[The hypotriglyceridemic action of the combination of L-carnitine + simvastatin vs. L-carnitine and vs. simvastatin].

PubMed

Savica, V; Bellinghieri, G; Lamanna, F

1992-01-01

Previous studies had determined the role played by L-carnitine and simvastatin in the treatment of altered lipidemia in dialyzed patients with chronic uremia. The authors carried out a study on the above substances either singly or together administered to the same patients with chronic uremia in hemodialysis. This study was aimed at demonstrating the possible synergic normolipidemic action of both substances in comparison with their single administration, because their different mechanism of action could be metabolically enhanced. The obtained results demonstrated that the therapeutic association proposed is preferable to the use of the single substances. Moreover, a higher and more rapid normolipidemic effect was obtained after using L-carnitina associated with simvastatin with respect to the separated substances.

Elevated hepatic 11β-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia

PubMed Central

Chapagain, Ananda; Caton, Paul W.; Kieswich, Julius; Andrikopoulos, Petros; Nayuni, Nanda; Long, Jamie H.; Harwood, Steven M.; Webster, Scott P.; Raftery, Martin J.; Thiemermann, Christoph; Walker, Brian R.; Seckl, Jonathan R.; Corder, Roger; Yaqoob, Muhammad Magdi

2014-01-01

Insulin resistance and associated metabolic sequelae are common in chronic kidney disease (CKD) and are positively and independently associated with increased cardiovascular mortality. However, the pathogenesis has yet to be fully elucidated. 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyzes intracellular regeneration of active glucocorticoids, promoting insulin resistance in liver and other metabolic tissues. Using two experimental rat models of CKD (subtotal nephrectomy and adenine diet) which show early insulin resistance, we found that 11βHSD1 mRNA and protein increase in hepatic and adipose tissue, together with increased hepatic 11βHSD1 activity. This was associated with intrahepatic but not circulating glucocorticoid excess, and increased hepatic gluconeogenesis and lipogenesis. Oral administration of the 11βHSD inhibitor carbenoxolone to uremic rats for 2 wk improved glucose tolerance and insulin sensitivity, improved insulin signaling, and reduced hepatic expression of gluconeogenic and lipogenic genes. Furthermore, 11βHSD1−/− mice and rats treated with a specific 11βHSD1 inhibitor (UE2316) were protected from metabolic disturbances despite similar renal dysfunction following adenine experimental uremia. Therefore, we demonstrate that elevated hepatic 11βHSD1 is an important contributor to early insulin resistance and dyslipidemia in uremia. Specific 11βHSD1 inhibitors potentially represent a novel therapeutic approach for management of insulin resistance in patients with CKD. PMID:24569863

Cerebrovascular recovery after stroke with individual and combined losartan and captopril treatment of SHRsp.

PubMed

Smeda, John S; Daneshtalab, Noriko

2017-09-01

We assessed whether the superior restoration of cerebrovascular function after hemorrhagic stroke by losartan versus captopril treatment was due to better BP, uremia, uricaemia, or aldosterone control in Kyoto Wistar stroke-prone-hypertensive rats and evaluated whether elevated angiotensin II (A2) levels enhanced the effectiveness of losartan treatment. Constriction was studied in the middle cerebral arteries (MCAs) using a pressure myograph. Post-stroke survival increased from 21 to 310 and 189days respectively with losartan and captopril treatment. Neither treatment reduced BP, both reversed uremia and hyperaldosteronism equally after 7days. Plasma uric acid remained low. At stroke, MCA constriction to pressure (PDC), protein kinase C (PKC) activation, depolarization, and sarcoplasmic Ca 2+ were attenuated. Endothelial-dependent-vasodilation by bradykinin and endogenous NO release were lost. Both treatments recovered these functions within 7days. These functions deteriorated after 116days of captopril but not losartan treatment. Inhibiting A2 formation during losartan treatment didn't alter BP or vascular recovery. The superior recovery of PDC by losartan over captopril was not produced by better BP, uremia or aldosterone control or elevated A2. PDC recovery was associated with improved PKC function and enhanced basal NO release. The re-establishment of PDC could reduce cerebrovascular over-perfusion and hematoma expansion after stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Osmolality - blood

MedlinePlus

... High blood sugar level ( hyperglycemia ) High level of nitrogen waste products in the blood ( uremia ) High sodium ... 2013:832-833. Verbalis JG. Disorders of water balance. In: Skorecki K, Chertow GM, Marsden PA, Taal ...

