, Amy E; Hur, Junguk; Eichinger, Felix; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

2017-09-01

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Safety Considerations in the Use of Ketorolac for Postoperative Pain.

PubMed

Maslin, Benjamin; Lipana, Lawrence; Roth, Brandon; Kodumudi, Gopal; Vadivelu, Nalini

2017-01-01

Ketorolac use has significantly expanded for postoperative pain management since it first became available in the United States, primarily due to well established effects on patient pain scores and its ability to reduce perioperative opioid requirements. As an inhibitor of cyclooxygenase, ketorolac use has raised clinical concern including particular controversy regarding its potential effects on bone healing, postoperative kidney function and perioperative bleeding. To review the supporting data from clinical studies addressing the safety of ketorolac use for postoperative pain. This review highlights the most up-to-date research from clinical trials as well as from retrospective studies and meta-analyses regarding the effects of perioperative use of ketorolac on bone healing, kidney function and blood loss. Based on the most up-to-date literature, ketorolac in normal doses has been demonstrated to be safe with respect to bone healing. In patients with normal kidney function, numerous studies have established the safety of Ketorolac; however other studies have raised safety concerns in patients with comorbid kidney, heart and liver disease. While there is evidence that ketorolac may cause prolonged bleeding time and may be associated with increased postoperative blood loss after tonsillectomy, large scale prospective randomized controlled trials and subsequent meta-analyses have failed to establish an association of ketorolac use and perioperative blood loss. Perioperative administration of ketorolac has been demonstrated to be safe and effective in healthy patients and is particularly beneficial as an opioid-sparing agent in vulnerable patient groups. However, in certain surgical and medical contexts, proper patient selection based on the multidisciplinary collaboration between perioperative clinician specialists will optimize patient safety and pain management outcomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[The specificity between "fei and dachang" in the lung injury of rats with ulcerative colitis].

PubMed

Zhu, Li; Wang, Xin-yue; Yang, Xue; Jing, Shan; Zhou, Bo; Huang, Xiu-xia; Jia, Xu

2013-03-01

To observe the features of bronchopulmonary lesions in ulcerative colitis (UC) rats and the specificity with Fei and Dachang, thus providing reliance for the theory of "intestinal diseases involved Fei". The UC rat model was duplicated by using rabbit intestine mucosa tissue allergenic model and TNBS-ethanol model. A normal rat group was set up as the control. The pulmonary functions [including inspiratory resistance (Ri), expiratory resistance (Re), forced vital capacity (FVC); FEV. 2/FVC, maximal voluntary ventilation (MVV), forced expiratory flow rate (FEF25% - 75%)], and indicators of liver and kidney functions [serum alanine aminotransferase (ALT), aspartate amino transferase (AST), blood urea nitrogen (BUN), and creatinine (Cr)] were detected in the two groups. The pathological changes of colon, lung, liver, and kidney were observed in the two groups. Rats in the model group in both acute and chronic stages had weight loss, mucus and loose stool. Partial rats had such symptoms as dyspnea, shortness of breath, and wheezing. Compared with the normal group, the MW, FVC, FEV0.2 and FEF25% -75% in the acute stage; Ri, Re, MVV, FVC, and FEF25% - 75% in the chronic stage all significantly decreased (P <0.05, P <0.01), and FEV0.2/FVC significantly increased in the model group (P <0.05). The pathological results showed interstitial pneumonia and pulmonary interstitial fibrosis in the model group. But the indicators of liver and kidney functions were all in the normal range. No obvious pathological change was seen in the renal and liver tissues in the two groups. UC could specifically induce bronchopulmonary lesions. Lung injury was one of UC's intestinal manifestations. The theory of "Fei and Dachang being interior-exteriorly correlated" was demonstrated from the theory of "intestinal diseases involved Fei".

Kidney outer medulla mitochondria are more efficient compared to cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment.

PubMed

Schiffer, Tomas A; Gustafsson, Håkan; Palm, Fredrik

2018-05-30

The kidneys receive approximately 25% of cardiac output, which is a prerequisite in order to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is relating to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation in order to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla functions at the verge of hypoxia and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats were estimated using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment.

Peculiar Expression of CD3-Epsilon in Kidney of Ginbuna Crucian Carp.

PubMed

Miyazawa, Ryuichiro; Murata, Norifumi; Matsuura, Yuta; Shibasaki, Yasuhiro; Yabu, Takeshi; Nakanishi, Teruyuki

2018-01-01

TCR/CD3 complex is composed of the disulfide-linked TCR-αβ heterodimer that recognizes the antigen as a peptide presented by the MHC, and non-covalently paired CD3γε- and δε-chains together with disulfide-linked ζ-chain homodimers. The CD3 chains play key roles in T cell development and T cell activation. In the present study, we found nor or extremely lower expression of CD3ε in head- and trunk-kidney lymphocytes by flow cytometric analysis, while CD3ε was expressed at the normal level in lymphocytes from thymus, spleen, intestine, gill, and peripheral blood. Furthermore, CD4-1 + and CD8α + T cells from kidney express Zap-70, but not CD3ε, while the T cells from other tissues express both Zap-70 and CD3ε, although expression of CD3ε was low. Quantitative analysis of mRNA expression revealed that the expression level of T cell-related genes including tcrb, cd3 ε, zap-70 , and lck in CD4-1 + and CD8α + T cells was not different between kidney and spleen. Western blot analysis showed that CD3ε band was detected in the cell lysates of spleen but not kidney. To be interested, CD3ε-positive cells greatly increased after 24 h in in vitro culture of kidney leukocytes. Furthermore, expression of CD3ε in both transferred kidney and spleen leukocytes was not detected or very low in kidney, while both leukocytes expressed CD3ε at normal level in spleen when kidney and spleen leukocytes were injected into the isogeneic recipient. Lower expression of CD3ε was also found in kidney T lymphocytes of goldfish and carp. These results indicate that kidney lymphocytes express no or lower level of CD3ε protein in the kidney, although the mRNA of the gene was expressed. Here, we discuss this phenomenon from the point of function of kidney as reservoir for T lymphocytes in teleost, which lacks lymph node and bone marrow.

Interconnected network motifs control podocyte morphology and kidney function.

PubMed

Azeloglu, Evren U; Hardy, Simon V; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y; Fang, Wei; Xiong, Huabao; Neves, Susana R; Jain, Mohit R; Li, Hong; Ma'ayan, Avi; Gordon, Ronald E; He, John Cijiang; Iyengar, Ravi

2014-02-04

Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3',5'-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element-binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor-driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease.

Interconnected Network Motifs Control Podocyte Morphology and Kidney Function

PubMed Central

Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi

2014-01-01

Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609

Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.

PubMed

Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying

2016-10-01

The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.

Creatine pretreatment prevents birth asphyxia-induced injury of the newborn spiny mouse kidney.

PubMed

Ellery, Stacey J; Ireland, Zoe; Kett, Michelle M; Snow, Rod; Walker, David W; Dickinson, Hayley

2013-02-01

Acute kidney injury (AKI) is a major complication for infants following an asphyxic insult at birth. We aimed to determine if kidney structure and function were affected in an animal model of birth asphyxia and if maternal dietary creatine supplementation could provide an energy reserve to the fetal kidney, maintaining cellular respiration during asphyxia and preventing AKI. Pregnant spiny mice were maintained on normal chow or chow supplemented with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty-four hours after insult, kidneys were collected for histological or molecular analysis. Urine and plasma were also collected for biochemical analysis. AKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a twofold increase (P < 0.02) in expression of Ngal (early marker of kidney injury), and decreased expression of the podocyte differentiation marker nephrin. Maternal creatine supplementation prevented the glomerular and tubular abnormalities observed in the kidney at 24 h and the increased expression of Ngal. Maternal creatine supplementation may prove useful in ameliorating kidney injury associated with birth asphyxia.

Role of mechanistic target of rapamycin (mTOR) in renal function and ischaemia-reperfusion induced kidney injury.

PubMed

Alshaman, Reem; Truong, Luan; Oyekan, Adebayo

2016-11-01

Despite the presence of many studies on the role of mechanistic target of rapamycin (mTOR) in cardiorenal tissues, the definitive role of mTOR in the pathogenesis of renal injury subsequent to ischaemia-reperfusion (IR) remains unclear. The aims of the current study were to characterize the role of mTOR in normal kidney function and to investigate the role of mTOR activation in IR-induced kidney injury. In euvolemic anaesthetized rats, treatment with the mTOR inhibitor rapamycin increased blood pressure (121 ± 2 to 144 ± 3 mmHg; P<.05), decreased glomerular filtration rate (GFR; 1.6 ± 0.3 to 0.5 ± 0.2 mL/min; P<.05) and increased urinary sodium excretion (UNaV; 14 ± 1 to 109 ± 25 mmol/L per hour; P<.05). In rats subjected to IR, autophagy induction, p-mTOR expression and serum creatinine increased (1.9 ± 0.2 to 3 ± 0.3 mg/dL; P<.05); treatment with rapamycin blunted p-mTOR expression but further increased autophagy induction and serum creatinine (3 ± 0.3 to 5 ± 0.6 mg/dL; P<.05). In contrast, clenbuterol, an mTOR activator, blunted the effect of rapamycin on serum creatinine (4 ± 0.6 vs 2.3 ± 0.3 mg/dL; P<.05), autophagy induction and p-mTOR expression. IR also increased 24 hour protein excretion (9 ± 3 to 17 ± 2 mg/day; P<.05) and kidney injury molecule-1 (KIM-1) expression, and rapamycin treatment further increased KIM-1 expression. Clenbuterol exacerbated protein excretion (13 ± 2 to 26 ± 4 mg/day; P<.05) and antagonized the effect of rapamycin on KIM-1 expression. Histopathological data demonstrated kidney injury in IR rats that was worsened by rapamycin treatment but attenuated by clenbuterol treatment. Thus, mTOR signalling is crucial for normal kidney function and protecting the kidney against IR injury through autophagy suppression. © 2016 John Wiley & Sons Australia, Ltd.

Diagnostic and management dilemma of a pancreas-kidney transplant recipient with aplastic anaemia.

PubMed

Viecelli, Andrea; Hessamodini, Hannah; Augustson, Bradley; Lim, Wai Hon

2014-09-25

We report a case of a 57-year-old woman with type I diabetes who had received a simultaneous pancreas-kidney (SPK) transplant maintained on tacrolimus, mycophenolic acid (MPA) and prednisolone. Her renal allograft failed 6 years post-transplant but she continued to have a normal functioning pancreatic allograft. Over the course of 5 years, she developed progressive bone marrow failure with repeat bone marrow aspirates demonstrating an evolution from erythroid hypoplasia to hypocellular marrow and eventual aplastic anaemia despite discontinuation of MPA and reduction of tacrolimus. She was transfusion-dependent and had frequent admissions for sepsis. Despite treatment with antithymocyte globulin and cyclosporine for aplastic anaemia, she developed fatal invasive pulmonary aspergillosis within 3 weeks of treatment. Even though the cause of aplastic anaemia is likely multifactorial, this case highlights the difficulty in balancing the need for versus the risk of ongoing immunosuppression in a SPK transplant recipient who continues to have normal pancreatic graft function. 2014 BMJ Publishing Group Ltd.

Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet

PubMed Central

Sivritas, Sema-Hayriye; Ploth, David W.; Fitzgibbon, Wayne R.

2008-01-01

The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B2 (BKB2) receptors to acutely increase papillary blood flow (PBF) and therefore Na+ excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB2 receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 μg·kg−1·h−1, treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na+ excretion (urinary Na+ extraction rate) and fractional Na+ excretion by 40 ± 5% and 40 ± 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB2 receptors to increase Na+ excretion independent of changes in inner medullary blood flow. PMID:18632797

Comparative effects of avocado oil and losartan on blood pressure, renal vascular function, and mitochondrial oxidative stress in hypertensive rats.

PubMed

Márquez-Ramírez, Cristian Adrián; Hernández de la Paz, José Lucio; Ortiz-Avila, Omar; Raya-Farias, Andrés; González-Hernández, Juan Carlos; Rodríguez-Orozco, Alain Raimundo; Salgado-Garciglia, Rafael; Saavedra-Molina, Alfredo; Godínez-Hernández, Daniel; Cortés-Rojo, Christian

2018-03-20

Angiotensin II (Ang-II) antagonism alleviates hypertensive kidney damage by improving mitochondrial function and decreasing oxidative stress. This condition also is associated with altered renal vascular tone due to enhanced constriction by Ang-II. Thus, approaches ameliorating these events are desirable to alleviate kidney damage. Avocado oil, a source of antioxidants and oleic acid, is known to improve mitochondrial function, while oleic acid has antihypertensive effects. Therefore, the aim of this study was to test whether avocado oil counteracts, to a similar degree as the Ang-II blocker losartan, the deleterious effects of hypertension on blood pressure, renal vascular performance, kidney mitochondrial function, and oxidative stress. Hypertensive rats induced with Nω-nitro-l-arginine methyl ester (L-NAME) were supplemented during 45 d with avocado oil or losartan. Vascular responses were analyzed in perfused kidney. Membrane potential, reactive oxygen species levels, and glutathione were analyzed in isolated kidney mitochondria. In hypertensive rats, avocado oil decreased 21.2% and 15.5% diastolic and systolic blood pressures, respectively, and alleviated impaired renal vasodilation. Hypertension decreased membrane potential by 83.7% and augmented reactive oxygen species levels by 51% in mitochondria fueled with a complex I substrate, whereas it augmented the levels of oxidized glutathione in 48%. These alterations were normalized by avocado oil at a comparable degree to losartan. Because avocado oil mimicked the effects of losartan, we propose that the effects of avocado oil might be mediated by decreasing the actions of Ang-II on mitochondria. These results suggest that avocado oil intake might be a nutritional approach to attenuate the deleterious effects of hypertension on kidney. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of tocopherol on atherosclerosis, vascular function, and inflammation in apolipoprotein E knockout mice with subtotal nephrectomy.

PubMed

Shing, Cecilia M; Fassett, Robert G; Peake, Jonathan M; Coombes, Jeff S

2014-12-01

Inflammation and endothelial dysfunction contribute to cardiovascular disease, prevalent in chronic kidney disease (CKD). Antioxidant supplements such as tocopherols may reduce inflammation and atherosclerosis. This study aimed to investigate the effect of tocopherol supplementation on vascular function, aortic plaque formation, and inflammation in apolipoprotein E(-/-) mice with 5/6 nephrectomy as a model of combined cardiovascular and kidney disease. Nephrectomized mice were assigned to a normal chow diet group (normal chow), a group receiving 1000 mg/kg diet of α-tocopherol supplementation or a group receiving 1000 mg/kg diet mixed-tocopherol (60% γ-tocopherol). Following 12 weeks, in vitro aortic endothelial-independent relaxation was enhanced with both α-tocopherol and mixed-tocopherol (P < 0.05), while mixed-tocopherol enhanced aortic contraction at noradrenaline concentrations of 3 × 10(-7) M to 3 × 10(-5) M (P < 0.05), when compared to normal chow. Supplementation with α- and mixed-tocopherol reduced systemic concentrations of IL-6 (P < 0.001 and P < 0.001, respectively) and IL-10 (P < 0.05 and P < 0.001, respectively), while α-tocopherol also reduced MCP-1 (P < 0.05) and tumor necrosis factor (TNF)-α (P < 0.05). Aortic sinus plaque area was significantly reduced with α-tocopherol supplementation when compared to normal chow (P < 0.01). Tocopherol supplementation favorably influenced vascular function and cytokine profile, while it was also effective in reducing atherosclerosis in the apolipoprotein E(-/-) mouse with CKD. © 2014 John Wiley & Sons Ltd.

An unusual case of crescentic lupus nephritis presenting with normal renal function.

PubMed

Manohar, Sandhya; Subramanian, Chamundeswari; Lakshmi, Kameswari

2015-11-01

Lupus nephritis is a life-threatening manifestation of systemic lupus erythematosus (SLE). This is commonly suspected when lupus patients present with elevated serum creatinine levels. But it is important to be aware that even patients with advanced disease in the kidney from SLE can have normal renal function, thus requiring a high index of suspicion. We present the case of a patient who presented with nonspecific musculoskeletal symptoms and was diagnosed with SLE. He also had nephrotic range proteinuria but his serum creatinine was normal. A renal biopsy revealed diffuse proliferative crescentic lupus nephritis. We have reviewed the literature for correlation between crescents; a sign of severe glomerular damage and creatinine levels.

[Recovery characteristic of donor's and receptor's renal function from age over 55 years living donors donate kidneys].

PubMed

Hu, Xiao-Peng; Yin, Hang; Zhang, Xiao-Dong; Wang, Wei; Ren, Liang; Yang, Xiao-Yong; Li, Xiao-Bei; Liu, Hang; Wang, Yong

2009-10-20

To observe and research clinical characteristics and curative effect and safety of renal transplantation from living elderly donors donating kidneys. Retrospective study on the 19 living kidney donors who were over 55 years old and on the renal transplantation operations completed by our center for the past few years. Among the 19 donors, with an average age of 58 years old. Their mean creatinine clearance was 81.7 +/- 2.2 ml/min. Among the 19 acceptors, with an average age of 34 years old. All kidney before the open circulation transplant performed routine 0 point puncture and histological examination. All donors smoothly spent their perioperative period without any surgical complications. All the donors keep their blood Cr in a normal range one week after the operation. There was no significant difference between posttransplantation one week and six month and one year in blood Cr and Ccr. Blood pressure and blood sugar didn't not have significant changes, urine protein(-). All receptors' renal functions recovered in early stages without DGF. 7 receptors who had Ccr lower than 80 ml/min had their blood Cr decreased slowly. Among the 19 kidneys donated, 3 donors' glomerulosclerosises were higher than 10 percent. The kidney source shortage is the main factor that restricts the development of the renal transplantation currently, undoubtedly, the application of elderly donors will expand the kidney source and save more uremic patients. Renal transplantation is safe and feasible with the help of living elderly donors.

GDF11 induces kidney fibrosis, renal cell epithelial-to-mesenchymal transition, and kidney dysfunction and failure.

PubMed

Pons, Marianne; Koniaris, Leonidas G; Moe, Sharon M; Gutierrez, Juan C; Esquela-Kerscher, Aurora; Zimmers, Teresa A

2018-05-03

GDF11 modulates embryonic patterning and kidney organogenesis. Herein, we sought to define GDF11 function in the adult kidney and in renal diseases. In vitro renal cell lines, genetic, and murine in vivo renal injury models were examined. Among tissues tested, Gdf11 was highest in normal adult mouse kidney. Expression was increased acutely after 5/6 nephrectomy, ischemia-reperfusion injury, kanamycin toxicity, or unilateral ureteric obstruction. Systemic, high-dose GDF11 administration in adult mice led to renal failure, with accompanying kidney atrophy, interstitial fibrosis, epithelial-to-mesenchymal transition of renal tubular cells, and eventually death. These effects were associated with phosphorylation of SMAD2 and could be blocked by follistatin. In contrast, Gdf11 heterozygous mice showed reduced renal Gdf11 expression, renal fibrosis, and expression of fibrosis-associated genes both at baseline and after unilateral ureteric obstruction compared with wild-type littermates. The kidney-specific consequences of GDF11 dose modulation are direct effects on kidney cells. GDF11 induced proliferation and activation of NRK49f renal fibroblasts and also promoted epithelial-to-mesenchymal transition of IMCD-3 tubular epithelial cells in a SMAD3-dependent manner. Taken together, these data suggest that GDF11 and its downstream signals are critical in vivo mediators of renal injury. These effects are through direct actions of GDF11 on renal tubular cells and fibroblasts. Thus, regulation of GDF11 presents a therapeutic target for diseases involving renal fibrosis and impaired tubular function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Serum concentrations of symmetric dimethylarginine and creatinine in cats with kidney stones.

PubMed

Hall, Jean A; Yerramilli, Maha; Obare, Edward; Li, Jun; Yerramilli, Murthy; Jewell, Dennis E

2017-01-01

Serum concentrations of symmetric dimethylarginine (SDMA) correlate with renal function in cats and SDMA has been shown to be a more reliable and earlier marker for chronic kidney disease (CKD) compared with serum creatinine (Cr). Calcium oxalate uroliths tend to develop in mid-to-older aged cats and kidney stones may cause a reduction in renal function with increased SDMA, but normal serum Cr. The purpose of this retrospective study was to determine if cats with kidney stones had increased serum SDMA concentrations, and whether SDMA increased earlier than serum creatinine concentrations. Cats in the colony with kidney stones diagnosed between August 2010 and December 2015 (n = 43) were compared with healthy geriatric cats (n = 21) without kidney stones. Serum SDMA concentrations were determined by liquid chromatography-mass spectrometry and serum Cr concentrations were determined by enzymatic colorimetry. Cats with kidney stones were diagnosed antemortem by radiographic imaging (n = 12) or by postmortem necropsy (n = 31). Retrospectively, serum SDMA was found to be increased above the upper reference limit in 39 of 43 cats with kidney stones. Serum Cr was increased above the upper reference limit in 18 of 43 cats; 6 of these 18 cats had terminal azotemia only. The mean time that serum SDMA was increased before serum Cr was increased was 26.9 months (range 0 to 60 months). Kidney stones were composed of calcium oxalate in 30 of 34 cats. The lifespan for cats with kidney stones (mean, 12.5 years; range, 6.1 to 18.1 years) was shorter (P < 0.001) than for control cats (mean, 15.2 years; range, 13.0 to 17.2 years), suggesting that non-obstructive kidney stones have an effect on mortality rate or rate of CKD progression. In conclusion, if SDMA concentrations are elevated in mid-to-older aged cats, further imaging studies are warranted to check for the presence of kidney stones.

Serum concentrations of symmetric dimethylarginine and creatinine in cats with kidney stones

PubMed Central

Hall, Jean A.; Yerramilli, Maha; Obare, Edward; Li, Jun; Yerramilli, Murthy; Jewell, Dennis E.

2017-01-01

Serum concentrations of symmetric dimethylarginine (SDMA) correlate with renal function in cats and SDMA has been shown to be a more reliable and earlier marker for chronic kidney disease (CKD) compared with serum creatinine (Cr). Calcium oxalate uroliths tend to develop in mid-to-older aged cats and kidney stones may cause a reduction in renal function with increased SDMA, but normal serum Cr. The purpose of this retrospective study was to determine if cats with kidney stones had increased serum SDMA concentrations, and whether SDMA increased earlier than serum creatinine concentrations. Cats in the colony with kidney stones diagnosed between August 2010 and December 2015 (n = 43) were compared with healthy geriatric cats (n = 21) without kidney stones. Serum SDMA concentrations were determined by liquid chromatography-mass spectrometry and serum Cr concentrations were determined by enzymatic colorimetry. Cats with kidney stones were diagnosed antemortem by radiographic imaging (n = 12) or by postmortem necropsy (n = 31). Retrospectively, serum SDMA was found to be increased above the upper reference limit in 39 of 43 cats with kidney stones. Serum Cr was increased above the upper reference limit in 18 of 43 cats; 6 of these 18 cats had terminal azotemia only. The mean time that serum SDMA was increased before serum Cr was increased was 26.9 months (range 0 to 60 months). Kidney stones were composed of calcium oxalate in 30 of 34 cats. The lifespan for cats with kidney stones (mean, 12.5 years; range, 6.1 to 18.1 years) was shorter (P < 0.001) than for control cats (mean, 15.2 years; range, 13.0 to 17.2 years), suggesting that non-obstructive kidney stones have an effect on mortality rate or rate of CKD progression. In conclusion, if SDMA concentrations are elevated in mid-to-older aged cats, further imaging studies are warranted to check for the presence of kidney stones. PMID:28384169

Trends in serum creatinine testing in Oxfordshire, UK, 1993-2013: a population-based cohort study.

PubMed

Oke, Jason; Shine, Brian; McFadden, Emily; Stevens, Richard; Lasserson, Daniel; Perera, Rafael

2015-12-16

To determine how many kidney function tests are done, on whom, how frequently they are performed and how they have changed over time. Retrospective study of all serum creatinine, urine albumin and urine creatinine tests. Primary and secondary care in Oxfordshire from 1993 to 2013. Unselected population of 1,220,447 people. The total number of creatinine and urinary protein tests ordered from primary and secondary care and the number of tests per year stratified by categories of estimated glomerular filtration rate (eGFR). The frequency of testing in patients having their kidney function monitored. Creatinine requests from primary care increased steadily from 1997 and exceeded 220,000 requests in 2013. Tests corresponding to normal kidney function (eGFR >60/mL/min/1.73 m(2)) constituted 59% of all kidney function tests in 1993 and accounted for 83% of all tests in 2013. Test corresponding to chronic kidney disease (CKD) stages 3-5 declined after 2007. Reduced kidney function, albuminuria, male gender, diabetes and age were independently associated with more frequent monitoring. For a female patient between 61 and 80 years and with stage 3a CKD, the average number of serum creatinine tests (95% CI) was 3.23/year (3.19 to 3.26) and for a similar woman with diabetes, the average number of tests was 5.50 (5.44 to 5.56) tests per year. There has been a large increase in the number of kidney function tests over the past two decades. However, we found little evidence that this increase is detecting more CKD. Tests are becoming more frequent in people with and without evidence of renal impairment. Future work using a richer data source could help unravel the underlying reasons for the increased testing and determine how much is necessary and useful. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

PubMed Central

Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

2014-01-01

Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney. PMID:24927349

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats.

PubMed

Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

2014-04-01

Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

Evaluation of renal allografts function early after transplantation using intravoxel incoherent motion and arterial spin labeling MRI.

PubMed

Ren, Tao; Wen, Cheng-Long; Chen, Li-Hua; Xie, Shuang-Shuang; Cheng, Yue; Fu, Ying-Xin; Oesingmann, Niels; de Oliveira, Andre; Zuo, Pan-Li; Yin, Jian-Zhong; Xia, Shuang; Shen, Wen

2016-09-01

To evaluate renal allografts function early after transplantation using intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) MRI. This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. A total of 82 participants with 62 renal allograft recipients (2-4weeks after kidney transplantation) and 20 volunteers were enrolled to be scanned using IVIM and ASL MRI on a 3.0T MR scanner. Recipients were divided into two groups with either normal or impaired function according to the estimated glomerular filtration rate (eGFR) with a threshold of 60ml/min/1.73m(2). The apparent diffusion coefficient (ADC) of pure diffusion (ADCslow), the ADC of pseudodiffusion (ADCfast), perfusion fraction (PF), and renal blood flow (RBF) of cortex were compared among three groups. The correlation of ADCslow, ADCfast, PF and RBF with eGFR was evaluated. The receiver operating characteristic (ROC) curve and binary logistic regression analyses were performed to assess the diagnostic efficiency of using IVIM and ASL parameters to discriminate allografts with impaired function from normal function. P<0.05 was considered statistically significant. In allografts with normal function, no significant difference of mean cortical ADCslow, ADCfast, and PF was found compared with healthy controls (P>0.05). Cortical RBF in allografts with normal function was statistically lower than that of healthy controls (P<0.001). Mean cortical ADCslow, ADCfast, PF and RBF were lower for allografts with impaired function than that with normal function (P<0.05). Mean cortical ADCslow, ADCfast, PF and RBF showed a positive correlation with eGFR (all P<0.01) for recipients. The combination of IVIM and ASL MRI showed a higher area under the ROC curve (AUC) (0.865) than that of ASL MRI alone (P=0.02). Combined IVIM and ASL MRI can better evaluate the diffusion and perfusion properties for allografts early after kidney transplantation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination in normal and pathological fetal kidneys.

PubMed

Chaumoitre, K; Colavolpe, N; Shojai, R; Sarran, A; D' Ercole, C; Panuel, M

2007-01-01

To assess the use of diffusion-weighted magnetic resonance imaging (DW-MRI) in the evaluation of the fetal kidney and to estimate age-dependent changes in the apparent diffusion coefficient (ADC) of normal and pathological fetal kidneys. DW-MRI was performed on a 1.5-T machine at 23-38 gestational weeks in 51 pregnant women in whom the fetal kidneys were normal and in 10 whose fetuses had renal pathology (three with suspected nephropathy, three with renal tract dilatation, one with unilateral renal venous thrombosis, and three with twin-twin transfusion syndrome (TTTS)). The ADC was measured in an approximately 1-cm2 region of interest within the renal parenchyma. ADC values in normal renal parenchyma ranged from 1.1 to 1.8 10(-3) mm2 s-1. There was no significant age-dependent change in the ADC of normal kidneys. In cases of nephropathy, the ADC value was not always pathological but an ADC map could show abnormal findings. In cases of dilatation, the ADC value was difficult to determine when the dilatation was huge. In cases of TTTS, the ADC of the donor twin was higher than that of the recipient twin and the difference seemed to be related to the severity of the syndrome. Evaluation of the ADC for fetal kidneys is feasible. Fetal measurement of the ADC value and ADC maps may be useful tools with which to explore the fetal kidney when used in conjunction with current methods. DW-MR images, ADC value and ADC map seem to be useful in cases of suspected nephropathy (hyperechoic kidneys), dilated kidney and vascular pathology (renal venous thrombosis, TTTS). Copyright (c) 2006 ISUOG.

Laparoscopic nephrectomy for giant staghorn calculus with non-functioning kidneys: Is associated unsuspected urothelial carcinoma responsible for conversion? Report of 2 cases

PubMed Central

Shah, Hemendra Navinchandra; Jain, Pritesh; Chibber, Percy Jal

2006-01-01

Background- Neglected renal stones remain a major cause of morbidity in developing countries. They not only result in functional impairment of affected kidney, but also act as an important predisposing factor for development of urothelial neoplasms. It is not uncommon to miss an associated urothelial tumor in a patient of nephrolithiasis preoperatively. Case presentation- In last 3 years, we came across two patients with giant staghorn calculus and poorly functioning kidneys who underwent laparoscopic nephrectomy. In view of significant perirenal adhesions & loss of normal tissue planes both these patients were electively converted to open surgery. The pathological examination of specimen revealed an unsuspected urothelial carcinoma in both these patients. The summary of our cases and review of literature is presented. Conclusion- It is important to keep a differential diagnosis of associated urothelial malignancy in mind in patient presenting with long standing renal calculi. The exact role of a computerized tomography and cytology in preoperative workup for detection of possible associated malignancy in such condition is yet to be defined. Similarly if laparoscopic dissection appears difficult during nephrectomy for a renal calculus with non-functional kidney, keeping a possibility of associated urothelial malignancy in mind it is advisable to dissect in a plane outside gerotas fascia as for radical nephrectomy. PMID:16398940

Increasing access to kidney transplantation for sensitized recipient through three-way kidney paired donation with desensitization: The first Indian report

PubMed Central

Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Rizvi, Sayyed J; Pal, Bipin C; Modi, Manisha P; Shah, Priya S; Varyani, Umesh T; Wakhare, Pavan S; Shinde, Saiprasad G; Ghodela, Viajay A; Patel, Minaxi H; Trivedi, Varsha B; Trivedi, Hargovind L

2016-01-01

The combination of kidney paired donation (KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation (LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT. PMID:27803919

Endovascular treatment of cerebral aneurysm after renal transplantation in polycystic kidney disease.

PubMed

Demartini, Zeferino; Galdino, Jennyfer; Koppe, Gelson L; Bignelli, Alexandre T; Francisco, Alexandre N; Gatto, Luana Am

2018-06-01

Background Patients with polycystic kidney disease have a higher prevalence of intracranial aneurysms and may progress to renal failure requiring transplantation. The endovascular treatment of intracranial aneurysms may improve prognosis, since rupture often causes premature death or disability, but the nephrotoxicity risk associated with contrast medium must be always considered in cases of renal impairment. Methods A 55-year-old female patient with polycystic kidney disease and grafted kidney associated with anterior communicant artery aneurysm was successfully treated by embolization. Results The renal function remained normal after the procedure. To the authors' knowledge, this is the first case of endovascular treatment of brain aneurysm in a transplanted patient reported in the medical literature. Conclusions The endovascular procedure in renal transplant patients is feasible and can be considered to treat this population. Further studies and cases are needed to confirm its safety.

Kidney Transplant Rejection and Tissue Injury by Gene Profiling of Biopsies and Peripheral Blood Lymphocytes

PubMed Central

Flechner, Stuart M.; Kurian, Sunil M.; Head, Steven R.; Sharp, Starlette M.; Whisenant, Thomas C.; Zhang, Jie; Chismar, Jeffrey D.; Horvath, Steve; Mondala, Tony; Gilmartin, Timothy; Cook, Daniel J.; Kay, Steven A.; Walker, John R.; Salomon, Daniel R.

2007-01-01

A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients. PMID:15307835

Renal F4/80+CD11c+ Mononuclear Phagocytes Display Phenotypic and Functional Characteristics of Macrophages in Health and in Adriamycin Nephropathy

PubMed Central

Wang, Yiping; Wang, Xin Maggie; Lu, Junyu; Lee, Vincent W.S.; Ye, Qianling; Nguyen, Hanh; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I.; Harris, David C.H.

2015-01-01

Conventional markers of macrophages (Mфs) and dendritic cells (DCs) lack specificity and often overlap, leading to confusion and controversy regarding the precise function of these cells in kidney and other diseases. This study aimed to identify the phenotype and function of renal mononuclear phagocytes (rMPs) expressing key markers of both Mфs and DCs. F4/80+CD11c+ cells accounted for 45% of total rMPs in normal kidneys and in those from mice with Adriamycin nephropathy (AN). Despite expression of the DC marker CD11c, these double-positive rMPs displayed the features of Mфs, including Mф-like morphology, high expression of CD68, CD204, and CD206, and high phagocytic ability but low antigen-presenting ability. F4/80+CD11c+ cells were found in the cortex but not in the medulla of the kidney. In AN, F4/80+CD11c+ cells displayed an M1 Mф phenotype with high expression of inflammatory mediators and costimulatory factors. Adoptive transfer of F4/80+CD11c+ cells separated from diseased kidney aggravated renal injury in AN mice. Furthermore, adoptive transfer of common progenitors revealed that kidney F4/80+CD11c+ cells were derived predominantly from monocytes, but not from pre-DCs. In conclusion, renal F4/80+CD11c+ cells are a major subset of rMPs and display Mф-like phenotypic and functional characteristics in health and in AN. PMID:25012165

Renal F4/80+ CD11c+ mononuclear phagocytes display phenotypic and functional characteristics of macrophages in health and in adriamycin nephropathy.

PubMed

Cao, Qi; Wang, Yiping; Wang, Xin Maggie; Lu, Junyu; Lee, Vincent W S; Ye, Qianling; Nguyen, Hanh; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I; Harris, David C H

2015-02-01

Conventional markers of macrophages (Mфs) and dendritic cells (DCs) lack specificity and often overlap, leading to confusion and controversy regarding the precise function of these cells in kidney and other diseases. This study aimed to identify the phenotype and function of renal mononuclear phagocytes (rMPs) expressing key markers of both Mфs and DCs. F4/80(+)CD11c(+) cells accounted for 45% of total rMPs in normal kidneys and in those from mice with Adriamycin nephropathy (AN). Despite expression of the DC marker CD11c, these double-positive rMPs displayed the features of Mфs, including Mф-like morphology, high expression of CD68, CD204, and CD206, and high phagocytic ability but low antigen-presenting ability. F4/80(+)CD11c(+) cells were found in the cortex but not in the medulla of the kidney. In AN, F4/80(+)CD11c(+) cells displayed an M1 Mф phenotype with high expression of inflammatory mediators and costimulatory factors. Adoptive transfer of F4/80(+)CD11c(+) cells separated from diseased kidney aggravated renal injury in AN mice. Furthermore, adoptive transfer of common progenitors revealed that kidney F4/80(+)CD11c(+) cells were derived predominantly from monocytes, but not from pre-DCs. In conclusion, renal F4/80(+)CD11c(+) cells are a major subset of rMPs and display Mф-like phenotypic and functional characteristics in health and in AN. Copyright © 2015 by the American Society of Nephrology.

Monosodium glutamate intake affect the function of the kidney through NMDA receptor.

PubMed

Mahieu, Stella; Klug, Maximiliano; Millen, Néstor; Fabro, Ana; Benmelej, Adriana; Contini, Maria Del Carmen

2016-03-15

We investigated whether the chronic intake of monosodium glutamate (MSG) with food affects kidney function, and renal response to glycine. We also established if the NMDA receptors are involved in the changes observed. Male Wistar rats (5weeks old) were fed a diet supplemented with MSG (3g/kg b.w./day), five days a week, and spontaneous ingestion of a 1% MSG solution during 16weeks. NaCl rats were fed a diet with NaCl (1g/kg b.w./day) and 0.35% NaCl solution at the same frequency and time. Control group was fed with normal chow and tap water. We utilized clearance techniques to examine glomerular filtration rate (GFR) and cortical renal plasma flow (CRPF) response to glycine and glycine+MK-801 (antagonist NMDA-R), and we determined NMDA-R1 in kidney by immunohistochemistry. The addition of MSG in the diet of rats increased both GFR and CRPF with an increase of absolute sodium reabsorption. However, hyperfiltration was accompanied with a normal response to glycine infusion. Immunostain of kidney demonstrate that the NMDA receptor is upregulated in rats fed with MSG diet. NMDA-R antagonist MK-801 significantly reduced both the GFR and CRPF; however the percentage of reduction was significantly higher in the group MSG. MK-801 also reduces fractional excretion of water, sodium and potassium in the three groups. Renal NMDAR may be conditioned by the addition of MSG in the diet, favoring the hyperfiltration and simultaneously Na retention in the body. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidental kidney stones: a single center experience with kidney donor selection

PubMed Central

Kim, Irene K.; Tan, Jane C.; Lapasia, Jessica; Elihu, Arvand; Busque, Stephan; Melcher, Marc L.

2014-01-01

The presence of kidney stones has been a relative contraindication for living donation. With the widespread use of more sensitive imaging techniques as part of the routine living donor workup, kidney stones are more frequently detected, and their clinical significance in this setting is largely unknown. Records from 325 potential kidney donors who underwent MRA or CT-angiography were reviewed; 294 proceeded to donation. The prevalence of kidney stones found incidentally during donor evaluation was 7.4% (24 of 325). Sixteen donors with stones proceeded with kidney donation. All incidental calculi were nonobstructing and small (median 2 mm; range 1–9 mm). Eleven recipients were transplanted with allografts containing stones. One recipient developed symptomatic nephrolithasis after transplantation. This recipient was found to have newly formed stones secondary to hyperoxaluria, suggesting a recipient-driven propensity for stone formation. The remaining ten recipients have stable graft function, postoperative ultrasound negative for nephrolithiasis, and no sequelae from stones. No donor developed symptomatic nephrolithiasis following donation. Judicious use of allografts with small stones in donors with normal metabolic studies may be acceptable, and careful follow-up in recipients of such allografts is warranted. PMID:22168332

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

PubMed

Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

2016-10-17

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Obesity in the Kidney Transplant Process.

PubMed

Ateş, Damla; Cebeci, Fatma

2018-03-01

Obesity, which has become an increasing problem worldwide, poses a risk for kidney transplant recipients both before and after surgery. In this literature review, we studied the effects of obesity before and after kidney transplant. There are numerous studies and different opinions on the effects of obesity on graft function before and after transplant. Obesity prolongs surgery time and the ischemic process. A large cohort study of 11 836 recipients noted a close association between body mass index and delayed renal transplant and delayed graft function. However, another study found that being overweight or obese before transplant did not have any effects over the medium and long term. A 20-year follow-up study indicated that the firstyear body mass index in recipients after renal transplant had a greater effect on graft function and survival than body mass index before transplant. Still, another study found that body mass index had no effects on graft function and survival. In the study, 3-year graft function and mortality rates of morbidly obese people without diabetes, the functional status without dialysis, and living-donor transplant were reported to be much lower than in those with normal weight. In conclusion, there is no consensus on the effects of obesity before and after transplant, and it has been pointed out that more research should be done on this subject.

Correlates of diuretic renography in experimental hydronephrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kekomaeki, M.R.; Rikalainen, H.; Ruotsalainen, P.

1989-02-01

We studied the correlations between diuretic renographs and kidney function in experimental hydronephrosis in rabbits. Features of furosemide-stimulated /sup 99m/Tc-diethylenetriamine-pentaacetic acid renographs were compared to the growth rate, thirst test and endogenous creatinine clearance rate in a chronic solitary-kidney animal model. Intravenous pyelograms, done four weeks after laparotomy, left nephrectomy, bladder resection and constriction of the right pyeloureteric junction, showed signs of obstruction in all the 12 animals of the experimental group. An absent tracer washout after intravenous furosemide, found in five animals, was associated with retarded growth, isosthenuria and an abnormal creatinine clearance. In all of the other sevenmore » animals, a distinct tracer washout after intravenous furosemide was accompanied with a normal growth rate and creatinine clearance. However, no one of these seven animals had a normal ability to retain water and concentrate urine in the thirst test. We conclude that, in this experimental model, a furosemide-induced tracer washout from the kidney pelvis cannot be taken as a proof of the absence of any upper urinary tract obstruction.« less

Requirement for Class II Phosphoinositide 3-Kinase C2α in Maintenance of Glomerular Structure and Function▿

PubMed Central

Harris, David P.; Vogel, Peter; Wims, Marie; Moberg, Karen; Humphries, Juliane; Jhaver, Kanchan G.; DaCosta, Christopher M.; Shadoan, Melanie K.; Xu, Nianhua; Hansen, Gwenn M.; Balakrishnan, Sanjeevi; Domin, Jan; Powell, David R.; Oravecz, Tamas

2011-01-01

An early lesion in many kidney diseases is damage to podocytes, which are critical components of the glomerular filtration barrier. A number of proteins are essential for podocyte filtration function, but the signaling events contributing to development of nephrotic syndrome are not well defined. Here we show that class II phosphoinositide 3-kinase C2α (PI3KC2α) is expressed in podocytes and plays a critical role in maintaining normal renal homeostasis. PI3KC2α-deficient mice developed chronic renal failure and exhibited a range of kidney lesions, including glomerular crescent formation and renal tubule defects in early disease, which progressed to diffuse mesangial sclerosis, with reduced podocytes, widespread effacement of foot processes, and modest proteinuria. These findings were associated with altered expression of nephrin, synaptopodin, WT-1, and desmin, indicating that PI3KC2α deficiency specifically impacts podocyte morphology and function. Deposition of glomerular IgA was observed in knockout mice; importantly, however, the development of severe glomerulonephropathy preceded IgA production, indicating that nephropathy was not directly IgA mediated. PI3KC2α deficiency did not affect immune responses, and bone marrow transplantation studies also indicated that the glomerulonephropathy was not the direct consequence of an immune-mediated disease. Thus, PI3KC2α is critical for maintenance of normal glomerular structure and function by supporting normal podocyte function. PMID:20974805

Laparoscopic robot-assisted pancreas transplantation: first world experience.

PubMed

Boggi, Ugo; Signori, Stefano; Vistoli, Fabio; D'Imporzano, Simone; Amorese, Gabriella; Consani, Giovanni; Guarracino, Fabio; Marchetti, Piero; Focosi, Daniele; Mosca, Franco

2012-01-27

Surgical complications are a major disincentive to pancreas transplantation, despite the undisputed benefits of restored insulin independence. The da Vinci surgical system, a computer-assisted electromechanical device, provides the unique opportunity to test whether laparoscopy can reduce the morbidity of pancreas transplantation. Pancreas transplantation was performed by robot-assisted laparoscopy in three patients. The first patient received a pancreas after kidney transplant, the second a simultaneous pancreas kidney transplantation, and the third a pancreas transplant alone. Operations were carried out through an 11-mm optic port, two 8-mm operative ports, and a 7-cm midline incision. The latter was used to introduce the grafts, enable vascular cross-clamping, and create exocrine drainage into the jejunum. The two solitary pancreas transplants required an operating time of 3 and 5 hr, respectively; the simultaneous pancreas kidney transplantation took 8 hr. Mean warm ischemia time of the pancreas graft was 34 min. All pancreatic transplants functioned immediately, and all recipients became insulin independent. The kidney graft, revascularized after 35 min of warm ischemia, also functioned immediately. No patient had complications during or after surgery. At the longer follow-up of 10, 8, and 6 months, respectively, all recipients are alive with normal graft function. We have shown the feasibility of laparoscopic robot-assisted solitary pancreas and simultaneous pancreas and kidney transplantation. If the safety and feasibility of this procedure can be confirmed by larger series, laparoscopic robot-assisted pancreas transplantation could become a new option for diabetic patients needing beta-cell replacement.

RBC indices

MedlinePlus

... sudden blood loss, long-term diseases, kidney failure , aplastic anemia , or man-made heart valves). MCV above normal. ... sudden blood loss, long-term diseases, kidney failure, aplastic anemia, or man-made heart valves). MCH above normal. ...

The impact of α-Lipoic acid on cell viability and expression of nephrin and ZNF580 in normal human podocytes.

PubMed

Leppert, Ulrike; Gillespie, Allan; Orphal, Miriam; Böhme, Karen; Plum, Claudia; Nagorsen, Kaj; Berkholz, Janine; Kreutz, Reinhold; Eisenreich, Andreas

2017-09-05

Human podocytes (hPC) are essential for maintaining normal kidney function and dysfunction or loss of hPC play a pivotal role in the manifestation and progression of chronic kidney diseases including diabetic nephropathy. Previously, α-Lipoic acid (α-LA), a licensed drug for treatment of diabetic neuropathy, was shown to exhibit protective effects on diabetic nephropathy in vivo. However, the effect of α-LA on hPC under non-diabetic conditions is unknown. Therefore, we analyzed the impact of α-LA on cell viability and expression of nephrin and zinc finger protein 580 (ZNF580) in normal hPC in vitro. Protein analyses were done via Western blot techniques. Cell viability was determined using a functional assay. hPC viability was dynamically modulated via α-LA stimulation in a concentration-dependent manner. This was associated with reduced nephrin and ZNF580 expression and increased nephrin phosphorylation in normal hPC. Moreover, α-LA reduced nephrin and ZNF580 protein expression via 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) inhibition. These data demonstrate that low α-LA had no negative influence on hPC viability, whereas, high α-LA concentrations induced cytotoxic effects on normal hPC and reduced nephrin and ZNF580 expression via NF-κB inhibition. These data provide first novel information about potential cytotoxic effects of α-LA on hPC under non-diabetic conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Elevated plasma TGF-beta1 in renal diseases: cause or consequence?

PubMed

Junker, U; Haufe, C C; Nuske, K; Rebstock, K; Steiner, T; Wunderlich, H; Junker, K; Reinhold, D

2000-07-01

We previously reported elevated levels of TGF-beta1 in patients with renal carcinoma. Certain aspects led us to ask whether they might be caused by chronic damage to the kidney(s). Here we report on an extended set of patients with various renal diseases, lung cancer, humoral immunodeficiency and controls. For latent TGF-beta1 in plasma, we find that the control, immunodeficiency, lung cancer and kidney transplant groups do not differ significantly (means, 7.0-8.8 ng/ml). Also, acute short-term renal stress (extracorporal lithotrypsy) does not lead to an increase of TGF-beta1. However, the pyelonephritis patients present with levels of 19.0 ng/ml, chronic extracorporal dialysis patients with 15.5 ng/ml, and renal cell carcinoma patients with 22.8 ng/ml. For active TGF-beta1 these findings are exactly recovered. For serum levels, only the renal carcinoma group presents with significantly elevated levels of TGF-beta1. Kidney transplantation seems to normalize TGF-beta1 levels, while in the kidney cancer patients surgery has an effect only in part of the group. We conclude that elevated plasma TGF-beta1 levels are common in at least two chronic renal disease conditions, and that it normalizes with restoration of renal function. It is tempting to speculate that chronic elevation of TGF-beta1 in these patients may be critically involved in these conditions predisposing to renal cancer. Copyright 2000 Academic Press.

Correlation between cognitive functions and syndromes of traditional Chinese medicine in amnestic mild cognitive impairment.