Pericardial Effusion

MedlinePlus

... heart was within the field of radiation Chemotherapy treatment for cancer, such as doxorubicin (Doxil) and cyclophosphamide Waste products in the blood due to kidney failure (uremia) Underactive thyroid (hypothyroidism) Viral, bacterial, fungal or parasitic infections Trauma or ...

Thrombotic Role of Blood and Endothelial Cells in Uremia through Phosphatidylserine Exposure and Microparticle Release

PubMed Central

Gao, Chunyan; Xie, Rui; Yu, Chengyuan; Ma, Ruishuang; Dong, Weijun; Meng, Huan; Zhang, Yan; Si, Yu; Zhang, Zhuo; Novakovic, Valerie; Zhang, Yong; Kou, Junjie; Bi, Yayan; Li, Baoxin; Xie, Rujuan; Gilbert, Gary E.; Zhou, Jin; Shi, Jialan

2015-01-01

The mechanisms contributing to an increased risk of thrombosis in uremia are complex and require clarification. There is scant morphological evidence of membrane-dependent binding of factor Xa (FXa) and factor Va (FVa) on endothelial cells (EC) in vitro. Our objectives were to confirm that exposed phosphatidylserine (PS) on microparticle (MP), EC, and peripheral blood cell (PBC) has a prothrombotic role in uremic patients and to provide visible and morphological evidence of PS-dependent prothrombinase assembly in vitro. We found that uremic patients had more circulating MP (derived from PBC and EC) than controls. Additionally, patients had more exposed PS on their MPs and PBCs, especially in the hemodialysis group. In vitro, EC exposed more PS in uremic toxins or serum. Moreover, reconstitution experiments showed that at the early stages, PS exposure was partially reversible. Using confocal microscopy, we observed that PS-rich membranes of EC and MP provided binding sites for FVa and FXa. Further, exposure of PS in uremia resulted in increased generation of FXa, thrombin, and fibrin and significantly shortened coagulation time. Lactadherin, a protein that blocks PS, reduced 80% of procoagulant activity on PBC, EC, and MP. Our results suggest that PBC and EC in uremic milieu are easily injured or activated, which exposes PS and causes a release of MP, providing abundant procoagulant membrane surfaces and thus facilitating thrombus formation. Blocking PS binding sites could become a new therapeutic target for preventing thrombosis. PMID:26580207

[The grey line of dialysis initiation: as early as possible that is, by the incremental modality].

PubMed

Casino, Francesco Gaetano

2010-01-01

In the past, the initiation of dialysis treatment was determined by the appearance of signs and symptoms of uremia along with biochemical parameters. More recently, based on the findings of observational studies, it was hypothesized that an earlier start would benefit patients. The endorsement of this concept by international guidelines has led to the current practice of starting dialysis at GFR levels of 10 to 15 mL/ min/1.73 m2. However, recent observational studies taking into proper account the lead time bias showed a worse rather than better prognosis in early starters, suggesting that the previous studies might have been flawed. The IDEAL (Initiating Dialysis Early And Late) study has shown that starting dialysis ''just in time'', i.e., at the occurrence of uremic symptoms, does not harm the patient in that it is associated with the same clinical outcomes as early dialysis initiation. We believe that these results are compatible with our hypothesis that starting peritoneal dialysis or hemodialysis with an incremental modality could be appropriate for an asymptomatic patient with objective signs of mild uremia and a measured GFR around 10 mL/min/1.73 m2. In fact, when the GFR is relatively high, a reduced dialysis dose and/or frequency could suffice to control mild uremia, while possibly preserving the residual renal function owing to the reduced contact time between blood and bio-incompatible dialysis materials. The dialysis dose and/or frequency could be increased step by step, at the occurrence of symptoms, marked biochemical derangements or problems with volume control, without computing weekly Kt/Vurea.