PubMed

Miao, Ying-chun; Tian, Jin-zhou; Shi, Jing; Mao, Min; Zhao, Xiao-dong; Fang, Li-yan; Zeng, Chui-you; Liu, Jian-ping; Wang, Zhi-liang; Li, Xiao-bin

2009-03-01

To explore the correlation between the cognitive functions and syndromes of traditional Chinese medicine (TCM) in amnestic mild cognitive impairment (aMCI), and to provide evidence for clinical syndrome differentiation treatment. Six hundred subjects from Dongzhimen Hospital and seven communities in Beijing, aged between 40 and 85 years, accepted neuropsychological assessments, imaging and biochemical examinations, and syndrome differentiation, from whom 159 aMCI patients, 213 normal control (NC) subjects and 171 Alzheimer's dementia (AD) patients were screened out. Correlation between the cognitive functions and TCM syndromes in aMCI patients was analyzed. Mini-Mental State Examination (MMSE) score in aMCI patients was closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.11; P = 0.003, P = 0.015). Delayed Word Recall (DWR) score was correlated with kidney essence vacuity (r = -0.20, P = 0.020). Instant Story Recall (ISR) and Delayed Story Recall (DSR) scores were respectively correlated with turbid phlegm blocking upper orifices (r = -0.11, r = -0.27; P = 0.021, P = 0.000). Language function was correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.11, r = -0.13; P = 0.042, P = 0.007). Attention/calculation was also closely correlated with kidney essence vacuity and deficiency of blood and qi (r = -0.10, r = -0.21; P = 0.039, P = 0.010). Attention score of aMCI patients was correlated with excess of heat toxin syndrome (r = -0.29, P = 0.026). The memory decline of aMCI is correlated with kidney essence vacuity and turbid phlegm blocking upper orifices. Furthermore, turbid phlegm blocking upper orifices is correlated with episodic memory decline, which is closely related to AD. The aMCI patients with phlegm have the risk to progress into AD. Although other cognitive functions of aMCI remain relatively intact, the patients' language function, attention/calculation and the whole cognitive function may be worsen as the aggravation of kidney essence vacuity, deficiency of blood and qi, phlegm and heat toxin, and may eventually lead to multiple cognitive domains impairment, even dementia.

Resveratrol influences platinum pharmacokinetics: A novel mechanism in protection against cisplatin-induced nephrotoxicity.

PubMed

Darwish, Mostafa A; Abo-Youssef, Amira M; Khalaf, Marwa M; Abo-Saif, Ali A; Saleh, Ibrahim G; Abdelghany, Tamer M

2018-06-15

Cisplatin (CP) is a widely used drug in treatment of solid tumors. However, the use of CP was hampered by its serious side effects especially nephrotoxicity. This study aims to investigate the effect of resveratrol (RES) on CP-induced nephrotoxicity, particularly, the effect of RES on CP pharmacokinetics (PKs). Male white albino rats were divided to four group's six rats each. The first group received (1%) tween 80 in normal saline and served as control. The second group received RES (30 mg kg -1 ) per day for 14 consecutive day's i.p. The third and fourth groups were given a single i.p. injection of CP (6 mg kg -1 ) with or without pre-treatment of RES (30 mg kg -1 per day for 14 consecutive days), respectively. Following administration of CP, plasma, urine and kidney platinum concentration were monitored to study PKs of CP. Five days after the CP injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CP treatment significantly deteriorated kidney functions with subsequent alteration in redox balance of the kidney. On the other hand, RES successfully ameliorated CP-induced kidney injury and recovered normal kidney tissue redox status. Importantly, while RES pre-treatment did not significantly alter the plasma CP level, it dramatically decreased the urine concentration of CP and lowered its accumulation into the kidneys. Moreover, it increased CP plasma half-life (t 1/2 ) with subsequent decrease in its elimination rate constant, indicating an important role of PKs modulation in RES protection against CP-induced renal damage. Taken together, RES may protect the kidney tissue from the deleterious effects of CP through constringe of CP renal accumulation and enhancement of CP-induced oxidative stress. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of cholesterol overload on mouse kidney and kidney-derived cells.

PubMed

Honzumi, Shoko; Takeuchi, Miho; Kurihara, Mizuki; Fujiyoshi, Masachika; Uchida, Masashi; Watanabe, Kenta; Suzuki, Takaaki; Ishii, Itsuko

2018-11-01

Dyslipidemia is one of the onset and risk factors of chronic kidney disease and renal function drop is seen in lipoprotein abnormal animal models. However, the detailed molecular mechanism of renal lipotoxicity has not been clarified. Therefore, the present study aimed to investigate the influence of cholesterol overload using mouse kidney tissue and kidney-derived cultured cells. C57BL/6 mice were fed normal diet (ND) or 1.25% cholesterol-containing high-cholesterol diet (HCD) for 11 weeks, and we used megalin as a proximal tubule marker for immunohistology. We added beta-very low density lipoprotein (βVLDL) to kidney-derived cells and examined the effect of cholesterol overload on megalin protein and mRNA expression level, cell proliferation and cholesterol content in cells. In the kidney of HCD mice, the gap between glomerulus and the surrounding Bowman's capsule decreased and the expression level of megalin decreased. After βVLDL treatment to the cells, the protein expression and mRNA expression level of megalin decreased and cell proliferation was restrained. We also observed an increase in cholesterol accumulation in the cell and free cholesterol/phospholipid ratios increased. These findings suggest that the increased cholesterol load on kidney contribute to the decrease of megalin and the overloaded cholesterol is taken into the renal tubule epithelial cells, causing suppression on cell proliferation, which may be the cause of kidney damage.

The Leaf of Diospyros kaki Thumb Ameliorates Renal Oxidative Damage in Mice with Type 2 Diabetes

PubMed Central

Choi, Myung-Sook; Jeong, Mi Ji; Park, Yong Bok; Kim, Sang Ryong; Jung, Un Ju

2016-01-01

Diabetic kidney disease is the most common and severe chronic complication of diabetes. The leaf of Diospyros kaki Thumb (persimmon) has been commonly used for herbal tea and medicinal purposes to treat a variety of conditions, including hypertension and atherosclerosis. However, the effect of persimmon leaf on kidney failure has not been investigated. This study aimed to examine the role of persimmon leaf in protecting the diabetes-associated kidney damage in a mouse model of type 2 diabetes. Mice were fed either a normal chow diet with or without powered persimmon leaf (5%, w/w) for 5 weeks. In addition to kidney morphology and blood markers of kidney function, we assessed levels of oxidative stress markers as well as antioxidant enzymes activities and mRNA expression in the kidney. Supplementation of the diet with powered persimmon leaf not only decreased the concentration of blood urea nitrogen in the plasma but also improved glomerular hypertrophy. Furthermore, the persimmon leaf significantly decreased the levels of hydrogen peroxide and lipid peroxide in the kidney. The activities of superoxide dismutase, catalase, and glutathione peroxidase and the mRNA expression of their respective genes were also increased in the kidney of persimmon leaf-supplemented db/db mice. Taken together, these results suggest that supplementation with the persimmon leaf may have protective effects against type 2 diabetes-induced kidney dysfunction and oxidative stress. PMID:28078262

The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats.

PubMed

Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Maicas, Nuria; Florquin, Sandrine; van den Heuvel, Lambertus P; Schreuder, Michiel F

2016-01-01

Diuretics are administered to neonates to control fluid balance. We studied whether clinical doses affected kidney development and function and whether extrauterine growth retardation (EUGR) could be a modulator. Wistar rats were cross-fostered in normal food or food restricted litters at postnatal day (PND) 2 and treated daily with 0.9% NaCl, 5 mg/kg furosemide or 5 mg/kg hydrochlorothiazide (HCTZ) up to PND 8. Kidneys were evaluated on proliferation, apoptosis and a set of mRNA target genes at PND 8, glomerular- and glomerular generation count at PND 35, clinical pathology parameters at 3- and 9 months, neutrophil gelatinase-associated lipocalin at PND 8, 3 and 6 months, monthly blood pressure from 3 months onward and histopathology at study end. Treatment with furosemide or HCTZ did not have relevant effects on measured parameters. EUGR resulted in lower body weight from day 3 onwards (-29% at weaning; p < 0.001, -10% at necropsy; p < 0.001), less glomerular generations (4.4 ± 0.32 vs. 5.0 ± 0.423; p = 0.025, males only), decreased glomerular numbers (27,861 ± 3,468 vs. 30,527 ± 4,096; p = 0.026), higher creatinine clearance (0.84 ± 0.1 vs. 0.77 ± 0.09 ml/min/kg; p = 0.047) at 3 months and lower plasma creatinine (25.7 ± 1.8 vs. 27.5 ± 2.8 µmol/l; p = 0.043) at 9 months. Furosemide and HCTZ did not influence kidney development or function when administered in a clinically relevant dose to rat pups at a stage of ongoing nephrogenesis. EUGR led to impaired kidney development but did not modify furosemide or HCTZ findings. © 2016 S. Karger AG, Basel.

Incubation relative humidity induces renal morphological and physiological remodeling in the embryo of the chicken (Gallus gallus domesticus).

PubMed

Bolin, Greta; Dubansky, Benjamin; Burggren, Warren W

2017-02-01

The metanephric kidneys of the chicken embryo, along with the chorioallantoic membrane, process water and ions to maintain osmoregulatory homeostasis. We hypothesized that changes in relative humidity (RH) and thus osmotic conditions during embryogenesis would alter the developmental trajectory of embryonic kidney function. White leghorn chicken eggs were incubated at one of 25-30% relative humidity, 55-60% relative humidity, and 85-90% relative humidity. Embryos were sampled at days 10, 12, 14, 16, and 18 to examine embryo and kidney mass, glomerular characteristics, body fluid osmolalities, hematological properties, and whole embryo oxygen consumption. Low and especially high RH elevated mortality, which was reflected in a 10-20% lower embryo mass on D18. Low RH altered several glomerular characteristics by day 18, including increased numbers of glomeruli per kidney, increased glomerular perfusion, and increased total glomerular volume, all indicating potentially increased functional kidney capacity. Hematological variables and plasma and amniotic fluid osmolalities remained within normal physiological values. However, the allantoic, amniotic and cloacal fluids had a significant increase in osmolality at most developmental points sampled. Embryonic oxygen consumption increased relative to control at both low and high relative humidities on Day 18, reflecting the increased metabolic costs of osmotic stress. Major differences in both renal structure and performance associated with changes in incubation humidity occurred after establishment of the metanephric kidney and persisted into late development, and likely into the postnatal period. These data indicate that the avian embryo deserves to be further investigated as a promising model for fetal programming of osmoregulatory function, and renal remodeling during osmotic stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal Parenchymal Area Growth Curves for Children 0 to 10 Months Old.

PubMed

Fischer, Katherine; Li, Chunming; Wang, Huixuan; Song, Yihua; Furth, Susan; Tasian, Gregory E

2016-04-01

Low renal parenchymal area, which is the gross area of the kidney in maximal longitudinal length minus the area of the collecting system, has been associated with increased risk of end stage renal disease during childhood in boys with posterior urethral valves. To our knowledge normal values do not exist. We aimed to increase the clinical usefulness of this measure by defining normal renal parenchymal area during infancy. In a cross-sectional study of children with prenatally detected mild unilateral hydronephrosis who were evaluated between 2000 and 2012 we measured the renal parenchymal area of normal kidney(s) opposite the kidney with mild hydronephrosis. Measurement was done with ultrasound from birth to post-gestational age 10 months. We used the LMS method to construct unilateral, bilateral, side and gender stratified normalized centile curves. We determined the z-score and the centile of a total renal parenchymal area of 12.4 cm(2) at post-gestational age 1 to 2 weeks, which has been associated with an increased risk of kidney failure before age 18 years in boys with posterior urethral valves. A total of 975 normal kidneys of children 0 to 10 months old were used to create renal parenchymal area centile curves. At the 97th centile for unilateral and single stratified curves the estimated margin of error was 4.4% to 8.8%. For bilateral and double stratified curves the estimated margin of error at the 97th centile was 6.6% to 13.2%. Total renal parenchymal area less than 12.4 cm(2) at post-gestational age 1 to 2 weeks had a z-score of -1.96 and fell at the 3rd percentile. These normal renal parenchymal area curves may be used to track kidney growth in infants and identify those at risk for chronic kidney disease progression. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Functional and morphological evaluation of radiation nephropathy and ureteral injury in the dog

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cloran, J.A.

1986-01-01

Intraoperative radiotherapy (IORT) may provide a therapeutic advantage in the treatment of certain intraabdominal malignancies. However, before the therapeutic potential of innovative modalities can be assessed adequately, the in vivo radiobiological effects and responses of normal tissues to clinical doses of irradiation must be determined. In this study, the reactions of normal canine kidneys, ureters, and major vessels wee assessed following IORT, fractionated x-irradiation, or a combination of these modalities. Radiographically derived morphological endpoints, including kidney size and cortical width, were monitored for one year following irradiation. The renal parenchymal atrophy, vascular alterations and functional impairment that developed was directlymore » related to the IORT dose, whether delivered alone or in combination with fractionated x-irradiation. The incidence of ureteral injury and secondary hydronephrosis increased with both the IORT dose and post-irradiation time. No ureteral changes were detected in dogs that received only fractionated x-irradiation (60-80 Gy). No significant arteriographic abnormalities could be detected in the caudal aorta during the one year follow-up period.« less

Sonographic Assessment of the Normal Dimensions of Liver, Spleen, and Kidney in Healthy Children at Tertiary Care Hospital.

PubMed

Thapa, N B; Shah, S; Pradhan, A; Rijal, K; Pradhan, A; Basnet, S

2015-01-01

Background Ultrasonography is one of the most common imaging modality to measure dimensions of visceral organs in children. However, the normal limit of size of visceral organs according to age and body habitus has not been specified in the standard textbooks. This might result in under detection of organomegaly in pediatrics population. Objective The objective of this study was to determine the normal range of dimensions for the liver, spleen, and kidney in healthy children. Method This is prospective cross-sectional, hospital-based study done at Tertiary-care teaching hospital. Participants included 272 pediatric subjects (152 male and 120 female) with normal physical or sonographic findings who were examined because of problems unrelated to the measured organs. The subjects were one month to 15 year (180 months) old. All measured organs were sonographically normal. Relationships of the dimensions of these organs with sex, age, body weight and height were investigated. Limits of normal dimensions of these organs were defined. Result Normal length of liver, kidneys and spleen were obtained sonographically for 272 children (152 male [55.9%] and 120 female [44.1%]) in the age group from 1 months to 15 (180 months) years. The mean age was 45.78 months (SD, 44.73). The measured dimensions of all these organs showed highest correlation with height and age so the descriptive analysis of the organ dimensions (mean, minimum, and maximum values, SD and 5th and 95th percentiles) were expressed in 10 age groups along with height range of the included children. The mean length of right kidney was shorter than the left kidney length, and the difference was statistically significant (p = 0.001). Conclusion This study provides practical and comprehensive guide to the normal visceral organ dimension in pediatric population. The normal range limit of the liver, spleen, and kidney determined in this study could be used as a reference in daily practice in local radiology clinics.

CD147 (EMMPRIN/Basigin) in kidney diseases: from an inflammation and immune system viewpoint.

PubMed

Kosugi, Tomoki; Maeda, Kayaho; Sato, Waichi; Maruyama, Shoichi; Kadomatsu, Kenji

2015-07-01

The glycosylated transmembrane protein CD147/basigin, also known as extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN), contributes to cell survival, migration and cancer invasion. In normal kidneys, high expression of CD147 is detected only in the basolateral side of tubular epithelial cells (TECs). The pathophysiological roles of CD147 in the kidneys are diverse, ranging from involvement in the occurrence of acute kidney injury (AKI) that is frequently accompanied by ischemia, inflammation and a loss of self-tolerance to the progression of chronic kidney disease (CKD) that is caused by an imbalance in extracellular matrix protein turnover. In AKI induced by ischemia, it is the CD147 on neutrophils, rather than that on TECs, that coordinately participates in massive neutrophil recruitment via acting as a physiological ligand for E-selectin, which is specifically enhanced in the endothelium upon inflammatory stimulation. In the CKD that follows AKI, a molecular circuit involving CD147, MMPs and transforming growth factor-β may be involved in the pathogenesis of progressive fibrosis through hyaluronan production and macrophage infiltration. Whereas CD147 thus plays deleterious roles in ischemic and fibrotic kidney injuries, CD147 expression on lymphocytes might decrease the disease activity of lupus nephritis (LN) by functioning as a potential negative regulator of the extraordinary proliferation of lymphocytes that occurs in this disease. In line with these basic studies, our clinical data indicate the potential of plasma CD147 to function as a critical biomarker for both ischemic AKI and LN. CD147 is also involved in crosstalk between the kidneys and distant organs, which may be mediated by chemotactic cytokines that are derived from circulating inflammatory cells and damaged organs. Disruption of such a vicious chain reaction involving CD147 would therefore be required in order to overcome kidney diseases. Multidisciplinary research regarding CD147 functions may open a new avenue for targeting therapeutics for kidney diseases. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Ipsilateral kidney sparing in treatment of pancreatic malignancies using volumetric-modulated arc therapy avoidance sectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Raymond W., E-mail: rwc3b@alumni.virginia.edu; Podgorsak, Matthew B.

Recent research has shown treating pancreatic cancer with volumetric-modulated arc therapy (VMAT) to be superior to either intensity-modulated radiation therapy or 3-dimensional conformal radiotherapy (3D-CRT), with respect to reducing normal tissue toxicity, monitor units, and treatment time. Furthermore, using avoidance sectors with RapidArc planning can further reduce normal tissue dose while maintaining target conformity. This study looks at the methods in reducing dose to the ipsilateral kidney, in pancreatic head cases, while observing dose received by other critical organs using avoidance sectors. Overall, 10 patients were retrospectively analyzed. Each patient had preoperative/unresectable pancreatic tumor and were selected based on themore » location of the right kidney being situated within the traditional 3D-CRT treatment field. The target planning target volume (286.97 ± 85.17 cm{sup 3}) was prescribed to 50.4 Gy using avoidance sectors of 30°, 40°, and 50° and then compared with VMAT as well as 3D-CRT. Analysis of the data shows that the mean dose to the right kidney was reduced by 11.6%, 15.5%, and 21.9% for avoidance angles of 30°, 40°, and 50°, respectively, over VMAT. The mean dose to the total kidney also decreased by 6.5%, 8.5%, and 11.0% for the same increasing angles. Spinal cord maximum dose, however, increased as a function of angle by 3.7%, 4.8%, and 6.1% compared with VMAT. Employing avoidance sector angles as a complement to VMAT planning can significantly reduce high dose to the ipsilateral kidney while not greatly overdosing other critical organs.« less

The aldo-keto reductase AKR1B7 coexpresses with renin without influencing renin production and secretion.

PubMed

Machura, Katharina; Iankilevitch, Elina; Neubauer, Björn; Theuring, Franz; Kurtz, Armin

2013-03-01

On the basis of evidence that within the adult kidney, the aldo-keto reductase AKR1B7 (aldo-keto reductase family 1, member 7, also known as mouse vas deferens protein, MVDP) is selectively expressed in renin-producing cells, we aimed to define a possible role of AKR1B7 for the regulation and function of renin cells in the kidney. We could confirm colocalization and corecruitment of renin and of AKR1B7 in wild-type kidneys. Renin cells in AKR1B7-deficient kidneys showed normal morphology, numbers, and intrarenal distribution. Plasma renin concentration (PRC) and renin mRNA levels of AKR1B7-deficient mice were normal at standard chow and were lowered by a high-salt diet directly comparable to wild-type mice. Treatment with a low-salt diet in combination with an angiotensin-converting enzyme inhibitor strongly increased PRC and renin mRNA in a similar fashion both in AKR1B7-deficient and wild-type mice. Under this condition, we also observed a strong retrograde recruitment of renin-expressing cell along the preglomerular vessels, however, without a difference between AKR1B7-deficient and wild-type mice. The isolated perfused mouse kidney model was used to study the acute regulation of renin secretion by ANG II and by perfusion pressure. Regarding these parameters, no differences were observed between AKR1B7-deficient and wild-type kidneys. In summary, our data suggest that AKR1B7 is not of major relevance for the regulation of renin production and secretion in spite of its striking coregulation with renin expression.

Serum phosphorus and association with anemia among a large diverse population with and without chronic kidney disease

PubMed Central

Tran, Lac; Batech, Michael; Rhee, Connie M.; Streja, Elani; Kalantar-Zadeh, Kamyar; Jacobsen, Steven J.; Sim, John J.

2016-01-01

Background We hypothesized that phosphorus has an effect on anemia in both normal kidney function and early chronic kidney disease (CKD). We sought to determine whether higher phosphorus levels are associated with anemia in a large diverse population without CKD and early CKD. Methods This study is a historical population-based study within the Kaiser Permanente Southern California health system (1 January 1998 to 31 December 2013) among individuals aged 18 years and older with estimated glomerular filtration rate >30 mL/min/1.73 m2 and measurements of serum phosphorus, creatinine and hemoglobin. Individuals were excluded if they had secondary causes of anemia. Odds ratio (OR) estimated for moderate anemia defined as hemoglobin <11 g/dL for both sexes. Mild anemia was defined as <12 g/dL (females) and <13 g/dL (males). Results Among 155 974 individuals, 4.1% had moderate anemia and 12.9% had mild anemia. Serum phosphorus levels ≥3.5 mg/dL were associated with both mild and moderate anemia. Moderate anemia OR (95% confidence interval) was 1.16 (1.04–1.29) for every 0.5 mg/dL phosphorus increase and 1.26 (1.07–1.48) in the highest versus middle phosphorus tertile. Additional independent anemia risk factors, including female sex, Asian race, diabetes, low albumin and low iron saturation, were observed, but did not alter the anemia–phosphorus association. Conclusions Higher phosphorus levels were associated with a greater likelihood for anemia in a population with early CKD and normal kidney function. Phosphorus may be a biomarker for anemia and may affect aspects of hematopoiesis. PMID:26254460

Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys.

PubMed

Kurihara, Osamu; Takano, Masamichi; Uchiyama, Saori; Fukuizumi, Isamu; Shimura, Tetsuro; Matsushita, Masato; Komiyama, Hidenori; Inami, Toru; Murakami, Daisuke; Munakata, Ryo; Ohba, Takayoshi; Hata, Noritake; Seino, Yoshihiko; Shimizu, Wataru

2015-12-01

Contrast-induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty-six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m(2) (CKD and non-CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = -0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non-CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non-CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media. © 2015 The Authors. Clinical and Experimental Pharmacology and Physiology Published by Wiley Publishing Asia Pty Ltd.

Age-related incidence of sclerotic glomeruli in human kidneys.

PubMed Central

Kaplan, C.; Pasternack, B.; Shah, H.; Gallo, G.

1975-01-01

The incidence of sclerotic glomeruli as a function of age in kidneys from 122 patients without clinical evidence of renal disease or hypertension was estimated by histologic quantitation. Based on statistical analysis of data from this sample, 95% of the normal population up to 40 years of age would be expected to have less than 10% sclerotic glomeruli. After the age of 40 years, the upper limit containing 95% of the normal population exceeds 10% sclerosis, and after the age of 50, there is a broad scatter of observed percentage of sclerotic glomeruli. These findings suggest that, in patients 40 years of age and younger, sclerosis of glomeruli at an incidence greater than 10% is disease-related, while in patients older than 40 years (and particularly those older than 50), there is a transition, and the distinction between abiotrophic involutional sclerosis and disease-related sclerosis becomes less clear. PMID:51591

Prevalence of Hypertension in Children with Early-Stage ADPKD.

PubMed

Massella, Laura; Mekahli, Djalila; Paripović, Dušan; Prikhodina, Larisa; Godefroid, Nathalie; Niemirska, Anna; Ağbaş, Ayşe; Kalicka, Karolina; Jankauskiene, Augustina; Mizerska-Wasiak, Malgorzata; Afonso, Alberto Caldas; Salomon, Rémi; Deschênes, Georges; Ariceta, Gema; Özçakar, Z Birsin; Teixeira, Ana; Duzova, Ali; Harambat, Jérôme; Seeman, Tomáš; Hrčková, Gabriela; Lungu, Adrian Catalin; Papizh, Svetlana; Peco-Antic, Amira; De Rechter, Stéphanie; Giordano, Ugo; Kirchner, Marietta; Lutz, Teresa; Schaefer, Franz; Devuyst, Olivier; Wühl, Elke; Emma, Francesco

2018-04-19

Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited. Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected. Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P =0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P =0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P =0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P =0.10). These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages. Copyright © 2018 by the American Society of Nephrology.

Inherited congenital bilateral atresia of the external auditory canal, congenital bilateral vertical talus and increased interocular distance.

PubMed

Rasmussen, N; Johnsen, N J; Thomsen, J

1979-01-01

Six out of twenty descendants of a reportedly affected grandfather have congenital bilateral symmetrical and isolated subtotal atresia of the external auditory canal. Four of the six affected descendants have bilateral foot anomalies--two affected cousins having congenital vertical talus. All of the three affected boys in the third generation have increased interocular distance. Short fifth fingers, bilateral single transverse palmar creases, pyloric stenosis and congenital exotropia were found infrequently and are considered coincidental features. Apart from the atresia, oto-rhinolaryngologic examination, mental function, dermatoglyphics, IgA, kidney function and heart function of the affected descendants were all normal. The karyotype of four affected descendants examined was normal. An autosomal dominant inheritance with variable expressivity is suggested.

Evaluation of renal quantitative T2* changes on MRI following administration of ferumoxytol as a T2* contrast agent.

PubMed

Hedgire, Sandeep S; McDermott, Shaunagh; Wojtkiewicz, Gregory R; Abtahi, Seyed Mahdi; Harisinghani, Mukesh; Gaglia, Jason L

2014-01-01

To evaluate the time-dependent changes in regional quantitative T2* maps of the kidney following intravenous administration of ferumoxytol. Twenty-four individuals with normal kidney function underwent T2*-weighted MRI of the kidney before, immediately after, and 48 hours after intravenous administration of ferumoxytol at a dose of 4 mg/kg (group A, n=12) or 6 mg/kg (group B, n=12). T2* values were statistically analyzed using two-tailed paired t-tests. In group A, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.3% and 64.2% for the cortex and 90.8% and 64.6% for the medulla, respectively. In group B, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.2% and 73.4% for the cortex and 94.5% and 74% for the medulla, respectively. This difference was significant for both groups (P<0.0001). There is significant and differential uptake of ferumoxytol in the cortex and medulla of physiologically normal kidneys. This differential uptake may offer the ability to interrogate renal cortex and medulla with possible clinical applications in medical renal disease and transplant organ assessment. We propose an organ of interest based dose titration of ferumoxytol to better differentiate circulating from intracellular ferumoxytol particles.

Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

PubMed

Raish, Mohammad; Ahmad, Ajaz; Jan, Basit L; Alkharfy, Khalid M; Ansari, Mushtaq Ahmad; Mohsin, Kazi; Jenoobi, Fahad Al; Al-Mohizea, Abdullah

2016-10-01

Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

The protective effects of aqueous extract of Carica papaya seeds in paracetamol induced nephrotoxicity in male wistar rats.

PubMed

Naggayi, Madinah; Mukiibi, Nozmo; Iliya, Ezekiel

2015-06-01

Oxidative stress plays a crucial role in the development of drug induced nephrotoxicity. The study aimed to determine the nephroprotective and ameliorative effects of Carica papaya seed extract in paracetamol-induced nephrotoxicity in rats. To carry out phytochemical screening of Carica papaya, measure serum urea, creatinine and uric acid and describe the histopathological status of the kidneys in the treated and untreated groups. Phytochemical screening of the extract was done. Thirty two adult male Wistar rats were divided into four groups (n= 8 in each group). Group A (control) animals received normal saline for seven days, group B (paracetamol group) received normal saline, and paracetamol single dose on the 8th day. Group C received Carica papaya extract (CPE) 500 mg/kg, and paracetamol on the 8th day, while group D, rats were pretreated with CPE 750 mg/kg/day,and paracetamol administration on the 8th day. Samples of kidney tissue were removed for histopathological examination. Screening of Carica papaya showed presence of nephroprotective pytochemicals. Paracetamol administration resulted in significant elevation of renal function markers. CPE ameliorated the effect of paracetamol by reducing the markers as well as reversing the paracetamol-induced changes in kidney architecture. Carica papaya contains nephroprotective phytochemicals and may be useful in preventing kidney damage induced by paracetamol.

Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling

PubMed Central

Kurian, S. M.; Williams, A. N.; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S.; Gaber, L.; Thompson, R.; Whisenant, T.; Lin, W.; Langfelder, P.; Robison, E. H.; Schaffer, R. L.; Fisher, J. S.; Friedewald, J.; Flechner, S. M.; Chan, L. K.; Wiseman, A. C.; Shidban, H.; Mendez, R.; Heilman, R.; Abecassis, M. M.; Marsh, C. L.; Salomon, D. R.

2015-01-01

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction. PMID:24725967

Renal venogram

MedlinePlus

... be black. Other structures will be shades of gray. Veins are not normally seen in an x- ... Venogram - kidney; Renal vein thrombosis - venogram Images Kidney anatomy Kidney - blood and urine flow Renal veins References ...

[Treatment of type 2 diabetes mellitus in patients with chronic kidney disease. Grupo de Trabajo para el Documento de Consenso sobre el tratamiento de la diabetes tipo 2 en el paciente con enfermedad renal crónica].

PubMed

Gómez-Huelgas, Ricardo; Martínez-Castelao, Alberto; Artola, Sara; Górriz, José Luis; Menéndez, Edelmiro

2014-01-21

Chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic diseases, which represent an important public health problem and require a multidisciplinary management. T2DM is the main cause of CKD and it also causes a significant comorbidity with regard to non-diabetic nephropathy. Patients with diabetes and kidney disease represent a special risk group as they have higher morbi-mortality as well as higher risk of hypoglycemia than diabetic individuals with a normal kidney function. Treatment of T2DM in patients with CKD is controversial because of the scarcity of available evidence. The current consensus report aims to ease the appropriate selection and dosage of antidiabetic treatments as well as the establishment of safety objectives of glycemic control in patients with CKD. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Molecular Abnormalities Underlying Bone Fragility in Chronic Kidney Disease

PubMed Central

Iwasaki, Yoshiko; Kazama, Junichiro James

2017-01-01

Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone. PMID:28421193

Diffusion-weighted MR imaging findings of kidneys in patients with early phase of obstruction.

PubMed

Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet

2009-04-01

Diffusion-weighted (DW) magnetic resonance (MR) imaging is an MR technique used to show molecular diffusion. The apparent diffusion coefficient (ADC), as a quantitative parameter calculated from the DW MR images. The purpose of this study is to evaluate the ability of DW MR imaging in early phase of obstruction due to urolithiasis. Twenty-six patients with acute dilatation of the pelvicalyceal system detected by intravenous urography were included in this study. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. DW imaging can be performed using single-shot spin-echo, echo-planar imaging (EPI) sequences with the following diffusion gradient b values: 100, 600, 1000 s/mm(2). Circular region of interest (ROI) was placed in the renal parenchyma for the measurement of ADC values in the normal and obstructed kidney. For statistical analyses, Paired t test were used. In spite of obstructed kidneys had the lower ADC values compared to normal kidneys, these alterations were statistically insignificant. We did not observe significantly different ADC values of early phase of obstructed kidneys compared to normal kidneys.

Left Ventricular Mass Progression Despite Stable Blood Pressure and Kidney Function in Stage 3 CKD

PubMed Central

Seifert, Michael E.; Fuentes, Lisa de las; Ginsberg, Charles; Rothstein, Marcos; Dietzen, Dennis J.; Cheng, Steven C.; Ross, Will; Windus, David; Dávila-Román, Victor G.; Hruska, Keith A.

2014-01-01

Background/Aims Progressive chronic kidney disease (CKD) is associated with worsening cardiovascular risk not explained by traditional risk factors. Left ventricular hypertrophy (LVH) is an important cardiovascular risk factor, but its progression has not been documented in early CKD. We explored whether progression of LVH in early CKD would occur despite stable kidney function. Methods We conducted a post hoc analysis of a 12-m nth study of lanthanum carbonate in stage 3 CKD, which included longitudinal assessments of cardiovascular biomarkers. Primary outcome for the analysis was the change in LV mass indexed to height in meters2.7 (LVM/Ht2.7). Secondary outcomes were changes in blood pressure (BP), pulse-wave velocity, LV systolic/diastolic function, fibroblast growth factor-23 (FGF23), klotho, and eGFR. Results 31 of 38 original subjects had sufficient data for analysis. LVM/Ht2.7 increased (47 ± 13 vs. 53 ± 13 g/m2.7, P=0.006) over 12 months despite stable BP, stable eGFR and normal LV systolic function. Vascular stiffness and LV diastolic dysfunction persisted throughout the study. Klotho levels decreased (748 ± 289 to 536 ± 410 pg/ml, P=0.03) but were unrelated to changes in LVM/Ht2.7. The change in FGF23/klotho ratio was strongly correlated with changes in LVM/Ht2.7 (r2 0.582, P=0.03). Conclusion Subjects with stage 3 CKD exhibited increasing LV mass, persistent LV diastolic dysfunction and vascular stiffness despite stable kidney function, BP and LV systolic function. Abnormal FGF23 signaling due to reduced klotho expression may be associated with increasing LV mass. These findings deserve further evaluation in a larger population, given the adverse prognostic value of these cardiovascular biomarkers. PMID:24818573

l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.

PubMed

Onaolapo, Olakunle J; Adekola, Moses A; Azeez, Taiwo O; Salami, Karimat; Onaolapo, Adejoke Y

2017-01-01

We compared the relative protective abilities of silymarin and l-methionine pre-treatment in acetaminophen overdose injuries of the liver, kidney and cerebral cortex by assessing behaviours, antioxidant status, tissue histological changes and biochemical parameters of hepatic/renal function. Rats were divided into six groups of ten each; animals in five of these groups were pre-treated with oral distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at 800mg/kg/day for 3days. Rats in the sixth group (normal control) received distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests were conducted 7days after last i.p treatment, and animals sacrificed on the 8th day. Plasma was assayed for biochemical markers of liver/kidney function; while sections of the liver, kidney and cerebral cortex were either homogenised for assay of antioxidant status or processed for histology. Acetaminophen overdose resulted in locomotor retardation, excessive self-grooming, working-memory impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant imbalance, and histological changes in the liver, kidney and cerebral cortex. Administration of silymarin or increasing doses of l-methionine counteracted the behavioural changes, reversed biochemical indices of liver/kidney injury, and improved antioxidant activity. Silymarin and l-methionine also conferred variable degrees of tissue protection, on histology. Either silymarin or l-methionine can protect vulnerable tissues from acetaminophen overdose injury; however, each offers variable protection to different tissues. This study highlights an obstacle to seeking the 'ideal' protective agent against acetaminophen overdose. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Adenine phosphoribosyltransferase deficiency in the United Kingdom: two novel mutations and a cross-sectional survey

PubMed Central

Arenas-Hernandez, Monica; Escuredo, Emilia; Fairbanks, Lynette; Marinaki, Tony; Mapplebeck, Sarah; Sheaff, Michael; Almond, Michael K.

2016-01-01

Background Adenine phosphoribosyltransferase deficiency is an inborn error of metabolism that can cause kidney disease from crystalline nephropathy or kidney stones. Methods We present three cases from a single centre with varied presentations to illustrate how increasing awareness led to better patient identification. We then undertook a cross-sectional survey of all the patients identified from the Purine Research Laboratory in the UK since 1974. Results Our index case presented with recurrent nephrolithiasis and was diagnosed on stone analysis, the second case presented with acute kidney injury and the third case was identified from a biopsy undertaken for acute on chronic kidney injury. Genetic studies identified two novel mutations. Twenty patients were retrospectively identified. The mean age at diagnosis was 25 years (range 2–70); eight were <20 years, seven were 20–40 years and five were >40 years. Five of the 20 patients were deceased, 3 after end-stage renal disease (ESRD). Twelve have normal renal function, one had CKD stage 3, one had severe kidney disease and one was on dialysis. Conclusions Adenine phosphoribosyltransferase deficiency presents in a wide spectrum in all age groups. Patients can be completely asymptomatic and kidney disease may be incorrectly attributed to other conditions. Outcome is poor in late diagnosis and there is a high prevalence of ESRD. Patients with unexplained renal stone disease or deterioration in kidney function should be considered for screening. Identification and surveillance of patients in the UK can improve. There is now a rare disease registry with meetings organized that include patients, families and health care providers to improve awareness. PMID:27994857

INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BY PERFLUORINATED COMPOUNDS IN RAT LIVER AND DOLPHIN KIDNEY EPITHELIAL CELL LINES IN VITRO AND SPRAGUE-DAWLEY RATS IN VIVO

EPA Science Inventory

Abstract

Gap Junctional Intercellular Communication (GJIC) is the major pathway of intercellular signal transduction, and is, thus, important for normal cell growth and function. Recent studies have revealed a global distribution of some perfluorinated organic compounds e...

Adoptive immunotherapy against allogeneic kidney grafts in dogs with stable hematopoietic trichimerism.

PubMed

Graves, Scott S; Hogan, William J; Kuhr, Christian; Diaconescu, Razvan; Harkey, Michael; Sale, George E; Stone, Brad; Georges, George E; Storb, Rainer

2008-11-01

Dogs given nonmyeloablative conditioning and marrow grafts from 2 dog leukocyte antigen (DLA)-identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. In this study, we used trichimeras to evaluate strategies for adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from 2 DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy of total body irradiation (TBI) and given a short course of postgraft immunosuppression. After stable hematopoietic engraftment was confirmed, a kidney was transplanted from 1 of the 2 marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes from each kidney donor were then used to sensitize the alternate marrow donor. The trichimeric recipients were given donor lymphocyte infusions (DLIs) from the sensitized dogs and monitored for chimerism, graft-versus-host disease (GVHD), and kidney rejection. After DLI, we observed both prompt rejection of the transplanted marrow and donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably due to shared minor histocompatibility antigens, host chimerism also disappeared, and GVHD in skin, gut, and liver developed. The native kidneys, although exhibiting lymphocytic infiltration, remained functionally normal. This study demonstrates that under certain experimental conditions, the kidney--an organ ordinarily not involved in graft-versus-host reactions--can be targeted by sensitized donor lymphocytes.

Adoptive Immunotherapy against Allogeneic Kidney Grafts in Dogs with Stable Hematopoietic Trichimerism

PubMed Central

Graves, Scott S.; Hogan, William J.; Kuhr, Christian; Diaconescu, Razvan; Harkey, Michael; Sale, George E.; Stone, Brad; Georges, George E.; Storb, Rainer

2008-01-01

Dogs given nonmyeloablative conditioning and marrow grafts from two dog leukocyte antigen- (DLA) identical littermate donors developed stable trichimerism and stably accepted a subsequent kidney graft from one of the marrow donors without the need for immunosuppression. Here, we used trichimeras to evaluate strategies of adoptive immunotherapy to solid tumors, using the kidney as a tumor surrogate. Three DLA-identical trichimeric recipients were established by simultaneously infusing marrow from two DLA-identical donor dogs into a DLA-identical recipient conditioned with 2 Gy total body irradiation and given a short course of postgrafting immunosuppression. After confirming stable hematopoietic engraftment, a kidney was transplanted from one of the two marrow donors into each respective trichimeric recipient. Peripheral blood lymphocytes (PBL) from each kidney donor were then used to sensitize the alternate marrow donor. Donor lymphocyte infusions (DLI) from the sensitized dogs were given to the trichimeric recipients, whereupon chimerism, graft-versus-host disease (GvHD), and kidney rejection were monitored. After DLI, we observed both prompt rejection of the transplanted marrow-donor kidney and disappearance of corresponding hematopoietic chimerism. Presumably, owing to shared minor histocompatibility antigens, host chimerism also disappeared and GvHD in skin, gut, and liver developed. The native kidneys, while showing lymphocytic infiltration, remained functionally normal. The current study demonstrated that under certain experimental conditions, the kidney, an organ ordinarily not involved in graft-versus-host reactions, can be targeted by sensitized donor lymphocytes. PMID:18940673

Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

PubMed

Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

2016-03-01

Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.

Casual blood pressure and neurocognitive function in children with chronic kidney disease: a report of the children with chronic kidney disease cohort study.

PubMed

Lande, Marc B; Gerson, Arlene C; Hooper, Stephen R; Cox, Christopher; Matheson, Matt; Mendley, Susan R; Gipson, Debbie S; Wong, Cynthia; Warady, Bradley A; Furth, Susan L; Flynn, Joseph T

2011-08-01

Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55). Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.

Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

PubMed Central

Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

2015-01-01

Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

Thyroid hormone levels and incident chronic kidney disease in euthyroid individuals: the Kangbuk Samsung Health Study.

PubMed

Zhang, Yiyi; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Pastor-Barriuso, Roberto; Rampal, Sanjay; Han, Won Kon; Shin, Hocheol; Guallar, Eliseo

2014-10-01

Overt and subclinical hypothyroidism are associated with higher levels of serum creatinine and with increased risk of chronic kidney disease (CKD). The prospective association between thyroid hormones and kidney function in euthyroid individuals,however, is largely unexplored. We conducted a prospective cohort study in 104 633 South Korean men and women who were free of CKD and proteinuria at baseline and had normal thyroid hormone levels and no history of thyroid disease or cancer. At each annual or biennial follow-up visit, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by radioimmunoassay. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. After a median follow-up of 3.5 years, 1032 participants developed incident CKD.There was a positive association between high-normal levels of TSH and increased risk of incident CKD. In fully-adjusted models including baseline eGFR, the hazard ratio comparing the highest vs the lowest quintiles of TSH was 1.26 [95% confidence interval (CI) 1.02 to 1.55; P for linear trend=0.03]. In spline models, FT3 levels below 3 pg/ml were also associated with increased risk of incident CKD. There was no association between FT4 levels and CKD. In a large cohort of euthyroid men and women, high levels of TSH and low levels of FT3, even within the normal range, were modestly associated with an increased risk of incident CKD.

Precise measurement of renal filtration and vascular parameters using a two-compartment model for dynamic contrast-enhanced MRI of the kidney gives realistic normal values.

PubMed

Tofts, Paul S; Cutajar, Marica; Mendichovszky, Iosif A; Peters, A Michael; Gordon, Isky

2012-06-01

To model the uptake phase of T(1)-weighted DCE-MRI data in normal kidneys and to demonstrate that the fitted physiological parameters correlate with published normal values. The model incorporates delay and broadening of the arterial vascular peak as it appears in the capillary bed, two distinct compartments for renal intravascular and extravascular Gd tracer, and uses a small-vessel haematocrit value of 24%. Four physiological parameters can be estimated: regional filtration K ( trans ) (ml min(-1) [ml tissue](-1)), perfusion F (ml min(-1) [100 ml tissue](-1)), blood volume v ( b ) (%) and mean residence time MRT (s). From these are found the filtration fraction (FF; %) and total GFR (ml min(-1)). Fifteen healthy volunteers were imaged twice using oblique coronal slices every 2.5 s to determine the reproducibility. Using parenchymal ROIs, group mean values for renal biomarkers all agreed with published values: K ( trans ): 0.25; F: 219; v ( b ): 34; MRT: 5.5; FF: 15; GFR: 115. Nominally cortical ROIs consistently underestimated total filtration (by ~50%). Reproducibility was 7-18%. Sensitivity analysis showed that these fitted parameters are most vulnerable to errors in the fixed parameters kidney T(1), flip angle, haematocrit and relaxivity. These renal biomarkers can potentially measure renal physiology in diagnosis and treatment. • Dynamic contrast-enhanced magnetic resonance imaging can measure renal function. • Filtration and perfusion values in healthy volunteers agree with published normal values. • Precision measured in healthy volunteers is between 7 and 15%.

Calcium citrate without aluminum antacids does not cause aluminum retention in patients with functioning kidneys

NASA Technical Reports Server (NTRS)

Sakhaee, K.; Wabner, C. L.; Zerwekh, J. E.; Copley, J. B.; Pak, L.; Poindexter, J. R.; Pak, C. Y.

1993-01-01

It has been suggested that calcium citrate might enhance aluminum absorption from food, posing a threat of aluminum toxicity even in patients with normal renal function. We therefore measured serum and urinary aluminum before and following calcium citrate therapy in patients with moderate renal failure and in normal subjects maintained on constant metabolic diets with known aluminum content (967-1034 mumol/day, or 26.1-27.9 mg/day, in patients and either 834 or 1579 mumol/day, or 22.5 and 42.6 mg/day, in normal subjects). Seven patients with moderate renal failure (endogenous creatinine clearance of 43 ml/min) took 50 mmol (2 g) calcium/day as effervescent calcium citrate with meals for 17 days. Eight normal women received 25 mmol (1 g) calcium/day as tricalcium dicitrate tablets with meals for 7 days. In patients with moderate renal failure, serum and urinary aluminum were normal before treatment at 489 +/- 293 SD nmol/l (13.2 +/- 7.9 micrograms/l) and 767 +/- 497 nmol/day (20.7 +/- 13.4 micrograms/day), respectively. They remained within normal limits and did not change significantly during calcium citrate treatment (400 +/- 148 nmol/l and 600 +/- 441 nmol/day, respectively). Similarly, no significant change in serum and urinary aluminum was detected in normal women during calcium citrate administration (271 +/- 59 vs 293 +/- 85 nmol/l and 515 +/- 138 vs 615 +/- 170 nmol/day, respectively). In addition, skeletal bone aluminum content did not change significantly in 14 osteoporotic patients (endogenous creatinine clearance of 68.5 ml/min) treated for 24 months with calcium citrate, 10 mmol calcium twice/day separately from meals (29.3 +/- 13.9 ng/mg ash bone to 27.9 +/0- 10.4, P = 0.727). In them, histomorphometric examination did not show any evidence of mineralization defect. Thus, calcium citrate given alone without aluminum-containing drugs does not pose a risk of aluminum toxicity in subjects with normal or functioning kidneys, when it is administered on an empty stomach at a recommended dose of 20 mmol calcium/day.

Liver alone or simultaneous liver-kidney transplant? Pretransplant chronic kidney disease and post-transplant outcome - a retrospective study.

PubMed

Nagai, Shunji; Safwan, Mohamed; Collins, Kelly; Schilke, Randolph E; Rizzari, Michael; Moonka, Dilip; Brown, Kimberly; Patel, Anita; Yoshida, Atsushi; Abouljoud, Marwan

2018-05-02

The new Organ Procurement and Transplant Network/United Organ Sharing Network (OPTN/UNOS) simultaneous liver-kidney transplant (SLK) policy has been implemented. The aim of this study was to review liver transplant outcomes utilizing the new SLK policy. Liver transplant alone (LTA) and SLK patients between 2009 and 2015 were reviewed. Graft survival and post-transplant kidney function were investigated among LTA patients meeting the chronic kidney disease (CKD) criteria of the new policy (LTA-CKD group). To validate our findings, we reviewed and applied our analysis to the OPTN/UNOS registry. A total of 535 patients were eligible from our series. The LTA-CKD group (n = 27) showed worse 1-year graft survival, compared with the SLK group (n = 44), but not significant (81% vs. 93%, P = 0.15). The LTA-CKD group significantly increased a risk of post-transplant dialysis (odds ratio = 5.59 [95% CI = 1.27-24.7], P = 0.02 [Ref. normal kidney function]). Post-transplant dialysis was an independent risk factor for graft loss (hazard ratio = 7.25, 95% CI = 3.3-15.91, P < 0.001 [Ref. SLK]). In the validation analysis based on the OPTN/UNOS registry, the hazard of 1-year-graft loss in the LTA-CKD group (n = 751) was 34.8% higher than the SLK group (n = 2856) (hazard ratio = 1.348, 95% CI = 1.157-1.572, P < 0.001). Indicating SLK for patients who meet the CKD criteria may significantly improve transplant outcomes. © 2018 Steunstichting ESOT.

The effect of fluid intake on chronic kidney transplant failure: a pilot study.

PubMed

Magpantay, Laurene; Ziai, Farzad; Oberbauer, Rainer; Haas, Martin

2011-11-01

Transplant recipients are generally instructed to increase their daily fluid intake so as to preserve kidney function. However, studies supporting this hypothesis are lacking. Prospective, randomized study at a tertiary care university hospital. Patients with chronic kidney transplant failure. Assignment to normal fluid intake (NFI: 2 L/day) or high fluid intake (HFI: 4 L/day) for 12 months. The effect of fluid intake on the decrease in estimated glomerular filtration rate (eGFR) was estimated by a mixed-effects general linear model. The analysis was adjusted for the observation period, age, intake of angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers, diuretics, and transplant duration. A total of 33 patients were randomized to NFI and 29 to HFI. After 12 months, the mean eGFR had decreased to a similar extent in both groups (NFI: 44 ± 9 mL/min vs. 41 ± 9 mL/min; HFI: 46 ± 15 mL/min vs. 44 ± 15 mL/min). In the multivariate analysis, only the observation period had a significant effect on the decrease in eGFR. Randomization to NFI or HFI nor any other variable was associated with kidney function. The association between urine volume and urine osmolality was lost after 12 months. Recommendation of higher fluid intake does not seem to improve chronic kidney transplant failure. However, the lack of association between urine osmolality and reported urine volume at a later stage implies a loss of adherence to fluid intake over time. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Antiproteinuric therapy and fabry nephropathy: sustained reduction of proteinuria in patients receiving enzyme replacement therapy with agalsidase-beta.

PubMed

Tahir, Hindia; Jackson, Leslie L; Warnock, David G

2007-09-01

This report describes an open-label, nonrandomized, prospective evaluation of the effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy on patients who have Fabry disease and also received enzyme replacement therapy with agalsidase-beta, given at 1 mg/kg body wt every 2 wk. Previous placebo-controlled phase III and phase IV trials with agalsidase-beta demonstrated clearing of globotriaosylceramide from vascular endothelia but little effect on proteinuria or progressive loss of kidney function in patients with Fabry disease and severe chronic kidney disease marked by overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m2. Angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker therapy is the standard of care for patients with proteinuric kidney diseases, but their use is challenging in patients with Fabry disease and low or low-normal baseline systemic BP. A group of patients with Fabry disease were treated with antiproteinuric therapy, in conjunction with agalsidase-beta; sustained reductions in proteinuria with stabilization of kidney function were achieved in a group of six patients who had severe Fabry nephropathy; the progression rate was -0.23 +/- 1.12 ml/min per 1.73 m2 per yr with 30 mo of follow-up.

Quantitative and semi-quantitative histopathological examination of renal biopsies in healthy individuals, and associations with kidney function.

PubMed

Bar, Yael; Barregard, Lars; Sallsten, Gerd; Wallin, Maria; Mölne, Johan

2016-05-01

This study assesed the prevalence of histopathological changes in renal biopsies from healthy individuals, and the association with age, sex and smoking. Donor biopsies from 109 subjects were obtained from living kidney donors, and blood and urine samples were collected together with medical history. All biopsies were scored according to the Banff '97 classification with some modifications. The parameters included in this study were tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, arteriolohyalinosis and a sclerosis score. An alternative scoring system for tubular atrophy was examined (using ≤5% rather than <1% as a cut-off for grade 0). Glomerular filtration rate was measured in most cases as chromium ethylenediaminetetra-acetic acid (Cr-EDTA) clearance. Age was a significant predictor for tubular atrophy, fibrosis and sclerosis. Pack-years of smoking increased the risk of tubular atrophy, fibrosis and arteriolohyalinosis. The alternative scoring of tubular atrophy showed a stronger association with smoking, but a weaker association with age, compared with the original one. Limited histopathological changes are common in healthy kidney donors around 50 years of age with normal kidney function. We propose that a cut-off of ≤5% yields a better definition of grade 0 tubular atrophy compared with the established cut-off of >0%. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Histopathologic Findings of Potential Kidney Donors With Asymptomatic Microscopic Hematuria: Impact on Donation.

PubMed

Hassan, E A; Ali, T Z; Abdulbaki, A; Ibrahim, I A; Almanae, H M; Aleid, H A

2017-10-01

Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors. The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation. In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016. Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation. IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality. Copyright © 2017 Elsevier Inc. All rights reserved.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Neural regulation of the kidney function in rats with cisplatin induced renal failure

PubMed Central

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

Urinalysis and associated laboratory procedures.

PubMed

Brobst, D

1989-09-01

Macroscopic examination of urine is an integral part of urinalysis, and blood and bile pigments are a common cause of abnormal coloration. Urine SG is a convenient index of urine concentration and should be correlated with the patient's hydration status to determine the ability of the kidneys to concentrate and dilute urine. The pH of urine of dogs and cats normally is dietary dependent, but alkaline urine may suggest that the urinary tract is infected with a urea splitting organism. The dipstick test for proteinuria is convenient but less reliable than the sulfosalicylic acid method. The dipstick test for blood should not be used as a substitute for microscopic examination of urine but is of value in detecting hemoglobinuria and myoglobinuria, when red cells may be absent in the sediment. The finding of glucose, ketones, and bilirubin in urine, when interpreted properly, may indicate the presence of disease processes not associated with the urogenital tract. Microscopic examination of urine sediment must be interpreted in combination with the physical and chemical composition of urine, but excessive numbers of cells, casts, crystals, and bacteria may provide evidence of disease. The absence of these structures in the sediment, however, does not eliminate the possibility of disease. The ability of the kidneys to concentrate urine is dependent on normal kidney function and the production and release of ADH. A urine SG greater than 1.030 in dogs and 1.035 in cats indicates that the functions associated with concentrating urine are adequate. In the evaluation of the patient's ability to form concentrated urine, the status of hydration must be considered; this may require water deprivation tests or administration of ADH. The estimation of blood urea nitrogen concentration, with the use of test strips, may provide a convenient but not specific measure of renal function.

Significant Acute Kidney Injury Due to Non-steroidal Anti-inflammatory Drugs: Inpatient Setting.

PubMed

Dixit, Mehul; Doan, Thuy; Kirschner, Rebecca; Dixit, Naznin

2010-04-26

In the United States non-steroidal anti-inflammatory drugs (NSAID) are freely available over-the-counter. Because of the adverse effects on the kidneys and the popularity of these drugs, unregulated use of NSAIDs is an under recognized and potentially dangerous problem. Fifteen inpatients, mean age of 15.2 ± 2.3 years (five males, 10 females), were referred to nephrology for acute kidney injury. All patients admitted to taking ibuprofen and six also consumed naproxen. None of the patients had underlying renal diseases at the time of admission. Nine patients had proteinuria and 12 had hematuria (including one with gross hematuria). One patient had nephrotic syndrome but the condition resolved spontaneously without steroids and has remained in remission for four years. Two patients required dialysis. Only one of the dialyzed patients required steroid therapy for recovery of renal function. The mean duration of hospitalization was 7.4 ± 5.5 days. The serum creatinine peaked at 4.09 ± 4.24 (range 1.2-15.3) mg/dL. All patients recovered renal function with normalization of serum creatinine to 0.71 ± 0.15 mg/dL. The estimated GFR (glomerular filtration rate) at peak of renal failure was 38.2 ± 20.5 mL/min but did improve to a baseline of 134 ± 26.2 mL/min (range 89-177, p < 0.01). However, the duration from onset to normalization of serum creatinine was 37 ± 42 days indicating that majority of patients had abnormal renal function for a prolonged period. In conclusion, NSAIDs pose a significant risk of renal failure for significant duration and as an entity may be under recognized.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Nephrectomy (Kidney Removal)

MedlinePlus

... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between First Nations ethnicity and progression to kidney failure by presence and severity of albuminuria.

PubMed

Samuel, Susan M; Palacios-Derflingher, Luz; Tonelli, Marcello; Manns, Braden; Crowshoe, Lynden; Ahmed, Sofia B; Jun, Min; Saad, Nathalie; Hemmelgarn, Brenda R

2014-02-04

Despite a low prevalence of chronic kidney disease (estimated glomerular filtration rate [GFR]<60 mL/min per 1.73 m2), First Nations people have high rates of kidney failure requiring chronic dialysis or kidney transplantation. We sought to examine whether the presence and severity of albuminuria contributes to the progression of chronic kidney disease to kidney failure among First Nations people. We identified all adult residents of Alberta (age≥18 yr) for whom an outpatient serum creatinine measurement was available from May 1, 2002, to Mar. 31, 2008. We determined albuminuria using urine dipsticks and categorized results as normal (i.e., no albuminuria), mild, heavy or unmeasured. Our primary outcome was progression to kidney failure (defined as the need for chronic dialysis or kidney transplantation, or a sustained doubling of serum creatinine levels). We calculated rates of progression to kidney failure by First Nations status, by estimated GFR and by albuminuria category. We determined the relative hazard of progression to kidney failure for First Nations compared with non-First Nations participants by level of albuminuria and estimated GFR. Of the 1 816 824 participants we identified, 48 669 (2.7%) were First Nations. First Nations people were less likely to have normal albuminuria compared with non-First Nations people (38.7% v. 56.4%). Rates of progression to kidney failure were consistently 2- to 3-fold higher among First Nations people than among non-First Nations people, across all levels of albuminuria and estimated GFRs. Compared with non-First Nations people, First Nations people with an estimated GFR of 15.0-29.9 mL/min per 1.73 m2 had the highest risk of progression to kidney failure, with similar hazard ratios for those with normal and heavy albuminuria. Albuminuria confers a similar risk of progression to kidney failure for First Nations and non-First Nations people.

[Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism after kidney transplantation: one-year follow-up multicentre study].

PubMed

Torregrosa, Josep V; Morales, Enrique; Díaz, Juan M; Crespo, Josep; Bravo, Juan; Gómez, Gonzalo; Gentil, Miguel A; Rodríguez-Benot, Alberto; Rodríguez-García, Minerva; López-Jiménez, Verónica; Gutiérrez-Dalmau, Álex; Jimeno, Luisa; Pérez-Sáez, M José; Romero, Rafael; Gómez-Alamillo, Carlos

2014-01-01

The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia. Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT. A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.4-10.2 mg/dl). Patients began treatment with cinacalcet in clinical practice. 32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after RT (median dose of 30 mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. In patients with normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability.

New Insights into the Effects of Chronic Kidney Failure and Dialysate Exposure on the Peritoneum.

PubMed

Vlahu, Carmen A; Aten, Jan; de Graaff, Marijke; van Veen, Henk; Everts, Vincent; de Waart, Dirk R; Struijk, Dirk G; Krediet, Raymond T

♦ INTRODUCTION: Chronic uremia and the exposure to dialysis solutions during peritoneal dialysis (PD) induce peritoneal alterations. Using a long-term peritoneal exposure model, we compared the effects of chronic kidney failure (CKD) itself and exposure to either a 'conventional' or a 'biocompatible' dialysis solution on peritoneal morphology and function. ♦ METHODS: Wistar rats (Harlan, Zeist, the Netherlands) were grouped into: normal kidney function (NKF), CKD induced by 70% nephrectomy, CKD receiving daily peritoneal infusions with 3.86% glucose Dianeal (CKDD), or Physioneal (both solutions from Baxter Healthcare, Castlebar, Ireland) (CKDP). At 16 weeks, a peritoneal function test was performed, and histology, ultrastructure, and hydroxyproline content of peritoneal tissue were assessed. ♦ RESULTS: Comparing CKD with NKF, peritoneal transport rates were higher, mesothelial cells (MC) displayed increased number of microvilli, blood and lymph vasculature expanded, vascular basal lamina appeared thicker, with limited areas of duplication, and fibrosis had developed. All alterations, except lymphangiogenesis, were enhanced by exposure to both dialysis fluids. Distinct MC alterations were observed in CKDD and CKDP, the latter displaying prominent basolateral protrusions. In addition, CKDP was associated with a trend towards less fibrosis compared to CKDD. ♦ CONCLUSIONS: Chronic kidney failure itself induced peritoneal alterations, which were in part augmented by exposure to glucose-based dialysis solutions. Overall, the conventional and biocompatible solutions had similar long-term effects on the peritoneum. Importantly, the latter may attenuate the development of fibrosis. Copyright © 2016 International Society for Peritoneal Dialysis.

Resident renal mononuclear phagocytes comprise five discrete populations with distinct phenotypes and functions

PubMed Central

Kawakami, Takahisa; Lichtnekert, Julia; Thompson, Lucas J.; Karna, Prasanthi; Bouabe, Hicham; Hohl, Tobias M.; Heinecke, Jay W.; Ziegler, Steven F.; Nelson, Peter J.; Duffield, Jeremy S.

2013-01-01

Recent reports have highlighted greater complexity, plasticity and functional diversity of mononuclear phagocytes (MPCs), including monocytes, macrophages and dendritic cells (DCs), in our organs, than previously understood. The functions and origins of MPCs resident within healthy organs, especially in the kidney, are less well understood, while studies suggest they play roles in disease states distinct from recruited monocytes. We developed an unbiased approach using flow cytometry to analyze MPCs residing in the normal mouse kidney, and identified five discrete subpopulations according to CD11b/CD11c expression as well as F4/80, CD103, CD14, CD16 and CD64 expression. In addition to distinct marker profiles, these subpopulations have different lineages and expression of genes involved in tissue homeostasis, including angiogenesis. Among them, the CD11bint CD11cint F4/80hi subpopulation notably exhibited high capacity to produce a representative anti-inflammatory cytokine, IL-10. Each subpopulation had different degrees of both macrophage (phagocytosis) and DC (antigen presentation) capacities, with a tendency to promote differentiation of regulatory T cells, while two of these showed expression of transcription factors reported to be highly expressed by classical DCs, and proclivity to exit the kidney following stimulation with LPS. In summary, resident kidney MPCs comprise discrete subpopulations, which cannot be simply classified into the conventional entities, and they produce anti-inflammatory and tissue-homeostatic factors to differing degrees. PMID:23956422

Overexpression of Robo2 causes defects in the recruitment of metanephric mesenchymal cells and ureteric bud branching morphogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji, Jiayao; Medical College of NanKai University, Tianjin; Li, Qinggang

2012-05-11

Highlights: Black-Right-Pointing-Pointer Overexpression of Robo2 caused reduced UB branching and glomerular number. Black-Right-Pointing-Pointer Fewer MM cells surrounding the UB after overexpression of Robo2 in vitro. Black-Right-Pointing-Pointer No abnormal Epithelial Morphology of UB or apoptosis of mm cells in the kidney. Black-Right-Pointing-Pointer Overexpression of Robo2 affected MM cells migration and caused UB deficit. Black-Right-Pointing-Pointer The reduced glomerular number can also be caused by fewer MM cells. -- Abstract: Roundabout 2 (Robo2) is a member of the membrane protein receptor family. The chemorepulsive effect of Slit2-Robo2 signaling plays vital roles in nervous system development and neuron migration. Slit2-Robo2 signaling is also importantmore » for maintaining the normal morphogenesis of the kidney and urinary collecting system, especially for the branching of the ureteric bud (UB) at the proper site. Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux. To understand the effect of Robo2 on kidney development, we used microinjection and electroporation to overexpress GFP-Robo2 in an in vitro embryonic kidney model. Our results show reduced UB branching and decreased glomerular number after in vitro Robo2 overexpression in the embryonic kidneys. We found fewer metanephric mesenchymal (MM) cells surrounding the UB but no abnormal morphology in the branching epithelial UB. Meanwhile, no significant change in MM proliferation or apoptosis was observed. These findings indicate that Robo2 is involved in the development of embryonic kidneys and that the normal expression of Robo2 can help maintain proper UB branching and glomerular morphogenesis. Overexpression of Robo2 leads to reduced UB branching caused by fewer surrounding MM cells, but MM cell apoptosis is not involved in this effect. Our study demonstrates that overexpression of Robo2 by microinjection in embryonic kidneys is an effective approach to study the function of Robo2.« less

Differential associations between glomerular filtration rate and duration of obesity depending on the presence or absence of left ventricular diastolic dysfunction.

PubMed

Ybarra, Juan; Sánchez-Hernández, Joan; Vilallonga, Ramon; Romeo, June H

2016-07-01

A robust and consistent association between increasing body mass index (BMI) and chronic kidney disease (CKD) has been reported in several observational studies. Obesity remains the main preventable risk factor for CKD because it largely mediates diabetes and hypertension, the 2 most common etiologies for end-stage kidney disease (ESKD). Obesity is associated weakly with early stages of kidney disease but strongly with kidney progression to ESKD, even after adjustment for hypertension and diabetes. To assess the relationship between estimated glomerular filtration rate (eGFR) and trans-thoracic echocardiography left ventricular function parameters in a cohort of patients with obesity. Cross-sectional study involving 324 obese (BMI=44.0±2.2Kg/m(2)) apparently healthy asymptomatic patients with an eGFR >60ml/min/1.73m(2). Each patient underwent transthoracic echocardiography and a blood testing. The eGFR was addressed by the CKD-EPI formula. All patients had a normal systolic function whereas 24.5% disclosed diastolic dysfunction (DD). Hypertension and type 2 diabetes mellitus prevalence were 34.5% and 4.5% (respectively). All patients disclosed an eGFR >60ml/min while none of them disclosed hyperfiltration (eGFR >120ml/min). eGFR correlated inversely with BMI and the duration of obesity and positively with diastolic function parameters (P<0.001 for all, respectively). Patients with diastolic dysfunction displayed lower eGFR (P<0.0005) and longer duration of obesity (P<0.0005). Obesity and its duration are likely to impose hemodynamic changes affecting simultaneously both heart (diastolic dysfunction) and kidney (decreased glomerular filtration rate). Larger prospective studies are warranted. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

PubMed

Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

2017-11-30

Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

Compensatory Renal Hypertrophy and the Uptake of Cysteine S-Conjugates of Hg2+ in Isolated S2 Proximal Tubular Segments.

PubMed

Bridges, Christy C; Barfuss, Delon W; Joshee, Lucy; Zalups, Rudolfs K

2016-12-01

Chronic kidney disease is characterized by a progressive and permanent loss of functioning nephrons. In order to compensate for this loss, the remaining functional nephrons undergo significant structural and functional changes. We hypothesize that luminal uptake of inorganic mercury (Hg 2+ ), as a conjugate of cysteine (Cys; Cys-S-Hg-S-Cys), is enhanced in S2 segments of proximal tubules from the remnant kidney of uninephrectomized (NPX) rabbits. To test this hypothesis, we measured uptake and accumulation of Cys-S-Hg-S-Cys in isolated perfused S2 segments of proximal tubules from normal (control) and NPX rabbits. The remnant kidney in NPX rabbits undergoes significant hypertrophy during the initial 3 weeks following surgery. Tubules isolated from NPX rabbits were significantly larger in diameter and volume than those from control rabbits. Moreover, real-time PCR analyses of proximal tubules indicated that the expression of selected membrane transporters was greater in kidneys of NPX animals than in kidneys of control animals. When S2 segments from control and NPX rabbits were perfused with cystine or Cys-S-Hg-S-Cys, we found that the rates of luminal disappearance and tubular accumulation of Hg 2+  were greater in tubules from NPX animals. These increases were inhibited by the addition of various amino acids to the perfusate. Taken together, our data suggest that hypertrophic changes in proximal tubules lead to an enhanced ability of these tubules to take up and accumulate Hg 2 . © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Concurrent use of methotrexate and celecoxib increases risk of silent liver fibrosis in rheumatoid arthritis patients with subclinical reduced kidney function.

PubMed

Park, Jin Su; Park, Min-Chan; Park, Yong-Beom; Lee, Soo-Kon; Lee, Sang-Won

2014-01-01

We evaluated the effects of concurrent use of methotrexate and celecoxib on silent liver and kidney damages in rheumatoid arthritis (RA) patients. We enrolled 92 RA patients with normal laboratory results related to liver and kidney functions, who had received methotrexate and celecoxib concurrently over 6 months. Liver stiffness measurement (LSM) using transient elastography and ultrasonography were performed along with blood and urine tests. Estimated glomerular filtration rate (eGFR) was calculated by both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) equations. Initial eGFR represented kidney function at the time of the initiation of celecoxib. The cutoff for abnormal LSM values was adopted as 5.3 kPa. The optimal cutoff of each eGFR for abnormal LSM values was also calculated. The median age of patients was 55 years old (74 women). The median LSM was 4.4 kPa and the median eGFRs and median initial eGFRs ranged from 89 to 99 mL/min/1.73 m(2). The cumulative doses of methotrexate and celecoxib and their concurrent administration duration did not affect LSM values and eGFRs. Both eGFRs were significantly associated with LSM values. Patients with initial eGFR(CKD-EPI), initial eGFR(MDRD), and eGFR(CKD-EPI) below each optimal cutoff had significantly high risks for silent liver fibrosis (RR 9.4, 10.3, and 4.4, p < 0.001, respectively). Both initial eGFRs (CKD-EPI and MDRD) and eGFR (CKD-EPI) were significant predictors for the development of silent liver fibrosis in RA patients who had received methotrexate and celecoxib concurrently for at least 6 months.

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats

PubMed Central

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D.; Planer, David; Ben-Dov, Iddo Z.; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-01-01

Aims Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Methods and results Sprague–Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks (‘diet group’). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet (‘low-phosphate group’, n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor κB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. Conclusion We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies. PMID:18390899

Uraemic hyperparathyroidism causes a reversible inflammatory process of aortic valve calcification in rats.

PubMed

Shuvy, Mony; Abedat, Suzan; Beeri, Ronen; Danenberg, Haim D; Planer, David; Ben-Dov, Iddo Z; Meir, Karen; Sosna, Jacob; Lotan, Chaim

2008-08-01

Renal failure is associated with aortic valve calcification (AVC). Our aim was to develop an animal model for exploring the pathophysiology and reversibility of AVC, utilizing rats with diet-induced kidney disease. Sprague-Dawley rats (n = 23) were fed a phosphate-enriched, uraemia-inducing diet for 7 weeks followed by a normal diet for 2 weeks ('diet group'). These rats were compared with normal controls (n = 10) and with uraemic controls fed with phosphate-depleted diet ('low-phosphate group', n = 10). Clinical investigations included serum creatinine, phosphate and parathyroid hormone (PTH) levels, echocardiography, and multislice computed tomography. Pathological examinations of the valves included histological characterization, Von Kossa staining, and antigen and gene expression analyses. Eight diet group rats were further assessed for reversibility of valve calcification following normalization of their kidney function. At 4 weeks, all diet group rats developed renal failure and hyperparathyroidism. At week 9, renal failure resolved with improvement in the hyperparathyroid state. Echocardiography demonstrated valve calcifications only in diet group rats. Tomographic calcium scores were significantly higher in the diet group compared with controls. Von Kossa stain in diet group valves revealed calcium deposits, positive staining for osteopontin, and CD68. Gene expression analyses revealed overexpression of osteoblast genes and nuclear factor kappaB activation. Valve calcification resolved after diet cessation in parallel with normalization of PTH levels. Resolution was associated with down-regulation of inflammation and osteoblastic features. Low-phosphate group rats developed kidney dysfunction similar to that of the diet group but with normal levels of PTH. Calcium scores and histology showed only minimal valve calcification. We developed an animal model for AVC. The process is related to disturbed mineral metabolism. It is associated with inflammation and osteoblastic features. Furthermore, the process is reversible upon normalization of the mineral homeostasis. Thus, our model constitutes a convenient platform for studying AVC and potential remedies.

Managing type 1 diabetes mellitus in pregnancy--from planning to breastfeeding.

PubMed

Ringholm, Lene; Mathiesen, Elisabeth R; Kelstrup, Louise; Damm, Peter

2012-11-01

Type 1 diabetes mellitus in pregnant women increases the risk of adverse outcomes for mother and offspring. Careful preconception counselling and screening is important, with particular focus on glycaemic control, indications for antihypertensive therapy, screening for diabetic nephropathy, diabetic retinopathy and thyroid dysfunction, as well as review of other medications. Supplementation with folic acid should be initiated before conception in order to minimize the risk of fetal malformations. Obtaining and maintaining tight control of blood glucose and blood pressure before and during pregnancy is crucial for optimizing outcomes; however, the risk of severe hypoglycaemia during pregnancy is a major obstacle. Although pregnancy does not result in deterioration of kidney function in women with diabetic nephropathy and normal serum creatinine levels, pregnancy complications such as pre-eclampsia and preterm delivery are more frequent in these women than in women with T1DM and normal kidney function. Rapid-acting insulin analogues are considered safe to use in pregnancy and studies on long-acting insulin analogues have provided reassuring results. Immediately after delivery the insulin requirement declines to approximately 60% of the prepregnancy dose, and remains 10% lower than before pregnancy during breastfeeding.

Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.

PubMed

Coresh, Josef; Astor, Brad C; Greene, Tom; Eknoyan, Garabed; Levey, Andrew S

2003-01-01

Recently developed clinical practice guidelines and calibration of the Third National Health and Nutrition Examination Survey (NHANES III) serum creatinine assay provide a basis for estimating the prevalence and distribution of chronic kidney disease (CKD) in the United States using standardized criteria based on estimated glomerular filtration rate (GFR) and persistent albuminuria. A nationally representative sample of 15,625 noninstitutionalized adults aged 20 years and older from the NHANES III was analyzed. Kidney function (GFR), kidney damage (albuminuria), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine level, spot urine albumin level, age, sex, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation and compared with the Cockcroft-Gault equation for creatinine clearance (CCr). The prevalence of CKD in the US adult population was 11% (19.2 million). By stage, an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage 5, or kidney failure. Aside from hypertension and diabetes, age is a key predictor of CKD, and 11% of individuals older than 65 years without hypertension or diabetes had stage 3 or worse CKD. Compared with GFR estimates, CCr estimates showed a steeper decline with age and were lower in non-Hispanic blacks. CKD is common and warrants improved detection and classification using standardized criteria to improve outcomes. Am J Kidney Dis 41:1-12. Copyright 2003 by the National Kidney Foundation, Inc.

A case of staghorn stones in a kidney with an ileal ureter treated by percutaneous nephrolithotomy.

PubMed

Gao, Xiaofeng; Zhou, Tie; Li, Jinyi; Sun, Yinghao

2008-12-01

A 59-year-old man was admitted to hospital for investigation of a 1-year history of intermittent hematuria. He had undergone ileal ureteral replacement for left renal stones 36 years earlier. Renal ultrasonography, physical examination, abdominal plain radiography, intravenous urography, CT urography, measurement of serum levels of creatinine, urea and electrolytes, renal scintigraphy, urinalysis and urine culture. Staghorn calculi in the left kidney, with a high-lying anastomosis between the renal pelvis and the proximal ileal segment. The patient underwent percutaneous nephrolithotomy via a middle-calyx access for the large staghorn stones. After surgery, no residual calculi were found and the patient was discharged with an uneventful postoperative course. At 1 month, renal scintigraphy showed normal bilateral kidney function. The patient received potassium citrate supplementation and was followed up with 6-monthly imaging studies. At the last report, he had been stone-free for 7 months.

Complementary role of magnetic resonance imaging in the study of the fetal urinary system.

PubMed

Gómez Huertas, M; Culiañez Casas, M; Molina García, F S; Carrillo Badillo, M P; Pastor Pons, E

2016-01-01

Urinary system birth defects represent the abnormality most often detected in prenatal studies, accounting for 30% to 50% of all structural anomalies present at birth. The most common disorders are urinary tract dilation, developmental variants, cystic kidney diseases, kidney tumors, and bladder defects. These anomalies can present in isolation or in association with various syndromes. They are normally evaluated with sonography, and the use of magnetic resonance imaging (MRI) is considered only in inconclusive cases. In this article, we show the potential of fetal MRI as a technique to complement sonography in the study of fetal urinary system anomalies. We show the additional information that MRI can provide in each entity, especially in the evaluation of kidney function through diffusion-weighted sequences. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

What is the fate of insignificant residual fragment following percutaneous nephrolithotomy in pediatric patients with anomalous kidney? A comparison with normal kidney.

PubMed

Purkait, Bimalesh; Sinha, Rahul Janak; Bansal, Ankur; Sokhal, Ashok Kumar; Singh, Kawaljit; Singh, Vishwajeet

2018-06-01

Pediatric population has increasing incidence of renal calculus and it is estimated to be around 50/10,000 population. The treatment of choice for large and complex stone in anomalous kidney is percutaneous nephrolithotomy (PCNL). The fate of insignificant residual fragment after PCNL in pediatric patients is not well documented. Here, we are reporting our long-term experience and follow-up of insignificant residual fragment in pediatric patients with anomalous kidney in comparison to normal kidney. Intuitional ethical approval was taken. A retrospective analysis of PCNL in pediatric (<18 years) anomalous kidney was performed from 2001 to 2013. The data of 52 pediatric patients with anomalous kidney (group B) have been compared to 251 normal kidneys (group A). The mean age of the patients was 7.83 + 3.45 (range 3-18) in group A and 8.21 ± 3.25 (range 5-18) in group B. The mean size of the insignificant residual fragment was 2.2 + 0.5 mm (1-4) in group A and 2.1 + 0.6 mm (range 1-4) in group B. Most of these residual fragments were single in number (72.55 vs. 67.30%, respectively). 54.98% children in group A and 67.30% in group B were symptomatic in the follow-up. Stone size was increased, stable and spontaneously passed in 49.8 vs. 71.15, 22.7 vs. 19.23 and 27.49 vs. 9.61% (p < 0.03), respectively, over mean follow-up of 50.34 months. Insignificant residual fragments in children are notorious for regrowth (49.8% in normal and 71.15% in anomalous kidney) in future. Most of the children will require symptomatic treatment (55.37 vs. 82.69%) or reintervention (39 vs. 46%) for insignificant residual fragment.

Pantoprazole-induced acute kidney injury: A case report.

PubMed

Peng, Tao; Hu, Zhao; Zheng, Hongnan; Zhen, Junhui; Ma, Chengjun; Yang, Xiangdong

2018-06-01

The present study reports a case of pantoprazole-induced acute kidney disease. The patient was diagnosed with acute kidney injury with wide interstitial inflammation and eosinophil infiltration. Following 1 month of glucocorticoid therapy, the patient's serum creatinine and urea nitrogen decreased to within normal ranges. The presentation, clinical course, diagnosis and prognosis of pantoprazole-induced acute kidney injury are discussed herein to highlight the importance of early and correct diagnosis for good prognosis. Disease characteristics include short-term increased serum creatinine levels that respond to glucocorticoid treatment. The patient had no history of chronic kidney disease or proteinuria and presented with increased serum creatinine following treatment with pantoprazole. Following the end of pantoprazole treatment, short-term RRT and long-term prednisolone was administered, then serum creatinine returned to normal. Pantoprazole-induced acute kidney injury is commonly misdiagnosed and late diagnosis results in poor patient prognoses. Misdiagnosis leads to the administration of treatments that may exacerbate the condition, so appropriate diagnosis and treatment for pantoprazole-induced acute kidney injury is necessary.

Anatomy and ultrasonography of the normal kidney in brown lemurs: Eulemur fulvus.

PubMed

Raharison, Fidiniaina; Mogicato, Giovanni; Sautet, Jean

2009-08-01

The purpose of this study is to describe the anatomy and obtain echographic measurements of normal kidneys in brown lemurs (Eulemur fulvus). The anatomical findings show that brown lemur kidneys are comparable to those of rats except for an elongated papilla. The kidneys of 16 (7 females and 9 males) lemurs were examined with two-dimensional and power Doppler ultrasonography under general anesthesia. Morphometrically, the left and right kidney surface areas are comparable (3.29 and 3.51 cm(2)). Kidney area has a significant linear correlation with body weight. Echo-Doppler findings show that the mean renal arterial blood flow speeds for the left and right kidneys are comparable (0.70 and 0.73 m/s). However, flow speed is higher in the male (0.79 m/s) than in the female (0.60 m/s). The renal arterial diameters are between 1.0 and 1.8 mm. The fact that anesthesia can have hemodynamic effects on renal vasculature should be taken into consideration when assessing these echographic results.

Molecular Imaging of the Kidneys

PubMed Central

Szabo, Zsolt; Alachkar, Nada; Xia, Jinsong; Mathews, William B.; Rabb, Hamid

2010-01-01

Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms in order to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive and accurate diagnosis. The most recent imaging technology, PET, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H215O, 82RbCl, and [64Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype AT1R using in vivo PET imaging. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc-99m MAG3 as well as some novel radiopharmaceuticals such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands have been utilized for molecular renal imaging. Additionally, other radioligands that interact with the organic cation transporters or peptide transporters have developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule- 1 (KIM-1) that is highly expressed in kidney injury and renal cancer but not in normal kidneys. While pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on upregulated molecules in response to tissue stress resulted from obstruction will be of great implication. Monocyte chemoattractant protein -1 (MCP-1) is a well-suited molecule in this case. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [18F]FDG, other radioligands such as [11C]acetate and anti-[18F]FACBC have emerged. Radioimmuno-imaging with [124I]G250 could lead to radioimmunotherapy for renal cancer. Considering the increasing age of general population, the incidence of kidney diseases such as atherosclerosis, diabetic nephropathy, and cancer is expected to increase. Successful management of these diseases offers an opportunity and a challenge for development of novel molecular imaging technologies. PMID:21111857

The effect of urothelial damage on ureteric motility. An ultrastructural and functional study.

PubMed

Ugaily-Thulesius, L; Thulesius, O; Sabha, M

1988-07-01

Evidence of a leaky urothelial barrier in bilharzial uropathy is presented. The ultrastructural basis of this concept is demonstrated together with its functional consequences. The study was conducted on 4 ureters obtained at surgery from patients with non-functioning kidneys due to chronic bilharzial infections. Six normal ureters from kidney donors served as controls. Light and electron microscopic studies showed a reduced thickness of the transitional epithelium together with localised disruption of intercellular junctions and infiltration of red blood cells. The functional studies involved in vitro demonstration of stable phasic peristaltic contractions which were fundamentally altered by the addition of urine. The changes in motility included increase in contractile frequency and elevation of basal tone, inducing a state of hypermotility which could be equated with ureteric spasm. These changes were partly reversible upon administration of the histamine l-blocker, mepyramine. Evidence is presented to show that these changes might be induced in vivo by histamine released from mast cells triggered by urine leaking through a damaged urothelial barrier. The functional consequences (pain, spasm) are discussed.

Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

PubMed

Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

2013-07-01

Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

Flavonoids in Kidney Health and Disease

PubMed Central

Vargas, Félix; Romecín, Paola; García-Guillén, Ana I.; Wangesteen, Rosemary; Vargas-Tendero, Pablo; Paredes, M. Dolores; Atucha, Noemí M.; García-Estañ, Joaquín

2018-01-01

This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect. Flavonoids prevent or attenuate the renal injury associated with arterial hypertension, both by decreasing blood pressure and by acting directly on the renal parenchyma. These outcomes derive from their interference with multiple signaling pathways known to produce renal injury and are independent of their blood pressure-lowering effects. Oral administration of flavonoids prevents or ameliorates adverse effects on the kidney of elevated fructose consumption, high fat diet, and types I and 2 diabetes. These compounds attenuate the hyperglycemia-disrupted renal endothelial barrier function, urinary microalbumin excretion, and glomerular hyperfiltration that results from a reduction of podocyte injury, a determinant factor for albuminuria in diabetic nephropathy. Several flavonoids have shown renal protective effects against many nephrotoxic agents that frequently cause acute kidney injury (AKI) or chronic kidney disease (CKD), such as LPS, gentamycin, alcohol, nicotine, lead or cadmium. Flavonoids also improve cisplatin- or methotrexate-induced renal damage, demonstrating important actions in chemotherapy, anticancer and renoprotective effects. A beneficial prophylactic effect of flavonoids has been also observed against AKI induced by surgical procedures such as ischemia/reperfusion (I/R) or cardiopulmonary bypass. In several murine models of CKD, impaired kidney function was significantly improved by the administration of flavonoids from different sources, alone or in combination with stem cells. In humans, cocoa flavanols were found to have vasculoprotective effects in patients on hemodialysis. Moreover, flavonoids develop antitumor activity against renal carcinoma cells with no toxic effects on normal cells, suggesting a potential therapeutic role in patients with renal carcinoma. PMID:29740333

Association of Chronic Kidney Disease With Small Vessel Disease in Patients With Hypertensive Intracerebral Hemorrhage.

PubMed

Tsai, Yuan-Hsiung; Lee, Meng; Lin, Leng-Chieh; Chang, Sheng-Wei; Weng, Hsu-Huei; Yang, Jen-Tsung; Huang, Yen-Chu; Lee, Ming-Hsueh

2018-01-01

Chronic kidney disease (CKD) has been closely associated with hypertension and stroke. Although studies have reported the relationship between CKD and cerebral small vessel disease (SVD), the link between CKD, hypertension, and SVD is uncertain. The aim of this study was to investigate the association between CKD and SVD in patients with strictly hypertensive intracerebral hemorrhage (ICH). 142 patients with acute hypertensive ICH were enrolled in this study. Magnetic resonance imaging was performed to assess imaging markers for SVD. Patients were categorized into three CKD groups based on the degree of kidney dysfunction [glomerular filtration rate (GFR) in milliliters per minute per 1.73 m 2 ]: normal kidney function (GFR ≥ 90), mild kidney disease (60 ≤ GFR < 90), and moderate to severe kidney disease (GFR < 60). The prevalence rate of mild and moderate to severe CKD was 50 and 14.8%, respectively. The stage of CKD was associated with history of chronic hypertension ( p  = 0.046) as well as the prevalence rate of overall and deep cerebral microbleed (CMB) ( p  = 0.001 and p  = 0.002, respectively). The stage of CKD was a significant risk factor for deep white matter hyperintensity (WMH) (OR 1.848; 95% CI 1.022-3.343, p  = 0.042), overall CMB (OR 2.628; 95% CI 1.462-4.724, p  = 0.001), lobar CMB (OR 2.106; 95% CI 1.119-3.963, p  = 0.021), and deep CMB (OR 2.237; 95% CI 1.263-3.960, p  = 0.006), even after adjustment for confounders. In patients with hypertensive ICH, the prevalence of CKD is high even at the early stage of renal function impairment and is associated with the prevalence of CMB and deep WMH. These results reinforce the notion of a link between hypertensive vasculopathy, renal function impairment, and cerebral SVD.

Flavonoids in Kidney Health and Disease.

PubMed

Vargas, Félix; Romecín, Paola; García-Guillén, Ana I; Wangesteen, Rosemary; Vargas-Tendero, Pablo; Paredes, M Dolores; Atucha, Noemí M; García-Estañ, Joaquín

2018-01-01

This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect. Flavonoids prevent or attenuate the renal injury associated with arterial hypertension, both by decreasing blood pressure and by acting directly on the renal parenchyma. These outcomes derive from their interference with multiple signaling pathways known to produce renal injury and are independent of their blood pressure-lowering effects. Oral administration of flavonoids prevents or ameliorates adverse effects on the kidney of elevated fructose consumption, high fat diet, and types I and 2 diabetes. These compounds attenuate the hyperglycemia-disrupted renal endothelial barrier function, urinary microalbumin excretion, and glomerular hyperfiltration that results from a reduction of podocyte injury, a determinant factor for albuminuria in diabetic nephropathy. Several flavonoids have shown renal protective effects against many nephrotoxic agents that frequently cause acute kidney injury (AKI) or chronic kidney disease (CKD), such as LPS, gentamycin, alcohol, nicotine, lead or cadmium. Flavonoids also improve cisplatin- or methotrexate-induced renal damage, demonstrating important actions in chemotherapy, anticancer and renoprotective effects. A beneficial prophylactic effect of flavonoids has been also observed against AKI induced by surgical procedures such as ischemia/reperfusion (I/R) or cardiopulmonary bypass. In several murine models of CKD, impaired kidney function was significantly improved by the administration of flavonoids from different sources, alone or in combination with stem cells. In humans, cocoa flavanols were found to have vasculoprotective effects in patients on hemodialysis. Moreover, flavonoids develop antitumor activity against renal carcinoma cells with no toxic effects on normal cells, suggesting a potential therapeutic role in patients with renal carcinoma.

Simultaneous pancreas and kidney transplantation for liver transplant recipients with diabetes and uremia.

PubMed

Tam, Ngalei; Zhang, Chuanzhao; Lin, Jianwei; Wu, Chenglin; Deng, Ronghai; Liao, Bing; Hu, Shuiqing; Wang, Dongping; Zhu, Xiaofeng; Wu, Linwei; He, Xiaoshun

2015-06-01

Chronic kidney disease (CKD) has become a critical problem due to immunosuppressant related nephrotoxicity in liver transplant (LTx) recipients, especially in patients with pre-transplant risk factors. LTx recipients with uraemia and diabetes have poor prognosis even when treated with dialysis and insulin. Simultaneous pancreas and kidney transplantation (SPK) has been proven to be an effective treatment for patients with diabetic uraemia, but rarely performed in patients after LTx. Two cases of SPK after LTx were performed in our centre and we present our experience here. Two patients received LTx because of HBV related liver cirrhosis; both of them had pre-transplant diabetes mellitus (DM), which worsened after the administration of immunosuppressive drugs. These two patients suffered from CKD and developed uraemia due to diabetic nephropathy and immunosuppressive drugs induced renal toxicity years after LTx. They relied on dialysis and insulin injection. SPK were performed years after LTx and the clinical data was retrospectively analyzed. SPK was successfully performed in these two patients. Pancreatic fluid drainage was achieved via a side-to-side duodenojejunostomy into the proximal jejunum. No serious surgical complications, including pancreatitis or pancreatic fistula were observed postoperatively. In both cases, kidney and pancreatic grafts were functioning well as evidenced by euglycemia without the need for insulin injections and normal serum-creatinine level 7days after the operation. One of the patients presented with renal graft impairment 1week after the operation. FK506 was tapered and rapamycin was used when the renal graft biopsy indicated drug toxicity. The patient's kidney graft function recovered gradually after the adjustment. Both patients have good function of liver, kidney and pancreas grafts during a 60-month and 30-month period of follow up. SPK could serve as an effective option for patients with diabetes and uremia after LTx. Perioperative management, especially the immunosuppressive strategy is crucial to improve the outcome of this procedure. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Outcome Measures Used to Report Kidney Function in Studies Investigating Surgical Management of Kidney Tumours: A Systematic Review.

PubMed

Ellis, Robert J; Cho, Yeoungjee; Del Vecchio, Sharon J; McStea, Megan; Morais, Christudas; Coombes, Jeff S; Wood, Simon T; Gobe, Glenda C; Francis, Ross S

2018-05-01

Most practice decisions relevant to preserving kidney function in patients managed surgically for kidney tumours are driven by observational studies. A wide range of outcome measures are used in these studies, which reduces comparability and increases the risk of reporting bias. To comprehensively and succinctly describe the outcomes used to evaluate kidney function in studies evaluating surgical management of kidney tumours. Electronic search of the PubMed database was conducted to identify studies with at least one measure of kidney function in patients managed surgically for kidney tumours, published between January 2000 and September 2017. Abstracts were initially screened for eligibility. Full texts of articles were then evaluated in more detail for inclusion. A narrative synthesis of the evidence was conducted. A total of 312 studies, involving 127905 participants, were included in this review. Most were retrospective (n=274) studies and conducted in a single centre (n=264). Overall, 78 unique outcome measures were identified, which were grouped into six outcome categories. Absolute postoperative kidney function (n=187), relative kidney function (n=181), and postoperative chronic kidney disease (n=131) were most frequently reported. Kidney function was predominantly quantified using estimated glomerular filtration rate or creatinine clearance (n=255), most using the modification of diet in renal disease equation (n=182). Only 70 studies provided rationale for specific outcome measures used. There is significant variability in the reporting and quantification of kidney function in studies evaluating patients managed surgically for kidney tumours. A standardised approach to measuring and reporting kidney function will increase the effectiveness of outcomes reported and improve relevance of research findings within a clinical context. Although we know that the removal of a kidney can reduce kidney function, clinical significance of various approaches is a matter of debate. This article demonstrates significant variability in the way kidney function was reported across all studies of patients with kidney cancer undergoing surgery, indicating a need for standardisation. Copyright © 2018 European Association of Urology. All rights reserved.

Population genetics of chronic kidney disease: the evolving story of APOL1.

PubMed

Wasser, Walter G; Tzur, Shay; Wolday, Dawit; Adu, Dwomoa; Baumstein, Donald; Rosset, Saharon; Skorecki, Karl

2012-01-01

Advances in human genome sequencing and generation of public databases of genomic diversity enable nephrologists to re-examine the genetics of common, complex kidney diseases. Non-diabetic kidney diseases prevalent in African ancestry populations and the allelic variation described in chromosome 22q12.3 is one such illustrative example. Newly available genomic database information enabled research groups to discover common functional DNA sequence risk variants in the APOL1 gene. These variants (termed G1 and G2) evolved to confer protection from a species of trypanosomal infection and thus achieved high prominence in many geographic regions of Africa and have been carried over to African diaspora communities worldwide. Since these discoveries two years ago, new insights have been gained: localization of APOL1 in normal and disease kidney tissues; influence of the APOL1 variants on the histopathology of HIV kidney disease; possible association with kidney transplant durability; onset of kidney failure at a younger age; association with blood lipid concentrations; more precise geographic localization of individuals with these variants to western and southern African ancestry; and the absence of the variants and kidney disease predisposition in Ethiopians. The definition of APOL1 nephropathy also confirms the long-held assumption by many clinicians that kidney disease attributed to hypertension in African populations represents an underlying glomerulopathy. Still awaited is the delineation of the biologic mechanisms of cellular injury related to these variants, to provide biologic proof of the APOL1 association and to provide potential targets for preventive and therapeutic intervention.

Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode.

PubMed

Jesmin, Subrina; Shimojo, Nobutake; Yamaguchi, Naoto; Mowa, Chishimba Nathan; Oki, Masami; Zaedi, Sohel; Sultana, Sayeeda Nusrat; Rahman, Arifur; Islam, Majedul; Sawamura, Atsushi; Gando, Satoshi; Kawano, Satoru; Miyauchi, Takashi; Mizutani, Taro

2014-05-02

Septic shock, the severe form of sepsis, is associated with development of progressive damage in multiple organs. Kidney can be injured and its functions altered by activation of coagulation, vasoactive-peptide and inflammatory processes in sepsis. Endothelin (ET)-1, a potent vasoconstrictor, is implicated in the pathogenesis of sepsis and its complications. Protease-activated receptors (PARs) are shown to play an important role in the interplay between inflammation and coagulation. We examined the time-dependent alterations of ET-1 and inflammatory cytokine, such as tumor necrosis factor (TNF)-α in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-α levels. Male Wistar rats at 8 weeks of age were administered with either saline solution or LPS at different time points (1, 3, 6 and 10h). Additionally, we treated LPS-administered rats with PAR2 blocking peptide for 3h to assess whether blockade of PAR2 has a regulatory role on the ET-1 level in septic kidney. An increase in ET-1 peptide level was observed in kidney tissue after LPS administration time-dependently. Levels of renal TNF-α peaked (around 12-fold) at 1h of sepsis. Interestingly, PAR2 blocking peptide normalized the LPS-induced elevations of renal ET-1 and TNF-α levels. The present study reveals a distinct chronological expression of ET-1 and TNF-α in LPS-administered renal tissues and that blockade of PAR2 may play a crucial role in treating renal injury, via normalization of inflammation, coagulation and vaso-active peptide. Copyright © 2014 Elsevier Inc. All rights reserved.

Kidney biopsy

MedlinePlus

... normal structure. What Abnormal Results Mean An abnormal result means there are changes in the kidney tissue. This may be due to: Infection Poor blood flow through the kidney Connective tissue diseases such as systemic lupus erythematosus Other diseases that may be affecting the ...

Serum osteoprotegerin and renal function in the general population: the Tromsø Study.

PubMed

Vik, Anders; Brodin, Ellen E; Mathiesen, Ellisiv B; Brox, Jan; Jørgensen, Lone; Njølstad, Inger; Brækkan, Sigrid K; Hansen, John-Bjarne

2017-02-01

Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m 2 ) eGFR increased by 0.35 mL/min/1.73 m 2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m 2 ), eGFR decreased by 1.54 (95% CI -2.06 to -1.01) per 1 SD increase in serum OPG. OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function.

Role of renal urothelium in the development and progression of kidney disease.

PubMed

Carpenter, Ashley R; McHugh, Kirk M

2017-04-01

The clinical and financial impact of chronic kidney disease (CKD) is significant, while its progression and prognosis is variable and often poor. Studies using the megabladder (mgb -/- ) model of CKD show that renal urothelium plays a key role in modulating early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical, and molecular characterization of Upk1b RFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/asymmetric membrane unit (AUM) formation, and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence that Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis, and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in normal development and pathogenesis of the urinary tract and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression.

Role of Renal Urothelium in the Development and Progression of Kidney Disease

PubMed Central

Carpenter, Ashley R.; McHugh, Kirk M.