Conformational Changes of Blood ACE in Chronic Uremia

PubMed Central

Petrov, Maxim N.; Shilo, Valery Y.; Tarasov, Alexandr V.; Schwartz, David E.; Garcia, Joe G. N.; Kost, Olga A.; Danilov, Sergei M.

2012-01-01

Background The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The “short” ACE inhibitor enalaprilat (tripeptide analog) and “long” inhibitor teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon anti-hypertensive therapy. PMID:23166630

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.

Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

PubMed

Druml, W; Kelly, R A; May, R C; Mitch, W E

1988-04-01

The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia.

Abnormal cation transport in uremia. Mechanisms in adipocytes and skeletal muscle from uremic rats.

PubMed Central

Druml, W; Kelly, R A; May, R C; Mitch, W E

1988-01-01

The cause of the abnormal active cation transport in erythrocytes of some uremic patients is unknown. In isolated adipocytes and skeletal muscle from chronically uremic chronic renal failure rats, basal sodium pump activity was decreased by 36 and 30%, and intracellular sodium was increased by 90 and 50%, respectively, compared with pair-fed control rats; insulin-stimulated sodium pump activity was preserved in both tissues. Lower basal NaK-ATPase activity in adipocytes was due to a proportionate decline in [3H]ouabain binding, while in muscle, [3H]ouabain binding was not changed, indicating that the NaK-ATPase turnover rate was decreased. Normal muscle, but not normal adipocytes, acquired defective Na pump activity when incubated in uremic sera. Thus, the mechanism for defective active cation transport in CRF is multifactorial and tissue specific. Sodium-dependent amino acid transport in adipocytes closely paralleled diminished Na pump activity (r = 0.91), indicating the importance of this defect to abnormal cellular metabolism in uremia. PMID:2832446

Image-guided intervention in the coagulopathic patient.

PubMed

Kohli, Marc; Mayo-Smith, William; Zagoria, Ronald; Sandrasegaran, Kumar

2016-04-01

Determining practice parameters for interventional procedures is challenging due to many factors including unreliable laboratory tests to measure bleeding risk, variable usage of standardized terminology for adverse events, poorly defined standards for administration of blood products, and the growing numbers of anticoagulant and antiplatelet medications. We aim to address these and other issues faced by radiologists performing invasive procedures through a review of available literature, and experiential guidance from three academic medical centers. We discuss the significant limitations with respect to using prothrombin-time and international normalized ratio to measure bleeding risk, especially in patients with synthetic defects due to liver function. Factors affecting platelet function including the impact of uremia; recent advances in laboratory testing, including platelet function testing; and thromboelastography are also discussed. A review of the existing literature of fresh-frozen plasma replacement therapy is included. The literature regarding comorbidities affecting coagulation including malignancy, liver failure, and uremia are also reviewed. Finally, the authors present a set of recommendations for laboratory thresholds, corrective transfusions, as well as withholding and restarting medications.

New urea-absorbing polymers for artificial kidney machines

NASA Technical Reports Server (NTRS)

Mueller, W. A.; Hsu, G. C.; Marsh, H. E., Jr.

1975-01-01

Etherified polymer is made from modified cellulose derivative which is reacted with periodate. It will absorb 2 grams of urea per 100 grams of polymer. Indications are that polymers could be used to help remove uremic wastes in artificial kidneys, or they could be administered orally as therapy for uremia.

PAROTID FLUID TOTAL PROTEIN IN PATIENTS WITH UREMIA AND PROTEINURIA.