2016-01-01

The clinical and financial impact of chronic kidney disease (CKD) is significant, while the progression and prognosis of CKD is variable and often poor. Studies using the megabladder (mgb−/−) model of CKD have shown that renal urothelium plays a key role in modulating the early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical and molecular characterization of Upk1bRFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/AUM formation and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in the normal development and pathogenesis of the urinary tract, and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression. PMID:27115886

Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Porter, Daniel S.; Pienkowski, David; Faugere, Marie-Claude

2012-01-01

Abnormal bone turnover is common in chronic kidney disease (CKD), but its effects on bone quality remain unclear. This study sought to quantify the relationship between abnormal bone turnover and bone quality. Iliac crest bone biopsies were obtained from CKD-5 patients on dialysis with low (n=18) or high (n=17) turnover, and from volunteers (n=12) with normal turnover and normal kidney function. Histomorphometric methods were used to quantify the microstructural parameters; Fourier transform infrared spectroscopy and nanoindentation were used to quantify the material and mechanical properties in bone. Reduced mineral-to-matrix ratio, mineral crystal size, stiffness and hardness were observed in bonemore » with high turnover compared to bone with normal or low turnover. Decreased cancellous bone volume and trabecular thickness were seen in bone with low turnover compared to bone with normal or high turnover. Bone quality, as defined by its microstructural, material, and mechanical properties, is related to bone turnover. These data suggest that turnover related alterations in bone quality may contribute to the known diminished mechanical competence of bone in CKD patients, albeit from different mechanisms for bone with high (material abnormality) vs. low (microstructural alteration) turnover. The present findings suggest that improved treatments for renal osteodystrophy should seek to avoid low or high bone turnover and aim for turnover rates as close to normal as possible.« less

Serum uric acid is a GFR-independent long-term predictor of acute and chronic renal insufficiency: the Jerusalem Lipid Research Clinic cohort study

PubMed Central

Kark, Jeremy D.

2011-01-01

Background. Kidney disease is commonly accompanied by hyperuricemia. However, the contribution of serum uric acid (SUA) to kidney injury is debated. Our objective was to assess the long-term prediction of renal failure by SUA. Methods. Visit 2 participants in the Jerusalem Lipid Research Clinic cohort with normal baseline kidney function were followed for 24–28 years. SUA levels were assessed for associations with acute renal failure (ARF) and chronic renal failure (CRF) as defined by hospital discharge records, and mortality, ascertained through linkage with the national population registry. Results. Among 2449 eligible participants (1470 men, 979 women aged 35–78 years in 1976–79), SUA was positively linked with male sex, serum creatinine and components of the metabolic syndrome but was lower in smokers and in diabetic subjects. The 22- to 25-year incidence of hospital-diagnosed kidney failure (145 first events, 67% CRF) and the 24- to 28-year mortality (587 events) were higher in subject with hyperuricemia (>6.5 mg/dL in men and >5.3 mg/dL in women, reflecting the upper quintiles), independent of baseline kidney function and covariates. Hyperuricemia conferred adjusted hazard ratios of 1.36 (P = 0.003), 2.14 (P < 0.001) and 2.87 (P = 0.003) for mortality, CRF and ARF, respectively. Conclusions. SUA predicts renal failure incidence and all-cause mortality independently of demographic and clinical covariates. These results lend support to the undertaking of clinical trials to examine the effect of uric acid-lowering strategies on kidney outcomes. PMID:21220750

Pregnancy outcomes in patients with Alport syndrome.

PubMed

Yefet, Enav; Tovbin, David; Nachum, Zohar

2016-04-01

To analyze the maternal and obstetric outcomes of patients with Alport syndrome. We describe the pregnancy course of 8 pregnancies of three family members with the autosomal dominant (the rarest) form of Alport syndrome. We also analyzed 10 previously reported pregnancies with other Alport mutations in order to explore risk factors for unfavorable obstetric outcomes and maternal renal deterioration. In 13 pregnancies (72 %), renal function did not deteriorate permanently. All of these women had pre-pregnancy mild chronic kidney disease (CKD stage G1). In all of them, only a transient increase in proteinuria was recorded and in one case there was a transient decrease in the estimated glomerular filtration rate. In four other pregnancies (22 %), renal function deteriorated following pregnancy. All of them were complicated with pre-eclampsia. One woman had pre-pregnancy CKD-G2A3 and chronic hypertension. Two women had CKD-G1A3 of whom one had pre-pregnancy proteinuria near the nephrotic range. In the fourth case, renal function deterioration was reported without information on the exact pre-pregnancy renal function. In the last case, CKD-G2 was reported after pregnancy without information on CKD stage prior to pregnancy. Severe proteinuria did not imply a permanent renal function deterioration if it developed during pregnancy. Ten pregnancies ended with preterm birth (56 %). Two stillbirths were reported (11 %); however, only one was attributed to maternal health deterioration. Data regarding pregnancy outcomes in Alport syndrome is limited. The outcome seems favorable when pre-pregnancy kidney function is normal or near normal and when chronic hypertension/pre-eclampsia is absent.

Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome

PubMed Central

2012-01-01

Background MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves. PMID:22353239

Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome.

PubMed

Piccoli, Giorgina Barbara; Bonino, Laura Davico; Campisi, Paola; Vigotti, Federica Neve; Ferraresi, Martina; Fassio, Federica; Brocheriou, Isabelle; Porpiglia, Francesco; Restagno, Gabriella

2012-02-21

MELAS syndrome (MIM ID#540000), an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS syndrome may increase as the support therapy of these patients improves.

Chronic Nephropathy from Dietary Hyperoxaluria: Sustained Improvement of Renal Function after Dietary Intervention.

PubMed

Sun, Yijuan; Horowitz, Bruce L; Servilla, Karen S; Fair, Joanna R; Vigil, Darlene; Ganta, Kavitha; Massie, Larry; Tzamaloukas, Antonios H

2017-03-20

A 56-year-old man with stable chronic kidney disease (CKD) for two years following a single episode of calcium oxalate urolithiasis developed progressive elevation of his serum creatinine concentration. Urinalysis revealed pyuria and white cell casts, a few red blood cells, minimal proteinuria, and no crystals. Urine culture was sterile. Gallium scintigraphy was consistent with interstitial nephritis. Proton pump inhibitor intake was discontinued, and a short course of oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because of the continued deterioration of renal function to a minimum estimated glomerular filtration rate (eGFR) value of 15 mL/min per 1.73 m 2 and persistent pyuria, revealed deposition of oxalate crystals in the tubules and interstitium, pronounced tubular changes, and interstitial nephritis and fibrosis. Urinary oxalate excretion was very high, in the range usually associated with primary hyperoxaluria. However, investigations for primary or enteric hyperoxaluria were negative. He reported a diet based on various nuts high in oxalate content. Estimated oxalate content in the diet was, for years, approximately four times higher than that in the average American diet. The institution of a diet low in oxalates resulted in the rapid normalization of urinary oxalate excretion and urinary sediment and in the slow, continuous improvement of renal function to near normal levels (eGFR 59 mL/min/1.73 m 2 ) before his death from a brain malignancy 3.5 years later. The manifestations of nephropathy secondary to dietary hyperoxaluria, including the urine findings, can be indistinguishable from other types of interstitial nephritis. The diagnosis of dietary hyperoxaluria requires careful dietary history and a kidney biopsy. Identifying dietary hyperoxaluria as the cause of CKD is important because the decrease in dietary oxalate intake without any other measures can lead to sustained improvement in renal function.

Chronic Nephropathy from Dietary Hyperoxaluria: Sustained Improvement of Renal Function after Dietary Intervention

PubMed Central

Sun, Yijuan; Horowitz, Bruce L; Servilla, Karen S; Fair, Joanna R; Vigil, Darlene; Ganta, Kavitha; Massie, Larry

2017-01-01

A 56-year-old man with stable chronic kidney disease (CKD) for two years following a single episode of calcium oxalate urolithiasis developed progressive elevation of his serum creatinine concentration. Urinalysis revealed pyuria and white cell casts, a few red blood cells, minimal proteinuria, and no crystals. Urine culture was sterile. Gallium scintigraphy was consistent with interstitial nephritis. Proton pump inhibitor intake was discontinued, and a short course of oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because of the continued deterioration of renal function to a minimum estimated glomerular filtration rate (eGFR) value of 15 mL/min per 1.73 m2 and persistent pyuria, revealed deposition of oxalate crystals in the tubules and interstitium, pronounced tubular changes, and interstitial nephritis and fibrosis. Urinary oxalate excretion was very high, in the range usually associated with primary hyperoxaluria. However, investigations for primary or enteric hyperoxaluria were negative. He reported a diet based on various nuts high in oxalate content. Estimated oxalate content in the diet was, for years, approximately four times higher than that in the average American diet. The institution of a diet low in oxalates resulted in the rapid normalization of urinary oxalate excretion and urinary sediment and in the slow, continuous improvement of renal function to near normal levels (eGFR 59 mL/min/1.73 m2) before his death from a brain malignancy 3.5 years later. The manifestations of nephropathy secondary to dietary hyperoxaluria, including the urine findings, can be indistinguishable from other types of interstitial nephritis. The diagnosis of dietary hyperoxaluria requires careful dietary history and a kidney biopsy. Identifying dietary hyperoxaluria as the cause of CKD is important because the decrease in dietary oxalate intake without any other measures can lead to sustained improvement in renal function. PMID:28435765

Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

PubMed Central

Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

2011-01-01

Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

Nephroprotective potential of artichoke leaves extract against gentamicin in rats: Antioxidant mechanisms.

PubMed

Khattab, Hala Ah; Wazzan, Maha Am; Al-Ahdab, Maha A

2016-09-01

Nephrotoxicity represents a major health problem. This study aims to determine nephroprotective of artichoke leaves extract (ALE) against gentamicin (GM) injection in male rats. Rats (n=30) were divided into; negative control, nephrotoxic (GM) injected intraperitoneally (i.p.) with GM (100 mg/kg b.wt/d for 10 days), and groups administered orally with ALE (200, 400 or 600 mg/kg b.wt/d) and injected with GM. The results revealed that, GM injection induced marked nephrotoxicity as evidenced by significant increase in kidney functions, albumin and potassium (K+), with significant decrease in serum levels of total protein and sodium (Na + ) as compared with negative control group. There was significant increase in malondialdehyde (MDA) level in GM group compared with negative control group. Renal examined tissues showed severe changes manifested by atrophy of glomerular tuft, necrosis of epithelial lining renal tubules with apoptosis of tubular epithelium and renal hemorrhage. Simultaneous administration of ALE during GM therapy protected kidney tissues as evidenced by normalization of kidney biochemical parameters and minimized the histopathological changes. Therefore, ALE has nephroprotective and antioxidant effects, thus could be beneficial for kidney patients.

Successful transplantation of donor organs from a hemlock poisoning victim.

PubMed

Foster, Preston F; McFadden, Robert; Trevino, Raul; Galliardt, Scott; Kopczewski, Lea Ann; Gugliuzza, Kristene; Gonzalez, Zulma; Wright, Francis

2003-09-15

The poison hemlock plant (Conium maculatum) has been a known poison since early in human history, most notably as the agent used for the execution/suicide of Socrates in ancient Greece. No experience has been reported regarding the suitability of a hemlock victim's organs for transplantation. This report documents successful transplantation of the liver, kidney, and pancreas from a 14-year-old girl who died of anoxic encephalopathy from asphyxia after the accidental ingestion of fresh hemlock while on a nature hike. Predonation laboratory values were not remarkable, and liver and kidney biopsy results were normal. All organs in the three recipients had immediate function, and no recipient had any clinical evidence of transmitted toxin. All recipients are well, with functioning transplants at greater than 6 months after transplantation. Poison hemlock intoxication does not seem to be a contraindication to organ donation.

[Quality assurance of the renal applications software].

PubMed

del Real Núñez, R; Contreras Puertas, P I; Moreno Ortega, E; Mena Bares, L M; Maza Muret, F R; Latre Romero, J M

2007-01-01

The need for quality assurance of all technical aspects of nuclear medicine studies is widely recognised. However, little attention has been paid to the quality assurance of the applications software. Our work reported here aims at verifying the analysis software for processing of renal nuclear medicine studies (renograms). The software tools were used to build a synthetic dynamic model of renal system. The model consists of two phases: perfusion and function. The organs of interest (kidneys, bladder and aortic artery) were simple geometric forms. The uptake of the renal structures was described by mathematic functions. Curves corresponding to normal or pathological conditions were simulated for kidneys, bladder and aortic artery by appropriate selection of parameters. There was no difference between the parameters of the mathematic curves and the quantitative data produced by the renal analysis program. Our test procedure is simple to apply, reliable, reproducible and rapid to verify the renal applications software.

Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.

PubMed

Xia, Yin; Babitt, Jodie L; Bouley, Richard; Zhang, Ying; Da Silva, Nicolas; Chen, Shanzhuo; Zhuang, Zhenjie; Samad, Tarek A; Brenner, Gary J; Anderson, Jennifer L; Hong, Charles C; Schneyer, Alan L; Brown, Dennis; Lin, Herbert Y

2010-04-01

The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.

MicroRNA profiling of human kidney cancer subtypes.

PubMed

Petillo, David; Kort, Eric J; Anema, John; Furge, Kyle A; Yang, Ximing J; Teh, Bin Tean

2009-07-01

Although the functions of most of the identified microRNAs (miRNAs) have yet to be determined, their use as potential biomarkers has been considered in several human diseases and cancers. In order to understand their role in renal tumorigenesis, we screened the expression levels of miRNAs in four subtypes of human renal neoplasms: clear cell, papillary, and chromophobe renal cell carcinomas (RCC) as well as benign renal oncocytomas. We found a unique miRNA signature for each subtype of renal tumor. Furthermore, we identified unique patterns of miRNA expression distinguishing clear cell RCC cases with favorable vs. unfavorable outcome. Specifically, we documented the overexpression of miRs 424 and 203 in clear cell RCC relative to papillary RCC, as well as the inversion of expression of miR-203 in the benign oncocytomas (where it is underexpressed relative to normal kidney) as compared to the malignant chromophobe RCC (where it is overexpressed relative to normal kidney). Our results further suggest that overexpression of S-has-miR-32 is associated with poor outcome. While previous studies have identified unique miRNA expression pattern distinguishing tumors from different anatomical locations, here we extend this principle to demonstrate the utility of miRNA expression profiling to identify a signature unique to various tumor subtypes at a single anatomic locus.

Cooperation of hTERT, SV40 T Antigen and Oncogenic Ras in Tumorigenesis: A Cell Transplantation Model Using Bovine Adrenocortical Cells1

PubMed Central

Thomas, Michael; Suwa, Tetsuya; Yang, Lianqing; Zhao, Lifang; Hawks, Christina L; Hornsby, Peter J

2002-01-01

Abstract Expression of TERT, the reverse transcriptase component of telomerase, is necessary to convert normal human cells to cancer cells. Despite this, “telomerization” by hTERT does not appear to alter the normal properties of cells. In a cell transplantation model in which bovine adrenocortical cells form vascularized tissue structures beneath the kidney capsule in scid mice, telomerization does not perturb the functional tissue-forming capacity of the cells. This cell transplantation model was used to study the cooperation of hTERT with SV40 T antigen (SV40 TAg) and oncogenic Ras in tumorigenesis. Only cells expressing all three genes were tumorigenic; this required large T, but not small t, antigen. These cells produced a continuously expanding tissue mass; they were invasive with respect to adjacent organs and eventually destroyed the kidney. Cells expressing only hTERT or only Ras produced minimally altered tissues. In contrast, SV40 TAg alone produced noninvasive nodules beneath the kidney capsule that had high proliferation rates balanced by high rates of apoptosis. The use of cell transplantation techniques in a cell type that is able to form tissue structures with or without full neoplastic conversion allows the phenotypes produced by individual cooperating oncogenes to be observed. PMID:12407443

Functional Activities and Immunohistochemical Distribution of Superoxide Dismutase in Normal, Dysplastic and Squamous Cell Carcinoma Oral Tissues

DTIC Science & Technology

2001-07-26

antioxidant enzymes: SOD, catalase ( CAT ), and glutathione peroxidase (GPO).2 ° SOD converts superoxide radical into hydrogen peroxide, while CAT and GPO convert...in endometriosis and adenomyosis. Fertility and Sterility 1999; 1:129-134. 45. Muse KE, Oberley TD, Sempf JM, Oberley LW. Immunolocalization of antioxidant enzymes in adult hamster kidney. Histochem J 1994;9:734-753. 43

Venovenous Bypass Is Associated With a Lower Incidence of Acute Kidney Injury After Liver Transplantation in Patients With Compromised Pretransplant Renal Function.

PubMed

Sun, Kai; Hong, Fu; Wang, Yun; Agopian, Vatche G; Yan, Min; Busuttil, Ronald W; Steadman, Randolph H; Xia, Victor W

2017-11-01

Although the hemodynamic benefits of venovenous bypass (VVB) during liver transplantation (LT) are well appreciated, the impact of VVB on posttransplant renal function is uncertain. The aim of this study was to determine if VVB was associated with a lower incidence of posttransplant acute kidney injury (AKI). Medical records of adult (≥18 years) patients who underwent primary LT between 2004 and 2014 at a tertiary hospital were reviewed. Patients who required pretransplant renal replacement therapy and intraoperative piggyback technique were excluded. Patients were divided into 2 groups, VVB and non-VVB. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups. Propensity match was used to control selection bias that occurred before VVB and multivariable logistic regression was used to control confounding factors during and after VVB. Of 1037 adult patients who met the study inclusion criteria, 247 (23.8%) received VVB. A total of 442 patients (221 patients in each group) were matched. Aftermatch patients were further divided according to a predicted probability AKI model using preoperative creatinine (Cr), VVB, and intraoperative variables into 2 subgroups: normal and compromised pretransplant renal functions. In patients with compromised pretransplant renal function (Cr ≥1.2 mg/dL), the incidence of AKI was significantly lower in the VVB group compared with the non-VVB group (37.2% vs 50.8%; P = .033). VVB was an independent risk factor negatively associated with AKI (odds ratio, 0.1; 95% confidence interval, 0.1-0.4; P = .001). Renal replacement in 30 days and 1-year recipient mortality were not significantly different between the 2 groups. The incidence of posttransplant AKI was not significantly different between the 2 groups in patients with normal pretransplant renal function (Cr <1.2 mg/dL). In this large retrospective study, we demonstrated that utilization of intraoperative VVB was associated with a significantly lower incidence of posttransplant AKI in patients with compromised pretransplant renal function. Further studies to assess the role of intraoperative VVB in posttransplant AKI are warranted.

Molecular pathophysiology of SLC4 bicarbonate transporters.

PubMed

Romero, Michael F

2005-09-01

Acid-base (H and HCO3) transport in the kidney is crucial for maintaining blood pH, cellular pH and excreting metabolic acid. HCO3 transport in the kidney is mediated by HCO3 transporter proteins which occur in two gene families in humans, vertebrates and invertebrates (SLC4 and SLC26). Since SLC26 transporters have other, non-HCO3 transport functions, this review highlights the history and recent advances in the SLC4 transporters in the kidney. The SLC4 gene and protein family (10 genes) contains three types of HCO3 transporters: Cl-HCO3 exchangers, Na/HCO3 cotransporters and Na-driven Cl-HCO3 exchangers. Function and human chromosomal location have been determined for most members. Human mutations in AE1 (SLC4A1) and NBCe1 (SLC4A4) are associated with distal and proximal renal tubular acidosis, respectively. Recent advances include the cellular and biophysical mechanisms by which AE1 and NBCe1 mutations lead to renal disease. Mutational and cellular trafficking studies have begun to elucidate the membrane topology and functional domains of AE1 and NBCe1. Knockout mice for AE2 and NBCn1 do not have obvious renal phenotypes. Recently, SLC4A11 (bicarbonate transporter 1) was shown to function as an electrogenic Na/borate cotransporter unable to transport HCO3 but involved in cell cycle control. SLC4 HCO3 transporters play critical roles in systemic and cellular pH homeostasis. Most of the SLC4 members are present at some level in the kidney. Future studies will likely continue to make use of knockout animals, for example mice and zebrafish, human mutations or polymorphisms to elucidate the normal and pathophysiologic roles of these proteins.

Blood disorders typically associated with renal transplantation

PubMed Central

Yang, Yu; Yu, Bo; Chen, Yun

2015-01-01

Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival. PMID:25853131

Asymptomatic cerebral lacunae in patients with chronic kidney disease.

PubMed

Kobayashi, Shuzo; Ikeda, Toshio; Moriya, Hidekazu; Ohtake, Takayasu; Kumagai, Hiromichi

2004-07-01

It remains unknown whether the prevalence of silent lacunar infarcts increases as renal function declines or what factors known as atherosclerotic risk factors are related to the development of lacunar infarcts. Fifty-one patients with chronic kidney disease without diabetes mellitus and 80 patients with essential hypertension with normal renal function were included in the study. The existence of lacunar infarcts was evaluated on brain magnetic resonance imaging scans. We evaluated the severity of carotid atherosclerosis by means of intima-media thickness of 1.0 mm or greater height in bilateral carotid arteries and by affecting factors, including plasma homocysteine levels. Lacunae prevalence was 25% in patients with a creatinine clearance (Ccr) greater than 40 mL/min/1.73 m2, 85% in patients with a Ccr less than 40 mL/min/1.73 m2, and 29% in patients with essential hypertension with normal renal function. Patients with lacunae had significantly lower hematocrits associated with increased fibrinogen and lipoprotein(a) levels compared with those without lacunae. Plasma total homocysteine and insulin levels at 2 hours after a 75-g glucose tolerance test correlated significantly with lacunae. Ischemic heart changes shown by electrocardiogram and thickened carotid intima-media thickness were significantly more frequent in patients with lacunae. However, logistic regression analysis showed that the most strongly contributing factor for lacunar infarcts was decline in Ccr (confidence interval, 0.933 to 0.995; P < 0.05). Decreased renal function, even without diabetes mellitus, is a risk factor for silent lacunar infarcts.

Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney.

PubMed

Nordholm, Anders; Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob; Morevati, Marya; Olgaard, Klaus; Lewin, Ewa

2018-05-01

In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-β and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.

Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obese fa/fa Zucker rats.

PubMed

Devassy, Jessay G; Wojcik, Jennifer L; Ibrahim, Naser H M; Zahradka, Peter; Taylor, Carla G; Aukema, Harold M

2017-02-01

Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.

A low-protein diet supplemented with ketoacids plays a more protective role against oxidative stress of rat kidney tissue with 5/6 nephrectomy than a low-protein diet alone.

PubMed

Gao, Xiang; Wu, Jianxiang; Dong, Zheyi; Hua, Can; Hu, Huimin; Mei, Changlin

2010-02-01

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD+KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague-Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD+KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD+KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD+KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.

Novel Functional Complexity of Polycystin-1 by GPS Cleavage In Vivo: Role in Polycystic Kidney Disease

PubMed Central

Kurbegovic, Almira; Kim, Hyunho; Xu, Hangxue; Yu, Shengqiang; Cruanès, Julie; Maser, Robin L.; Boletta, Alessandra; Trudel, Marie

2014-01-01

Polycystin-1 (Pc1) cleavage at the G protein-coupled receptor (GPCR) proteolytic site (GPS) is required for normal kidney morphology in humans and mice. We found a complex pattern of endogenous Pc1 forms by GPS cleavage. GPS cleavage generates not only the heterodimeric cleaved full-length Pc1 (Pc1cFL) in which the N-terminal fragment (NTF) remains noncovalently associated with the C-terminal fragment (CTF) but also a novel (Pc1) form (Pc1deN) in which NTF becomes detached from CTF. Uncleaved Pc1 (Pc1U) resides primarily in the endoplasmic reticulum (ER), whereas both Pc1cFL and Pc1deN traffic through the secretory pathway in vivo. GPS cleavage is not a prerequisite, however, for Pc1 trafficking in vivo. Importantly, Pc1deN is predominantly found at the plasma membrane of renal epithelial cells. By functional genetic complementation with five Pkd1 mouse models, we discovered that CTF plays a crucial role in Pc1deN trafficking. Our studies support GPS cleavage as a critical regulatory mechanism of Pc1 biogenesis and trafficking for proper kidney development and homeostasis. PMID:24958103

Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

PubMed

Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

2017-07-01

Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Sustained Pyridoxine Response in Primary Hyperoxaluria Type 1 Recipients of Kidney Alone Transplant

PubMed Central

Lorenz, Elizabeth C; Lieske, John C; Seide, Barbara M; Meek, Alicia M; Olson, Julie B; Bergstralh, Eric J; Milliner, Dawn S

2015-01-01

Combined kidney liver transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) given that it removes the hepatic source of oxalate production and improves renal allograft survival. However, PH1 patients homozygous for the G170R mutation can develop normal urine oxalate levels with pyridoxine therapy and may be candidates for kidney alone transplant. We examined the efficacy of pyridoxine therapy following kidney alone transplant in five patients homozygous for G170R transplanted between 9/1999 and 7/2013. All patients were maintained on pyridoxine post-transplant. Median age at transplant was 39 years (range 33–67 years). Median follow-up post-transplant was 8.5 years (range 0.2–13.9 years). At the end of follow-up, 4 grafts were functioning. One graft failed 13.9 years post-transplant due to recurrent oxalate nephropathy following an acute medical illness. After tissue oxalate stores had cleared, post-transplant urine oxalate levels were < 0.5 mmol/24 hr the majority of times checked. Calcium oxalate crystals were noted in only 3/13 allograft biopsies. This series suggests that a subgroup of PH1 patients demonstrate sustained response to pyridoxine therapy following kidney alone transplant. Therefore, pyridoxine combined with kidney alone transplantation should be considered for PH1 patients with a homozygous G170R mutation. PMID:24797341

Optimizing SGLT inhibitor treatment for diabetes with chronic kidney diseases.

PubMed

Layton, Anita T

2018-06-28

Diabetes induces glomerular hyperfiltration, affects kidney function, and may lead to chronic kidney diseases. A novel therapeutic treatment for diabetic patients targets the sodium-glucose cotransporter isoform 2 (SGLT2) in the kidney. SGLT2 inhibitors enhance urinary glucose, [Formula: see text] and fluid excretion and lower hyperglycemia in diabetes by inhibiting [Formula: see text] and glucose reabsorption along the proximal convoluted tubule. A goal of this study is to predict the effects of SGLT2 inhibitors in diabetic patients with and without chronic kidney diseases. To that end, we applied computational rat kidney models to assess how SGLT2 inhibition affects renal solute transport and metabolism when nephron population are normal or reduced (the latter simulates chronic kidney disease). The model predicts that SGLT2 inhibition induces glucosuria and natriuresis, with those effects enhanced in a remnant kidney. The model also predicts that the [Formula: see text] transport load and thus oxygen consumption of the S3 segment are increased under SGLT2 inhibition, a consequence that may increase the risk of hypoxia for that segment. To protect the vulnerable S3 segment, we explore dual SGLT2/SGLT1 inhibition and seek to determine the optimal combination that would yield sufficient urinary glucose excretion while limiting the metabolic load on the S3 segment. The model predicts that the optimal combination of SGLT2/SGLT1 inhibition lowers the oxygen requirements of key tubular segments, but decreases urine flow and [Formula: see text] excretion; the latter effect may limit the cardiovascular protection of the treatment.

Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury.

PubMed

Canaud, Guillaume; Bonventre, Joseph V

2015-04-01

For several decades, acute kidney injury (AKI) was generally considered a reversible process leading to complete kidney recovery if the individual survived the acute illness. Recent evidence from epidemiologic studies and animal models, however, have highlighted that AKI can lead to the development of fibrosis and facilitate the progression of chronic renal failure. When kidney injury is mild and baseline function is normal, the repair process can be adaptive with few long-term consequences. When the injury is more severe, repeated, or to a kidney with underlying disease, the repair can be maladaptive and epithelial cell cycle arrest may play an important role in the development of fibrosis. Indeed, during the maladaptive repair after a renal insult, many tubular cells that are undergoing cell division spend a prolonged period in the G2/M phase of the cell cycle. These tubular cells recruit intracellular pathways leading to the synthesis and the secretion of profibrotic factors, which then act in a paracrine fashion on interstitial pericytes/fibroblasts to accelerate proliferation of these cells and production of interstitial matrix. Thus, the tubule cells assume a senescent secretory phenotype. Characteristic features of these cells may represent new biomarkers of fibrosis progression and the G2/M-arrested cells may represent a new therapeutic target to prevent, delay or arrest progression of chronic kidney disease. Here, we summarize recent advances in our understanding of the biology of the cell cycle and how cell cycle arrest links AKI to chronic kidney disease. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

l-Arginine normalizes NOS activity and zinc-MT homeostasis in the kidney of mice chronically exposed to inorganic mercury.

PubMed

Piacenza, Francesco; Malavolta, Marco; Cipriano, Catia; Costarelli, Laura; Giacconi, Robertina; Muti, Elisa; Tesei, Silvia; Pierpaoli, Sara; Basso, Andrea; Bracci, Massimo; Bonacucina, Viviana; Santarelli, Lory; Mocchegiani, Eugenio

2009-09-28

Inorganic mercury (HgCl2) exposure provokes damage in many organs, especially kidney. Inducible nitric oxide synthase (iNOS) expression, total NOS activity and the profiles of zinc (Zn), copper (Cu) and Hg as well as their distribution when bound to specific intracellular proteins, including metallothioneins (MT), were studied during HgCl2 exposure and after l-arginine treatment in C57BL/6 mouse kidney. HgCl2 exposure modulates differently iNOS expression and NOS activity, increasing iNOS expression but, conversely, decreasing total NOS activity in the mouse kidney. Moreover, during Hg exposure an increased MT production occurs. The kidney damage leads to a loss of urinary proteins, increased plasma creatinine and high Zn mobilization with consequent increased urinary Zn excretion. l-arginine treatment recovers NOS activity and induces a normalization of MT induction, plasma creatinine values and urinary proteins excretion, suggesting that l-arginine may limit kidney damages by Hg exposure.

Application of prescribing recommendations in older people with reduced kidney function: a cross-sectional study in general practice.

PubMed

Wood, Su; Petty, Duncan; Glidewell, Liz; Raynor, Dk Theo

2018-05-01

Kidney function reduces with age, increasing the risk of harm from increased blood levels of many medicines. Although estimated glomerular filtration rate (eGFR) is reported for prescribing decisions in those aged ≥65 years, creatinine clearance (Cockcroft-Gault) gives a more accurate estimate of kidney function. To explore the extent of prescribing outside recommendations for people aged ≥65 years with reduced kidney function in primary care and to assess the impact of using eGFR instead of creatinine clearance to calculate kidney function. A cross-sectional survey of anonymised prescribing data in people aged ≥65 years from all 80 general practices (70 900 patients) in a north of England former primary care trust. The prevalence of prescribing outside recommendations was analysed for eight exemplar drugs. Data were collected for age, sex, actual weight, serum creatinine, and eGFR. Kidney function as creatinine clearance (Cockcroft-Gault) was calculated using actual body weight and estimated ideal body weight. Kidney function was too low for recommended prescribing in 4-40% of people aged ≥65 years, and in 24-80% of people aged ≥85 years despite more than 90% of patients having recent recorded kidney function results. Using eGFR overestimated kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years. Increased age predicted higher odds of having a kidney function estimate too low for recommended prescribing of the study drugs. Prescribing recommendations when kidney function is reduced are not applied for many people aged ≥65 years in primary care. Using eGFR considerably overestimates kidney function for prescribing and, therefore, creatinine clearance (Cockcroft-Gault) should be assessed when prescribing for these people. Interventions are needed to aid prescribers when kidney function is reduced. © British Journal of General Practice 2018.

Life after transplantation: new transitions in quality of life and psychological distress.

PubMed

Muehrer, Rebecca J; Becker, Bryan N

2005-01-01

Individuals with kidney failure often elect to undergo kidney transplantation because they believe that they will be more active and return a sense of normality to their lives with a functioning transplant. Therefore it is important to assess whether these objectives are being met. To do so, we can examine health-related quality of life (HRQOL) in transplant recipients. A number of tools have been used for this purpose, including general HRQOL instruments such as the 36-item short-form health survey (SF-36) and transplant-specific surveys such as the Kidney Transplant Questionnaire. In general, HRQOL assessments improve with transplantation in functional and physical domains. However, many factors actually influence HRQOL in a negative way, including comorbid conditions, kidney function per se, rejection episodes and hospitalizations, employment status, and adverse effects of medications. Perceived physical appearance, issues related to sexuality, stress, anxiety, and even guilt complicate the emotional and psychological landscape after transplantation. This constellation of factors may be predictive of posttransplant life events, such as resumption of employment. Posttransplant HRQOL may be exceedingly important in understanding the issues related to adherence with treatment regimens, especially in the pediatric and adolescent transplant populations. HRQOL is now established as an important issue after transplantation. Nonetheless, shortcomings still exist in our ability to address HRQOL after transplantation. In particular, more study of patient-centered interventions is needed. The use of standardized methodologies for patient assessment could improve our ability to identify if such patient-centered interventions actually succeed across populations, and help us further address the panoply of factors encompassed within posttransplant HRQOL.

Kidney outcomes three years after bariatric surgery in severely obese adolescents.

PubMed

Nehus, Edward J; Khoury, Jane C; Inge, Thomas H; Xiao, Nianzhou; Jenkins, Todd M; Moxey-Mims, Marva M; Mitsnefes, Mark M

2017-02-01

A significant number of severely obese adolescents undergoing bariatric surgery have evidence of early kidney damage. To determine if kidney injury is reversible following bariatric surgery, we investigated renal outcomes in the Teen-Longitudinal Assessment of Bariatric Surgery cohort, a prospective multicenter study of 242 severely obese adolescents undergoing bariatric surgery. Primary outcomes of urine albumin-to-creatinine ratio and cystatin C-based estimated glomerular filtration rate (eGFR) were evaluated preoperatively and up to 3 years following bariatric surgery. At surgery, mean age of participants was 17 years and median body mass index (BMI) was 51 kg/m 2 . In those with decreased kidney function at baseline (eGFR under 90 mL/min/1.73m 2 ), mean eGFR significantly improved from 76 to 102 mL/min/1.73m 2 at three-year follow-up. Similarly, participants with albuminuria (albumin-to-creatinine ratio of 30 mg/g and more) at baseline demonstrated significant improvement following surgery: geometric mean of ACR was 74 mg/g at baseline and decreased to 17 mg/g at three years. Those with normal renal function and no albuminuria at baseline remained stable throughout the study period. Among individuals with a BMI of 40 kg/m 2 and more at follow-up, increased BMI was associated with significantly lower eGFR, while no association was observed in those with a BMI under 40 kg/m 2 . In adjusted analysis, eGFR increased by 3.9 mL/min/1.73m 2 for each 10-unit loss of BMI. Early kidney abnormalities improved following bariatric surgery in adolescents with evidence of preoperative kidney disease. Thus, kidney disease should be considered as a selection criteria for bariatric surgery in severely obese adolescents who fail conventional weight management. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Chronic Kidney Disease Is Associated With White Matter Hyperintensity Volume

PubMed Central

Khatri, Minesh; Wright, Clinton B.; Nickolas, Thomas L.; Yoshita, Mitsuhiro; Paik, Myunghee C.; Kranwinkel, Grace; Sacco, Ralph L.; DeCarli, Charles

2010-01-01

Background and Purpose White matter hyperintensities have been associated with increased risk of stroke, cognitive decline, and dementia. Chronic kidney disease is a risk factor for vascular disease and has been associated with inflammation and endothelial dysfunction, which have been implicated in the pathogenesis of white matter hyperintensities. Few studies have explored the relationship between chronic kidney disease and white matter hyperintensities. Methods The Northern Manhattan Study is a prospective, community-based cohort of which a subset of stroke-free participants underwent MRIs. MRIs were analyzed quantitatively for white matter hyperintensities volume, which was log-transformed to yield a normal distribution (log-white matter hyperintensity volume). Kidney function was modeled using serum creatinine, the Cockcroft-Gault formula for creatinine clearance, and the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate. Creatinine clearance and estimated glomerular filtration rate were trichotomized to 15 to 60 mL/min, 60 to 90 mL/min, and >90 mL/min (reference). Linear regression was used to measure the association between kidney function and log-white matter hyperintensity volume adjusting for age, gender, race–ethnicity, education, cardiac disease, diabetes, homocysteine, and hypertension. Results Baseline data were available on 615 subjects (mean age 70 years, 60% women, 18% whites, 21% blacks, 62% Hispanics). In multivariate analysis, creatinine clearance 15 to 60 mL/min was associated with increased log-white matter hyperintensity volume (β 0.322; 95% CI, 0.095 to 0.550) as was estimated glomerular filtration rate 15 to 60 mL/min (β 0.322; 95% CI, 0.080 to 0.564). Serum creatinine, per 1-mg/dL increase, was also positively associated with log-white matter hyperintensity volume (β 1.479; 95% CI, 1.067 to 2.050). Conclusions The association between moderate–severe chronic kidney disease and white matter hyperintensity volume highlights the growing importance of kidney disease as a possible determinant of cerebrovascular disease and/or as a marker of microangiopathy. PMID:17962588

Tc-99m Ethylenedicysteine and Tc-99m Dimercaptosuccinic Acid Scintigraphy-Comparison of the Two for Detection of Scarring and Differential Cortical Function.

PubMed

Dharmalingam, Anitha; Pawar, Shwetal U; Parelkar, Sandesh V; Shetye, Suruchi S; Ghorpade, Mangala K; Tilve, Gundu H

2017-01-01

The differential cortical function obtained by Tc-99m EC is comparable to that of Tc-99m DMSA. However, identification of scars on Tc-99m EC images needs to be studied. The aim of the study is to evaluate role of Tc-99m EC for detection of scarring and differential cortical function by comparing with Tc-99m DMSA. Prospective observational study of recurrent UTI; minimum 6 weeks after acute episode; when urine examination is negative for pus cells. Forty-seven children with normal positioned kidneys underwent Tc-99m EC and DMSA scintigraphy. The DRF and cortical phase images of both studies in the same image matrix size were evaluated by two independent observers for scarring; Tc-99m DMSA was considered as the gold standard. MS Excel 2007 and GraphPad Instat V3.1 and ROC analysis. There was no significant difference in the detection of scarring using two studies with Cohen's kappa coefficient (κ) 0.932. The sensitivity and specificity of Tc-99m EC for detection of scarring was 98.75% and 99.15%, respectively. There was good agreement between the differential cortical function calculated using two studies. The summed Tc-99m EC images with an acceptable high image contrast allow detection of cortical scarring in patients with normal kidney positions. It is an excellent single-modality comprehensive investigational agent for renal parenchymal defects, function, and excretion evaluation with the added advantages of lower cost, convenience, and low radiation exposure to the child.

Hydrogen sulfide ameliorates aging-associated changes in the kidney.

PubMed

Lee, Hak Joo; Feliers, Denis; Barnes, Jeffrey L; Oh, Sae; Choudhury, Goutam Ghosh; Diaz, Vivian; Galvan, Veronica; Strong, Randy; Nelson, James; Salmon, Adam; Kevil, Christopher G; Kasinath, Balakuntalam S

2018-04-01

Aging is associated with replacement of normal kidney parenchyma by fibrosis. Because hydrogen sulfide (H 2 S) ameliorates kidney fibrosis in disease models, we examined its status in the aging kidney. In the first study, we examined kidney cortical H 2 S metabolism and signaling pathways related to synthesis of proteins including matrix proteins in young and old male C57BL/6 mice. In old mice, increase in renal cortical content of matrix protein involved in fibrosis was associated with decreased H 2 S generation and AMPK activity, and activation of insulin receptor (IR)/IRS-2-Akt-mTORC1-mRNA translation signaling axis that can lead to increase in protein synthesis. In the second study, we randomized 18-19 month-old male C57BL/6 mice to receive 30 μmol/L sodium hydrosulfide (NaHS) in drinking water vs. water alone (control) for 5 months. Administration of NaHS increased plasma free sulfide levels. NaHS inhibited the increase in kidney cortical content of matrix proteins involved in fibrosis and ameliorated glomerulosclerosis. NaHS restored AMPK activity and inhibited activation of IR/IRS-2-Akt-mTORC1-mRNA translation axis. NaHS inhibited age-related increase in kidney cortical content of p21, IL-1β, and IL-6, components of the senescence-associated secretory phenotype. NaHS abolished increase in urinary albumin excretion seen in control mice and reduced serum cystatin C levels suggesting improved glomerular clearance function. We conclude that aging-induced changes in the kidney are associated with H 2 S deficiency. Administration of H 2 S ameliorates aging-induced kidney changes probably by inhibiting signaling pathways leading to matrix protein synthesis.

Inflammatory PAF Receptor Signaling Initiates Hedgehog Signaling and Kidney Fibrogenesis During Ethanol Consumption

PubMed Central

Latchoumycandane, Calivarathan; Hanouneh, Mohamad; Nagy, Laura E.; McIntyre, Thomas M.

2015-01-01

Acute inflammation either resolves or proceeds to fibrotic repair that replaces functional tissue. Pro-fibrotic hedgehog signaling and induction of its Gli transcription factor in pericytes induces fibrosis in kidney, but molecular instructions connecting inflammation to fibrosis are opaque. We show acute kidney inflammation resulting from chronic ingestion of the common xenobiotic ethanol initiates Gli1 transcription and hedgehog synthesis in kidney pericytes, and promotes renal fibrosis. Ethanol ingestion stimulated transcription of TGF-ß, collagens I and IV, and alpha-smooth muscle actin with accumulation of these proteins. This was accompanied by deposition of extracellular fibrils. Ethanol catabolism by CYP2E1 in kidney generates local reactive oxygen species that oxidize cellular phospholipids to phospholipid products that activate the Platelet-activating Factor receptor (PTAFR) for inflammatory phospholipids. Genetically deleting this ptafr locus abolished accumulation of mRNA for TGF-ß, collagen IV, and α-smooth muscle actin. Loss of PTAFR also abolished ethanol-stimulated Sonic (Shh) and Indian hedgehog (Ihh) expression, and abolished transcription and accumulation of Gli1. Shh induced in pericytes and Ihh in tubules escaped to urine of ethanol-fed mice. Neutrophil myeloperoxidase (MPO) is required for ethanol-induced kidney inflammation, and Shh was not present in kidney or urine of mpo -/- mice. Shh also was present in urine of patients with acute kidney injury, but not in normal individuals or those with fibrotic liver cirrhosis We conclude neither endogenous PTAFR signaling nor CYP2E1-generated radicals alone are sufficient to initiate hedgehog signaling, but instead PTAFR-dependent neutrophil infiltration with myeloperoxidase activation is necessary to initiate ethanol-induced fibrosis in kidney. We also show fibrogenic mediators escape to urine, defining a new class of urinary mechanistic biomarkers of fibrogenesis for an organ not commonly biopsied. PMID:26720402

Impact of transplant nephrectomy on peak PRA levels and outcome after kidney re-transplantation

PubMed Central

Tittelbach-Helmrich, Dietlind; Pisarski, Przemyslaw; Offermann, Gerd; Geyer, Marcel; Thomusch, Oliver; Hopt, Ulrich Theodor; Drognitz, Oliver

2014-01-01

AIM: To determine the impact of transplant nephrectomy on peak panel reactive antibody (PRA) levels, patient and graft survival in kidney re-transplants. METHODS: From 1969 to 2006, a total of 609 kidney re-transplantations were performed at the University of Freiburg and the Campus Benjamin Franklin of the University of Berlin. Patients with PRA levels above (5%) before first kidney transplantation were excluded from further analysis (n = 304). Patients with graft nephrectomy (n = 245, NE+) were retrospectively compared to 60 kidney re-transplants without prior graft nephrectomy (NE-). RESULTS: Peak PRA levels between the first and the second transplantation were higher in patients undergoing graft nephrectomy (P = 0.098), whereas the last PRA levels before the second kidney transplantation did not differ between the groups. Age adjusted survival for the second kidney graft, censored for death with functioning graft, were comparable in both groups. Waiting time between first and second transplantation did not influence the graft survival significantly in the group that underwent nephrectomy. In contrast, patients without nephrectomy experienced better graft survival rates when re-transplantation was performed within one year after graft loss (P = 0.033). Age adjusted patient survival rates at 1 and 5 years were 94.1% and 86.3% vs 83.1% and 75.4% group NE+ and NE-, respectively (P < 0.01). CONCLUSION: Transplant nephrectomy leads to a temporary increase in PRA levels that normalize before kidney re-transplantation. In patients without nephrectomy of a non-viable kidney graft timing of re-transplantation significantly influences graft survival after a second transplantation. Most importantly, transplant nephrectomy is associated with a significantly longer patient survival. PMID:25032103

The science of Stewardship: due diligence for kidney donors and kidney function in living kidney donation--evaluation, determinants, and implications for outcomes.

PubMed

Poggio, Emilio D; Braun, William E; Davis, Connie

2009-10-01

Living kidney donor transplantation is now a common treatment for ESRD because it provides excellent outcomes to transplant recipients and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of this procedure. Whereas the initial experiences with living kidney donors mostly included the healthiest, the increase in the need for organs and the changing demographic characteristics of the general population have subtly reshaped the suitability for donation. Kidney function assessment is a critical component of the evaluation of prospective donors; therefore, special emphasis is usually placed on this aspect of the evaluation. At the same time, consideration of kidney function after donation is important because it assists with the determination of renal health in donors. This review summarizes the process of predonation kidney function assessment, determinants of pre- and postdonation renal function, and, importantly, the potential implications of kidney function to the long-term outcomes of kidney donors.

Renal synthesis of leukaemia inhibitory factor (LIF), under normal and inflammatory conditions.

PubMed

Morel, D S; Taupin, J L; Potier, M; Deminière, C; Potaux, L; Gualde, N; Moreau, J F

2000-03-01

Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine that is particularly involved in nephrogenesis and repair of the extracellular matrix. Transgenic mice overexpressing LIF have mesangial proliferative glomerulonephritis. Also, during local inflammatory reactions, such as kidney graft rejection or urinary tract infections, urinary LIF excretion is enhanced. The aim of the study therefore was to study LIF production by normal and inflammatory diseased kidneys (glomerulonephritis or graft rejection), maintained in short cultures. To determine the responsibility of the kidney itself in LIF synthesis, we measured LIF secretion into the culture supernatants of human mesangial or renal tubular epithelial cells. Fragments from diseased kidneys, whether grafts or not, released more LIF than normal human kidney fragments, mesangial or renal tubular epithelial cells. However, LIF production was delayed in renal transplants compared to glomerulonephritic samples taken from untreated patients. In every case, LIF production was enhanced by interleukin 1beta (IL-1beta) and inhibited by IL-4 or dexamethasone, except in two severe rejection episodes. So, LIF appeared to respond to pro- and anti-inflammatory stimuli, in vitro and in vivo. Considering its biological effects, LIF could play a role in inflammatory renal diseases. Copyright 2000 Academic Press.

Ameliorative effects of sildenafil and/or febuxostat on doxorubicin-induced nephrotoxicity in rats.

PubMed

Khames, Ali; Khalaf, Marwa M; Gad, Amany M; Abd El-Raouf, Ola M

2017-06-15

Sildenafil and febuxostat protect against doxorubicin-induced nephrotoxicity; however the exact mechanism remains to be elucidated. The effect of sildenafil and febuxostat on doxorubicin-induced nephrotoxicity in rats was studied. Male rats were subdivided into nine groups. The 1st group served as normal control, the 2nd group received dimethylsulfoxide 50% (DMSO), the 3rd group received doxorubicin (3.5mg/kg, i.p.), twice weekly for 3 weeks. The next 3 groups received sildenafil (5mg/kg; p.o.), febuxostat (10mg/kg; p.o.) and their combination, respectively daily for 21 days. The last 3 groups received doxorubicin in combination with sildenafil, febuxostat or their combination. Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically through measuring the following parameters, Kidney function biomarkers [serum levels of urea, creatinine and uric acid], oxidative stress biomarkers [kidney contents of glutathione reduced (GSH) and malondialdehyde (MDA)], The apoptotic marker namely; caspase-3 in kidney tissue and the inflammatory mediator tumor necrosis factor alpha (TNF-α). doxorubicin-induced a significant elevation in nephrotoxicity markers, expression of caspase-3 and caused induction of inflammation and oxidative stress. Histological changes in the kidney was tubular necrosis. Sildenafil and/or febuxostat administration with doxorubicin caused a significant decrease in nephrotoxicity markers and inflammatory mediators, restoration of normal values of oxidative stress biomarkers and hampering the expression of renal caspase-3. They also ameliorate histological changes induced by doxorubicin. sildenafil and febuxostat are promising protective agents against doxorubicin-nephrotoxicity through improving biochemical, inflammatory, histopathological and immunohistochemical alterations induced by doxorubicin. Copyright © 2017 Elsevier B.V. All rights reserved.

SWIR dispersive Raman spectroscopy for discrimination of normal and malignant kidney tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Haifler, Miki; Pence, Isaac J.; Zisman, Amnon; Uzzo, Robert G.; Greenberg, Richard; Kutikov, Alexander; Smaldone, Marc; Chen, David; Viterbo, Rosalia; Ristau, Benjamin; Mahadevan-Jansen, Anita; Dumont, Alexander; Patil, Chetan A.

2017-02-01

Kidney cancer affects 65,000 new patients every. As computerized tomography became ubiquitous, the number of small, incidentally detected renal masses increased. About 6,000 benign cases are misclassified radiographically as malignant and removed surgically. Raman spectroscopy (RS) has been widely demonstrated for disease discrimination, however intense near-infrared auto-fluorescence of certain tissues (e.g kidney) can present serious challenges to bulk tissue diagnosis. A 1064nm excitation dispersive detection RS system demonstrated the ability to collect spectra with superior quality in tissues with strong auto-fluorescence. Our objective is to develop a 1064 nm dispersive detection RS system capable of differentiating normal and malignant renal tissue. We will report on the design and development of a clinical system for use in nephron sparing surgeries. We will present pilot data that has been collected from normal and malignant ex vivo kidney specimens using a benchtop RS system. A total of 93 measurements were collected from 12 specimens (6 Renal Cell Carcinoma, 6 Normal ). Spectral classification was performed using sparse multinomial logistic regression (SMLR). Correct classification by SMLR was obtained in 78% of the trials with sensitivity and specificity of 82% and 75% respectively. We will present the association of spectral features with biological indicators of healthy and diseased kidney tissue. Our findings indicate that 1064nm RS is a promising technique for differentiation of normal and malignant renal tissue. This indicates the potential for accurately separating healthy and cancerous tissues and suggests implications for utilizing RS for optical biopsy and surgical guidance in nephron sparing surgery.

Renal Control of Calcium, Phosphate, and Magnesium Homeostasis

PubMed Central

Chonchol, Michel; Levi, Moshe

2015-01-01

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. PMID:25287933

Casual Blood Pressure and Neurocognitive Function in Children with Chronic Kidney Disease: A Report of the Children with Chronic Kidney Disease Cohort Study

PubMed Central

Gerson, Arlene C.; Hooper, Stephen R.; Cox, Christopher; Matheson, Matt; Mendley, Susan R.; Gipson, Debbie S.; Wong, Cynthia; Warady, Bradley A.; Furth, Susan L.; Flynn, Joseph T.

2011-01-01

Summary Background and objectives Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP. Design, setting, participants, & measurements This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project. Results Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90th percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95th percentile BP) correlated inversely with Performance IQ score (systolic, r = −0.13, P = 0.01; diastolic, r = −0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = −3.7, 95% confidence interval [CI]: −7.3 to −0.06; systolic BP index, β = −1.16 to 95% CI: −2.1, −0.21; diastolic BP index, β = −1.17, 95% CI: −1.8 to −0.55). Conclusions Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD. PMID:21700829

Kidney function after off-pump or on-pump coronary artery bypass graft surgery: a randomized clinical trial.

PubMed

Garg, Amit X; Devereaux, P J; Yusuf, Salim; Cuerden, Meaghan S; Parikh, Chirag R; Coca, Steven G; Walsh, Michael; Novick, Richard; Cook, Richard J; Jain, Anil R; Pan, Xiangbin; Noiseux, Nicolas; Vik, Karel; Stolf, Noedir A; Ritchie, Andrew; Favaloro, Roberto R; Parvathaneni, Sirish; Whitlock, Richard P; Ou, Yongning; Lawrence, Mitzi; Lamy, Andre

2014-06-04

Most acute kidney injury observed in the hospital is defined by sudden mild or moderate increases in the serum creatinine concentration, which may persist for several days. Such acute kidney injury is associated with lower long-term kidney function. However, it has not been demonstrated that an intervention that reduces the risk of such acute kidney injury better preserves long-term kidney function. To characterize the risk of acute kidney injury with an intervention in a randomized clinical trial and to determine if there is a difference between the 2 treatment groups in kidney function 1 year later. The Coronary Artery Bypass Grafting Surgery Off- or On-pump Revascularisation Study (CORONARY) enrolled 4752 patients undergoing first isolated coronary artery bypass graft (CABG) surgery at 79 sites in 19 countries. Patients were randomized to receive CABG surgery either with a beating-heart technique (off-pump) or with cardiopulmonary bypass (on-pump). From January 2010 to November 2011, 2932 patients (from 63 sites in 16 countries) from CORONARY were enrolled into a kidney function substudy to record serum creatinine concentrations during the postoperative period and at 1 year. The last 1-year serum creatinine concentration was recorded on January 18, 2013. Acute kidney injury within 30 days of surgery (≥50% increase in serum creatinine concentration from prerandomization concentration) and loss of kidney function at 1 year (≥20% loss in estimated glomerular filtration rate from prerandomization level). Off-pump (n = 1472) vs on-pump (n = 1460) CABG surgery reduced the risk of acute kidney injury (17.5% vs 20.8%, respectively; relative risk, 0.83 [95% CI, 0.72-0.97], P = .01); however, there was no significant difference between the 2 groups in the loss of kidney function at 1 year (17.1% vs 15.3%, respectively; relative risk, 1.10 [95% CI, 0.95-1.29], P = .23). Results were consistent with multiple alternate continuous and categorical definitions of acute kidney injury or kidney function loss, and in the subgroup with baseline chronic kidney disease. Use of off-pump compared with on-pump CABG surgery reduced the risk of postoperative acute kidney injury, without evidence of better preserved kidney function with off-pump CABG surgery at 1 year. In this setting, an intervention that reduced the risk of mild to moderate acute kidney injury did not alter longer-term kidney function. clinicaltrials.gov Identifier: NCT00463294.

Nocturnal Hypoxia and Loss of Kidney Function

PubMed Central

Ahmed, Sofia B.; Ronksley, Paul E.; Hemmelgarn, Brenda R.; Tsai, Willis H.; Manns, Braden J.; Tonelli, Marcello; Klarenbach, Scott W.; Chin, Rick; Clement, Fiona M.; Hanly, Patrick J.

2011-01-01

Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function. PMID:21559506

Reversible vascular calcifications associated with hypervitaminosis D.

PubMed

Cirillo, Massimo; Bilancio, Giancarlo; Cirillo, Chiara

2016-02-01

A 64-year-old man was hospitalized in 2002 with symptoms of stupor, weakness, and renal colic. The clinical examination indicated borderline hypertension, small masses in the glutei, and polyuria. Laboratory tests evidenced high serum concentrations of creatinine, calcium, and phosphate. Imaging assessments disclosed widespread vascular calcifications, gluteal calcifications, and pelvic ectasia. Subsequent lab tests indicated suppressed serum parathyroid hormone, extremely high serum 25-hydroxy vitamin D, and normal serum 1,25-dihydroxy vitamin D. Treatment was started with intravenous infusion of saline and furosemide due to the evidence of hypercalcemia. Prednisone and omeprazole were added given the evidence of hypervitaminosis D. The treatment improved serum calcium, kidney function, and consciousness. The medical history disclosed recent treatment with exceptionally high doses of slow-release intra-muscular cholecalciferol and the recent excretion of urinary stones. The patient was discharged when it was possible to stop the intravenous treatment. The post-discharge treatment included oral hydration, furosemide, prednisone and omeprazole for approximately 6 months up to complete resolution of the hypercalcemia. The patient came back 12 years later because of microhematuria. Lab tests were normal for calcium/phosphorus homeostasis and kidney function. Imaging tests indicated only minor vascular calcifications. This is the first evidence of reversible vascular calcifications secondary to hypervitaminosis D.

Cryptic B cell response to renal transplantation.

PubMed

Lynch, R J; Silva, I A; Chen, B J; Punch, J D; Cascalho, M; Platt, J L

2013-07-01

Transplantation reliably evokes allo-specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of antidonor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor-specific antibodies reflects absence of a B cell response to the donor, tolerance to the donor or immunity masked by binding of donor-specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third-party fibroblasts as targets. We enumerated donor-specific antibody-secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor-specific antibodies before or after transplantation, all exhibited increases in the frequency of donor-specific antibody-secreting cells eight weeks after transplantation. The responses were directed against the donor HLA-class I antigens. The increase in frequency of donor-specific antibody-secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought. © 2013 The Authors. American Journal of Transplantation Published by Wiley Periodicals Inc.

The meridian system and mechanism of acupuncture: a comparative review. Part 3: Mechanisms of acupuncture therapies.

PubMed

Chang, Shyang

2013-06-01

The human body is a hierarchical organism containing many levels of mutually interacting oscillatory systems. From the viewpoint of traditional Chinese medicine, health is a state of harmony emergent from the interactions of these systems and disease is a state of discord. Hence, human diseases are considered as disturbed functions rather than changed structures. Indeed, the change from normal to abnormal structure may be beneficent rather than maleficent. For example, when one kidney becomes twice the normal size following the destruction of the other kidney, it is good and not bad for us because we might be dead otherwise. Therefore, in Part 3 of this three-part series, emphasis is mainly laid on the acupuncture mechanisms of treating disturbed physiological functions rather than disordered structures. At first, the basic tenets of conventional neuroscience and cardiology are reevaluated so that clear understanding of how nervous and cardiovascular systems work together can be obtained. Then, the general principles of diagnosis and treatment in traditional Chinese medicine from the integrative perspective of complex dynamic systems are proposed. Finally, mechanisms of acupuncture therapies for treating 14 different categories of disorders will be elucidated via the magneto-electric inductive effects of the meridian system. Copyright © 2013. Published by Elsevier B.V.

Kidney removal - slideshow

MedlinePlus

... this page: //medlineplus.gov/ency/presentations/100069.htm Kidney removal (nephrectomy) - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The kidneys are paired organs that lie posterior to the ...

[A cohort study of longer-term impact of melamine contaminated formula on infant health].

PubMed

Wang, Pei-xin; Li, Hong-tian; Wang, Lin-lin; Zhang, Long; Zhou, Yu-bo; Liu, Jian-meng

2013-10-15

To prospectively evaluate the health status of infants with exposure to melamine-contaminated milk formula prior to September 2008. The cohort study was conducted in an area close to the manufacturer of Sanlu dairy products. There were three groups (n = 47 each). In September 2008, the exposure group I included infants with exposure to melamine and a diagnosis of renal abnormalities, the exposure group IIhad exposure to melamine but there was no diagnosis of renal abnormalities and the non-exposure group had no exposure to melamine. The exposure II and non-exposure groups were matched with those of exposure group I by birthplaces, gender and date of birth ( ± 3 months). Kidney function tests (urea nitrogen, serum creatinine, uric acid, serum albumin, β2-microglobulin and cystatin C), liver function tests (alanine aminotransferase and aspartate aminotransferase), growth and development assessment and urinary system ultrasonography were implemented between November 2011 and June 2012. The analysis of covariance (least significant difference method) was performed to compare the differences of relevant variables among three groups. The urinary system ultrasonography showed that all abnormalities disappeared in exposure group I and all infants of another two groups had normal ultrasonography. There were statistically significant differences in serum uric acid and albumin of kidney function in exposure group I, exposure group II and non-exposure group ((344 ± 75) and (338 ± 98) and (282 ± 69) µmol/L , (47 ± 5) and (47 ± 6) and (43 ± 5) g/L, all P < 0.05) among three groups. However the differences in the remaining markers of kidney function, markers of liver function and Z scores of weight-for-age and height-for age were all statistically insignificant (all P > 0.05). Further pair-wise comparisons showed that the levels of serum uric acid and albumin in exposure group I were higher than those in non-exposure group (P = 0.001 and 0.010). And the levels of serum uric acid and albumin in exposure group II were also higher than those in non-exposure group (P = 0.003 and 0.005). All affected infants have recovered from kidney abnormalities. Early infant exposure to melamine-contaminated milk formula appears to have no obvious impact on liver function and growth. But its potential impact on kidney function should be further assessed.

The effects of environmental chemicals on renal function.

PubMed

Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

2015-10-01

The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease.

The effects of environmental chemicals on renal function

PubMed Central

Kataria, Anglina; Trasande, Leonardo; Trachtman, Howard

2015-01-01

The global incidence of chronic kidney disease (CKD) is increasing among individuals of all ages. Despite advances in proteomics, genomics and metabolomics, there remains a lack of safe and effective drugs to reverse or stabilize renal function in patients with glomerular or tubulointerstitial causes of CKD. Consequently, modifiable risk factors that are associated with a progressive decline in kidney function need to be identified. Numerous reports have documented the adverse effects that occur in response to graded exposure to a wide range of environmental chemicals. This Review summarizes the effects of such chemicals on four aspects of cardiorenal function: albuminuria, glomerular filtration rate, blood pressure and serum uric acid concentration. We focus on compounds that individuals are likely to be exposed to as a consequence of normal consumer activities or medical treatment, namely phthalates, bisphenol A, polyfluorinated alkyl acids, dioxins and furans, polycyclic aromatic hydrocarbons and polychlorinated biphenyls. Environmental exposure to these chemicals during everyday life could have adverse consequences on renal function and might contribute to progressive cumulative renal injury over a lifetime. Regulatory efforts should be made to limit individual exposure to environmental chemicals in an attempt to reduce the incidence of cardiorenal disease. PMID:26100504

Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure

PubMed Central

Wang, Jiali; Xu, Jiankun; Liu, Waiching; Li, Yangde; Qin, Ling

2016-01-01

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns. PMID:27210744

Biodegradable Magnesium (Mg) Implantation Does Not Impose Related Metabolic Disorders in Rats with Chronic Renal Failure

NASA Astrophysics Data System (ADS)

Wang, Jiali; Xu, Jiankun; Liu, Waiching; Li, Yangde; Qin, Ling

2016-05-01

Mg and its alloys have been considered as one of the most promising biodegradable medical devices, but it was still unclear whether hypermagnesemia involved health risks would occur in persons with kidney disease due to their deteriorated kidney function for Mg ions excretion from their body. In this study, we established a chronic renal failure (CRF) model in rats induced by adenine administration prior to Mg implantation, aiming to predict if CRF patients are suitable for the use of Mg implants. The results showed that Mg levels in serum, urine, feces and internal organs had no significant changes after Mg implantation for both normal and CRF rats. Biochemical indices detection and histopathological analysis in kidney, liver and heart tissue confirmed that Mg implants did not induce any extra damage in animals even with renal failure. Our study indicates that Mg based orthopaedic medical device may be considered for use in CRF patients without biosafety concerns.

Distinct effects of omeprazole and rabeprazole on the tacrolimus blood concentration in a kidney transplant recipient.

PubMed

Takahashi, Kazushige; Yano, Ikuko; Fukuhara, Yuga; Katsura, Toshiya; Takahashi, Takeshi; Ito, Noriyuki; Yamamoto, Shingo; Ogawa, Osamu; Inui, Ken-ichi

2007-12-01

Proton-pump inhibitors (PPIs, e.g. omeprazole and rabeprazole) are often administered to transplant patients as a treatment or prophylaxis for ulcers after surgery. Since tacrolimus and PPIs share the CYP3A4 system for metabolism, pharmacokinetic interactions are anticipated when they are administered simultaneously. We present a Japanese male patient who underwent a living-donor kidney transplantation having received tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression. The concentration/dose (C/D) ratio for tacrolimus was markedly higher during the period of treatment with omeprazole than ranitidine or rabeprazole. The results of liver functional tests were within the normal range during the use of these three antacid drugs. Since the higher C/D ratio for tacrolimus when omeprazole was being administered did not result from a decrease in the elimination of tacrolimus due to hepatic dysfunction, drug interaction between omeprazole and tacrolimus was strongly suspected. The present case indicates that rabeprazole can be used safely in place of omeprazole in kidney transplant recipients receiving tacrolimus.

Monolateral dual kidney transplantation from marginal donors.

PubMed

Veroux, M; Corona, D; Gagliano, M; Macarone, M; Sorbello, M; Giuffrida, G; Cutuli, M; Morello, G; Vizcarra, D; Paratore, A; Veroux, P

2007-01-01

Dual kidney transplantation (DKT) offers a safe way to face the organ shortage with good short-term and medium-term renal function. However, its application is limited by the longer operating time and the risk of surgical complication. This study reviews our results with DKT performed with an ipsilateral technique in terms of graft loss, graft and patient survival rates, and surgical complications. From January 2002 to March 2006, 23 patients underwent DKT through a monolateral Gibson incision with placement of both kidneys. One primary nonfunction occurred (4%). Delayed graft function was observed in 3 DKT (13.3%). Acute rejection rate was 4.3% (1 patient). All patients are alive at a mean follow-up of 28 months. One-year and 2-year graft survival rates were 100% and 96%, respectively. Mean serum creatinine level at 1-year posttransplantation was 1.3 mg/dL (range, 0.8-2.1 mg/dL). One DKG recipient lost 1 graft, retaining the second normal functioning graft due to ureteral necrosis. The mean hospital stay after transplantation was 15 days (range, 12-34 days). Monolateral placement in DKT offers the advantage of a single incision, minimizing the surgical risk. Tailored immunosuppression and careful selection of potential recipients, by excluding those with severe cardiopulmonary pathologies, could significantly improve both patient and graft survival in this group of patients.

Creatinine clearance test

MedlinePlus

Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... the body entirely by the kidneys. If kidney function is abnormal, creatinine level increases in the blood ...

In vivo antioxidant effect of aqueous root bark, stem bark and leaves extracts of Vitex doniana in CCl4 induced liver damage rats.

PubMed

Adetoro, Kadejo Olubukola; Bolanle, James Dorcas; Abdullahi, Sallau Balarebe; Ahmed, Ozigi Abdulrahaman

2013-05-01

The antioxidant effects of aqueous root bark, stem bark and leaves of Vitex doniana (V. doniana) were evaluated in carbon tetrachloride (CCl4) induced liver damage and non induced liver damage albino rats. A total of 60 albino rats (36 induced liver damage and 24 non induced liver damage) were assigned into liver damage and non liver damage groups of 6 rats in a group. The animals in the CCl4 induced liver damage groups, were induced by intraperitoneal injection with a single dose of CCl4 (148 mg·ml(-1)·kg(-1) body weight) as a 1:1 (v/v) solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark, stem bark and leaves extracts of V. doniana and vitamin E as standard drug (100 mg/kg body weighy per day) for 21 d, while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same dose. The administration of CCl4 was done once a week for a period of three weeks. The liver of CCl4 induced not treated group showed that the induction with CCl4, significantly (P<0.05) increased thiobarbituric acid reactive substance (TBARS) and significantly (P<0.05) decreased superoxide dismutase (SOD) and catalase (CAT). However there was no significant (P>0.05) difference between TBARS, SOD and CAT in the liver of the induced treated groups and normal control group. In the kidney, TBARS showed no significant (P>0.05) difference between the normal and the induced groups, SOD was significantly (P<0.05) reduced in the CCl4 group compared to standard drug and normal control groups, CAT was significantly (P<0.05) increased in root and vitamin E groups when compared to induced not treated group. The studies also showed that when the extracts were administered to normal animals, there was no significant (P>0.05) change in the liver and kidney level of TBARS, SOD and CAT compared with the normal control except in the kidney of animals treated with stem extract where TBARS was significantly (P<0.05) lowered compared to control group. The result of the present study suggests that application of V. doniana plant would play an important role in increasing the antioxidant effect and reducing the oxidative damage that formed both in liver and in kidney tissues. However stem bark has potential to improve renal function in normal rats.

Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys

PubMed Central

Lawrence, Melanie L.; Chang, C-Hong; Davies, Jamie A.

2015-01-01

Recent advances in renal tissue engineering have shown that dissociated, early renogenic tissue from the developing embryo can self-assemble into morphologically accurate kidney-like organs arranged around a central collecting duct tree. In order for such self-assembled kidneys to be useful therapeutically or as models for drug screening, it is necessary to demonstrate that they are functional. One of the main functional characteristics of mature kidneys is transport of organic anions and cations into and out of the proximal tubule. Here, we show that the transport function of embryonic kidneys allowed to develop in culture follows a developmental time-course that is comparable to embryonic kidney development in vivo. We also demonstrate that serially-reaggregated engineered kidneys can transport organic anions and cations through specific uptake and efflux channels. These results support the physiological relevance of kidneys grown in culture, a commonly used model for kidney development and research, and suggest that serially-reaggregated kidneys self-assembled from separated cells have some functional characteristics of intact kidneys. PMID:25766625

The Importance of Residual Kidney Function in Haemodialysis Patients.

PubMed

Kong, Jessica; Davies, Matthew; Mount, Peter

2018-06-19

In contrast to peritoneal dialysis, residual kidney function is commonly disregarded for haemodialysis patients, and not regularly monitored or taken into account in routine clinical care. This is despite evidence that higher levels of residual kidney function in haemodialysis patients associate with better outcomes including survival, total solute clearance, nutrition, inflammation, and fluid balance. This review aims to summarise the clinical effects of residual kidney function specifically in haemodialysis patients. Some level of residual kidney function is present in over 80% of patients at the time of dialysis initiation, and while this declines over time, up to 30% of patients on haemodialysis for 5 years still have a measurable level of native kidney function. There is little evidence on how best to preserve residual kidney function in haemodialysis patients, although it has been observed that intensive haemodialysis regimens in incident haemodialysis patients appear to accelerate residual kidney function decline. Residual kidney function is not commonly factored in to haemodialysis prescription and measures of adequacy, despite the fact that some guidelines such as KDOQI and European Best Practice Guidelines suggest that it is reasonable to do. This likely relates, at least in part, to perceived concerns regarding the inconvenience of timed urine collections, and to the complexity and lack of consensus regarding the methods for integrating the intermittent clearance of haemodialysis with the continuous clearance of native renal function. Further research is required into how best to maintain and maximise the benefits of residual kidney function in haemodialysis patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

PubMed

Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

2015-09-01

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation.

PubMed

Rassaf, Tienush; Balzer, Jan; Rammos, Christos; Zeus, Tobias; Hellhammer, Katharina; v Hall, Silke; Wagstaff, Rabea; Kelm, Malte

2015-04-01

In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous mitral valve repair (PMVR) with the MitraClip® system can be a therapeutic alternative to surgical valve repair. The influence of MitraClip® therapy on renal function and clinical outcome parameters is unknown. Sixty patients with severe MR underwent PMVR using the MitraClip® system in an open-label observational study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2-3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0-1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1-2) compared to severe (KDOQI 3-4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA-stadium, and 6-minute walk test. Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre-existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR. © 2014 Wiley Periodicals, Inc.

[Methodological aspects related to the determination of the relative renal function using 99mTC MAG3].

PubMed

Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G

2002-01-01

The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.

Kidney function monitoring and nonvitamin K oral anticoagulant dosage in atrial fibrillation.

PubMed

Andreu Cayuelas, Jose Manuel; Caro Martínez, Cesar; Flores Blanco, Pedro Jose; Elvira Ruiz, Gines; Albendin Iglesias, Helena; Cerezo Manchado, Juan Jose; Bailen Lorenzo, Jose Luis; Januzzi, James L; García Alberola, Arcadio; Manzano-Fernández, Sergio

2018-06-01

Clinical practice guidelines recommend regular kidney function monitoring in atrial fibrillation patients on nonvitamin K oral anticoagulants (NOAC); however, information regarding compliance with these recommendations in daily life conditions is scarce. We sought to determine the compliance with kidney function monitoring recommendations in nonvalvular atrial fibrillation (NVAF) patients starting NOAC and its implication on the appropriateness of NOAC dosage. This study involves the retrospective analysis of a multicentre registry including consecutive NVAF patients who started NOAC (n = 692). Drug dosage changes and serum creatinine determinations were recorded during 1-year follow-up. European Heart Rhythm Association criteria were used to define the appropriateness of kidney function monitoring as well as adequate NOAC dosage. During the follow-up (334 ± 89 days), the compliance with kidney function monitoring recommendations was 61% (n = 425). After multivariate adjustment, age (OR × year: 0.92 (CI 95%: 0.89-0.95) P < .001), creatinine clearance (OR × mL/min: 1.02 (CI 95%: 1.01-1.03) P < .001) and adequate NOAC dosage at baseline (OR: 1.54 (CI 95%: 1.06-2.23), P = .024) were independent predictors of appropriate kidney function monitoring. Compliance with kidney function monitoring recommendations was independently associated with change to appropriate NOAC dose after 1 year (OR: 2.80 (CI 95%: 1.01-7.80), P = .049). Noncompliance with kidney function monitoring recommendations is common in NVAF patients starting NOAC, especially in elderly patients with kidney dysfunction. Compliance with kidney function monitoring recommendations was associated with adequate NOAC dosage at 1-year follow-up. Further studies are warranted to evaluate the implication of kidney function monitoring on prognosis. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Resistive index for kidney evaluation in normal and diseased cats.

PubMed

Tipisca, Vlad; Murino, Carla; Cortese, Laura; Mennonna, Giuseppina; Auletta, Luigi; Vulpe, Vasile; Meomartino, Leonardo

2016-06-01

The objectives were to determine the resistive index (RI) in normal cats and in cats with various renal diseases, and to evaluate the effect of age on RI. The subjects were cats that had ultrasonography (US) of the urinary tract and RI measurement at our centre between January 2003 and April 2014. Based on clinical evaluation, biochemical and haematological tests, urinalysis and US, the cats were classified as healthy or diseased. RI measurements were made from the interlobar or arcuate arteries. Data were analysed for differences between the right and the left kidney, the two sexes, different age groups in healthy cats, and between healthy and diseased cats. A total of 116 cats (68 males, 48 females) were included: 24 healthy and 92 diseased. In the healthy cats, RI (mean ± SD) differed significantly (P = 0.02) between the right kidney (0.54 ± 0.07) and the left kidney (0.59 ± 0.08). For the left kidney, RI was significantly higher in cats with chronic kidney disease (0.73 ± 0.12) and acute kidney injury (0.72 ± 0.08) (P = 0.0008). For the right kidney, RI was significantly higher in cats with chronic kidney disease (0.72 ± 0.11), acute kidney injury (0.74 ± 0.08), polycystic kidney disease (0.77 ± 0.11) and renal tumour (0.74 ± 0.001) (P <0.0001). There was no significant effect on RI value in either kidney in terms of age or sex. RI could be considered a valuable diagnostic tool in cats, useful in the differential diagnosis of diffuse renal diseases. While it does not change with the age of the cat, ultrasonographers should be aware that RI may differ between the two kidneys. © ISFM and AAFP 2015.

Factors associated with renal function compensation after donor nephrectomy.

PubMed

Burballa, Carla; Crespo, Marta; Redondo-Pachón, Dolores; Pérez-Sáez, María José; Arias-Cabrales, Carlos; Mir, Marisa; Francés, Albert; Fumadó, Lluís; Cecchini, Lluís; Pascual, Julio

2018-05-14

Kidney transplant donors lose 50% of their renal mass after nephrectomy. The remaining kidney compensates for this loss and it is estimated that 70% of the baseline renal function prior to donation is recovered. Factors associated with post-donation renal compensation are not well understood. Retrospective study of 66 consecutive kidney donors (mean age 48.8 years, 74.2% women). We analysed the potential factors associated with the compensatory mechanisms of the remaining kidney by comparing donors according to their renal compensation rate (RCR) (Group A, infra-compensation [<70%]; Group B, normal compensation [>70%]). We compared Group A (n=38) and group B (n=28). Predictors for RCR>70% were higher baseline creatinine (A vs B: 0.73±0.14 vs 0.82±0.11; P=.03) and a lower baseline glomerular filtration rate (GFR), estimated both by MDRD-4 (A vs B: 97.7±18.8 vs 78.6±9.6ml/min; P<.001) and CKD-EPI (A vs B: 101.7±15 vs. 88.3±11.7ml/min; P≤.001). Age, gender, smoking, hypertension and GFR measured by Tc-DTPA did not show any correlation with the RCR. The multivariate analysis confirmed baseline estimated glomerular filtration rate (eGFR) to be a predictor of compensation: the higher the baseline eGFR, the lower the likelihood of >70% compensation (MDRD-4, OR=0.94 [95% CI 0.8-0.9], P=.01). The compensation rate decreased by 0.4% (P<.001) and 0.3% (P=.006) for every ml/min increase in baseline eGFR estimated by MDRD-4 and CKD-EPI, respectively. One year after living donor nephrectomy, the remaining kidney partially compensates baseline renal function. In our experience, baseline eGFR is inversely proportional to the one-year renal compensation rate. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

[Microalbuminuria in pediatric patients diagnosed with hemolytic uremic syndrome].

PubMed

Cubillos C, María Paz; Del Salas, Paulina; Zambrano, Pedro O

2015-01-01

Hemolytic uremic syndrome (HUS) is characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. It is the leading cause of acute kidney failure in children under 3 years of age. A variable number of patients develop proteinuria, hypertension, and chronic renal failure. To evaluate the renal involvement in pediatric patients diagnosed with HUS using the microalbumin/creatinine ratio. Descriptive concurrent cohort study that analyzed the presence of microalbuminuria in patients diagnosed with HUS between January 2001 and March 2012, who evolved without hypertension and normal renal function (clearance greater than 90ml/min using Schwartz formula). Demographic factors (age, sex), clinical presentation at time of diagnosis, use of antibiotics prior to admission, and need for renal replacement therapy were evaluated. Of the 24 patients studied, 54% were male. The mean age at diagnosis was two years. Peritoneal dialysis was required in 45%, and 33% developed persistent microalbuminuria. Antiproteinuric treatment was introduce in 4 patients, with good response. The mean follow-up was 6 years (range 6 months to 11 years). The serum creatinine returned to normal in all patients during follow up. The percentage of persistent microalbuminuria found in patients with a previous diagnosis of HUS was similar in our group to that described in the literature. Antiproteinuric treatment could delay kidney damage, but further multicenter prospective studies are necessary. Copyright © 2015. Publicado por Elsevier España, S.L.U.

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

PubMed

Oktar, Süleyman; Ilhan, Selçuk; Meydan, Sedat; Aydin, Mehmet; Yönden, Zafer; Gökçe, Ahmet

2010-01-01

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.

Cortical Bone Mechanical Properties Are Altered in an Animal Model of Progressive Chronic Kidney Disease

PubMed Central

Newman, Christopher L.; Moe, Sharon M.; Chen, Neal X.; Hammond, Max A.; Wallace, Joseph M.; Nyman, Jeffry S.; Allen, Matthew R.

2014-01-01

Chronic kidney disease (CKD), which leads tocortical bone loss and increasedporosity,increases therisk of fracture. Animal models have confirmed that these changes compromise whole bone mechanical properties. Estimates from whole bone testing suggest that material properties are negatively affected, though tissue-level assessmentshavenot been conducted. Therefore, the goal of the present study was to examine changes in cortical bone at different length scales using a rat model with theprogressive development of CKD. At 30 weeks of age (∼75% reduction in kidney function), skeletally mature male Cy/+ rats were compared to their normal littermates. Cortical bone material propertieswere assessed with reference point indentation (RPI), atomic force microscopy (AFM), Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from animals with CKD had higher (+18%) indentation distance increase and first cycle energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader distribution of elastic modulus values in CKD animals witha greater proportion of both higher and lower modulus values compared to normal controls. Yet, tissue composition, collagen morphology, and collagen cross-linking fail to account for these differences. Though the specific skeletal tissue alterations responsible for these mechanical differences remain unclear, these results indicate that cortical bone material properties are altered in these animals and may contribute to the increased fracture risk associated with CKD. PMID:24911162

Adipocytes play an etiological role in the podocytopathy of high-fat diet-fed rats.

PubMed

Chen, Jinn-Yang; Jian, Deng-Yuan; Lien, Chih-Chan; Lin, Yu-Ting; Ting, Ching-Heng; Chen, Luen-Kui; Hsu, Ting-Chia; Huang, Hsuan-Min; Wu, Yu-Ting; Kuan, Tse-Ting; Chao, Yu-Wen; Wu, Liang-Yi; Huang, Seng-Wong; Juan, Chi-Chang

2016-11-01

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy. © 2016 Society for Endocrinology.

9 CFR 311.3 - Hog cholera.

Code of Federal Regulations, 2011 CFR

2011-01-01

... kidneys and the lymph nodes which resemble lesions of hog cholera, they shall be regarded as those of hog... kidneys and lymph nodes of carcasses of hogs which appeared normal on ante-mortem inspection, further..., characteristic lesions of hog cholera are found in some organ or tissue in addition to those in the kidneys or in...

9 CFR 311.3 - Hog cholera.

Code of Federal Regulations, 2010 CFR

2010-01-01

... kidneys and the lymph nodes which resemble lesions of hog cholera, they shall be regarded as those of hog... kidneys and lymph nodes of carcasses of hogs which appeared normal on ante-mortem inspection, further..., characteristic lesions of hog cholera are found in some organ or tissue in addition to those in the kidneys or in...

Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury.

PubMed

Fani, Filippo; Regolisti, Giuseppe; Delsante, Marco; Cantaluppi, Vincenzo; Castellano, Giuseppe; Gesualdo, Loreto; Villa, Gianluca; Fiaccadori, Enrico

2018-06-01

Sepsis is a serious medical condition that can lead to multi-organ failure and shock, and it is associated with increased mortality. Acute kidney injury (AKI) is a frequent complication of sepsis in critically ill patients, and often requires renal replacement therapy. The pathophysiology of AKI in sepsis has not yet been fully defined. In the past, classic theories were mainly focused on systemic hemodynamic derangements, underscoring the key role of whole kidney hypoperfusion due to reduced renal blood flow. However, a growing body of experimental and clinical evidence now shows that, at least in the early phase of sepsis-associated AKI, renal blood flow is normal, or even increased. This could suggest a dissociation between renal blood flow and kidney function. In addition, the scant data available from kidney biopsies in human studies do not support diffuse acute tubular necrosis as the predominant lesion. Instead, increasing importance is now attributed to kidney damage resulting from a complex interaction between immunologic mechanisms, inflammatory cascade activation, and deranged coagulation pathways, leading to microvascular dysfunction, endothelial damage, leukocyte/platelet activation with the formation of micro-thrombi, epithelial tubular cell injury and dysfunction. Moreover, the same processes, through maladaptive responses leading to fibrosis acting from the very beginning, may set the stage for progression to chronic kidney disease in survivors from sepsis-associated AKI episodes. The aim of this narrative review is to summarize and discuss the latest evidence on the pathophysiological mechanisms involved in septic AKI, based on the most recent data from the literature.

Novel Proinflammatory Function of Renal Intercalated Cells.

PubMed

Breton, Sylvie; Brown, Dennis

2018-01-01

Serious and often fatal acute kidney injury (AKI) is frequently seen after major surgery, local and remote organ damage, and sepsis. It is associated with uncontrolled inflammation, and is usually diagnosed only after the kidneys have gone through significant and often irreversible damage. During our work involving another type of kidney disease that leads to acid-base disorders of the blood, we unexpectedly found high levels of a protein called the P2Y14 "purinergic" receptor, in specialized kidney epithelial cells called intercalated cells (ICs). These cells are responsible for maintaining whole body acid-base balance by regulating the secretion of excess protons into the urine, which normalizes blood pH. However, it turns out that the P2Y14 receptor in these cells responds to a molecule called uridine diphosphate (UDP)-glucose, which is a danger signal released by damaged cells anywhere in the body. When UDP-glucose reaches the kidney, it stimulates ICs to produce chemoattractant cytokines; this results in renal inflammation and contributes to the onset of AKI. Key Message: Thus, our work now points to ICs as key mediators of renal inflammation and AKI, following surgery and/or damage to remote organs, sepsis, and also local insults to the kidney itself. The link between the proton secreting ICs of the kidney and AKI is an example of how a fundamental research project with a defined aim, in this case understanding acid-base homeostasis, can lead to a novel observation that has unexpected but major implications in another area of human health. © 2018 The Author(s) Published by S. Karger AG, Basel.

Use of Self-Expanding Metallic Ureteral Stents in the Secondary Treatment of Ureteral Stenosis Following Kidney Transplantation.

PubMed

Xu, Guibin; Li, Xun; He, Yongzhong; Zhao, Haibo; Yang, Weiqing; Xie, Qingling

2015-10-01

To evaluate the safety and efficacy of self-expanding metal stents in the treatment of ureteral stenosis following kidney transplantation. Seven patients who developed benign stenosis after kidney transplantation were treated by a self-expanding metallic stent implantation from June 2007 to March 2014. All patients had undergone at least one open surgical procedure and one endourologic procedure for treatment of the stenosis. The extent of stenosis varied from 1.2 to 3.7 cm. Ultrasonography, urography, diuretic renography, and urine culture were performed every 3 months after stent insertion. Ureteroscopic examination was performed when needed. Stent placement was technically effective in all cases. The mean operative time was 37 minutes (range, 26-59 minutes). Lower urinary-tract symptoms and the ipsilateral flank pain were common early-stage complications and were greatly relieved after an average of 3 months. The mean follow-up duration was 38 months (range, 13-86 months), and no stent migration or fragmentation was observed. Urothelial hyperplasia occurred in only one patient and was effectively managed with a Double-J stent. Five patients had normal stable renal function; the remaining two had impaired renal function, including one patient with a preoperative renal failure who required dialysis at the end of the follow-up period (36 months). As an alternative to open surgery, implantation of a self-expanding metal stent is a safe and effective treatment for ureteral stenosis in patients who have undergone kidney transplantation.

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.

PubMed

Tanaka, Mari; Asada, Misako; Higashi, Atsuko Y; Nakamura, Jin; Oguchi, Akiko; Tomita, Mayumi; Yamada, Sachiko; Asada, Nariaki; Takase, Masayuki; Okuda, Tomohiko; Kawachi, Hiroshi; Economides, Aris N; Robertson, Elizabeth; Takahashi, Satoru; Sakurai, Takeshi; Goldschmeding, Roel; Muso, Eri; Fukatsu, Atsushi; Kita, Toru; Yanagita, Motoko

2010-03-01

The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

Enhanced hepatic and kidney cytochrome p-450 activities in nandrolone decanoate treated albino mice.

PubMed

Acharjee, B K; Mahanta, R

2009-04-01

Anabolic androgenic steroids are the xenobiotic substrates that are metabolized in the body by the protective enzyme systems. Mixed function oxygenase enzymes include a group of enzymes which play an essential role in the metabolism of a broad range of xenobiotics including endogenous and exogenous substrates. Cytochrome P-450, a member of mixed function oxygenase enzymes, plays an important role in oxidative metabolism of drugs and xenobiotics entering human body. Various anabolic steroids are found either to increase or decrease the activity of cytochrome P-450. However, effect of nandrolone decanoate, most commonly abused anabolic steroid, on cytochrome P-450 activity is still fragmentary. In the present study, albino mice were administered intramuscular 2.5 mg of nandrolone decanoate injection at 15 days interval. Cytochrome P-450 activity is determined by following the method of Omura and Sato (1964) in liver and kidney tissues of both normal and experimental groups upto 90 days. Investigation shows a significant (p <0.01) increase of cytochrome P-450 (nmol/mg) activity in liver tissue as compared to that of kidney tissues. A tissue specific and dose specific increase of cytochrome P-450 activity is observed. Mean cytochrome P-450 is found highest in liver tissue on 45(th) day whereas the activity in kidney tissue is noticed on 90(th) day of treatment. From the above observation, nandrolone decanoate can be suggested as a potent inducer of cytochrome P-450 activity like other anabolic steroids.

Renal Vascular Structure and Rarefaction

PubMed Central

Chade, Alejandro R.

2014-01-01

An intact microcirculation is vital for diffusion of oxygen and nutrients and for removal of toxins of every organ and system in the human body. The functional and/or anatomical loss of microvessels is known as rarefaction, which can compromise the normal organ function and have been suggested as a possible starting point of several diseases. The purpose of this overview is to discuss the potential underlying mechanisms leading to renal microvascular rarefaction, and the potential consequences on renal function and on the progression of renal damage. Although the kidney is a special organ that receives much more blood than its metabolic needs, experimental and clinical evidence indicates that renal microvascular rarefaction is associated to prevalent cardiovascular diseases such as diabetes, hypertension, and atherosclerosis, either as cause or consequence. On the other hand, emerging experimental evidence using progenitor cells or angiogenic cytokines supports the feasibility of therapeutic interventions capable of modifying the progressive nature of microvascular rarefaction in the kidney. This overview will also attempt to discuss the potential renoprotective mechanisms of the therapeutic targeting of the renal microcirculation. PMID:23720331

Optimal conditions of LDR to protect the kidney from diabetes: exposure to 12.5 mGy X-rays for 8 weeks efficiently protects the kidney from diabetes.

PubMed

Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

2014-05-08

We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day by suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Male C57BL/6J mice with type 1 diabetes were induced with multiple injections of low-dose streptozotocin. Diabetic mice received whole body X-irradiation at a dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th weeks of the study. Diabetes induced renal dysfunction is shown by the decreased creatinine and increased microalbumin in the urine. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best protective effect on the kidney of diabetic mice. Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

Serine proteases, inhibitors and receptors in renal fibrosis

PubMed Central

Eddy, Allison A.

2011-01-01

Summary Chronic kidney disease (CKD) is estimated to affect one in eight adults. Their kidney function progressively deteriorates as inflammatory and fibrotic processes damage nephrons. New therapies to prevent renal functional decline must build on basic research studies that identify critical cellular and molecular mediators. Plasminogen activator inhibitor-1 (PAI-1), a potent fibrosis-promoting glycoprotein, is one promising candidate. Absent from normal kidneys, PAI-1 is frequently expressed in injured kidneys. Studies in genetically engineered mice have demonstrated its potency as a pro-fibrotic molecule. Somewhat surprising, its ability to inhibit serine protease activity does not appear to be its primary pro-fibrotic effect in CKD. Both tissue-type plasminogen activator and plasminogen deficiency significantly reduced renal fibrosis severity after ureteral obstruction, while genetic urokinase (uPA) deficiency had no effect. PAI-1 expression is associated with enhanced recruitment of key cellular effectors of renal fibrosis – interstitial macrophages and myofibroblasts. The ability of PAI-1 to promote cell migration involves interactions with the low-density lipoprotein receptor-associate protein-1 and also complex interactions with uPA bound to its receptor (uPAR) and several leukocyte and matrix integrins that associate with uPAR as co-receptors. uPAR is expressed by several cell types in damaged kidneys, and studies in uPAR-deficient mice have shown that its serves a protective role. uPAR mediates additional anti-fibrotic effects - it interacts with specific co-receptors to degrade PAI-1 and extracellular collagens, and soluble uPAR has leukocyte chemoattractant properties. Molecular pathways activated by serine proteases and their inhibitor, PAI-1, are promising targets for future anti-fibrotic therapeutic agents. PMID:19350108

Qualitative and quantitative radiological analysis of non-contrast CT is a strong indicator in patients with acute pyelonephritis.

PubMed

El-Merhi, Fadi; Mohamad, May; Haydar, Ali; Naffaa, Lena; Nasr, Rami; Deeb, Ibrahim Al-Sheikh; Hamieh, Nadine; Tayara, Ziad; Saade, Charbel

2018-04-01

To evaluate the performance of non-contrast computed tomography (CT) by reporting the difference in attenuation between normal and inflamed renal parenchyma in patients clinically diagnosed with acute pyelonephritis (APN). This is a retrospective study concerned with non-contrast CT evaluation of 74 patients, admitted with a clinical diagnosis of APN and failed to respond to 48h antibiotics treatment. Mean attenuation values in Hounsfield units (HU) were measured in the upper, middle and lower segments of the inflamed and the normal kidney of the same patient. Independent t-test was performed for statistical analysis. Image evaluation included receiver operating characteristic (ROC), visual grading characteristic (VGC) and kappa analyses. The mean attenuation in the upper, middle and lower segments of the inflamed renal cortex was 32%, 25%, and 29% lower than the mean attenuation of the corresponding cortical segments of the contralateral normal kidney, respectively (p<0.01). The mean attenuation in the upper, middle, and lower segments of the inflamed renal medulla was 48%, 21%, and 30%, lower than the mean attenuation of the corresponding medullary segments of the contralateral normal kidney (p<0.02). The mean attenuation between the inflamed and non-inflamed renal cortex and medulla was 29% and 30% lower respectively (p<0.001). The AUCROC (p<0.001) analysis demonstrated significantly higher scores for pathology detection, irrespective of image quality, compared to clinical and laboratory results with an increased inter-reader agreement from poor to substantial. Non-contrast CT showed a significant decrease in the parenchymal density of the kidney affected with APN in comparison to the contralateral normal kidney of the same patient. This can be incorporated in the diagnostic criteria of APN in NCCT in the emergency setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative MRI of kidneys in renal disease.

PubMed

Kline, Timothy L; Edwards, Marie E; Garg, Ishan; Irazabal, Maria V; Korfiatis, Panagiotis; Harris, Peter C; King, Bernard F; Torres, Vicente E; Venkatesh, Sudhakar K; Erickson, Bradley J

2018-03-01

To evaluate the reproducibility and utility of quantitative magnetic resonance imaging (MRI) sequences for the assessment of kidneys in young adults with normal renal function (eGFR ranged from 90 to 130 mL/min/1.73 m 2 ) and patients with early renal disease (autosomal dominant polycystic kidney disease). This prospective case-control study was performed on ten normal young adults (18-30 years old) and ten age- and sex-matched patients with early renal parenchymal disease (autosomal dominant polycystic kidney disease). All subjects underwent a comprehensive kidney MRI protocol, including qualitative imaging: T1w, T2w, FIESTA, and quantitative imaging: 2D cine phase contrast of the renal arteries, and parenchymal diffusion weighted imaging (DWI), magnetization transfer imaging (MTI), blood oxygen level dependent (BOLD) imaging, and magnetic resonance elastography (MRE). The normal controls were imaged on two separate occasions ≥24 h apart (range 24-210 h) to assess reproducibility of the measurements. Quantitative MR imaging sequences were found to be reproducible. The mean ± SD absolute percent difference between quantitative parameters measured ≥24 h apart were: MTI-derived ratio = 4.5 ± 3.6%, DWI-derived apparent diffusion coefficient (ADC) = 6.5 ± 3.4%, BOLD-derived R2* = 7.4 ± 5.9%, and MRE-derived tissue stiffness = 7.6 ± 3.3%. Compared with controls, the ADPKD patient's non-cystic renal parenchyma (NCRP) had statistically significant differences with regard to quantitative parenchymal measures: lower MTI percent ratios (16.3 ± 4.4 vs. 23.8 ± 1.2, p < 0.05), higher ADCs (2.46 ± 0.20 vs. 2.18 ± 0.10 × 10 -3  mm 2 /s, p < 0.05), lower R2*s (14.9 ± 1.7 vs. 18.1 ± 1.6 s -1 , p < 0.05), and lower tissue stiffness (3.2 ± 0.3 vs. 3.8 ± 0.5 kPa, p < 0.05). Excellent reproducibility of the quantitative measurements was obtained in all cases. Significantly different quantitative MR parenchymal measurement parameters between ADPKD patients and normal controls were obtained by MT, DWI, BOLD, and MRE indicating the potential for detecting and following renal disease at an earlier stage than the conventional qualitative imaging techniques.

Outcome after prenatal diagnosis of congenital anomalies of the kidney and urinary tract.

PubMed

Nef, Samuel; Neuhaus, Thomas J; Spartà, Giuseppina; Weitz, Marcus; Buder, Kathrin; Wisser, Josef; Gobet, Rita; Willi, Ulrich; Laube, Guido F

2016-05-01

Congenital anomalies of the kidney and urinary tract are common findings on fetal ultrasound. The aim of this prospective observational study was to describe outcome and risk factors in 115 patients born 1995-2001. All prenatally diagnosed children were stratified into low- and high-risk group and followed postnatally clinically and by imaging at defined endpoints. Risk factors were evaluated using odds ratios. Neonatal diagnosis included pelvi-ureteric junction obstruction (n = 33), vesicoureteral reflux (n = 27), solitary mild pelvic dilatation (postnatal anteroposterior diameter 5-10 mm; n = 25), and further diagnosis as primary obstructive megaureter, unilateral multicystic dysplastic kidney, renal dysplasia and posterior urethral valves. In 38 children with prenatal isolated hydronephrosis, ultrasound normalized at median age of 1.2 years (range 0.1-9). Surgery was performed in 34 children at median age of 0.4 years (0.1-10.8). Persistent renal anomalies without surgery were present in 43 children and followed in 36 for median time of 16 years (12.2-18). Oligohydramnios and postnatal bilateral anomalies were significantly associated with surgery and impaired renal function. The majority of children had a favourable postnatal outcome, in particular children with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis. Oligohydramnios and postnatal bilateral anomalies were risk factors for non-favourable outcome. • In congenital anomalies of the kidney and urinary tract significantly poorer outcome is known in patients with bilateral renal hypoplasia or solitary kidney associated with posterior urethral valves. • Other factors as proteinuria and vesicoureteral reflux were associated with a higher risk of progression to chronic renal failure in these patients. What is New: • Unlike other studies giving us above-mentioned information, we included all patients with any kind of prenatally diagnosed congenital anomalies of the kidney and urinary tract. Our study shows long-term follow up (median 16 years, range 12.2-18 years), especially in patients not needing surgery, but with persistent anomalies. • During postnatal long-term follow up (median 2.2 years, range 0.1-18 years) one third each showed normalization, need of surgery or persistence of anomalies without need of surgery. Our study revealed a good prognosis in the majority of these children, in particular with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis, and revealed oligohydramnios and postnatal bilateral anomalies as risk factors for a non-favourable outcome, defined as need of surgery, persistent anomalies with impaired renal function, end stage renal failure or death.