DTIC Science & Technology

Stimulated parotid fluid samples (238) were collected from 32 patients to determine if altered renal function was associated with deviations in...tubular necrosis, and 15 had normal renal function. There were no significant differences in parotid fluid protein concentration or minute secretion associated with the state of renal function. (Author)

The EHEC type III effector NleL is an E3 ubiquitin ligase that modulates pedestal formation

USDA-ARS?s Scientific Manuscript database

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and may result in potentially fatal hemolytic uremia syndrome in humans. EHEC colonize the intestinal mucosa and promote formation of “pedestals” in the tissue beneath the adherent bacteria. Secreted proteins are key playe...

HYDRONEPHROSIS IN THE GOAT DUE TO NEOPLASIA. A CASE REPORT.

DTIC Science & Technology

The clinical history, gross and microscopic necropsy findings are presented in a case of hydronephrosis in a goat due to a primary neoplasm of the...urinary tract. The neoplasm, a transitional cell adenocarcinoma, had interfered with urine flow to a degree that hydronephrosis and subsequent uremia resulted. Metastases were found in the regional lymph nodes and lungs. (Author)

Acute and Subacute Oral Toxicity of Periodate in Rats

DTIC Science & Technology

2014-11-17

presence of decreased TSH, a pattern associated with uremia. Sodium periodate exposed rats exhibited both activation of the innate immune system and...associated with kidney disease are characterized by activation of the innate immune system coupled with immune deficiency. Sodium periodate exposed rats...exhibited both activation of the innate immune system and lymphocyte depletion; however, the pattern of effects was more indicative of a stress leukogram

Relationship between serum total bilirubin levels and mortality in uremia patients undergoing long-term hemodialysis: A nationwide cohort study.

PubMed

Su, Hui-Hsien; Kao, Chia-Man; Lin, Yi-Chun; Lin, Yen-Chung; Kao, Chih-Chin; Chen, Hsi-Hsien; Hsu, Chih-Cheng; Chen, Kuan-Chou; Peng, Chiung-Chi; Wu, Mai-Szu

2017-10-01

Previous studies show that serum bilirubin has potent antioxidant effect and is associated with protection from kidney damage and reduce cardiovascular events. The aim of this study was to examine the association of serum total bilirubin level and mortality in uremia patients who underwent hemodialysis. This is a nationwide retrospective long-term cohort study. Patients were registered in the Taiwan Renal Registry Data System (TWRDS) from 2005 to 2012. A total of 115,535 hemodialysis patients were surveyed and those with valid baseline total bilirubin (TB) data were enrolled. All-cause mortality was the primary outcome. A total of 47,650 hemodialysis patients followed for 27.6 ± 12 months, were divided into 3 groups according to different baseline serum total bilirubin levels (0.1-0.3, 0.3-0.7, 0.7-1.2 mg/dL). Mean age was 61.4 ± 13.6 years, 50% were male, 13% were hepatitis B carriers, and 20% were hepatitis C carriers. Primary outcome was the 3-year mortality. The TB level 0.7-1.2 mg/dL group had high mortality, statistically significant hazard ratio of mortality was 1.14 (crude HR, 95% 1.07-1.20, p < 0.01), and adjusted HR was 1.18 (model 1, 95% CI 1.11-1.25), 1.21 (model 2, 95% CI 1.14-1.29, p < 0.01), 1.44 (model 3, 95% CI 1.06-1.96, p < 0.01), respectively. Sensitivity test showed that after excluding 14,899 patients with hepatitis B or C, or abnormal liver function, the highest level of TB associated with higher significant mortality was still robust. In our study, high TB level is associated with mortality in uremia patients undergoing long-term hemodialysis, but further studies of the different effects of unconjugated or conjugated bilirubin on hemodialysis patients are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of Klotho in Osteoporosis and Renal Osteodystrophy