Outcome of renal transplantation from a donor with polycystic kidney disease.

PubMed

Migone, Silvia Regina da Cruz; Bentes, Camila Guerreiro; Nunes, Débora Bacellar Cruz; Nunes, Juliana Bacellar Cruz; Pinon, Rodolfo Marcial da Silva; Silva, Thales Xavit Souza E

2016-01-01

Faced with the long waiting list for a kidney transplant, the use of donors with expanded criteria, like polycystic kidneys, is an option that aims to increase in a short time the supply of kidneys for transplant. This report of two cases of transplants performed from a donor with polycystic kidneys showed promising results, and the receptors evolved with good renal function, serum creatinine measurements within the normal range and with adequate glomerular filtration rate, evaluated over a period of four years post transplant. This fact confirms that the option of using donors with polycystic kidneys is safe and gives good results. Resumo Diante da longa fila de espera por um transplante renal, a utilização de doadores com critério expandido, a exemplo de rins policísticos, torna-se uma opção que visa aumentar a oferta de rins para transplante a curto prazo. O presente relato de dois casos de transplantes realizados a partir de um doador com rins policísticos apresentou resultado promissor, tendo os receptores evoluído com boa função renal, dosagens de creatinina sérica dentro da faixa de normalidade e com taxa de filtração glomerular adequada, avaliados num período de quatro anos pós-transplante. Isto confirma que a opção da utilização de doadores com rins policísticos é segura e apresenta bons resultados.

Molecular mechanisms of acid-base sensing by the kidney.

PubMed

Brown, Dennis; Wagner, Carsten A

2012-05-01

A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.

Morphological and functional renovascular changes as cause of resistant arterial hypertension - case report and literature review.

PubMed

Costache, Irina Iuliana; Costea, Claudia Florida; Fotea, Vasile; Rusu, Victor Laurian; Aursulesei, Viviana; Al Namat, Razan; Costache, Dan Alexandru; Dumitrescu, Nicoleta; Buzdugă, Cătălin Mihai; Dumitrescu, Gabriela Florenţa; Sava, Anca; Bogdănici, Camelia Margareta

2018-01-01

Resistant hypertension is defined by the inability to maintain within normal limits the blood pressure values of an individual, while he is under treatment with maximal tolerated doses of three antihypertensive agents. One of the most common types of resistant hypertension is renovascular hypertension (RVH), which is caused by the narrowing of the renal arteries, in the context of existing atherosclerotic plaques at that level. We are presenting the case of a hypertensive 56-year-old man admitted in the Clinic of Cardiology for a sudden rise of his blood pressure values, despite undergoing the scheduled treatment. The abdominal bruit discovered at the clinical examination and the hypokalemia, together with the mild impairment of the renal function raised the suspicion of an existing stenosis of the main renal blood vessels. Simple grey scale kidney ultrasound, Doppler ultrasound of the renal arteries, abdominal computed tomography and magnetic resonance angiography of the renal arteries, along with invasive renal angiography demonstrated a smaller right kidney, adrenal incidentalomas, reduced vascular diameter of renal arteries due to atheromatous lesions, thrombosis of the infrarenal segment of the abdominal aorta, and reduced vascular hemodynamics in the same territories. After the renal arteries revascularization and with minimal antihypertensive treatment, the patient had a favorable outcome, with normalization of blood pressure and renal function. Atherosclerotic disease causing renal artery stenosis is essential to be taken into consideration in the etiopathogenesis of resistant hypertension especially because RVH is a potentially curable disease.

Integrative genome-wide analysis of the determinants of RNA splicing in kidney renal clear cell carcinoma.

PubMed

Lehmann, Kjong-Van; Kahles, André; Kandoth, Cyriac; Lee, William; Schultz, Nikolaus; Stegle, Oliver; Rätsch, Gunnar

2015-01-01

We present a genome-wide analysis of splicing patterns of 282 kidney renal clear cell carcinoma patients in which we integrate data from whole-exome sequencing of tumor and normal samples, RNA-seq and copy number variation. We proposed a scoring mechanism to compare splicing patterns in tumor samples to normal samples in order to rank and detect tumor-specific isoforms that have a potential for new biomarkers. We identified a subset of genes that show introns only observable in tumor but not in normal samples, ENCODE and GEUVADIS samples. In order to improve our understanding of the underlying genetic mechanisms of splicing variation we performed a large-scale association analysis to find links between somatic or germline variants with alternative splicing events. We identified 915 cis- and trans-splicing quantitative trait loci (sQTL) associated with changes in splicing patterns. Some of these sQTL have previously been associated with being susceptibility loci for cancer and other diseases. Our analysis also allowed us to identify the function of several COSMIC variants showing significant association with changes in alternative splicing. This demonstrates the potential significance of variants affecting alternative splicing events and yields insights into the mechanisms related to an array of disease phenotypes.

Reduced Abd-B Hox function during kidney development results in lineage infidelity.

PubMed

Magella, Bliss; Mahoney, Robert; Adam, Mike; Potter, S Steven

2018-06-15

Hox genes can function as key drivers of segment identity, with Hox mutations in Drosophila often resulting in dramatic homeotic transformations. In addition, however, they can serve other essential functions. In mammals, the study of Hox gene roles in development is complicated by the presence of four Hox clusters with a total of 39 genes showing extensive functional overlap. In this study, in order to better understand shared core Hox functions, we examined kidney development in mice with frameshift mutations of multiple Abd-B type Hox genes. The resulting phenotypes included dramatically reduced branching morphogenesis of the ureteric bud, premature depletion of nephron progenitors and abnormal development of the stromal compartment. Most unexpected, however, we also observed a cellular level lineage infidelity in nephron segments. Scattered cells within the proximal tubules, for example, expressed genes normally expressed only in collecting ducts. Multiple combinations of inappropriate nephron segment specific marker expression were found. In some cases, cells within a tubule showed incorrect identity, while in other cases cells showed ambiguous character, with simultaneous expression of genes associated with more than one nephron segment. These results give evidence that Hox genes have an overlapping core function at the cellular level in driving and/or maintaining correct differentiation decisions. Copyright © 2018 Elsevier Inc. All rights reserved.

Statin Use during Hospitalization and Short-Term Mortality in Acute Ischaemic Stroke with Chronic Kidney Disease.

PubMed

Zhang, Xinmiao; Jing, Jing; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Pan, Yuesong; Meng, Xia; Wang, Yilong; Wang, Yongjun

2018-05-31

Statin use during hospitalization improves prognosis in patients with ischaemic stroke. However, it remains uncertain whether acute ischaemic stroke patients with chronic kidney disease (CKD) benefit from statin therapy. We investigated the effect of statin use during hospitalization in reducing short-term mortality of patients with ischaemic stroke and CKD. Data of first-ever ischaemic stroke patients without a history of pre-stroke statin treatment was derived from the China National Stroke Registry. Patients were stratified according to estimated glomerular filtration rate (eGFR): normal renal function (eGFR ≥90 mL/min/1.73 m2), mild CKD (eGFR 60-90 mL/min/1.73 m2) and moderate CKD (eGFR < 60 mL/min/1.73 m2). Multivariate logistic regression analysis was used to evaluate the association between statin use during hospitalization and all-cause mortality with different renal functions at 3-month follow-up. Among 5,951 patients included, 2,595 (43.6%) patients were on statin use during hospitalization after stroke (45.7% in patients with normal renal function, 42.0% in patients with mild CKD, and 39.0% in patients with moderate CKD). Compared with the non-statin group, statin use during hospitalization was associated with decreased all-cause mortality in patients with normal renal function (OR 0.65, 95% CI 0.43-0.97, p = 0.04), mild CKD (OR 0.59, 95% CI 0.38-0.91, p = 0.02) and moderate CKD (OR 0.41, 95% CI 0.23-0.75, p = 0.004) at 3-month follow-up. Statin use during hospitalization was associated with decreased 3-month mortality of ischaemic stroke patients with mild and moderate CKD. However, the conclusion should be confirmed in further studies with larger population, especially with moderate CKD. © 2018 S. Karger AG, Basel.

Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats

PubMed Central

Qinna, Nidal A; Badwan, Adnan A

2015-01-01

Streptozotocin (STZ) is currently the most used diabetogenic agent in testing insulin and new antidiabetic drugs in animals. Due to the toxic and disruptive nature of STZ on organs, apart from pancreas, involved in preserving the body’s normal glucose homeostasis, this study aims to reassess the action of STZ in inducing different glucose response states in diabetic rats while testing insulin. Diabetic Sprague-Dawley rats induced with STZ were classified according to their initial blood glucose levels into stages. The effect of randomizing rats in such a manner was investigated for the severity of interrupting normal liver, pancreas, and kidney functions. Pharmacokinetic and pharmacodynamic actions of subcutaneously injected insulin in diabetic and nondiabetic rats were compared. Interruption of glucose homeostasis by STZ was challenged by single and repeated administrations of injected insulin and oral glucose to diabetic rats. In diabetic rats with high glucose (451–750 mg/dL), noticeable changes were seen in the liver and kidney functions compared to rats with lower basal glucose levels. Increased serum levels of recombinant human insulin were clearly indicated by a significant increase in the calculated maximum serum concentration and area under the concentration–time curve. Reversion of serum glucose levels to normal levels pre- and postinsulin and oral glucose administrations to STZ diabetic rats were found to be variable. In conclusion, diabetic animals were more responsive to insulin than nondiabetic animals. STZ was capable of inducing different levels of normal glucose homeostasis disruption in rats. Both pharmacokinetic and pharmacodynamic actions of insulin were altered when different initial blood glucose levels of STZ diabetic rats were selected for testing. Such findings emphasize the importance of selecting predefined and unified glucose levels when using STZ as a diabetogenic agent in experimental protocols evaluating new antidiabetic agents and insulin delivery systems. PMID:26005328

Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).

PubMed

Mace, T F

1976-01-01

Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.

Consumption of Dietary Resistant Starch Partially Corrected the Growth Pattern Despite Hyperglycemia and Compromised Kidney Function in Streptozotocin-Induced Diabetic Rats.

PubMed

Koh, Gar Yee; Rowling, Matthew J; Schalinske, Kevin L; Grapentine, Kelly; Loo, Yi Ting

2016-10-12

We previously demonstrated that feeding of dietary resistant starch (RS) prior to the induction of diabetes delayed the progression of diabetic nephropathy and maintained vitamin D balance in streptozotocin (STZ)-induced type 1 diabetic (T1D) rats. Here, we examined the impact of RS on kidney function and vitamin D homeostasis following STZ injection. Male Sprague-Dawley rats were administered STZ and fed a standard diet containing cornstarch or 20, 10, or 5% RS for 4 weeks. T1D rats fed 10 and 20% RS, but not 5% RS, gained more weight than cornstarch-fed rats. Yet, renal health and glucose metabolism were not improved by RS. Our data suggest that RS normalized growth patterns in T1D rats after diabetes induction in a dose-dependent manner despite having no effect on blood glucose and vitamin D balances. Future interventions should focus on the preventative strategies with RS in T1D.

Long-term tolerance to kidney allografts in a preclinical canine model.

PubMed

Kuhr, Christian S; Yunusov, Murad; Sale, George; Loretz, Carol; Storb, Rainer

2007-08-27

Durable immune tolerance supporting vascularized allotransplantation offers the possibility of extending graft survival and avoiding harmful complications of chronic immunosuppression. Immune tolerance to renal allografts was induced in a preclinical canine model through engraftment of donor hematopoietic cells using a combination of low-dose total body irradiation and a short course of immunosuppression. Subsequently, donor renal allografts were transplanted accompanied by bilateral native nephrectomies. With 5-year follow up, we found normal renal function in all recipients and no histological evidence of acute or chronic rejection. This tolerance does not extend universally to donor skin grafts, however, with two of four animals rejecting delayed donor skin grafts. Hematopoietic chimerism produces durable and robust immune tolerance to kidney allografts, although incomplete tolerance to donor skin grafting.

Renal control of calcium, phosphate, and magnesium homeostasis.

PubMed

Blaine, Judith; Chonchol, Michel; Levi, Moshe

2015-07-07

Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys. Copyright © 2015 by the American Society of Nephrology.

Excess Podocyte Semaphorin-3A Leads to Glomerular Disease Involving PlexinA1–Nephrin Interaction

PubMed Central

Reidy, Kimberly J.; Aggarwal, Pardeep K.; Jimenez, Juan J.; Thomas, David B.; Veron, Delma; Tufro, Alda

2014-01-01

Semaphorin-3A (Sema3a), a guidance protein secreted by podocytes, is essential for normal kidney patterning and glomerular filtration barrier development. Here, we report that podocyte-specific Sema3a gain-of-function in adult mice leads to proteinuric glomerular disease involving the three layers of the glomerular filtration barrier. Reversibility of the glomerular phenotype upon removal of the transgene induction provided proof-of-principle of the cause-and-effect relationship between podocyte Sema3a excess and glomerular disease. Mechanistically, excess Sema3a induces dysregulation of nephrin, matrix metalloproteinase 9, and αvβ3 integrin in vivo. Sema3a cell-autonomously disrupts podocyte shape. We identified a novel direct interaction between the Sema3a signaling receptor plexinA1 and nephrin, linking extracellular Sema3a signals to the slit-diaphragm signaling complex. We conclude that Sema3a functions as an extracellular negative regulator of the structure and function of the glomerular filtration barrier in the adult kidney. Our findings demonstrate a crosstalk between Sema3a and nephrin signaling pathways that is functionally relevant both in vivo and in vitro. PMID:23954273

[Atherosclerotic renovascular hypertension: clinical findings and results of treatment over 15 years].

PubMed

Alfonzo, J P; Rosario, M N; Ugarte, C; Banasco, J; Fraxedas, R; Lahera, J

2003-01-01

The aim of this study was to present our clinical experience and results of different treatments in 83 atherosclerotic renovascular hypertensive patients treated in the last 15 years in the Instituto de nefrologia in Havana. Regardless of the type of treatment the patients were divided in two groups. Group I: 52 (62.3%) cases with standard oral hypotensive drugs alone and control of other cardiovascular risk factors (mean age 53 years old, sex m/f 50/50%, race white/no-white 75/25%, mean known hypertension follow-up 10.2 +/- 10 years, mean SBP 208 +/- 30 mmHg, mean DBP 123 +/- 17 mmHg, mean serum creatinina 1.62 mg/dl and increase peripheral plasma renin value in 61.6% of patients) and group II: 31 (37.7%) cases treated with revascularización procedures (PTA or surgery) or nephrectomy in selected patients (mean age 50 years old, sex m/f 68/32%, race white/no-white 16/84%, mean known hypertension follow-up 8.5 +/- 8.6 years, mean SBP 214 +/- 32 mmHg, mean DBP 1.31 +/- 16 mmHg, mean serum creatinina 1.85 mg/dl and increase peripheral plasma renin value 78.3% of patients). As end point for treatment results we selected: 1) hypertension cure or control, 2) evolution of the serum creatinine value and 3) kidney and patients survival. In those cases with a follow up for more than one year, in 82.9% the blood pressure was cure (21.4%) or controlled (61.4%). The proportion of failed was superior in group I (20.9%) than in group II (11.1%). All 18 cases treated by PTA with a follow up period longer than a year, blood pressure cure in 10 (55.6%), ameliorate in 5 (27.8%) and in 3 (16.6%) was unchanged (one patient lost of follow up). Nine patients were treated by surgery (3 revascularization and 6 nephrectomy), 5 (55.5%) cases cured and 4 (44.5%) ameliorate his blood pressure. Patients in group II maintain normal renal function in more cases than in group I (48.4% vs 30.8%). Both group had similar percentage of normal-normal + pathology-normal renal function (G I: 65.4% vs G II: 77.4%) p = 0.29. When chronic renal function was present at the base line study none of the revascularization procedure were superior. Patient and Kidney actuarial survivals rate do not showed superiority for any treatment procedure after 10 years of follow up. In atherosclerosis renovascular hypertension patients treated with intervention procedure had better BP control than those treated by hypotensive drugs. Not significant different between intervention procedures and drugs treatment in renal function preservation or in patient and kidney actuarial survival rate were found in these patients.

"Normal" Creatinine Levels Predict Persistent Kidney Injury and Waitlist Mortality in Outpatients with Cirrhosis.

PubMed

Cullaro, Giuseppe; Park, Meyeon; Lai, Jennifer C

2018-04-26

Acute kidney injury (AKI) is a critical determinant of outcomes in hospitalized patients with cirrhosis, but little is known of the impact of AKI in the outpatient setting. We analyzed 385 adult outpatients with cirrhosis listed for liver transplant at a single center; excluded were those with severe hepatic encephalopathy, hepatocellular carcinoma or on hemodialysis. Baseline serum creatinine (bCr) was defined as the lowest value recorded; peak creatinine (pCr) as the highest value; delta creatinine (ΔCr) as pCr minus bCr; AKI as a rise in sCR by ≥0.3 mg/dl from bCr; persistent kidney injury as elevation of sCR by ≥0.3 mg/dl from bCr on each subsequent clinical assessment. Among 385 outpatients with cirrhosis, bCr was ≤0.70, 0.70 - 0.97, and ≥0.97 mg/dL in 28%, 38%, and 34%, respectively. At a median follow-up of 16 (8 - 28) months, 143 (37%) had ≥1 AKI episode, which increased significantly by bCr group (24v.37v.48%, p=0.001). Of these 143 with AKI, 13% developed persistent kidney injury. A multivariable cox-regression analysis highlighted that bCr (HR 2.96) and ΔCr (HR 2.05) were the only factors independently associated with the development of persistent kidney injury [p<0.001]. The likelihood of death/delisting increased by bCr group (14v.19v.28%, p=0.03). A competing risk analysis demonstrated that each 1 mg/dL increase in bCr was independently associated with a 62% higher risk of death/delisting when accounting for transplantation and adjusting for confounders. In conclusion, not only is AKI common in outpatients with cirrhosis, but even "clinically normal" bCr levels significantly impact the risk of persistent kidney injury and waitlist mortality, supporting the need for a lower clinical threshold to initiate monitoring of renal function and implementation of renal-protective strategies. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl.

PubMed

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl

PubMed Central

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent. PMID:22787387

Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells

NASA Technical Reports Server (NTRS)

Nauli, Surya M.; Alenghat, Francis J.; Luo, Ying; Williams, Eric; Vassilev, Peter; Li, Xiaogang; Elia, Andrew E H.; Lu, Weining; Brown, Edward M.; Quinn, Stephen J.;

Colchicine intoxication in familial Mediterranean fever patients using clarithromycin for the treatment of Helicobacter pylori: a series of six patients.

PubMed

Haj Yahia, Soad; Ben Zvi, Ilan; Livneh, Avi

2018-01-01

Familial Mediterranean fever is a hereditary disease, characterized by recurrent episodes of inflammation. Colchicine, the mainstay of therapy, is administered continuously to all diagnosed FMF patients. Drug-drug interaction between colchicine and clarithromycin, resulting in colchicine intoxication, has been noted, mainly in association with gout and pneumonia. In FMF, this adverse event has been scarcely described. We present and characterize six patients with clarithromycin-related colchicine intoxication, aiming mainly at characterizing the FMF-specific features of this event. This study is a retrospective analysis, based on clinical and hospital records of all FMF patients admitted to one hospital during 2002-2015, for colchicine intoxication, precipitated by consumption of clarithromycin. All six patients were women who received colchicine for FMF, and clarithromycin for Helicobacter pylori (HBP) gastric infection. Their daily dosages of colchicine ranged from 1.5 to 2.5 mg. Two had mild FMF, two moderate and two severe diseases. Colchicine intoxication occurred despite intact kidney function and was characterized by abdominal pain, diarrhea, weakness, rhabdomyolysis, hepatitis, kidney impairment and bone marrow injury. It is concluded that clarithromycin-induced colchicine intoxication is a hazard in FMF. It occurs despite normal kidney function and standard colchicine dose and is associated with female sex and moderate to severe FMF.

Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

PubMed

Lauritzen, Didde; Andreassen, Bente Utoft; Heegaard, Niels Henrik H; Klinge, Lone Gabriels; Walsted, Anne-Mette; Neland, Mette; Nielsen, Rasmus Gaardskær; Wittenhagen, Per

2018-04-26

Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

Augmenting kidney mass at transplantation abrogates chronic renal allograft injury in rats.

PubMed

Mackenzie, H S; Azuma, H; Troy, J L; Rennke, H G; Tilney, N L; Brenner, B M

1996-03-01

Conventional renal transplantation, which substitutes a single allograft for two native kidneys, imposes an imbalance between nephron supply and the metabolic and excretory demands of the recipient. This discrepancy, which stimulates hyperfunction and hypertrophy of viable allograft nephrons, may be intensified by nephron loss through ischemia-reperfusion injury or acute rejection episodes occurring soon after transplantation. In other settings where less than 50% of the total renal mass remains, progressive glomerular injury develops through mechanisms associated with compensatory nephron hyperfiltration and hypertrophy. To determine whether responses to nephron loss contribute to chronic injury in renal allografts, nephron supply was restored to near-normal levels by transplanting Lewis recipients with two Fisher 344 kidneys (group 2A) compared with the standard single allograft F344 --> LEW rat model of late renal allograft failure (group 1A). At 20 weeks, indices of injury were observed in 1A but not 2A rats. These indices included proteinuria (1A: 45 +/- 13; 2A: 4.0 +/- 0.29 mg/day) and glomerulosclerosis (1A: 23 +/- 4.9%, 2A: 0.7 +/- 0.3%) (p < .05). Double-allograft recipients maintained near normal renal structure and function, whereas 1A rats showed evidence of compensatory hyperfiltration (single-nephron glomerular filtration rate of 63 +/- 10 versus 44 +/- 2.0 nl/min in 2A rats) and hypertrophy (mean glomerular volume of 2.64 +/- 0.15 versus 1.52 +/- 0.05 microns3 x 10(6) in 2A rats) (p < .05). Thus, we conclude that a major component of late allograft injury is attributable to processes associated with inadequate transplanted renal mass, a finding that has major implications for kidney transplantation biology and policy.

Role for transforming growth factor-beta1 in alport renal disease progression.

PubMed

Sayers, R; Kalluri, R; Rodgers, K D; Shield, C F; Meehan, D T; Cosgrove, D

1999-11-01

Alport syndrome results from mutations in either the alpha3(IV), alpha4(IV), or alpha5(IV) collagen genes. The disease is characterized by a progressive glomerulonephritis usually associated with a high-frequency sensorineural hearing loss. A mouse model for an autosomal form of Alport syndrome [collagen alpha3(IV) knockout] was produced and characterized. In this study, the model was exploited to demonstrate a potential role for transforming growth factor-beta1 (TGF-beta1) in Alport renal disease pathogenesis. Kidneys from normal and Alport mice, taken at different stages during the course of renal disease progression, were analyzed by Northern blot, in situ hybridization, and immunohistology for expression of TGF-beta1 and components of the extracellular matrix. Normal and Alport human kidney was examined for TGF-beta1 expression using RNase protection. The mRNAs encoding TGF-beta1 (in both mouse and human), entactin, fibronectin, and the collagen alpha1(IV) and alpha2(IV) chains were significantly induced in total kidney as a function of Alport renal disease progression. The induction of these specific mRNAs was observed in the glomerular podocytes of animals with advanced disease. Type IV collagen, laminin-1, and fibronectin were markedly elevated in the tubulointerstitium at 10 weeks, but not at 6 weeks, suggesting that elevated expression of specific mRNAs on Northern blots reflects events associated with tubulointerstitial fibrosis. The concomitant accumulation of mRNAs encoding TGF-beta1 and extracellular matrix components in the podocytes of diseased kidneys may reflect key events in Alport renal disease progression. These data suggest a role for TGF-beta1 in both glomerular and tubulointerstitial damage associated with Alport syndrome.

Sodium urine test

MedlinePlus

... or monitor many types of kidney diseases. Normal Results For adults, normal urine sodium values are generally ... meaning of your specific test result. What Abnormal Results Mean A higher than normal urine sodium level ...

Kidney function tests

MedlinePlus

Kidney function tests are common lab tests used to evaluate how well the kidneys are working. Such tests include: ... Oh MS, Briefel G. Evaluation of renal function, water, electrolytes ... and Management by Laboratory Methods . 23rd ed. Philadelphia, ...

Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutations: seek and you will find.

PubMed

Raffler, Gabriele; Zitt, Emanuel; Sprenger-Mähr, Hannelore; Nagel, Mato; Lhotta, Karl

2016-04-01

Uromodulin (UMOD)-associated kidney disease belongs to the group of autosomal dominant interstitial kidney diseases and is caused by mutations in the UMOD gene. Affected patients present with hyperuricemia, gout, and progressive renal failure. The disease is thought to be very rare but is probably underdiagnosed. Two index patients from two families with tubulointerstitial nephropathy and hyperuricemia were examined, including blood and urine chemistry, ultrasound, and mutation analysis of the UMOD gene. In addition, other available family members were studied. In a 46-year-old female patient with a fractional excretion of uric acid of 3 %, analysis of the UMOD gene revealed a p.W202S missense mutation. The same mutation was found in her 72-year-old father, who suffers from gout and end-stage renal disease. The second index patient was a 47-year-old female with chronic kidney disease and gout for more than 10 years. Her fractional uric acid excretion was 3.5 %. Genetic analysis identified a novel p.H250Q UMOD mutation that was also present in her 12-year-old son, who had normal renal function and uric acid levels. In patients suffering from chronic tubulointerstitial nephropathy, hyperuricemia, and a low fractional excretion of uric acid mutation, analysis of the UMOD gene should be performed to diagnose UMOD-associated kidney disease.

Incidence of kidney stones with topiramate treatment in pediatric patients.

PubMed

Mahmoud, Adel A H; Rizk, Tamer; El-Bakri, Nahid K; Riaz, Muhammad; Dannawi, Samer; Al Tannir, Mohamad

2011-10-01

We ran this study to assess the incidence of nephrolithiasis in a group of children on topiramate (TPM) therapy for at least 1 year. In this retrospective observational surveillance study, we reviewed the medical charts of children on TPM for at least 1 year seen at the pediatric neurology department during the period from 2005 to 2010 at King Fahad Medical City. Children with a normal baseline ultrasound report were included. Follow-up ultrasound reports after at least 1 year were collected. However, patients with any evidence of chronic illness or medications that may affect the kidney functions in addition to those who are not compliant with the prescribed dose were excluded. Family history of renal stones, symptoms suggestive of urologic disorders, and comorbidities were recorded. Medical charts of 96 children on TPM with a mean age of 6.9 (±3.8) years were reviewed; 52 (54.2%) of the children were male. The follow-up ultrasound showed that five children (5.2%) had developed kidney stones. The occurrence of kidney stones was found in four female patients (80%) versus one male (20%) (p > 0.05). Long-term use of TPM may result in increased incidence of asymptomatic kidney stones in the pediatric population. Hence, routine baseline and follow-up ultrasound of the urinary system should be recommended during the use of TPM in children. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Imaging regional renal function parameters using radionuclide tracers

NASA Astrophysics Data System (ADS)

Qiao, Yi

A compartmental model is given for evaluating kidney function accurately and noninvasively. This model is cast into a parallel multi-compartment structure and each pixel region (picture element) of kidneys is considered as a single kidney compartment. The loss of radionuclide tracers from the blood to the kidney and from the kidney to the bladder are modelled in great detail. Both the uptake function and the excretion function of the kidneys can be evaluated pixel by pixel, and regional diagnostic information on renal function is obtained. Gamma Camera image data are required by this model and a screening test based renal function measurement is provided. The regional blood background is subtracted from the kidney region of interest (ROI) and the kidney regional rate constants are estimated analytically using the Kuhn-Pucker multiplier method in convex programming by considering the input/output behavior of the kidney compartments. The detailed physiological model of the peripheral compartments of the system, which is not available for most radionuclide tracers, is not required in the determination of the kidney regional rate constants and the regional blood background factors within the kidney ROI. Moreover, the statistical significance of measurements is considered to assure the improved statistical properties of the estimated kidney rate constants. The relations between various renal function parameters and the kidney rate constants are established. Multiple renal function measurements can be found from the renal compartmental model. The blood radioactivity curve and the regional (or total) radiorenogram determining the regional (or total) summed behavior of the kidneys are obtained analytically with the consideration of the statistical significance of measurements using convex programming methods for a single peripheral compartment system. In addition, a new technique for the determination of 'initial conditions' in both the blood compartment and the kidney compartment is presented. The blood curve and the radiorenogram are analyzed in great detail and a physiological analysis from the radiorenogram is given. Applications of Kuhn-Tucker multiplier methods are illustrated for the renal compartmental model in the field of nuclear medicine. Conventional kinetic data analysis methods, the maximum likehood method, and the weighted integration method are investigated and used for comparisons. Moreover, the effect of the blood background subtraction is shown by using the gamma camera images in man. Several functional images are calculated and the functional imaging technique is applied for evaluating renal function in man quantitatively and visually and compared with comments from a physician.

Anatomy of the collecting system of lower pole of the kidney in patients with a single renal stone: a comparative study with individuals with normal kidneys.

PubMed

Zomorrodi, Afshar; Buhluli, Abulfazel; Fathi, Samad

2010-07-01

At least 5% of women and 12% of men during their lives will experience renal colic, at least once. Many theories have been suggested for the etiology of renal stones and variations in the anatomy of the collecting system have been suggested to have a role in stone formation. This study was conducted to examine the role of variation of lower pole collecting system in patients with lower pole kidney stone and compared the same in normal persons (kidney donors). Investigation for the anatomy of the lower pole of the kidney (angle between lower infundibulum and pelvis, length and diameter of the infundibulum and number and pattern distribution of calyces) was carried out using intravenous pyelogram (IVP) in 100 cases with urinary stone (study cases) and 400 persons with normal kidneys (control subjects). The study was a retrospective cross-sectional case control study. Results were analyzed by Mann-Whitney and independent sample chi square tests. The mean infundibulum-pelvic angle (IPA) in control subjects and in patients was 112.5 +/- 10.7 and 96.6 +/- 28.8, respectively. There was significant correlation between reduced angle and stone formation (P= < 0.001). The mean infundibulum-uretero-pelvic angle (IUPA) in control subjects and study cases was 53.5 +/- 12.7 and 42.6 +/- 13.4, respectively. There was significant correlation between decreased angle and stone formation (P = or < 0.001). The mean length of infundibulum of lower pole of kidney (IPIL) in controls and study patients was 22.5 +/- 4.1 and 27.5 +/- 7.7, respectively, which was statistically significant (P< 0.001). The mean number of calyces in lower pole of the kidney (LPCN) in controls and study patients was 2.6 +/- 0.6 and 3 +/- 0.9, respectively, which was statistically significant (P = or < 0.002). There was no significant correlation between distribution of calyces and stone formation (P= 0.366). Our study suggests that abnormal renal anatomy was more common in patients with lower pole kidney stone and should be considered a risk factor for forming lower pole kidney stone.

Gender and urinary pH affect melamine-associated kidney stone formation risk

PubMed Central

Lu, Xiuli; Wang, Jing; Cao, Xiangyu; Li, Mingxin; Xiao, Chunling; Yasui, Takahiro; Gao, Bing

2011-01-01

Objectives: Melamine was known as a new risk for kidney stone due to recent incidences of milk powder contamination in China. Here, we performed a retrospective study to investigate whether age, gender, and urinary pH affect melamine-associated kidney stone risk. Materials and Methods: A retrospective review was performed of 217 children aged less than 3 years old. All children had a history of being fed with Sanlu milk powder contaminated by melamine, and underwent a clinical screening on kidney stone in Shenyang from November 2008 to February 2009. A comparison with the Chi-square was conducted between 83 cases and 125 normal subjects. The difference between children's gender, age, and urinary pH was evaluated. Results: A total of 208 subjects, 136 boys and 72 girls, were included in the study. Significant association was observed between melamine-associated kidney stone risk and gender [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.11-3.74; P=0.02] and urinary pH (OR, 1.78; 95% CI, 1.01-3.11; P=0.04), respectively. Male children were at about twofold increased melamine-associated kidney stone risk compared with female children. Acidic urine showed about 1.78-fold increased melamine-associated kidney stone risk compared with normal urine. Conclusions: Our investigation results showed an association of gender and urinary pH with melamine-associated kidney stone formation risk. PMID:21747595

Kidney Replacement Therapy

MedlinePlus

... week, and lasts 3 to 5 hours each time. Blood travels through the artificial kidney, where waste products are ... eat a more normal diet and have more time for work and travel. Peritoneal dialysis is not for everyone, however. A ...

[Effect of fermented cordyceps powder and prednisone on the Notch2/Hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy].

PubMed

Huang, Ren-fa; Liang, Qun-qing; Cheng, Xin; Long, Yun; Wu, Jin-yu

2013-08-01

To investigate the effect of both fermented Cordyceps powder (CS) and prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy (AAAN). Totally 50 SD rats were randomly divided into 4 groups, i.e., the normal group, the model group, the CS group, the prednisone group, and the CS plus prednisone group, 10 in each group. The AAAN rat model was induced by intragastric administration of pure aristolochic acid A at the daily dose of 100 mg/kg for 3 days. Rats in the CS group were administered with CS at the daily dose of 5.0 g/kg by gastrogavage, while those in the prednisone group were administered with prednisone at the daily dose of 0.5 mg/kg. Rats in the CS plus prednisone group were treated by CS and prednisone. All treatment lasted for 3 successive weeks. Kidney functions [urea nitrogen (BUN) and serum creatinine (SCr)] were detected. The pathological changes of kidneys were observed by Hematoxylin-Eosin staining. The apoptosis of the renal tubular epithelial cells was detected by TUNEL. The protein expressions of Notch2 and Hes-1 in the renal tissue were detected by immunohistochemical assay and Western blot. Results of HE staining showed the structure in the nephridial tissue was regular in rats of the normal group. The renal tubular necrosis occurred in the rats of the model group. The pathological changes of kidneys were obviously improved in the CS group, the prednisone group, and the CS plus prednisone group. Compared with the normal group, levels of BUN and SCr, semi-quantitative score of the tubular interstitial tissue, ratio of apoptotic cells, and expressions of Notch2 and Hes-1 proteins significantly increased in the model group (P < 0.01). Compared with the model group, the aforesaid indices significantly decreased in the 3 treatment groups (P < 0.01). All indices decreased most obviously in the CS plus prednisone group (P < 0.05, P < 0. 01). Notch2/hes-1 signaling activation might be associated with apoptosis of renal tubular epithelial cells. Both CS and prednisone could play a nephroprotective role for AAAN. But CS plus prednisone could achieve the best effect. Inhabiting the Notch2/hes-1 signaling activation could be its nephroprotective mechanism.

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development.

PubMed

Bedell, Victoria M; Person, Anthony D; Larson, Jon D; McLoon, Anna; Balciunas, Darius; Clark, Karl J; Neff, Kevin I; Nelson, Katie E; Bill, Brent R; Schimmenti, Lisa A; Beiraghi, Soraya; Ekker, Stephen C

2012-02-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity.

Association of pulse wave velocity and pulse pressure with decline in kidney function.

PubMed

Kim, Chang Seong; Kim, Ha Yeon; Kang, Yong Un; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

2014-05-01

The association between arterial stiffness and decline in kidney function in patients with mild to moderate chronic kidney disease (CKD) is not well established. This study investigated whether pulse wave velocity (PWV) and pulse pressure (PP) are independently associated with glomerular filtration rate (GFR) and rapid decline in kidney function in early CKD. Carotid femoral PWV (cfPWV), brachial-ankle PWV (baPWV), and PP were measured in a cohort of 913 patients (mean age, 63±10 years; baseline estimated GFR, 84±18 mL/min/1.73 m(2) ). Estimated GFR was measured at baseline and at follow-up. The renal outcome examined was rapid decline in kidney function (estimated GFR loss, >3 mL/min/1.73 m(2) per year). The median follow-up duration was 3.2 years. Multivariable adjusted linear regression model indicated that arterial PWV (both cfPWV and baPWV) and PP increased as estimated GFR declined, but neither was associated with kidney function after adjustment for various covariates. Multivariable logistic regression analysis found that cfPWV and baPWV were not associated with rapid decline in kidney function (odds ratio [OR], 1.39, 95% confidence interval [CI], 0.41-4.65; OR, 2.51, 95% CI, 0.66-9.46, respectively), but PP was (OR, 1.22, 95% CI, 1.01-1.48; P=.045). Arterial stiffness assessed using cfPWV and baPWV was not correlated with lower estimated GFR and rapid decline in kidney function after adjustment for various confounders. Thus, PP is an independent risk factor for rapid decline in kidney function in populations with relatively preserved kidney function (estimated GFR ≥30 mL/min/1.73 m(2) ). ©2014 Wiley Periodicals, Inc.

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant in persons with reduced kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Pure Ethiodized Oil-based Transcatheter Ablative Therapy in Normal Rabbit Kidneys and Kidneys Inoculated with VX-2 Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konya, Andras, E-mail: akonya@mdanderson.org; Stephens, L. Clifton; Wright, Kenneth C.

2011-10-15

Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol-Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization andmore » coil placement followed 7 days later (group 2, n = 6) or 11-14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean {+-} standard deviation) 0.47 {+-} 0.03, 0.53 {+-} 0.02, and 0.56 {+-} 0.04 ml of pure Ethiodol, followed by 0.47 {+-} 0.05, 0.42 {+-} 0.03, and 0.38 {+-} 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.« less

Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier Inflammatory Burden Than Kidneys From Standard Criteria Donors

PubMed Central

Mazeti-Felicio, Camila M.; Caldas, Heloisa C.; Fernandes-Charpiot, Ida M.M.; Dezotti, Camila Z.; Baptista, Maria A.S.F.; Abbud-Filho, Mario

2017-01-01

Background Donors after brain death develop a systemic proinflammatory state that may predispose the kidneys to injury after transplantation. Because it is not known whether this inflammatory environment similarly affects the kidneys from expanded criteria donor (ECD) and standard criteria donors (SCD), we sought to evaluate differences in the gene expression of inflammatory cytokines in preimplantation biopsies (PIBx) from ECD and SCD kidneys. Methods Cytokines gene expression was measured in 80 PIBx (SCD, 52; ECD, 28) and associated with donor variables. Results Normal histology and chronic histological lesions were not different between both types of kidneys. ECD kidneys showed significant increase in the transcripts of MCP-1, RANTES, TGF-β1, and IL-10 when compared with SCD. Kidneys presenting normal histology had similar inflammatory profile except by a higher expression of RANTES observed in ECD (P = 0.04). Interstitial fibrosis and tubular atrophy (interstitial fibrosis and tubular atrophy ≥ 1) were associated with higher expression of TGF-β1, RANTES, and IL-10 in ECD compared with SCD kidneys. Cold ischemia time of 24 hours or longer was significantly associated with upregulation of FOXP3, MCP-1, RANTES, and IL10, whereas longer duration of donor hospitalization significantly increased gene expression of all markers. High FOXP3 expression was also associated with lower level of serum creatinine at 1 year. Donor age was not associated with any of the transcripts studied. Conclusions PIBx of ECD exhibit a higher gene expression of inflammatory cytokines when compared with SCD kidneys. This molecular profile may be a specific ECD kidney response to brain death and may help to predict the posttransplant outcomes of ECD recipients. PMID:28706983

Chronic allograft nephropathy: expression and localization of PAI-1 and PPAR-gamma.

PubMed

Revelo, Monica P; Federspiel, Charles; Helderman, Harold; Fogo, Agnes B

2005-12-01

Chronic allograft nephropathy (CAN) is a major cause of loss of renal allografts. Mechanisms postulated to be involved include sequelae of rejection, warm ischaemia time, drug toxicity, ongoing hypertension and dyslipidaemia. Plasminogen activator inhibitor-1 (PAI-1) is implicated not only in thrombosis, but also in fibrosis, by inhibiting matrix degradation, and is expressed in renal parenchymal cells as well as in macrophages. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the steroid receptor superfamily, and plays a major beneficial role in lipid regulation, insulin sensitivity and macrophage function, factors that may play a role in CAN. We therefore studied the expression of these molecules in CAN. All renal biopsy/nephrectomy files from Vanderbilt and Nashville VAMC from a 6 year period were reviewed to identify all renal transplant biopsies or nephrectomies more than 6 months after transplant with CAN. CAN was defined as fibrosis in the graft, vascular, interstitial or glomerular. All cases were scored for severity of fibrosis in vasculature (0-3 scale), glomeruli (% affected with either segmental and/or global sclerosis) and interstitial fibrosis (% of sample affected). PAI-1 and PPAR-gamma immunostaining was assessed on a 0-3 scale in glomeruli, vessels and tubules. Eighty-two patients with a total of 106 samples met entry criteria. The population consisted of 59 Caucasians and 23 African-Americans; 49 males, 33 females with average age 37.9+/-1.7 years. Average time after transplant at time of biopsy was 60.5+/-4.9 months (range 7-229). Glomerulosclerosis extent in CAN was on average 26.5+/-2.4% compared with 3.6+/-1.2% in normal control kidneys from native kidney cancer nephrectomies and 0% in transplanted kidney biopsies from patients obtained > or =6 months after transplantation without CAN. Native control kidneys showed mild interstitial fibrosis (8.0+/-1.2%), whereas transplant controls showed very minimal fibrosis (2.0+/-2.0%). Interstitial fibrosis in CAN kidneys was on average 47.9+/-2.4%. Glomerular PAI-1 and PPAR-gamma staining scores were markedly increased in CAN (1.8+/-0.1, 2.3+/-0.1, respectively) compared with normal control kidneys from native kidney cancer nephrectomies (PAI-1 0.2+/-0.2 and PPAR-gamma 0.4+/-0.2, P<0.001) and transplanted kidney biopsies from patients obtained > or =6 months after transplantation without CAN (PAI-1 0 and PPAR-gamma 0, P<0.001). Tubular PAI-1 and PPAR-gamma staining scores were 1.9+/-0.1 and 1.9+/-0.1, respectively, and also increased over both native and transplant kidney controls (0.8+/-0.2 for both categories for PAI-1, 1.2+/-0.2 for both categories for PPAR-gamma, respectively). Vascular sclerosis in CAN was 1.0+/-0.1 with increased PAI-1 and PPAR-gamma scores (1.7+/-0.1, 1.2+/-0.1, respectively) compared with controls. Infiltrating macrophages were increased in CAN, and were positive for both PAI-1 and PPAR-gamma. Biopsies with less sclerosis overall showed a trend for less PAI-1 and PPAR-gamma staining. PAI-1 and PPAR-gamma are both increased in CAN compared with non-scarred native or transplant control kidneys. We speculate that altered matrix metabolism and macrophage function might be involved in the development of CAN.

Chronic kidney disease alters lipid trafficking and inflammatory responses in macrophages: effects of liver X receptor agonism.

PubMed

Kaseda, Ryohei; Tsuchida, Yohei; Yang, Hai-Chun; Yancey, Patricia G; Zhong, Jianyong; Tao, Huan; Bian, Aihua; Fogo, Agnes B; Linton, Mac Rae F; Fazio, Sergio; Ikizler, Talat Alp; Kon, Valentina

2018-01-27

Our aim was to evaluate lipid trafficking and inflammatory response of macrophages exposed to lipoproteins from subjects with moderate to severe chronic kidney disease (CKD), and to investigate the potential benefits of activating cellular cholesterol transporters via liver X receptor (LXR) agonism. LDL and HDL were isolated by sequential density gradient ultracentrifugation of plasma from patients with stage 3-4 CKD and individuals without kidney disease (HDL CKD and HDL Cont , respectively). Uptake of LDL, cholesterol efflux to HDL, and cellular inflammatory responses were assessed in human THP-1 cells. HDL effects on inflammatory markers (MCP-1, TNF-α, IL-1β), Toll-like receptors-2 (TLR-2) and - 4 (TLR-4), ATP-binding cassette class A transporter (ABCA1), NF-κB, extracellular signal regulated protein kinases 1/2 (ERK1/2) were assessed by RT-PCR and western blot before and after in vitro treatment with an LXR agonist. There was no difference in macrophage uptake of LDL isolated from CKD versus controls. By contrast, HD CKD was significantly less effective than HDL Cont in accepting cholesterol from cholesterol-enriched macrophages (median 20.8% [IQR 16.1-23.7] vs control (26.5% [IQR 19.6-28.5]; p = 0.008). LXR agonist upregulated ABCA1 expression and increased cholesterol efflux to HDL of both normal and CKD subjects, although the latter continued to show lower efflux capacity. HDL CKD increased macrophage cytokine response (TNF-α, MCP-1, IL-1β, and NF-κB) versus HDL Cont . The heightened cytokine response to HDL CKD was further amplified in cells treated with LXR agonist. The LXR-augmentation of inflammation was associated with increased TLR-2 and TLR-4 and ERK1/2. Moderate to severe impairment in kidney function promotes foam cell formation that reflects impairment in cholesterol acceptor function of HDL CKD . Activation of cellular cholesterol transporters by LXR agonism improves but does not normalize efflux to HDL CKD . However, LXR agonism actually increases the pro-inflammatory effects of HDL CKD through activation of TLRs and ERK1/2 pathways.

[Banff score changes in kidneys from marginal donors].

PubMed

Borda, Bernadett; Szederkényi, Edit; Ottlakán, Aurél; Kemény, Éva; Szabó, Viktor; Hódi, Zoltán; Lázár, György

2016-02-21

Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients.

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

PubMed

Mazidi, Moshen; Rezaie, Peyman; Covic, Adriac; Malyszko, Jolanta; Rysz, Jacek; Kengne, Andre Pascal; Banach, Maciej

2017-10-06

Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p <0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

Constructing kidney-like tissues from cells based on programs for organ development: toward a method of in vitro tissue engineering of the kidney.

PubMed

Rosines, Eran; Johkura, Kohei; Zhang, Xing; Schmidt, Heidi J; Decambre, Marvalyn; Bush, Kevin T; Nigam, Sanjay K

2010-08-01

The plausibility of constructing vascularized three-dimensional (3D) kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct (WD), and the metanephric mesenchyme (MM). We found that isolated MMs were capable of inducing branching morphogenesis of the WD (an epithelial tube) in recombination cultures; suggesting that the isolated MM retains inductive capacity for WD-derived epithelial tubule cells other than those from the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells from UB and mouse inner medullary collecting duct cell (IMCD) lines, which are ultimately of WD origin, were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (IMCD). This supports the view that the collecting system can be constructed from certain epithelial cells (those ultimately of WD origin) when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced factors that stimulate UB branching morphogenesis, whereas another, rat inducible metanephric mesenchyme (RIMM-18), supported WD budding as a feeder layer. This indicates that some MM functions can be recapitulated by cells. Although engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, we addressed the issue of optimal macro- and micro-patterning of kidney-like tissue, which might be necessary for function of an organ assembled using a tissue engineering approach. To identify suitable conditions, 3D reconstructions of HoxB7-green fluorescent protein mouse rudiments (E12) cultured on a filter or suspended in a collagen gel (type I or type IV) revealed that type IV collagen 3D culture supports the deepest tissue growth (600 +/- 8 microm) and the largest kidney volume (0.22 +/- 0.02 mm(3)), and enabled the development of an umbrella-shaped collecting system such as occurs in vivo. Taken together with prior work (Rosines et al., 2007; Steer et al., 2002), these results support the plausibility of a developmental strategy for constructing and propagating vascularized 3D kidney-like tissues from recombinations of cultured renal progenitor cells and/or primordial tissue.

Physiology and pathophysiology of ClC-K/barttin channels.

PubMed

Fahlke, Christoph; Fischer, Martin

2010-01-01

ClC-K channels form a subgroup of anion channels within the ClC family of anion transport proteins. They are expressed predominantly in the kidney and in the inner ear, and are necessary for NaCl resorption in the loop of Henle and for K+ secretion by the stria vascularis. Subcellular distribution as well as the function of these channels are tightly regulated by an accessory subunit, barttin. Barttin improves the stability of ClC-K channel protein, stimulates the exit from the endoplasmic reticulum and insertion into the plasma membrane and changes its function by modifying voltage-dependent gating processes. The importance of ClC-K/barttin channels is highlighted by several genetic diseases. Dysfunctions of ClC-K channels result in Bartter syndrome, an inherited human condition characterized by impaired urinary concentration. Mutations in the gene encoding barttin, BSND, affect the urinary concentration as well as the sensory function of the inner ear. Surprisingly, there is one BSND mutation that causes deafness without affecting renal function, indicating that kidney function tolerates a reduction of anion channel activity that is not sufficient to support normal signal transduction in inner hair cells. This review summarizes recent work on molecular mechanisms, physiology, and pathophysiology of ClC-K/barttin channels.

A decreased soluble Klotho level with normal eGFR, FGF23, serum phosphate, and FEP in an ADPKD patient with enlarged kidneys due to multiple cysts.

PubMed

Kanai, Takahiro; Shiizaki, Kazuhiro; Betsui, Hiroyuki; Aoyagi, Jun; Yamagata, Takanori

2018-05-16

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR. It remains unclear whether the decrease in the Klotho level precedes the increase in FGF23. Here, we present an ADPKD patient with enlarged kidneys due to multiple cysts who had a decreased soluble Klotho level but a normal eGFR and a normal FGF23 level. The patient's serum phosphate level was normal, as was the fractional excretion of phosphate (FEP). This appears to be the first reported case to show a decreased soluble Klotho level plus normal eGFR, FGF23, and FEP. These results suggest that Klotho decreases before FGF23 increases and further suggest that Klotho is not required to maintain normal serum phosphate levels in ADPKD if the FEP and serum phosphate levels are normal.

Increased degradation of ATP is driven by memory regulatory T cells in kidney transplantation tolerance.

PubMed

Durand, Maxim; Dubois, Florian; Dejou, Cécile; Durand, Eugénie; Danger, Richard; Chesneau, Mélanie; Brosseau, Carole; Guerif, Pierrick; Soulillou, Jean-Paul; Degauque, Nicolas; Eliaou, Jean-François; Giral, Magali; Bonnefoy, Nathalie; Brouard, Sophie

2018-05-01

Regulatory T cells were recently proposed as the central actor in operational tolerance after renal transplantation. Tolerant patients harbor increased FoxP3hi memory Treg frequency and increased demethylation in the Foxp3 Treg-specific demethylated region when compared to stable kidney recipients and exhibit greater memory Treg suppressive capacities and higher expression of the ectonucleotidase CD39. However, in this particular and unique situation the mechanisms of action of Tregs were not identified. Thus, we analyzed the ability of memory Tregs to degrade extracellular ATP in tolerant patients, healthy volunteers, and patients with stable graft function under immunosuppression and determined the role of immunosuppressive drugs on this process. The conserved proportion of memory Tregs leads to the establishment of a pro-tolerogenic balance in operationally tolerant patients. Memory Tregs in tolerant patients display normal capacity to degrade extracellular ATP/ADP. In contrast, memory Tregs from patients with stable graft function do not have this ability. Finally, in vitro, immunosuppressive drugs may favor the lower proportion of memory Tregs in stable patients, but they have no effect on CD39-dependent ATP degradation and do not explain memory Treg lack of extracellular ATP/ADP degradation ability. Thus, intrinsic active regulatory mechanisms may act long after immunosuppressive drug arrest in operationally tolerant patients and may contribute to kidney allograft tolerance via the maintenance of CD39 Treg function. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

What Is Atherosclerosis?

MedlinePlus

... builds up in the renal arteries. These arteries supply oxygen-rich blood to your kidneys. Over time, chronic kidney disease causes a slow loss of kidney function. The main function of the kidneys is to remove waste and extra water from the body. Overview The cause of atherosclerosis ...

Prion Protein Promotes Kidney Iron Uptake via Its Ferrireductase Activity*

PubMed Central

Haldar, Swati; Tripathi, Ajai; Qian, Juan; Beserra, Amber; Suda, Srinivas; McElwee, Matthew; Turner, Jerrold; Hopfer, Ulrich; Singh, Neena

2015-01-01

Brain iron-dyshomeostasis is an important cause of neurotoxicity in prion disorders, a group of neurodegenerative conditions associated with the conversion of prion protein (PrPC) from its normal conformation to an aggregated, PrP-scrapie (PrPSc) isoform. Alteration of iron homeostasis is believed to result from impaired function of PrPC in neuronal iron uptake via its ferrireductase activity. However, unequivocal evidence supporting the ferrireductase activity of PrPC is lacking. Kidney provides a relevant model for this evaluation because PrPC is expressed in the kidney, and ∼370 μg of iron are reabsorbed daily from the glomerular filtrate by kidney proximal tubule cells (PT), requiring ferrireductase activity. Here, we report that PrPC promotes the uptake of transferrin (Tf) and non-Tf-bound iron (NTBI) by the kidney in vivo and mainly NTBI by PT cells in vitro. Thus, uptake of 59Fe administered by gastric gavage, intravenously, or intraperitoneally was significantly lower in PrP-knock-out (PrP−/−) mouse kidney relative to PrP+/+ controls. Selective in vivo radiolabeling of plasma NTBI with 59Fe revealed similar results. Expression of exogenous PrPC in immortalized PT cells showed localization on the plasma membrane and intracellular vesicles and increased transepithelial transport of 59Fe-NTBI and to a smaller extent 59Fe-Tf from the apical to the basolateral domain. Notably, the ferrireductase-deficient mutant of PrP (PrPΔ51–89) lacked this activity. Furthermore, excess NTBI and hemin caused aggregation of PrPC to a detergent-insoluble form, limiting iron uptake. Together, these observations suggest that PrPC promotes retrieval of iron from the glomerular filtrate via its ferrireductase activity and modulates kidney iron metabolism. PMID:25572394

Effects of Coffee Intake on Incident Chronic Kidney Disease: Community-Based Prospective Cohort Study.

PubMed

Jhee, Jong Hyun; Nam, Ki Heon; An, Seong Yeong; Cha, Min-Uk; Lee, Misol; Park, Seohyun; Kim, Hyoungnae; Yun, Hae-Ryong; Kee, Youn Kyung; Park, Jung Tak; Chang, Tae-Ik; Kang, Ea Wha; Yoo, Tae-Hyun; Kang, Shin-Wook; Han, Seung Hyeok

2018-06-12

Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population. We analyzed 8717 subjects with normal renal function recruited from the KoGES cohort. Based on food frequency questionnaire, coffee consumption was categorized into five groups: 0/week, <1 cup/week, 1-6 cups/week, 1 cup/day, and ≥2 cups/day. The primary outcome was incident chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 . The mean age of study subjects was 52.0 (8.8) years and 47.8% were male. Among the subjects, 52.8% were daily coffee consumers. During a mean follow-up of 11.3 [5.9-11.5] years, 9.5% of participants developed chronic kidney disease. The incident chronic kidney disease occurred less in daily coffee consumers. Unadjusted HRs was significantly lower in daily coffee consumers. In multivariable Cox model even after adjustment of blood pressure, hypertension, cardiovascular disease, diabetes, and amount of daily intake for caffeine-containing foods such as tea and chocolate, coffee consumers with 1 cup/day (HR, 0.76; 95% CI, 0.63-0.92) and ≥2 cups/day (HR, 0.80; 95% CI, 0.65-0.98) were associated with a lower risk of chronic kidney disease development than non-drinkers. Time-averaged and time-varying Cox models yielded similar results. The rates of decline in eGFR were lower in daily coffee consumers. Our findings suggest that daily coffee intake is associated with decreased risk of the development of CKD. Copyright © 2018. Published by Elsevier Inc.

(Re)Building a Kidney

PubMed Central

Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

2017-01-01

(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

Sulfur compounds in therapy: Radiation-protective agents, amphetamines, and mucopolysaccharide sulfation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foye, W.O.

1992-09-01

Sulfur-containing compounds have been used in the search for whole-body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS wasmore » determined by electrophoresis. Whole-body radiation-protective agents with a high degree of protection against lethal doses of gamma-radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects.« less

Predicting Outcome in Patients with Anti-GBM Glomerulonephritis.

PubMed

van Daalen, Emma E; Jennette, J Charles; McAdoo, Stephen P; Pusey, Charles D; Alba, Marco A; Poulton, Caroline J; Wolterbeek, Ron; Nguyen, Tri Q; Goldschmeding, Roel; Alchi, Bassam; Griffiths, Meryl; de Zoysa, Janak R; Vincent, Beula; Bruijn, Jan A; Bajema, Ingeborg M

2018-01-06

Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 ( P =0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated ( P <0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3. Copyright © 2018 by the American Society of Nephrology.

MRI tools for assessment of microstructure and nephron function of the kidney.

PubMed

Xie, Luke; Bennett, Kevin M; Liu, Chunlei; Johnson, G Allan; Zhang, Jeff Lei; Lee, Vivian S

2016-12-01

MRI can provide excellent detail of renal structure and function. Recently, novel MR contrast mechanisms and imaging tools have been developed to evaluate microscopic kidney structures including the tubules and glomeruli. Quantitative MRI can assess local tubular function and is able to determine the concentrating mechanism of the kidney noninvasively in real time. Measuring single nephron function is now a near possibility. In parallel to advancing imaging techniques for kidney microstructure is a need to carefully understand the relationship between the local source of MRI contrast and the underlying physiological change. The development of these imaging markers can impact the accurate diagnosis and treatment of kidney disease. This study reviews the novel tools to examine kidney microstructure and local function and demonstrates the application of these methods in renal pathophysiology. Copyright © 2016 the American Physiological Society.

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

Comprehensive functional analysis of Rab GTPases in Drosophila nephrocytes.

PubMed

Fu, Yulong; Zhu, Jun-Yi; Zhang, Fujian; Richman, Adam; Zhao, Zhanzheng; Han, Zhe

2017-06-01

The Drosophila nephrocyte is a critical component of the fly renal system and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system. Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity. Rabs 1, 5, 7, 11 and 35 were most important. Gene silencing of the nephrocyte-specific Rab5 eliminated all intracellular vesicles and the specialized plasma membrane structures essential for nephrocyte function. Rab7 silencing dramatically increased clear vacuoles and reduced lysosomes. Rab11 silencing increased lysosomes and reduced clear vacuoles. Our results suggest that Rab5 mediates endocytosis that is essential for the maintenance of functionally critical nephrocyte plasma membrane structures and that Rabs 7 and 11 mediate alternative downstream vesicle trafficking pathways leading to protein degradation and membrane recycling, respectively. Elucidating molecular pathways underlying nephrocyte function has the potential to yield important insights into human kidney cell physiology and mechanisms of cell injury that lead to disease. The Drosophila nephrocyte is emerging as a useful in vivo model system for molecular target identification and initial testing of therapeutic approaches in humans.

Role of cytogenetic biomarkers in management of chronic kidney disease patients: A review.

PubMed

Khan, Zeba; Pandey, Manoj; Samartha, Ravindra M

2016-10-01

Chronic kidney disease (CKD) is much more common than people recognize, and habitually goes undetected and undiagnosed until the disease is well advanced or when their kidney functions is down to 25% of normal function. Genetic and non-genetic factors contribute to cause CKD. Non-genetic factors include hypertension, High level of DNA damage due to the production of reactive oxygen species and nucleic acid oxidation has been reported in CKD patients. Main genetic factor which causes CKD is diabetic nephropathy. A three- to nine-fold greater risk of End Stage Renal Disease (ESRD) is observed in individuals with a family history of ESRD. This greater risk have led researchers to search for genes linked to diabetic and other forms of nephropathy for the management of CKD. Multicenter consortia are currently recruiting large numbers of multiplex diabetic families with index cases having nephropathy for linkage and association analyses using various cytogenetic techniques. In addition, large-scale screening studies are underway, with the goals of better defining the overall prevalence of chronic kidney disease, as well as educating the population about risk factors for nephropathy, including family history. Cytogenetic biomarkers play an imperative role for the linkage study using G banding and detection of genomic instability in CKD patients. Classical and molecular cytogenetic tools with cytogenetic biomarkers provide remarkable findings in CKD patients. The aim of the present review is to draw outline of classical and molecular cytogenetic findings in CKD patients and their possible role in management to reduce genomic instability in CKD patients.

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

PubMed Central

Schold, Jesse D.; Arrigain, Susana; Jolly, Stacey E.; Wehbe, Edgard; Raina, Rupesh; Simon, James F.; Srinivas, Titte R.; Jain, Anil; Schreiber, Martin J.; Nally, Joseph V.

2011-01-01

Summary Background and objectives The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients. Design, setting, participants, & measurements We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan–Meier survival curves, and time-dependent analysis. Results Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality. Conclusions Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients. PMID:21885787

Optimal conditions of LDR to protect the kidney from diabetes

PubMed Central

Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

2014-01-01

Aims We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day via suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Main methods Type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic mice received whole body X-irradiation at dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th week of the study. Key findings Diabetes induced renal dysfunction, shown by the decreased creatinine and increased microalbumin in urinary. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best preventive effect on the kidney of diabetic mice. Significance Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. PMID:24631139

Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

PubMed Central

Lerret, Nadine M.; Li, Ting; Wang, Jiao-Jing; Kang, Hee-Kap; Wang, Sheng; Wang, Xueqiong; Jie, Chunfa; Kanwar, Yashpal S.; Abecassis, Michael M.

2015-01-01

The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b−Gr-1+ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection. PMID:25788530

Albumin contributes to kidney disease progression in Alport syndrome

PubMed Central

Knutsen, Russell H.; Mecham, Robert P.

2016-01-01

Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb−/−) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb+/− mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3−/−) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3−/−;Alb−/− mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3−/−;Alb+/+ and Col4a3−/−;Alb+/− mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. PMID:27147675

Albumin contributes to kidney disease progression in Alport syndrome.

PubMed

Jarad, George; Knutsen, Russell H; Mecham, Robert P; Miner, Jeffrey H

2016-07-01

Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. Copyright © 2016 the American Physiological Society.

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats.

PubMed

Han, Jing; Liang, Hua; Yi, Jianhua; Tan, Wuhong; He, Shulan; Wu, Xiaofang; Shi, Xiaowei; Ma, Jing; Guo, Xiong

2016-03-01

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney. Copyright © 2015 Elsevier GmbH. All rights reserved.

High and Low Salt Intake during Pregnancy: Impact on Cardiac and Renal Structure in Newborns.

PubMed

Seravalli, Priscila; de Oliveira, Ivone Braga; Zago, Breno Calazans; de Castro, Isac; Veras, Mariana Matera; Alves-Rodrigues, Edson Nogueira; Heimann, Joel C

2016-01-01

Previous studies from our laboratory demonstrated that dietary salt overload and salt restriction during pregnancy were associated with cardiac and renal structural and/or functional alterations in adult offspring. The present study evaluated renal and cardiac structure and the local renin-angiotensin system in newborns from dams fed high-, normal- or low-salt diets during pregnancy. Female Wistar rats were fed low- (LS, 0.15% NaCl), normal- (NS, 1.3% NaCl) or high- (HS, 8% NaCl) salt diets during pregnancy. Kidneys and hearts were collected from newborns (n = 6-8/group) during the first 24 hours after birth to evaluate possible changes in structure using stereology. Protein expression of renin-angiotensin system components was evaluated using an indirect enzyme-linked immunosorbent assay (ELISA). No differences between groups were observed in total renal volume, volume of renal compartments or number of glomeruli. The transverse diameter of the nuclei of cardiomyocytes was greater in HS than NS males in the left and right ventricles. Protein expression of the AT1 receptor was lower in the kidneys of the LS than in those of the NS and HS males but not females. Protein expression of the AT2 receptor was lower in the kidneys of the LS males and females than in those of the NS males and females. High salt intake during pregnancy induced left and right ventricular hypertrophy in male newborns. Salt restriction during pregnancy reduced the expression of renal angiotensin II receptors in newborns.

The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases.

PubMed

Tam, Joseph

2016-05-01

Endocannabinoids (eCBs) are endogenous lipid ligands that bind to cannabinoid receptors that also mediate the effects of marijuana. The eCB system is comprised of eCBs, anandamide, and 2-arachidonoyl glycerol, their cannabinoid-1 and cannabinoid-2 receptors (CB1 and CB2, respectively), and the enzymes involved in their biosynthesis and degradation. It is present in both the central nervous system and peripheral organs including the kidney. The current review focuses on the role of the eCB system in normal kidney function and various diseases, such as diabetes and obesity, that directly contributes to the development of renal pathologies. Normally, activation of the CB1 receptor regulates renal vascular hemodynamics and stimulates the transport of ions and proteins in different nephron compartments. In various mouse and rat models of obesity and type 1 and 2 diabetes mellitus, eCBs generated in various renal cells activate CB1 receptors and contribute to the development of oxidative stress, inflammation, and renal fibrosis. These effects can be chronically ameliorated by CB1 receptor blockers. In contrast, activation of the renal CB2 receptors reduces the deleterious effects of these chronic diseases. Because the therapeutic potential of globally acting CB1 receptor antagonists in these conditions is limited due to their neuropsychiatric adverse effects, the recent development of peripherally restricted CB1 receptor antagonists may represent a novel pharmacological approach in treating renal diseases.

Renal development: a complex process dependent on inductive interaction.

PubMed

Upadhyay, Kiran K; Silverstein, Douglas M

2014-01-01

Renal development begins in-utero and continues throughout childhood. Almost one-third of all developmental anomalies include structural or functional abnormalities of the urinary tract. There are three main phases of in-utero renal development: Pronephros, Mesonephros and Metanephros. Within three weeks of gestation, paired pronephri appear. A series of tubules called nephrotomes fuse with the pronephric duct. The pronephros elongates and induces the nearby mesoderm, forming the mesonephric (Woffian) duct. The metanephros is the precursor of the mature kidney that originates from the ureteric bud and the metanephric mesoderm (blastema) by 5 weeks of gestation. The interaction between these two components is a reciprocal process, resulting in the formation of a mature kidney. The ureteric bud forms the major and minor calyces, and the collecting tubules while the metanephrogenic blastema develops into the renal tubules and glomeruli. In humans, all of the nephrons are formed by 32 to 36 weeks of gestation. Simultaneously, the lower urinary tract develops from the vesico urethral canal, ureteric bud and mesonephric duct. In utero, ureters deliver urine from the kidney to the bladder, thereby creating amniotic fluid. Transcription factors, extracellular matrix glycoproteins, signaling molecules and receptors are the key players in normal renal development. Many medications (e.g., aminoglycosides, cyclooxygenase inhibitors, substances that affect the renin-angiotensin aldosterone system) also impact renal development by altering the expression of growth factors, matrix regulators or receptors. Thus, tight regulation and coordinated processes are crucial for normal renal development.

Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

PubMed

Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

2018-06-01

The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Delayed Presentation of Ureteropelvic Junction Obstruction and Loss of Renal Function After Initially Mild (SFU Grade 1-2) Hydronephrosis.

PubMed

Bowen, Diana K; Yerkes, Elizabeth B; Lindgren, Bruce W; Gong, Edward M; Faasse, Mark A

2015-07-01

We report 4 pediatric cases of ureteropelvic junction obstruction involving delayed progression of initially mild postnatal hydronephrosis. All 4 children became symptomatic; however, 3 already had a substantial decrement of ipsilateral kidney function by the time of diagnosis. Two of these 3 patients had previous renal scintigraphy demonstrating normal differential function. We caution that counseling regarding hydronephrosis should emphasize the importance of prompt re-evaluation for any symptoms potentially referable to delayed presentation of ureteropelvic junction obstruction, irrespective of initial hydronephrosis grade. Future studies are needed to determine the optimal follow-up regimen for conservative management of hydronephrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Asymptomatic proteinuria. Clinical significance.

PubMed

Papper, S

1977-09-01

Patients with asymptomatic proteinuria have varied reasons for the proteinuria and travel diverse courses. In the individual with normal renal function and no systemic cause, ie, idiopathic asymptomatic proteinuria, the outlook is generally favorable. Microscopic hematuria probably raises some degree of question about prognosis. The kidney shows normal glomeruli, subtle changes, or an identifiable lesion. The initial approach includes a clinical and laboratory search for systemic disease, repeated urinalyses, quantitative measurements of proteinuria, determination of creatinine clearance, protein electrophoresis where indicated, and intravenous pyelography. The need for regularly scheduled follow-up evaluation is emphasized. Although the initial approach need not include renal biopsy, a decline in creatinine clearance, an increase in proteinuria, or both are indications for biopsy and consideration of drug therapy.

Nigella sativa oil protects against tartrazine toxicity in male rats.

PubMed

Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Hamed, Amani Mohammed; Zamazami, Mazin A

2018-01-01

This study aimed to evaluate the protective role of Nigella sativa oil against the adverse effects of tartrazine on male rats. 18 albino rats were divided randomly into four groups (n = 6). The first (G1) is the negative control, the second group (G2) is the positive control received 10 mg/kg b.w. tartrazine in the diet and the third (G3) received the same dose of tartrazine as in G2 and co-treated with Nigella sativa oil for 8 weeks. Tartrazine decreased total protein, antioxidants and high density lipoproteins, whereas increased liver enzyme, kidney function parameters, total cholesterol, triglycerides, low density lipoproteins and lipid peroxidation in the positive control group. In addition, it caused pathological changes in the tissues of liver, kidney, testes and stomach. Treating tartrazine supplemented rats of G3 with Nigella sativa oil for 8 weeks significantly improved all biochemical parameters and restored the tissues of kidney, stomach, testes and liver to normal. It could be concluded that N. sativa oil succeeded in protecting male rats against the adverse conditions resulted from tartrazine administration.

Iron deficiency anaemia in chronic kidney disease.

PubMed

Wittwer, Iain

2013-09-01

Iron Deficiency Anaemia (IDA) has been shown to be the most common cause of anaemia worldwide. It is accepted that people with chronic kidney disease (CKD) develop anaemia as their kidney function declines. To better understand IDA in CKD, it is necessary to appreciate the normal iron metabolism and utilisation of iron and how these processes can be disordered in patients with CKD. The problems related to infection / inflammation and oxidative stress are examined. Whilst National and international guidelines recommend specific tests for IDA, these and alternative tests are reviewed. Whilst iron supplementation is necessary for CKD patients with IDA, iron metabolism and utilisation can be affected by factors such as infection or inflammation. Iron is essential element for all life, it can be toxic to cells through the process of oxidative stress. The recommended tests for IDA may be affected by factors such as infection and inflammation. Alternative tests are available, which may be a more accurate indicator of IDA as they are not affected by external factors. © 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Life-threatening hyperkalemia – an overlooked acute kidney injury with a serum creatinine rise in the ‘normal’ range

PubMed Central

Latus, Joerg; Braun, Niko; Alscher, M Dominik; Kimmel, Martin

2012-01-01

A 76-year-old woman (51 kg, 158 cm, body mass index 20.5) was admitted to the hospital because of an acute kidney injury with hyperkalemia. On admission, she reported progredient muscle weakness of all limbs for several days. Serum potassium level was dramatically elevated and ECG showed QRS with a ‘sine-wave’ pattern and haemodialysis was started. 45 days ago, Hartmann’s operation was done because of stenosing sigmoid diverticulitis. At this time, the serum creatinine was 0.4 mg/dl (‘normal’ 0.5–1.2). Thereafter, she got severe ‘high output-ileostoma’ with severe intestinal fluid losses and treatment with potassium supplementation and spironolactone was started by the surgeons. She was discharged with elevated serum potassium levels and serum creatinine of 1.0 mg/dl (‘normal’ range (0.5–1.2 mg/dl)). This case illustrates impressively the lack of serum creatinine as an ideal kidney function test, because it is depending on muscle mass and there is no interindividual normal range. PMID:22605836

Discordant effects of guanidines on renal structure and function and on regional vascular dysfunction and collagen changes in diabetic rats.

PubMed

Nyengaard, J R; Chang, K; Berhorst, S; Reiser, K M; Williamson, J R; Tilton, R G

1997-01-01

We examined the effects of aminoguanidine and methylguanidine on vascular dysfunction, glomerular structural changes, and indexes of early and late nonenzymatic glycation in 7-month streptozotocin-induced diabetic rats. Kidney weight, glomerular volume, fractional mesangial volume, glomerular capillary basement membrane width, and urinary albumin excretion were increased in diabetic rats. Diabetes also 1) increased vascular albumin permeation twofold in retina, sciatic nerve, aorta, skin, and kidney; 2) decreased renal collagenase-soluble collagen; 3) increased collagen-associated fluorescence in kidney and skin but not in aorta; and 4) increased glycated hemoglobin levels and aortic pentosidine levels. Aminoguanidine reduced albuminuria by 70% after 4 months, and both guanidines 1) normalized aortic pentosidine levels and renal collagenase-soluble collagen, 2) had no effect on glycated hemoglobin levels or collagen-associated fluorescence (in aorta, kidney, or skin), and 3) had little or no effect on regional albumin permeation. These discordant effects of aminoguanidine on diabetes-induced vascular changes versus parameters of nonenzymatic glycation are consistent with a multifactorial pathogenesis of diabetic complications, including roles for metabolic imbalances independent of nonenzymatic glycation. To the extent that glomerular matrix accumulation and increased regional albumin permeation in chronically diabetic rats are sequelae of nonenzymatic glycation, these findings point to an important role for early glycation reactions and products.

Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.

PubMed

Mesnage, Robin; Arno, Matthew; Costanzo, Manuela; Malatesta, Manuela; Séralini, Gilles-Eric; Antoniou, Michael N

2015-08-25

Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH, such as Roundup, pose a particular health risk to liver and kidneys although low environmentally relevant doses have not been examined. To address this issue, a 2-year study in rats administering 0.1 ppb Roundup (50 ng/L glyphosate equivalent) via drinking water (giving a daily intake of 4 ng/kg bw/day of glyphosate) was conducted. A marked increased incidence of anatomorphological and blood/urine biochemical changes was indicative of liver and kidney structure and functional pathology. In order to confirm these findings we have conducted a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 transcript clusters (a group of probes corresponding to a known or putative gene) were found to be altered respectively in liver and kidney (p < 0.01, q < 0.08). Changes in gene expression varied from -3.5 to 3.7 fold in liver and from -4.3 to 5.3 in kidneys. Among the 1319 transcript clusters whose expression was altered in both tissues, ontological enrichment in 3 functional categories among 868 genes were found. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. Pathway analysis suggests a modulation of the mTOR and phosphatidylinositol signalling pathways. Gene disturbances associated with the chronic administration of ultra-low dose Roundup reflect a liver and kidney lipotoxic condition and increased cellular growth that may be linked with regeneration in response to toxic effects causing damage to tissues. Observed alterations in gene expression were consistent with fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with and thus confirm observations of pathology made at an anatomical, histological and biochemical level. Our results suggest that chronic exposure to a GBH in an established laboratory animal toxicity model system at an ultra-low, environmental dose can result in liver and kidney damage with potential significant health implications for animal and human populations.

Performance of the chronic kidney disease-epidemiology study equations for estimating glomerular filtration rate before and after nephrectomy.

PubMed

Lane, Brian R; Demirjian, Sevag; Weight, Christopher J; Larson, Benjamin T; Poggio, Emilio D; Campbell, Steven C

2010-03-01

Accurate renal function determination before and after nephrectomy is essential for proper prevention and management of chronic kidney disease due to nephron loss and ischemic injury. We compared the estimated glomerular filtration rate using several serum creatinine based formulas against the measured rate based on (125)I-iothalamate clearance to determine which most accurately reflects the rate in this setting. Of 7,611 patients treated at our institution since 1975 the measured glomerular filtration rate was selectively determined before and after nephrectomy in 268 and 157, respectively. Performance of the Cockcroft-Gault, Modification of Diet in Renal Disease Study, re-expressed Modification of Diet in Renal Disease Study and Chronic Kidney Disease-Epidemiology Study equations, each of which estimates the glomerular filtration rate, were determined using serum creatinine, age, gender, weight and body surface area. The performance of serum creatinine, reciprocal serum creatinine and the 4 formulas was compared with the measured rate using Pearson's correlation, Lin's concordance coefficient and residual plots. Median serum creatinine was 1.4 mg/dl and the median measured glomerular filtration rate was 50 ml per minute per 1.73 m(2). The correlation between serum creatinine and the measured rate was poor (-0.66) compared with that of reciprocal serum creatinine (0.78) and the 4 equations (0.82 to 0.86). The Chronic Kidney Disease-Epidemiology Study equation performed with greatest precision and accuracy, and least bias of all equations. Stage 3 or greater chronic kidney disease ((125)I-iothalamate glomerular filtration rate 60 ml per minute per 1.73 m(2) or less) was present in 44% of patients with normal serum creatinine (1.4 mg/dl or less) postoperatively. Such missed diagnoses of chronic kidney disease decreased 42% using the Chronic Kidney Disease-Epidemiology Study equation. Glomerular filtration rate estimation equations outperform serum creatinine and better identify patients with perinephrectomy compromised renal function. The newly developed, serum creatinine based, Chronic Kidney Disease-Epidemiology Study equation has sufficient accuracy to render direct glomerular filtration rate measurement unnecessary before and after nephrectomy for cause in most circumstances. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Renal glucose metabolism in normal physiological conditions and in diabetes.

PubMed

Alsahli, Mazen; Gerich, John E

2017-11-01

The kidney plays an important role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate. After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis. In this post-absorptive state, the kidneys utilize about 10% of all glucose utilized by the body. After glucose ingestion, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release in the postprandial period. Each day, the kidneys filter approximately 180g of glucose and virtually all of this is reabsorbed into the circulation. Hormones (most importantly insulin and catecholamines), substrates, enzymes, and glucose transporters are some of the various factors influencing the kidney's role. Patients with type 2 diabetes have an increased renal glucose uptake and release in the fasting and the post-prandial states. Additionally, glucosuria in these patients does not occur at plasma glucose levels that would normally produce glucosuria in healthy individuals. The major abnormality of renal glucose metabolism in type 1 diabetes appears to be impaired renal glucose release during hypoglycemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of the morphometric features of the left and right horse kidneys: a stereological approach.

PubMed

Bolat, D; Bahar, S; Tipirdamaz, S; Selcuk, M L

2013-12-01

The aims of this study were to determine the total volume of the horse kidney and volume fractions of its functional subcomponents (cortex, medulla, renal pelvis) using stereological methods and investigate any possible difference in the functional subcomponents of the right and left kidneys that may arise from differences in shape. The study was carried out on the kidneys of 5 horses of different breed and sex. The weight of the kidneys was measured by a digital scale, and kidney volume was calculated by Archimedes' principle. Total kidney volume and volume fractions of subcomponents of the right and left kidneys were estimated by the Cavalieri's principle. The weights of the right and left kidneys were 550 ± 25 g and 585 ± 23 g, respectively. The volumes of the right and left kidneys estimated using the Cavalieri method were 542 ± 46 ml and 581 ± 29 ml. The relative organ weight of the kidneys was calculated as 1:330. The densities of the right and left kidneys were determined to be 1.01 and 1.00, respectively. The mean volume fractions of the cortex, medulla and renal pelvis were determined as 55.6, 42.7 and 1.7 in both kidneys. No statistically significant difference existed between morphometric data pertaining to the right and left kidneys (P > 0.05). To determine precisely whether differences in shape cause any difference in the functional subcomponents of the right and left kidneys requires further investigation of differences in the number of microscopically functional unit of the kidney such as renal glomeruli and nephrons. © 2013 Blackwell Verlag GmbH.

Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia.

PubMed

Mace, Maria L; Gravesen, Eva; Nordholm, Anders; Hofman-Bang, Jacob; Secher, Thomas; Olgaard, Klaus; Lewin, Ewa

2017-07-01

Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting a disrupted feedback regulatory loop or an extra-skeletal source of this phosphatonin. Since induction of FGF23 expression in injured organs has been reported we decided to examine the regulation of FGF23 gene and protein expressions in the kidney and whether kidney-derived FGF23 contributes to the high plasma levels of FGF23 in uremia. FGF23 mRNA was not detected in normal kidneys, but was clearly demonstrated in injured kidneys, already after four hours in obstructive nephropathy and at 8 weeks in the remnant kidney of 5/6 nephrectomized rats. No renal extraction was found in uremic rats in contrast to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Low-protein diet supplemented with ketoacids reduces the severity of renal disease in 5/6 nephrectomized rats: a role for KLF15.

PubMed

Gao, Xiang; Huang, Lianghu; Grosjean, Fabrizio; Esposito, Vittoria; Wu, Jianxiang; Fu, Lili; Hu, Huimin; Tan, Jiangming; He, Cijian; Gray, Susan; Jain, Mukesh K; Zheng, Feng; Mei, Changlin

2011-05-01

Dietary protein restriction is an important treatment for chronic kidney disease. Herein, we tested the effect of low-protein or low-protein plus ketoacids (KA) diet in a remnant kidney model. Rats with a remnant kidney were randomized to receive normal protein diet (22%), low-protein (6%) diet (LPD), or low-protein (5%) plus KA (1%) diet for 6 months. Protein restriction prevented proteinuria, decreased blood urea nitrogen levels, and renal lesions; however, the LPD retarded growth and decreased serum albumin levels. Supplementation with KA corrected these abnormalities and provided superior renal protection compared with protein restriction alone. The levels of Kruppel-like factor-15 (KLF15), a transcription factor shown to reduce cardiac fibrosis, were decreased in remnant kidneys. Protein restriction, which increased KLF15 levels in the normal kidney, partially recovered the levels of KLF15 in remnant kidney. The expression of KLF15 in mesangial cells was repressed by oxidative stress, transforming growth factor-β, and tumor necrosis factor (TNF)-α. The suppressive effect of TNF-α on KLF15 expression was mediated by TNF receptor-1 and nuclear factor-κB. Overexpression of KLF15 in mesangial and HEK293 cells significantly decreased fibronectin and type IV collagen mRNA levels. Furthermore, KLF15 knockout mice developed glomerulosclerosis following uninephrectomy. Thus, KLF15 may be an antifibrotic factor in the kidney, and its decreased expression may contribute to the progression of kidney disease.

Exercise and CKD: Skeletal Muscle Dysfunction and Practical Application of Exercise to Prevent and Treat Physical Impairments in CKD.

PubMed

Roshanravan, Baback; Gamboa, Jorge; Wilund, Kenneth

2017-06-01

Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. As kidney disease progresses, skeletal muscle dysfunction forms a common pathway for mobility limitation, loss of functional independence, and vulnerability to disease complications. Screening for those at high risk for mobility disability by self-reported and objective measures of function is an essential first step in developing an interdisciplinary approach to treatment that includes rehabilitative therapies and counseling on physical activity. Exercise has beneficial effects on systemic inflammation, muscle, and physical performance in chronic kidney disease. Kidney health providers need to identify patient and care delivery barriers to exercise in order to effectively counsel patients on physical activity. A thorough medical evaluation and assessment of baseline function using self-reported and objective function assessment is essential to guide an effective individualized exercise prescription to prevent function decline in persons with kidney disease. This review focuses on the impact of kidney disease on skeletal muscle dysfunction in the context of the disablement process and reviews screening and treatment strategies that kidney health professionals can use in clinical practice to prevent functional decline and disability. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

SU-F-T-395: Evaluation of Best Dosimetry Achievable with VMAT and IMRT Treatment Techniques Targeting Borderline Resectable Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harpool, K; Schnell, E; Herman, T

Purpose: To determine from retrospective study the most appropriate technique for targeting small borderline operable pancreatic cancer surrounding blood vessels by evaluating the dosimetry and normal tissue sparing achievable using Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Radiation Therapy (IMRT). Methods: Treatment plans from ten patients who have undergone treatment with a prescribed dose of 4950 cGy, at 275 cGy per fraction, were analyzed. All plans were replanned using Eclipse TPS (Varian Medical Systems, Palo Alto, CA) with complementary VMAT or IMRT techniques to obtain paired data sets for comparison. The coverage to at least 95% of the plannedmore » target volume (PTV) was normalized to receive 100% of the prescription dose. The normal tissue constraints followed the quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines and the organs at risks (OARs) were liver, kidneys, spinal cord and bowel. The plan evaluation was based on conformity index (CI), homogeneity index (HI), uniformity index (UI), DVH parameters, and student’s-t statistics (2 tails). Results: The VMAT technique delivered less maximum dose to the right kidney, left kidney, total kidney, liver, spinal cord, and bowel by 9.3%, 5.9%, 6.7%, 3.9%, 15.1%, 3.9%, and 4.3%, respectively. The averaged V15 for the total kidney was 10.21% for IMRT and 7.29% for VMAT. The averaged V20 for the bowel was 19.89% for IMRT and 14.06% for VMAT. On average, the CI for IMRT was 1.20 and 1.16 for VMAT (p = 0.20). The HI was 0.08 for both techniques (p = 0.91) and UI was 1.05 and 1.06 for IMRT and VMAT respectively (p = 0.59). Conclusion: Both techniques achieve adequate PTV coverage. Although VMAT techniques show better normal tissue sparing from excessive dose, no significant differences were observed. Slight discrepancies may rise from different versions of calculation algorithms.« less

Kidney growth and renal functions under the growth hormone replacement therapy in children.

PubMed

Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

2014-05-01

The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p<0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p<0.05). Height was the most significant predictor of kidney volume in rhGH received children (p<0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p<0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p>0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p<0.05). In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

Disruption of IFT Complex A Causes Cystic Kidneys without Mitotic Spindle Misorientation

PubMed Central

Jonassen, Julie A.; SanAgustin, Jovenal; Baker, Stephen P.

2012-01-01

Intraflagellar transport (IFT) complexes A and B build and maintain primary cilia. In the mouse, kidney-specific or hypomorphic mutant alleles of IFT complex B genes cause polycystic kidneys, but the influence of IFT complex A proteins on renal development is not well understood. In the present study, we found that HoxB7-Cre–driven deletion of the complex A gene Ift140 from collecting ducts disrupted, but did not completely prevent, cilia assembly. Mutant kidneys developed collecting duct cysts by postnatal day 5, with rapid cystic expansion and renal dysfunction by day 15 and little remaining parenchymal tissue by day 20. In contrast to many models of polycystic kidney disease, precystic Ift140-deleted collecting ducts showed normal centrosomal positioning and no misorientation of the mitotic spindle axis, suggesting that disruption of oriented cell division is not a prerequisite to cyst formation in these kidneys. Precystic collecting ducts had an increased mitotic index, suggesting that cell proliferation may drive cyst expansion even with normal orientation of the mitotic spindle. In addition, we observed significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis in highly cystic, but not precystic, kidneys. Taken together, these studies indicate that loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression. PMID:22282595

Abrupt Decline in Kidney Function Before Initiating Hemodialysis and All-Cause Mortality: The Chronic Renal Insufficiency Cohort (CRIC) Study.

PubMed

Hsu, Raymond K; Chai, Boyang; Roy, Jason A; Anderson, Amanda H; Bansal, Nisha; Feldman, Harold I; Go, Alan S; He, Jiang; Horwitz, Edward J; Kusek, John W; Lash, James P; Ojo, Akinlolu; Sondheimer, James H; Townsend, Raymond R; Zhan, Min; Hsu, Chi-Yuan

2016-08-01

It is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy. Prospective cohort study. The Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation. The primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point. All-cause mortality within 1 year after initiating hemodialysis therapy. Multivariable Cox proportional hazards. Among 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76). Relatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data. Abrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

Type 4 renal tubular acidosis in a kidney transplant recipient.

PubMed

Kulkarni, Manjunath

2016-02-01

We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

PubMed Central

Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun

2017-01-01

Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093

CDP-choline circumvents mercury-induced mitochondrial damage and renal dysfunction.

PubMed

Buelna-Chontal, Mabel; Franco, Martha; Hernández-Esquivel, Luz; Pavón, Natalia; Rodríguez-Zavala, José S; Correa, Francisco; Jasso, Ricardo; Pichardo-Ramos, Gregorio; Santamaría, José; González-Pacheco, Héctor; Soto, Virgilia; Díaz-Ruíz, Jorge L; Chávez, Edmundo

2017-12-01

Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg 2+ in kidney tissue may induce renal failure. In this work, the protective effect of CDP-choline against the deleterious effects induced by Hg 2+ on renal function was studied. CDP-choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg 2+ administration at a dose of 3 mg/kg body weight. The findings indicate that CDP-choline guards mitochondria against Hg 2+ -toxicity by preserving their ability to retain matrix content, such as accumulated Ca 2+ . This nucleotide also protected mitochondria from Hg 2+ -induced loss of the transmembrane electric gradient and from the generation of hydrogen peroxide and membrane TBARS. In addition, CDP-choline avoided the oxidative damage of mtDNA and inhibited the release of the interleukins IL-1 and IL6, recognized as markers of acute inflammatory reaction. After the administration of Hg 2+ and CDP, CDP-choline maintained nearly normal levels of renal function and creatinine clearance, as well as blood urea nitrogen (BUN) and serum creatinine. © 2017 International Federation for Cell Biology.

Renal Abnormalities Among Egyptian Children With Hemophilia A Using Renal Scintigraphy: Relation to Risk Factors and Disease Severity.

PubMed

Hamed, Ahmed Alsaeed; Shalaby, Mennatallah Hatem; El-Kinawy, Nihal Saad; Elamawy, Alaa Adel; Abd El-Ghany, Shereen Mohamed

2017-07-01

Many risk factors may contribute to renal disease in patients with hemophilia A. We aimed to evaluate functional and structural renal abnormalities among a group of Egyptian children with severe and moderate hemophilia A using technetium-99m diethylene triamine pentaacetic acid ( 99m Tc-DTPA) and technetium-99 m dimercaptusuccinic acid ( 99m Tc-DMSA) scan. We also aimed to determine the relation between these abnormalities and different risk factors and disease severity. Forty male patients, 16 with severe and 24 with moderate hemophilia A, were enrolled in this study. Their mean age was 10.2 ± 4.3 years (range, 5-17 years). Full history taking, clinical examination, laboratory, and radionuclide investigations including serum creatinine, blood urea nitrogen (BUN), urine analysis, creatinine clearance, 24-hour urinary protein, 99m Tc-DTPA scan, and 99m Tc-DMSA scan were performed to all enrolled patients. Serum creatinine and BUN were normal in all patients, and corrected creatinine clearance was diminished in 2 patients. However, 99m Tc-DTPA results yielded 19 (47.5%) patients with diminished glomerular filtration rate (GFR). Moreover, it showed that 14 (35%) had obstructive uropathy, 15 (37.5%) had obstructive nephropathy, while 11 (27.5%) patients showed normal scan. One patient had atrophy of 1 kidney on 99m Tc-DMSA scan. Among our cohort, 5 (12.5%) patients were hypertensive. Microscopic hematuria was detected in 14 (35%) patients while 72.5% had proteinuria. We found an association between hematuria and hypertension with diminished GFR. Despite normal kidney functions (serum creatinine and BUN), we found a high rate of diminished GFR and obstructive uropathy and nephropathy as detected by 99m Tc-DTPA scan among children with hemophilia A.

Severe falciparum malaria with dengue coinfection complicated by rhabdomyolysis and acute kidney injury: an unusual case with myoglobinemia, myoglobinuria but normal serum creatine kinase.

PubMed

Yong, Kok Pin; Tan, Ban Hock; Low, Chian Yong

2012-12-20

Acute kidney injury (AKI) is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK). A 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus. In patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.

[Prevalence of chronic kidney disease in hypertensive persons attended in primary care from Spain determined by application of estimating equations].

PubMed

Gómez Navarro, Rafael

2009-01-01

To study the renal function (FR) of the hypertensive patients by means of estimating equations and serum creatinine (Crp). To calculate the percentage of patients with chronic kidney disease (ERC) that present normal values of Crp. To analyze which factors collaborate in the deterioration of the FR. Descriptive cross-sectional study of patients with HTA. Crp and arterial tension (TA) were determined. The glomerular filtration rate was calculated by means of Cockroft-Gault and MDRD's formula. The years of evolution of the HTA were registered. A descriptive study of the variables and the possible dependence among them was completed, using several times linear multiple regression. 52 patients were studied (57,7% women). Average age 72,4 +/- 10,8. 32,6% (Cockcroft-Gault) or 21,5% (MDRD) were fulfilling ERC criterion. The ERC was mainly diagnosed in females. 21,4% (Cockcroft-Gault) and 9,5 % patients (MDRD) with ERC had normal Crp values. We do not find linear dependence between the numbers of TA and the FR. The TA check-up objectives do not suppose less development of ERC. In males we find linear dependence within the FR (MDRD) and the years of evolution of the HTA. The ERC is a frequent pathology in the hypertense persons. The systematical utilization of estimating equations facilitates the detection of hidden ERC in patients with normal Crp.

[The determination of the natural content of chemical elements in human biological objects (liver, kidney, stomach) by mass spectrometry with inductively coupled plasma].

PubMed

Luzanova, I S; Svetlolobov, D Iu; Zorin, Iu V

2014-01-01

The objective of the present work was to continue the studies of the sites of concentration of the chemical elements corresponding to normal homeostasis in human biological objects by mass spectrometry with inductively coupled plasma. The study yielded the data on the natural content of 27 elements in the cadaveric liver, kidney, and stomach. It is recommended to use these findings as the reference parameters corresponding to normal homeostasis.

Protective effect of propolis on methotrexate-induced kidney injury in the rat.

PubMed

Ulusoy, Hasan Basri; Öztürk, İsmet; Sönmez, Mehmet Fatih

2016-06-01

Objectives Propolis is a potent antioxidant and a free radical scavenger. Pharmacological induction of heat shock proteins (HSPs) has been investigated for restoring normal cellular function following an injury. In this study, effect of propolis on HSP-70 expression in methotrexate-induced nephrotoxicity and direct preventive effect of propolis in this toxicity were investigated. Material and methods A total of 40 male Wistar albino rats were divided into four groups: Group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20 mg/kg. Groups 3 and 4 received 100 mg/kg/day propolis (by oral gavage) for 15 d by the first day of the experimental protocol. Then the rats were decapitated under ketamine esthesia and their kidney tissues were removed. HSP-70 expression, apoptosis, and histopathological damage scores were then compared. Results MTX caused epithelial desquamation into the lumen of the tubules, dilatation, and congestion of the peritubular vessels and renal corpuscles with obscure Bowman's space. The number of apoptotic cells (p = 0.000) and HSP-70 (p = 0.002) expression were increased in group 2. Propolis prevented the rise in number of apoptotic cells (p = 0.017), HSP-70 (p = 0.000) expression, and improved kidney morphology. Conclusions It was found that methotrexate gives rise to serious damage in the kidney and propolis is a potent antioxidant agent in preventing kidney injury.

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

PubMed

Dong, Jianghu J; Wang, Liangliang; Gill, Jagbir; Cao, Jiguo

2017-01-01

This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

Effects of feline hyperthyroidism on kidney function: a review.

PubMed

Vaske, Heather H; Schermerhorn, Thomas; Grauer, Gregory F

2016-02-01

Chronic kidney disease and hyperthyroidism are two commonly diagnosed conditions in the geriatric feline population, and are often seen concurrently. Management of both diseases is recommended; however, the physiologic implications of both diseases must be understood to ensure the most favorable outcome for each patient. This report reviews the complex interplay between hyperthyroidism and kidney function, as well as the effects of hyperthyroid therapy on kidney function. © ISFM and AAFP 2015.

Validation of serum free light chain reference ranges in primary care.

PubMed

Galvani, Luca; Flanagan, Jane; Sargazi, Mansour; Neithercut, William D

2016-05-01

The demand for measurement of serum immunoglobulin free kappa (κ) and lambda (λ) light chains has increased. The κ:λ ratio is used to assist in diagnosis/monitoring of plasma cell disorders. The binding site reference range for serum-free light chain κ:λ ratios of 0.26-1.65 was derived from healthy volunteers. Subsequently, a reference range of 0.37-3.1 for patients with chronic kidney disease has been proposed. Elevated free light chain concentrations and borderline raised free light chain ratios also may be found in polyclonal gammopathies and with other non-renal illnesses. This assessment was conducted to validate the established free light chain reference ranges in individuals from primary care. A total of 130 samples were identified from routine blood samples collected in primary care for routine biochemistry testing and estimated glomerular filtration rate calculation. The median and range of κ:λ ratios found in each estimated glomerular filtration rate group used for chronic kidney disease classification were higher than previously described. This was the case for individuals with normal or essentially normal renal function with estimated glomerular filtration rates>90, (0.58-1.76) and estimated glomerular filtration rate of 60-90 mL/min/1.73 m(2), (0.71-1.93). Individuals with estimated glomerular filtration rate 15-30, (0.72-4.50) and estimated glomerular filtration rate <15 ml/min/1.73 m(2) (0.71-4.95) also had higher values when compared to the current renal reference range of 0.37-3.10. Elevation of free light chain-κ:λ ratios may occur in the absence of a reduced renal function shown by a normal estimated glomerular filtration rate and in the presence of reduced renal function by estimated glomerular filtration rate when comparing results with the established reference ranges. Explanations include choice of analytical systems or the presence of other concurrent non-plasma cell illness. © The Author(s) 2016.

Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective.

PubMed

Al Otaibi, Torki; Ahmadpoor, Pedram; Allawi, Ali Abdulmajid Dyab; Habhab, Wael Taher; Khatami, Mohammad Reza; Nafar, Mohsen; Glotz, Denis

2016-02-01

With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question.

Influence of low-level laser radiation on kidney functions

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.

1998-12-01

Most of all renal diseases are accompanied by lowering of kidney functions. That makes the quality of the treatment worse. On an example 69 patients receiving Low-Level Laser Therapy (LLLT), the influence of the laser radiation on a contracting system of blood, on current of an active and inactive tubercular inflammation and on partial functions of kidneys were investigated. Is established, that LLLT does not render influence to a contracting system; promotes stopping of unspecific and moderate peaking of a specific inflammation of kidneys. Is proved, that after a rate of laserotherapy the improving of a blood micricirculation in kidney occurs in 57.9% of patients; a secretion - in 63.1% of the patients; a stimulation of urodynamic is fixed in 79% of cases. Magnification of diuresis, improving filtration and concentration functions of kidneys also is marked.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

PubMed

Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

2011-10-01

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Loss of the ciliary kinase Nek8 causes left-right asymmetry defects.

PubMed

Manning, Danielle K; Sergeev, Mikhail; van Heesbeen, Roy G; Wong, Michael D; Oh, Jin-Hee; Liu, Yan; Henkelman, R Mark; Drummond, Iain; Shah, Jagesh V; Beier, David R

2013-01-01

A missense mutation in mouse Nek8, which encodes a ciliary kinase, produces the juvenile cystic kidneys (jck) model of polycystic kidney disease, but the functions of Nek8 are incompletely understood. Here, we generated a Nek8-null allele and found that homozygous mutant mice die at birth and exhibit randomization of left-right asymmetry, cardiac anomalies, and glomerular kidney cysts. The requirement for Nek8 in left-right patterning is conserved, as knockdown of the zebrafish ortholog caused randomized heart looping. Ciliogenesis was intact in Nek8-deficient embryos and cells, but we observed misexpression of left-sided marker genes early in development, suggesting that nodal ciliary signaling was perturbed. We also generated jck/Nek8 compound heterozygotes; these mutants developed less severe cystic disease than jck homozygotes and provided genetic evidence that the jck allele may encode a gain-of-function protein. Notably, NEK8 and polycystin-2 (PC2) proteins interact, and we found that Nek8(-/-) and Pkd2(-/-) embryonic phenotypes are strikingly similar. Nek8-deficient embryos and cells did express PC2 normally, which localized properly to the cilia. However, similar to cells lacking PC2, NEK8-depleted inner medullary collecting duct cells exhibited a defective response to fluid shear, suggesting that NEK8 may play a role in mediating PC2-dependent signaling.

THE EFFECT OF FICUS CARICA L. (ANJIR) LEAF EXTRACT ON GENTAMICIN INDUCED NEPHROTOXICITY IN ADULT MALE ALBINO MICE.

PubMed

Ghaffar, Ammara; Tahir, Mohammad; Lone, Khalid Pervez; Faisal, Bushra; Latif, Waqas

2015-01-01

Gentamicin is an aminoglycoside isolated from Micromonospora purpurea known for its nephrotoxicity. Ficus carica L is known to treat many ailments. This study was designed to investigate the effects of Ficus carica L. (Anjir) leaf extract on renal oxidative stress induced by gentamicin in albino mice. In this laboratory based experimental study 30 mice were divided into three groups, containing 10 mice each. Group A being the control; groups B and C were experimental and treated with gentamicin 200 mg/kg/day intraperitoneally and, Ficus carica L. leaf extract 400 mg/kg/day orally with gentamicin 200 mg/kg/day intraperitoneally respectively for a period of 8 days. Blood samples were taken 24 hours after completion of the experimental period by cardiac puncture under anesthesia and kidneys of each mouse were taken out for microscopic examination. Gentamicin treatment increased serum urea and creatinine levels (group B). Ficus carica L. leaf extract treated animals showed significant reduction in biochemical markers of kidney functions in group C. The histopathological examination of group A showed normal renal structure which was deranged in group B treated with only gentamicin, whereas, group C exhibited marked improvement in histological structure. Ficus carica L. leaf extract is effective in preventing gentamicin induced functional and structural changes in kidney of albino mice.

Chronic kidney disease and diabetes in the national health service: a cross-sectional survey of the U.K. national diabetes audit.

PubMed

Hill, C J; Cardwell, C R; Patterson, C C; Maxwell, A P; Magee, G M; Young, R J; Matthews, B; O'Donoghue, D J; Fogarty, D G

2014-04-01

We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large U.K.-based diabetes population. The U.K. National Diabetes Audit provided data from 1 January 2007 to 31 March 2008. Inclusion criteria were a documented urinary albumin:creatinine ratio and serum creatinine. Patients were stratified according to chronic kidney disease stage and albuminuria status. Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2) , albuminuria or both. The proportions of patients achieving nationally defined glycaemic and systolic blood pressure targets were determined. The cohort comprised 1,423,669 patients, of whom 868,616 (61%) met inclusion criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor in advanced chronic kidney disease. For example, mean (standard deviation) systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1 diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic kidney disease stage 5 and macroalbuminuria. The high prevalence of chronic kidney disease and poor attainment of treatment targets highlights a large subset of the diabetes population at increased risk of cardiovascular mortality or progressive kidney disease. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Effects of home-based exercise on pre-dialysis chronic kidney disease patients: a randomized pilot and feasibility trial.

PubMed

Hiraki, Koji; Shibagaki, Yugo; Izawa, Kazuhiro P; Hotta, Chiharu; Wakamiya, Akiko; Sakurada, Tsutomu; Yasuda, Takashi; Kimura, Kenjiro

2017-06-17

Only a few research is available on the effects of home-based exercise training on pre-dialysis chronic kidney disease (CKD) patients. Therefore, we aimed to elucidate the effect of home-based exercise therapy on kidney function and arm and leg muscle strength in pre-dialysis CKD patients. Thirty-six male stage 3-4 pre-dialysis CKD patients (age, 68.7 ± 6.8 years; estimated glomerular filtration rate (eGFR), 39.0 ± 11.6 ml/min/1.73 m 2 ) who were being treated as outpatients were included. The subjects were randomly assigned to an exercise intervention group (Ex group: 18) and a control group (C group: 18). The Ex group wore accelerometer pedometers and were instructed to perform home-based aerobic and resistance exercises, such as brisk walking for 30 min per day, for 12 months. The C group subjects wore accelerometer pedometers but received no exercise therapy guidance; the number of steps covered during normal daily activities was recorded for the C group. The outcome measures were changes in kidney function and handgrip and knee extension muscle strength. Values at the baseline (T1) and 12 months later (T2) were compared. There were no significant differences in baseline characteristics between the two groups; however, the C group was more physically active than the Ex group. Eight subjects dropped out, and 28 subjects (14 in each group) were included in the final analysis. Physical activity increased significantly only in the Ex group. Grip strength (F = 7.0, p = 0.01) and knee extension muscle strength (F = 14.3, p < 0.01) were found to improve only in the Ex group. Further, the changes in eGFR were not significantly different between the two groups (F = 0.01, p = 0.93). Home-based exercise therapy for pre-dialysis CKD patients was feasible and improved arm and leg muscle strength without affecting kidney function. UMIN Clinical Trials Registry ( UMIN000005091 ). Registered 2/15/2011.

Xuezhikang ameliorates contrast media-induced nephropathy in rats via suppression of oxidative stress, inflammatory responses and apoptosis.

PubMed

Chu, Shichun; Hu, Liuhua; Wang, Xiaolei; Sun, Shiqun; Zhang, Tuo; Sun, Zhe; Shen, Linghong; Jin, Shuxuan; He, Ben

2016-11-01

The aim of this study was to assess the preventive effect of xuezhikang (XZK) to replace atorvastatin on the contrast media-induced acute kidney injury (CI-AKI). The male Sprague-Dawley rats were divided into five groups: group 1 (sham), injected with normal saline; group 2 (XZK), treated with XZK; group 3 contrast media (CM), injected with CM; group 4 (CM + ATO), injected with CM + pretreatment with atorvastatin; group 5 (CM + XZK), injected with CM + pretreatment with XZK. Twenty-four hours after injection with normal saline or CM, the blood sample and the kidneys were collected for the measurement of biochemical parameters, oxidative stress markers, nitric oxide production, inflammatory parameters, as well as renal histopathology and apoptosis detection. Our results indicated that XZK restored the renal function by reducing serum blood urea nitrogen (BUN) and serum creatinine (Scr), depressing renal malondialdehyde (MDA), increasing renal NO production, decreasing TNF-ɑ and IL-6 expression, attenuating renal pathological changes and inhibiting the apoptosis of renal tubular cells. XZK's therapeutic effect is similar, or even better than atorvastatin at the same effectual dose in some parts.

Acute and subacute effects of EV iron sucrose on endothelial functions in hemodialysis patients.

PubMed

Ozkurt, Sultan; Ozenc, Fatma; Degirmenci, Nevbahar Akcar; Temiz, Gokhan; Musmul, Ahmet; Sahin, Garip; Yalcin, Ahmet Ugur

2012-01-01

Iron support is an important component of treatment of anemia in hemodialysis (HD) patients. However, there are concerns about endovenous (EV) iron therapy that may cause endothelial dysfunction (ED) by increasing oxidative stress (OS) and lead to cardiovascular events. In this study, we aimed to evaluate the effects of high and repeated doses of EV iron sucrose on endothelial functions in acute and subacute phases. We included 15 HD patients to our study. There were 16 patients with iron deficiency but normal kidney functions in control group. We also evaluated endothelium-dependent vasodilatation (EDV) and nitroglycerin-induced vasodilatation (NIV) from the brachial artery by ultrasonography at the beginning of the study, and then 200 mg EV iron sucrose was given initially to both groups for 1 h in 250 cc 0.9% saline and 4 h after the end of the infusion (acute phase) sonographic vasodilatation parameters were measured from brachial artery. These measurements and laboratory tests were repeated 1 week after the end of a total 1000 mg EV iron sucrose replacement (200 mg/week). There was a statistically significant increase in hemoglobin and ferritin levels after the EV iron sucrose therapy in both control and patient groups. EDV values in the HD group were significantly lower than that in the control group before therapy (6.25% vs. 10.53%, p < 0.05). EV iron sucrose therapy did not alter EDV and NIV values at the 4th hour and 6th week in both control and patient groups. According to our study, compared with the control group with normal kidney functions, HD patients had impaired endothelial functions. However, in HD patients, high and repeated doses of EV iron sucrose do not have deleterious effects on endothelial functions at acute and subacute phases and can be used safely in that patient group.

Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

PubMed Central

Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

2013-01-01

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

Myosin-X functions in polarized epithelial cells

PubMed Central

Liu, Katy C.; Jacobs, Damon T.; Dunn, Brian D.; Fanning, Alan S.; Cheney, Richard E.

2012-01-01

Myosin-X (Myo10) is an unconventional myosin that localizes to the tips of filopodia and has critical functions in filopodia. Although Myo10 has been studied primarily in nonpolarized, fibroblast-like cells, Myo10 is expressed in vivo in many epithelia-rich tissues, such as kidney. In this study, we investigate the localization and functions of Myo10 in polarized epithelial cells, using Madin-Darby canine kidney II cells as a model system. Calcium-switch experiments demonstrate that, during junction assembly, green fluorescent protein–Myo10 localizes to lateral membrane cell–cell contacts and to filopodia-like structures imaged by total internal reflection fluorescence on the basal surface. Knockdown of Myo10 leads to delayed recruitment of E-cadherin and ZO-1 to junctions, as well as a delay in tight junction barrier formation, as indicated by a delay in the development of peak transepithelial electrical resistance (TER). Although Myo10 knockdown cells eventually mature into monolayers with normal TER, these monolayers do exhibit increased paracellular permeability to fluorescent dextrans. Importantly, knockdown of Myo10 leads to mitotic spindle misorientation, and in three-dimensional culture, Myo10 knockdown cysts exhibit defects in lumen formation. Together these results reveal that Myo10 functions in polarized epithelial cells in junction formation, regulation of paracellular permeability, and epithelial morphogenesis. PMID:22419816

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

NASA Astrophysics Data System (ADS)

Meneton, Pierre; Bloch-Faure, May; Hagege, Albert A.; Ruetten, Hartmut; Huang, Wei; Bergaya, Sonia; Ceiler, Debbie; Gehring, Doris; Martins, Isabelle; Salmon, Georges; Boulanger, Chantal M.; Nussberger, Jürg; Crozatier, Bertrand; Gasc, Jean-Marie; Heudes, Didier; Bruneval, Patrick; Doetschman, Tom; Ménard, Joël; Alhenc-Gelas, François

2001-02-01

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to βadrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein-kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein-kinin system could be involved in the development or progression of cardiovascular diseases.

Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients.

PubMed

Hanai, Ko; Tauchi, Eriko; Nishiwaki, Yui; Mori, Tomomi; Yokoyama, Yoichi; Uchigata, Yasuko; Babazono, Tetsuya

2018-05-30

Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.

Prognostic Value of Improved Kidney Function After Transcatheter Aortic Valve Implantation for Aortic Stenosis.

PubMed

Nijenhuis, Vincent Johan; Peper, Joyce; Vorselaars, Veronique M M; Swaans, Martin J; De Kroon, Thom; Van der Heyden, Jan A S; Rensing, Benno J W M; Heijmen, Robin; Bos, Willem-Jan W; Ten Berg, Jurrien M

2018-05-15

Transcatheter aortic valve implantation (TAVI) is associated with acute kidney injury (AKI), but can also improve the kidney function (IKF). We assessed the effects of kidney function changes in relation to baseline kidney function on 2-year clinical outcomes after TAVI. In total, 639 consecutive patients with aortic stenosis who underwent TAVI were stratified into 3 groups according to the ratio of serum creatinine post- to pre-TAVI: IKF (≤0.80; n = 95 [15%]), stable kidney function (0.80 to 1.5; n = 477 [75%]), and AKI (≥1.5; n = 67 [10%]). Different AKI risk scores were compared using receiving-operator characteristics. Median follow-up was 24 (8 to 44) months. At 3 months, the increase in estimated glomerular filtration rate in the IKF group remained, and the decreased estimated glomerular filtration rate in the AKI group recovered. Compared with a stable kidney function, AKI showed a higher 2-year mortality rate (adjusted hazard ratio [HR] 3.69, 95% confidence interval [CI] 2.43 to 5.62) and IKF a lower mortality rate (adjusted hazard ratio 0.53, 95% CI 0.30 to 0.93). AKI also predicted major and life-threatening bleeding (adjusted odds ratio 2.94, 95% CI 1.27 to 6.78). Independent predictors of AKI were chronic kidney disease and pulmonary hypertension. Independent predictors of IKF were female gender, a preserved kidney function, absence of atrial fibrillation, and hemoglobin level. Established AKI risk scores performed moderately and did not differentiate between AKI and IKF. In conclusion, AKI is transient and is independently associated with a higher mortality rate, whereas IKF is sustained and is associated with a lower mortality rate. These effects are independent of baseline kidney function. Further studies are warranted to investigate the role of IKF and generate a dedicated prediction model. Copyright © 2018 Elsevier Inc. All rights reserved.

Laparoscopic versus open nephrectomy for live kidney donors.

PubMed

Wilson, Colin H; Sanni, Aliu; Rix, David A; Soomro, Naeem A

2011-11-09

Waiting lists for kidney transplantation continue to grow and live organ donation has become more important as the number of brain stem dead cadaveric organ donors continues to fall. The major disincentive to potential kidney donors is the pain and morbidity associated with open surgery. To identify the benefits and harms of using laparoscopic compared to open nephrectomy techniques to recover kidneys from live organ donors. We searched the online databases CENTRAL (in The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to January 2010) and EMBASE (January 1980 to January 2010) and handsearched textbooks and reference lists. Randomised controlled trials comparing laparoscopic donor nephrectomy (LDN) with open donor nephrectomy (ODN). Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta-analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0.06 to 1.48), delayed graft function (RR 1.09, 95% CI 0.52 to 2.30), acute rejection (RR 1.41, 95 % CI 0.87 to 2.27), ureteric complications (RR 1.51, 95% CI 0.69 to 3.31), kidney function at one year (SMD 0.15, 95% CI -0.11 to 0.41) or graft loss at one year (RR 0.76, 95% CI 0.15 to 3.85). LDN is associated with less pain compared with open surgery; however, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using LDN procedures were exposed to longer warm ischaemia periods than ODN-acquired grafts, although this has not been reported as being associated with short-term consequences.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Assessing the effect of immunosuppression on engraftment of pancreatic islets

PubMed Central

Vallabhajosyula, Prashanth; Hirakata, Atsushi; Shimizu, Akira; Okumi, Masayoshi; Tchipashvili, Vaja; Hong, Hanzhou; Yamada, Kazuhiko; Sachs, David H.

2013-01-01

Objective In addition to ischemia and immunologic factors, immunosuppressive drugs have been suggested as a possible contributing factor to the loss of functional islets following allogeneic islet cell transplantation. Using our previously described islet-kidney transplantation model in miniature swine, we studied whether an islet toxic triple-drug immunosuppressive regimen (cyclosporine + azathioprine + prednisone) affects the islet engraftment process and thus long-term islet function. Design and Methods Donor animals underwent partial pancreatectomy, autologous islet preparation and injection of these islets under the autologous kidney capsule to prepare an islet-kidney (IK). Experimental animals received daily triple drug immunosuppression during the islet engraftment period. Control animals did not receive any immunosuppression during this period. Four to eight weeks later, these engrafted IK were transplanted across a minor histocompatibility mismatched barrier into pancreatectomized, nephrectomized recipient animals at an islet dose of ~ 4500 islet equivalents (IE)/kg recipient weight. Cyclosporine was administered for 12 days to the recipients to induce tolerance of the IK grafts and the animals were followed long-term. Results Diabetes was corrected by IK transplantation in all pancreatectomized recipients on both the control (n=3) and the experimental (n=4) arms of the study and all animals showed normal glucose regulation over the follow-up period. Intravenous glucose tolerance tests performed at 1, 2, > 3 months post-IK transplant showed essentially equivalent glycemic control in both control and experimental animals. Conclusion In this pre-clinical, in vivo large animal model of islet transplantation, the effect of triple drug immunosuppression on islet function does not negatively affect islet engraftment, as assessed by the long-term function of engrafted islets. PMID:23883972

Synthesis, spectroscopic and thermal studies of Mg(II), Ca(II), Sr(II) and Ba(II) diclofenac sodium complexes as anti-inflammatory drug and their protective effects on renal functions impairment and oxidative stress

NASA Astrophysics Data System (ADS)

El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

2015-01-01

The main task of our present study is the preparation of newly complexes of Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac which succeeded to great extent in alleviating the side effects of diclofenac alone and ameliorating the kidney function parameters and antioxidant capacities with respect to diclofenac treated group alone. The Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac have been synthesized and characterized using infrared, electronic and 1H NMR spectral, thermogravimetric and conductivity measurements. The diclofenac ligand has been found to act as bidentate chelating agent. Diclofenac complexes coordinate through the oxygen's of the carboxyl group. The molar ratio chelation is 1:2 (M2+-dic) with general formula [M(dic)2(H2O)2]ṡnH2O. Antibacterial screening of the alkaline earth metal complexes against Escherichia coli (Gram - ve), Bacillus subtilis (Gram + ve) and anti-fungal (Asperagillus oryzae, Asperagillus niger, Asperagillus flavus) were investigated. The kidney functions in male albino rats were ameliorated upon treatment with metal complexes of dic, which are represented by decreasing the levels of urea and uric acid to be located within normal values. The other looks bright spot in this article is the assessment of antioxidant defense system including SOD, CAT and MDA with the help of Sr2+, Mg2+ and Ca2+-dic complexes. The hormones related to kidney functions and stresses have been greatly ameliorated in groups treated with dic complexes in comparable with dic treated group.

The lineage-specific gene ponzr1 is essential for zebrafish pronephric and pharyngeal arch development

PubMed Central

Bedell, Victoria M.; Person, Anthony D.; Larson, Jon D.; McLoon, Anna; Balciunas, Darius; Clark, Karl J.; Neff, Kevin I.; Nelson, Katie E.; Bill, Brent R.; Schimmenti, Lisa A.; Beiraghi, Soraya; Ekker, Stephen C.

2012-01-01

The Homeobox (Hox) and Paired box (Pax) gene families are key determinants of animal body plans and organ structure. In particular, they function within regulatory networks that control organogenesis. How these conserved genes elicit differences in organ form and function in response to evolutionary pressures is incompletely understood. We molecularly and functionally characterized one member of an evolutionarily dynamic gene family, plac8 onzin related protein 1 (ponzr1), in the zebrafish. ponzr1 mRNA is expressed early in the developing kidney and pharyngeal arches. Using ponzr1-targeting morpholinos, we show that ponzr1 is required for formation of the glomerulus. Loss of ponzr1 results in a nonfunctional glomerulus but retention of a functional pronephros, an arrangement similar to the aglomerular kidneys found in a subset of marine fish. ponzr1 is integrated into the pax2a pathway, with ponzr1 expression requiring pax2a gene function, and proper pax2a expression requiring normal ponzr1 expression. In addition to pronephric function, ponzr1 is required for pharyngeal arch formation. We functionally demonstrate that ponzr1 can act as a transcription factor or co-factor, providing the first molecular mode of action for this newly described gene family. Together, this work provides experimental evidence of an additional mechanism that incorporates evolutionarily dynamic, lineage-specific gene families into conserved regulatory gene networks to create functional organ diversity. PMID:22274699

Changes in leucocyte migration after renal transplantation

PubMed Central

Smith, M. G. M.; Eddleston, A. L. W. F.; Dominguez, J. A.; Evans, D. B.; Bewick, M.; Williams, Roger

1969-01-01

The leucocyte migration test, an in-vitro measure of cellular immunity, has been used to follow the changes in cell-mediated hypersensitivity to kidney and histocompatibility antigens in three patients after renal transplantation. Inhibition of leucocyte migration, indicating strong sensitization to the antigens used, occurred in each patient, starting five to seven days after transplantation. Satisfactory renal function had not been established in any of the patients at this time. In one case inhibition of leucocyte migration persisted almost continuously until the 24th day and was associated with poor renal function proved histologically to be due to rejection. Treatment with increased dosage of prednisone was associated with a rapid reversion to normal of the migration index and improvement in renal function. Later, inhibition of migration occurred again, and shortly afterwards the graft ceased to function. In the other two cases the migration index became normal without alteration in immunosuppressive therapy and a satisfactory diuresis followed. It is suggested that this simple test should prove useful in the specific diagnosis of rejection and in control of immunosuppressive therapy. ImagesFig. 3Fig. 4 PMID:4899455

[Advances in the research of effects of glutamine on immune function of burn patients].

PubMed

Liu, Y H; Guo, P F; Chen, G Y; Bo, Y C; Ma, Y; Cui, Z J

2018-04-20

Glutamine is the most abundant amino acid found in plasma and cells. It is the preferred fuel for enterocytes in the small intestine, macrophages, and lymphocytes. After serious burn, increased requirement of glutamine by the gastrointestinal tract, kidney and lymphocytes, and relatively insufficient self synthesis likely contribute to the rapid decline of glutamine in circulation and cells. Glutamine supplementation can not only protect intestinal mucosa, maintain normal intestinal barrier function, reduce bacterial translocation, and enhance the intestinal immune function, but also increase the number of lymphocytes, enhance the phagocytic function of macrophage, promote the synthesis of immunoglobulin, and reduce the body's inflammatory response, so as to enhance the immune function. Therefore, glutamine supplementation can improve and enhance the immune function, reduce complications and promote the prognosis of severely burned patients.

Resolution of hypercalcemia and acute kidney injury after treatment for pulmonary tuberculosis without the use of corticosteroids.

PubMed

Araujo, Constance A A; Araujo, Nicole A A; Daher, Elizabeth F; Oliveira, José Daniel B; Kubrusly, Marcos; Duarte, Pastora M A; Silva, Sonia L; Araujo, Sonia M H A

2013-03-01

Abstract. Hypercalcemia caused by tuberculosis is rare and it is usually asymptomatic. Tuberculosis (TB) -related hypercalcemia associated with acute kidney injury (AKI) is rarely reported. We report a case of a 22-year-old immunocompetent man with 1-month history of daily fever, asthenia and weight loss. Laboratory findings on admission included serum calcium 14.9 mg/dL, urinary Ca(2+) 569.6 mg/24 hours, low level of parathyroid hormone, serum creatinine = 2.2 mg/dL and sodium fractional excretion (FeNa) 2.73%. The result of the tuberculin skin test was 17 mm. A chest X-ray revealed micronodular pulmonary infiltrate in the apex of the right lung, which was confirmed by computed tomography scan. The patient was diagnosed with hypercalcemia associated with pulmonary TB and AKI. A general improvement of the hypercalcemia and renal function was observed in the first 2 weeks after effective hydration and treatment of TB without corticosteroids. The patient was discharged with normal calcium levels and renal function.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aburano, T.; Takayama, T.; Nakajima, K.

The three different methods to evaluate the alterations of split renal function following continued captopril treatment were studied in patients with hypertension. Five patients had unilateral and 2 had bilateral renal artery stenosis, and 13 had normal renal arteries. The studies were performed the day prior to receiving captopril (baseline), and 6th or 7th day following continued captorpril treatment (37.5mg or 75mg/day): Split effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) after injections of I-131 iodohippuran and Tc-99m DTPA were measured respectively by the methods using kidney counting corrected for depth and dose, described by Schlegel and Gates.more » And Tc-99m DMSA uptake was also evaluated qualitatively. In most of patients with renal artery stenosis, split GFR and Tc-99m DMSA uptake in the affected kidney were markedly decreased 6th or 7th day following continued captorpril treatment. These findings suggest that the captopril induced alterations of split renal function may be of importance for the diagnosis of renovascular hypertension. For this purpose, split GFR determination and Tc-99m DMSA study are more useful than split ERPF determination.« less

Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney.

PubMed

Drake, Keri A; Adam, Mike; Mahoney, Robert; Potter, S Steven

2018-04-20

Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

Herbal and dietary supplements related to diarrhea and acute kidney injury: a case report.

PubMed

Wanitsriphinyo, Suphamat; Tangkiatkumjai, Mayuree

2017-03-01

Background There is very little evidence relating to the association of herbal medicine with diarrhea and the development of acute kidney injury (AKI). This study reports a case of diarrhea-induced AKI, possibly related to an individual ingesting copious amounts of homemade mixed fruit and herb puree. Case presentation A 45-year-old Thai man with diabetes had diarrhea for 2 days, as a result of taking high amounts of a puree made up of eight mixed fruits and herbs over a 3-day period. He developed dehydration and stage 2 AKI, with a doubling of his serum creatinine. He had been receiving enalapril, as a prescribed medication, over one year. After he stopped taking both the puree and enalapril, and received fluid replacement therapy, within a week his serum creatinine had gradually decreased. The combination of puree, enalapril and AKI may also have induced hyperkalemia in this patient. Furthermore, the patient developed hyperphosphatemia due to his worsening kidney function, exacerbated by regularly taking some dietary supplements containing high levels of phosphate. His serum levels of potassium and phosphate returned to normal within a week, once the patient stopped both the puree and all dietary supplements, and had begun receiving treatment for hyperkalemia. Results The mixed fruit and herb puree taken by this man may have led to his diarrhea due to its effect; particularly if the patient was taking a high concentration of such a drink. Both the puree and enalapril are likely to attenuate the progression of kidney function. The causal relationship between the puree and AKI was probable (5 scores) assessed by the modified Naranjo algorithm. This is the first case report, as far as the authors are aware, relating the drinking of a mixed fruit and herbal puree to diarrhea and AKI in a patient with diabetes. Conclusions This case can alert health care providers to the possibility that herbal medicine could induce diarrhea and develop acute kidney injury.

Preliminary findings of serum creatinine and estimated glomerular filtration rate (eGFR) in adolescents with intellectual disabilities.

PubMed

Lin, Jin-Ding; Lin, Lan-Ping; Hsieh, Molly; Lin, Pei-Ying

2010-01-01

The present study aimed to describe the kidney function profile - serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents with ID who participated in annual health examinations as they enrolled into special education schools in Taiwan. We used serum samples to determine participants' creatinine profiles, and the Cockcroft-Gault formula to calculate the data of eGFR to present the chronic kidney disease. The results found 22% of the participants have abnormal serum creatinine value (creatinine>1.0mg/dl) and 59.6%, 36.4% and 4.0% at chronic kidney disease (CKD) stage 1, 2 and 3 cases accordingly based on the Cockcroft-Gault formula. No CKD stage 4 and 5 cases in this study. That is, there were 4% CKD cases (eGFR <60 mL/min/1.73 m(2); CKD stage 3, 4 and 5) in adolescents with ID in this study. The results also indicated that gender and BMI could significantly predict abnormal creatinine condition in multivariate logistic regression analysis. Those boys with ID were more likely to have abnormal creatinine value than girls with ID (OR=10.13, 95% CI=5.96-17.23). In term of BMI, those underweight adolescents with ID were less likely to have high creatinine value compared to normal weight group (OR=0.45, 95% CI=0.28-0.72). In summary, this study provides the preliminary information of creatinine and estimated GFR in people with ID; we suggest the public health policy should initiate appropriate management strategies to monitor kidney function and to improve treatment outcomes of chronic kidney disease for this vulnerable population. Copyright © 2010 Elsevier Ltd. All rights reserved.

Glomerular disease augments kidney accumulation of synthetic anionic polymers.

PubMed

Liu, Gary W; Prossnitz, Alexander N; Eng, Diana G; Cheng, Yilong; Subrahmanyam, Nithya; Pippin, Jeffrey W; Lamm, Robert J; Ngambenjawong, Chayanon; Ghandehari, Hamidreza; Shankland, Stuart J; Pun, Suzie H

2018-06-02

Polymeric drug carriers can alter the pharmacokinetics of their drug cargoes, thereby improving drug therapeutic index and reducing side effects. Understanding and controlling polymer properties that drive tissue-specific accumulation is critical in engineering targeted drug delivery systems. For kidney disease applications, targeted drug delivery to renal cells that reside beyond the charge- and size-selective glomerular filtration barrier could have clinical potential. However, there are limited reports on polymer properties that might enhance kidney accumulation. Here, we studied the effects of molecular weight and charge on the in vivo kidney accumulation of polymers in health and disease. We synthesized a panel of well-defined polymers by atom transfer radical polymerization to answer several questions. First, the biodistribution of low molecular weight (23-27 kDa) polymers composed of various ratios of neutral:anionic monomers (1:0, 1:1, 1:4) in normal mice was determined. Then, highly anionic (1:4 monomer ratio) low molecular and high molecular weight (47 kDa) polymers were tested in both normal and experimental focal segmental glomerulosclerosis (FSGS) mice, a model that results in loss of glomerular filtration selectivity. Through these studies, we observed that kidney-specific polymer accumulation increases with anionic monomer content, but not molecular weight; experimental FSGS increases kidney accumulation of anionic polymers; and anionic polymers accumulate predominantly in proximal tubule cells, with some distribution in kidney glomeruli. These findings can be applied to the design of polymeric drug carriers to enhance or mitigate kidney accumulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

PubMed

George, Lekha K; Koshy, Santhosh K G; Molnar, Miklos Z; Thomas, Fridtjof; Lu, Jun L; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2017-08-01

Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min -1 1.73 m -2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min -1 1.73 m -2 y -1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min -1 1.73 m -2 and in patients without HF were 59±14 years and 84±16 mL min -1 1.73 m -2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications. © 2017 American Heart Association, Inc.

Age at Immigration and Kidney Function among Self-Identified Healthy Africans in the United States.

PubMed

Ali, Mana; Mwendwa, Denée T; Sims, Regina; Ricks, Madia; Sumner, Anne E

2016-02-01

Kidney disease disparately affects those of African descent. Age trends have generally been established for kidney function in the overall US population, but the contribution of age at the time of immigration for African immigrants is unknown. To examine the independent and joint effects of age and age at the time of immigration, and kidney function. Estimated glomerular filtration rate (eGFR) was calculated for 93 African immigrants (60 % male; mean age = 33.5). Hierarchical regression and post hoc analyses revealed a significant age × age at the time of immigration interaction after accounting for traditional risk factors among those who immigrated at age ≤21. Younger age at the time of immigration to the US may exacerbate an inverse relationship between age and kidney function in a self-identified healthy African immigrant sample. Investigation of biopsychosocial factors associated with kidney health among African immigrants is warranted.

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

PubMed

Lang, Joshua; Katz, Ronit; Ix, Joachim H; Gutierrez, Orlando M; Peralta, Carmen A; Parikh, Chirag R; Satterfield, Suzanne; Petrovic, Snezana; Devarajan, Prasad; Bennett, Michael; Fried, Linda F; Cummings, Steven R; Sarnak, Mark J; Shlipak, Michael G

2018-06-01

Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders. We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years. We examined the associations of serum albumin concentration with longitudinal kidney function decline by estimated glomerular filtration rate (eGFR). Outcomes included linear eGFR decline, rapid kidney function decline defined as >30% decrease in eGFR, defined as a final eGFR <60 mL/min/1.73 m2 in those with an eGFR >60 mL/min/1.73 m2 at baseline. Cystatin C-based eGFR was calculated at baseline, Year 3 and Year 10. Mean age was 74 years, and mean eGFR was 73 mL/min/1.73 m2 at baseline. The mean rate of eGFR change was 1.81 mL/min/1.73 m2 per year. After multivariate adjustment, lower serum albumin concentrations were strongly and independently associated with kidney function decline (-0.11 mL/min/1.73 m2 per year for each standard deviation decrease serum albumin; -0.01 to - 0.20) with no attenuation after adjustment for urine albumin and inflammatory markers (-0.12, -0.03 to - 0.22). When divided into quartiles, serum albumin levels ≤3.80 g/dL were associated with increased odds of rapid kidney function decline (odds ratio 1.59; 1.12-2.26) and increased risk of incident chronic kidney disease (incident rate ratio 1.29; 1.03-1.62) relative to levels >4.21g/dL. Urine albumin to creatinine ratio (ACR) was also significantly and independently associated with kidney function decline (-0.08 mL/min/1.73 m2 per year for urine ACR >30 mg/g; -0.82 to - 0.13). Lower serum albumin levels are strongly and independently associated with kidney function decline in elders, independent of clinical risk factors, urine albumin and measured inflammatory markers.

Growth Disorders

MedlinePlus

... take the missing hormone as a pill. Other Reasons Why Kids Might Not Grow Normally Hormones play ... but kids might not grow normally for other reasons, including: Chronic diseases. These include heart and kidney ...

Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease.

PubMed

Wolf, Myles; White, Kenneth E

2014-07-01

High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

NASA Astrophysics Data System (ADS)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

Obesity-induced changes in kidney mitochondria and endoplasmic reticulum in the presence or absence of leptin

PubMed Central

do Carmo, Jussara M.; Hosler, Jonathan P.; Hall, John E.

2015-01-01

We investigated obesity-induced changes in kidney lipid accumulation, mitochondrial function, and endoplasmic reticulum (ER) stress in the absence of hypertension, and the potential role of leptin in modulating these changes. We compared two normotensive genetic mouse models of obesity, leptin-deficient ob/ob mice and hyperleptinemic melanocortin-4 receptor-deficient mice (LoxTB MC4R−/−), with their respective lean controls. Compared with controls, ob/ob and LoxTB MC4R−/− mice exhibit significant albuminuria, increased creatinine clearance, and high renal triglyceride content. Renal ATP levels were decreased in both obesity models, and mitochondria isolated from both models showed alterations that would lower mitochondrial ATP production. Mitochondria from hyperleptinemic LoxTB MC4R−/− mice kidneys respired NADH-generating substrates (including palmitate) at lower rates due to an apparent decrease in complex I activity, and these mitochondria showed oxidative damage. Kidney mitochondria of leptin-deficient ob/ob mice showed normal rates of respiration with no evidence of oxidative damage, but electron transfer was partially uncoupled from ATP synthesis. A fourfold induction of C/EBP homologous protein (CHOP) expression indicated induction of ER stress in kidneys of hyperleptinemic LoxTB MC4R−/− mice. In contrast, ER stress was not induced in kidneys of leptin-deficient ob/ob mice. Our findings show that obesity, in the absence of hypertension, is associated with renal dysfunction in mice but not with major renal injury. Alterations to mitochondria that lower cellular ATP levels may be involved in obesity-induced renal injury. The type and severity of mitochondrial and ER dysfunction differs depending upon the presence or absence of leptin. PMID:26290368

Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

PubMed Central

Mason, Roger M

2013-01-01

Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

Ultrasonographic anatomy of the healthy southern tigrina ( Leopardus guttulus) abdomen: comparison with domestic cat references.

PubMed

Müller, Thiago R; Marcelino, Raquel S; de Souza, Livia P; Teixeira, Carlos R; Mamprim, Maria J

2017-02-01

Objectives The aim of the study was to describe the normal abdominal echoanatomy of the tigrina and to compare it with the abdominal echoanatomy of the domestic cat. Reference intervals for the normal abdominal ultrasonographic anatomy of individual species are important for accurate diagnoses and interpretation of routine health examinations. The hypothesis was that the echoanatomy of the tigrina was similar to that of the domestic cat. Methods Eighteen clinically healthy tigrina were selected for abdominal ultrasound examination, in order to obtain normal parameters of the bladder, spleen, adrenal gland, kidney, gastrointestinal tract, liver and gall bladder, and Doppler parameters of liver and kidney vessels. Results The splenic parenchyma was consistently hyperechoic to the kidneys and liver. The liver, kidneys and spleen had similar echotexture, shape and dimensions when compared with the domestic cat. The gall bladder was lobulated and surrounded by a clearly visualized thin, smooth, regular echogenic wall. The adrenal glands had a bilobulated shape. The urinary bladder had a thin echogenic wall. The Doppler parameters of the portal vein and renal artery were similar to the domestic cat. Conclusions and relevance The results support the hypothesis that the ultrasonographic parameters of the abdominal viscera of the southern tigrina are similar to those of the domestic cat.

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy

PubMed Central

2014-01-01

Background Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). Methods In 38 patients, standard activity of 177Lu-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. Results At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%). Conclusions A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying ‘high-risk’ patients prone to PRRT. PMID:25977880

Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

PubMed Central

Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

2017-01-01

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

Awareness level of kidney functions and diseases among adults in a Nigerian population

PubMed Central

Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

Association between physical activity and kidney function: National Health and Nutrition Examination Survey.

PubMed

Hawkins, Marquis S; Sevick, Mary Ann; Richardson, Caroline R; Fried, Linda F; Arena, Vincent C; Kriska, Andrea M

2011-08-01

Chronic kidney disease is a condition characterized by the deterioration of the kidney's ability to remove waste products from the body. Although treatments to slow the progression of the disease are available, chronic kidney disease may eventually lead to a complete loss of kidney function. Previous studies have shown that physical activities of moderate intensity may have renal benefits. Few studies have examined the effects of total movement on kidney function. The purpose of this study was to determine the association between time spent at all levels of physical activity intensity and sedentary behavior and kidney function. Data were obtained from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey, a cross-sectional study of a complex, multistage probability sample of the US population. Physical activity was assessed using an accelerometer and questionnaire. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease study formula. To assess linear associations between levels of physical activity and sedentary behavior with log-transformed estimated GFR (eGFR), linear regression was used. In general, physical activity (light and total) was related to log eGFR in females and males. For females, the association between light and total physical activity with log eGFR was consistent regardless of diabetes status. For males, the association between light and total physical activity and log eGFR was only significant in males without diabetes. When examining the association between physical activity, measured objectively with an accelerometer, and kidney function, total and light physical activities were found to be positively associated with kidney function.

Four years follow-up of 101 children with melamine-related urinary stones.

PubMed

Yang, Li; Wen, Jian Guo; Wen, Jian Jun; Su, Zhi Qiang; Zhu, Wen; Huang, Chen Xu; Yu, Si Long; Guo, Zhan

2013-06-01

The melamine-contaminated milk powder incidence occurred in China in 2008. Many studies have been published regarding the epidemiology, clinical symptoms, diagnosis and treatment of melamine-related urinary stones. The objective of this study is to follow-up the effects of melamine-contaminated milk powder consumption on kidney and body growth in children with melamine-related urinary stones 4 years ago. One hundred and one children with melamine-related urinary stones were followed up by urinalysis, renal function tests and urinary ultrasonography. The data of body weight and height, clinical signs and complications were collected. Eighty normal children without the history of consuming melamine-contaminated milk powder were collected as controls. Eighty-one children with melamine-related urinary stones were successfully followed up. Of 45 cases with melamine-related urinary stones treated conservatively after discharge, 34 disappeared completely, 6 dissolved partially, 1 increased in size and 4 did not change at 4 years follow-up. The percentages of under-height and under-weight infants were significantly higher in melamine-related urinary stones group compared to the controls, respectively (p < 0.05). Routine blood, renal and bladder function tests as well as urinalysis were normal in all children. No urological tumors were detected. No noticeable impact of melamine-related urinary stones on kidney and bladder was found at 4 years follow-up. However, whether or not melamine-related urinary stones had effect on body growth needs follow-up in future.

Nephrotoxic effects on offspring of rats chronically treated with mercuric chloride

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusk, T.L.

1983-08-01

Repeated subcutaneous injections of HgCl/sub 2/ at a dose of either 4.0 or 2.0 mg/kg produced toxic effects in rats when administered during the last 9 days of gestation. Females exhibited diarrhea, anorexia and weight loss of varying severity. Maternal renal function was monitored by urinalysis and was shown to be impaired during the early days of treatment but returned to normal later. Histological evaluation of adult kidneys after 2 days of treatment demonstrated the nephrotoxic effects of HgCl/sub 2/. Evidence of the regenerative process was found in tubules lined with densely packed, flattened cuboidal epithelial cells. Pup birth weightmore » among HgCl/sub 2/-exposed litters was significantly lower than that of control litters. Nephrotoxic effects were not identifiable in pups though the presence of mercury was confirmed in fetal kidneys. 93 refs., 7 figs., 3 tabs.« less

Renal effects of anti-gravity suit inflation in man in relation to cardiovascular and hormonal changes

NASA Technical Reports Server (NTRS)

Geelen, G.; Kravik, S. E.; Hadj-Aissa, A.; Vincent, M.; Sem-Jacobsen, C. W.; Greenleaf, J.; Gharib, C.

1987-01-01

It is shown that inflation for 3 hr of an antigravity suit that covered the legs and abdomen of normal standing subjects results in significant increases in urine flow, osmolar and free water clearances, total and fractional sodium excretion, and potassium excretion, while glomerular filtration rate and renal plasma flow are transiently increased. Such changes in kidney function are the consequence of the increase in thoracic blood volume induced by inflation which also results in an immediate increase in blood pressure and reflex bradycardia, together with a progressive lowering of plasma renin activity and aldosterone. The changes in kidney excretory patterns brought about by suit inflation appear to be similar in nature and magnitude to those observed during water immersion or in the early phase of bed rest, situations known to result in a headward redistribution of blood.

Human water, sodium, and calcium regulation during space flight and exercise

NASA Astrophysics Data System (ADS)

Doty, S. E.; Seagrave, R. C.

When one is exposed to microgravity, fluid which is normally pooled in the lower extremities is redistributed headward and weight bearing bones begin to demineralize due to reduced mechanical stresses. The kidney, which is the primary regulator of body fluid volume and composition, responds to the fluid shift and bone demineralization by increasing the urinary output of water, sodium, and calcium. This research involves developing a mathematical description of how water and electrolytes are internally redistributed and exchanged with the environment during space flight. This model consequently involves kidney function and the associated endocrine system. The model agrees well with actual data, including that a low sodium diet can prevent bone demineralization. Therefore, assumptions made to develop the model are most likely valid. Additionally, various levels of activity are also considered in the model since exercise may help to eliminate some of the undesired effects of space flight such as muscle atrophy and bone demineralization.

Human water, sodium, and calcium regulation during space flight and exercise

NASA Astrophysics Data System (ADS)

Doty, S. E.; Seagrave, R. C.

2000-05-01

When one is exposed to microgravity, fluid which is normally pooled in the lower extremities is redistributed headward and weight bearing bones begin to demineralize due to reduced mechanical stresses. The kidney, which is the primary regulator of body fluid volume and composition, responds to the fluid shift and bone demineralization by increasing the urinary output of water, sodium, and calcium. This research involves developing a mathematical description of how water and electrolytes are internally redistributed and exchanged with the environment during space flight. This model consequently involves kidney function and the associated endocrine system. The model agrees well with actual data, including that a low sodium diet can prevent bone demineralization. Therefore, assumptions made to develop the model are most likely valid. Additionally, various levels of activity are also considered in the model since exercise may help to eliminate some of the undesired effects of space flight such as muscle atrophy and bone demineralization.

Reduced Kidney Function Is Associated With Cardiometabolic Risk Factors, Prevalent and Predicted Risk of Cardiovascular Disease in Chinese Adults: Results From the REACTION Study.

PubMed

Lu, Jieli; Mu, Yiming; Su, Qing; Shi, Lixin; Liu, Chao; Zhao, Jiajun; Chen, Lulu; Li, Qiang; Yang, Tao; Yan, Li; Wan, Qin; Wu, Shengli; Liu, Yan; Wang, Guixia; Luo, Zuojie; Tang, Xulei; Chen, Gang; Huo, Yanan; Gao, Zhengnan; Ye, Zhen; Wang, Youmin; Qin, Guijun; Deng, Huacong; Yu, Xuefeng; Shen, Feixia; Chen, Li; Zhao, Liebin; Sun, Jichao; Sun, Wanwan; Wang, Tiange; Du, Rui; Lin, Lin; Dai, Meng; Xu, Yu; Xu, Min; Bi, Yufang; Lai, Shenghan; Li, Donghui; Wang, Weiqing; Ning, Guang

2016-07-22

Chronic kidney disease (CKD) increases cardiovascular disease (CVD) risk. However, the association of mildly reduced kidney function with CVD risk is unclear. This study investigated the association of estimated glomerular filtration rate (eGFR) with prevalent CVDs, 10-year Framingham risk for coronary heart disease (CHD), and 10-year risk of atherosclerotic cardiovascular diseases (ASCVD) in 239 832 participants from the baseline of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study. With an interviewer-assisted questionnaire, we collected information on CVD, including reported CHD, stroke, or myocardial infarction. Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Compared with individuals with normal eGFR (≥90 mL/min per 1.73 m(2)), those with decreased eGFR (75-89, 60-74, and <60 mL/min per 1.73 m(2)) had higher risk of prevalent obesity, diabetes mellitus, hypertension, and dyslipidemia in both men and women (P for trend all <0.001). Moreover, a significantly higher 10-year Framingham risk for CHD and 10-year risk for ASCVD was observed in both men and women with mildly decreased eGFR (60-89 mL/min per 1.73 m(2)). Even mildly reduced eGFR (under 90 mL/min per 1.73 m(2)) is associated with elevated 10-year Framingham risk for CHD and 10-year ASCVD risk among Chinese adults. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Adult dual kidney transplantations obtained from marginal donors: two case reports.

PubMed

Kim, Y H; Jung, J H; Song, K B; Chung, Y S; Park, J B; Cho, Y M; Jang, H J; Kim, S-C; Han, D J

2012-01-01

Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts. Copyright © 2012. Published by Elsevier Inc.