DTIC Science & Technology

2015-10-01

uremia induced increases in FGF23 transcription (Figure 6). VEGFa Runx2 Osx Col1a1 ALP OC 0 2 4 6 8 KL fl/fl Prx1-Cre; KL fl/fl m R N A ex pr es...week old mice revealed that Prx1cre;Klothofl/fl mice have significantly higher expression of osteoblastic and osteocytic markers such as Col1a1 , Runx2

The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin

PubMed Central

Perna, Alessandra F.; Zacchia, Miriam; Trepiccione, Francesco; Ingrosso, Diego

2017-01-01

Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin. PMID:28075397

Purtscher-like retinopathy associated with squamous cell carcinoma of the cervix.

PubMed

Ting, Darren Shu Jeng; Smith, Jonathan; Talks, Stephen James

2018-02-01

To describe a previously unreported case of Purtscher-like retinopathy secondary to severe acute renal failure associated with squamous cell carcinoma of the cervix. This is a case report. A 31-year-old female presented with a week history of acute abdominal pain, vomiting and severe renal failure followed by a sudden onset of bilateral visual loss. Vision was hand movement in either eye with central scotoma. Ophthalmic examination demonstrated bilateral retinal thickening and whitening with intraretinal hemorrhages localized to the peripapillary area, consistent with the diagnosis of Purtscher-like retinopathy. Further systemic examination revealed bilateral hydronephrosis secondary to underlying undiagnosed cervical carcinoma. Patient was treated with a short course of high-dose steroids. At 2 months, patient vision remained poor despite the resolution of retinal edema and hemorrhages. This case serves as the first report of Purtscher-like retinopathy secondary to acute renal failure associated with cervical carcinoma, expanding the list of causes of Purtscher's or Purtscher-like retinopathies. In the presence of significant uremia and absence of previously known association, the authors postulate that the sudden surge of uremia causes increase of endothelin-1 (a potent vasoconstrictor), resulting in downstream endothelin-induced vasculopathy with subsequent occlusion of the pre-capillary arteriolar network.

Zebrafish, a Novel Model System to Study Uremic Toxins: The Case for the Sulfur Amino Acid Lanthionine.

PubMed

Perna, Alessandra F; Anishchenko, Evgeniya; Vigorito, Carmela; Zacchia, Miriam; Trepiccione, Francesco; D'Aniello, Salvatore; Ingrosso, Diego

2018-04-29

The non-proteinogenic amino acid lanthionine is a byproduct of hydrogen sulfide biosynthesis: the third endogenous vasodilator gas, after nitric oxide and carbon monoxide. While hydrogen sulfide is decreased in uremic patients on hemodialysis, lanthionine is increased and has been proposed as a new uremic toxin, since it is able to impair hydrogen sulfide production in hepatoma cells. To characterize lanthionine as a uremic toxin, we explored its effects during the early development of the zebrafish ( Danio rerio ), a widely used model to study the organ and tissue alterations induced by xenobiotics. Lanthionine was employed at concentrations reproducing those previously detected in uremia. Light-induced visual motor response was also studied by means of the DanioVision system. Treatment of zebrafish embryos with lanthionine determined acute phenotypical alterations, on heart organogenesis (disproportion in cardiac chambers), increased heart beating, and arrhythmia. Lanthionine also induced locomotor alterations in zebrafish embryos. Some of these effects could be counteracted by glutathione. Lanthionine exerted acute effects on transsulfuration enzymes and the expression of genes involved in inflammation and metabolic regulation, and modified microRNA expression in a way comparable with some alterations detected in uremia. Lanthionine meets the criteria for classification as a uremic toxin. Zebrafish can be successfully used to explore uremic toxin effects.

Stress of anesthesia with M.S. 222 and Benzocaine in Rainbow Trout (Salmo gairdneri)

USGS Publications Warehouse

Wedemeyer, Gary

1970-01-01

Rainbow trout (Salmo gairdneri) anesthetized with M.S. 222 for periods up to 12 min experience interrenal ascorbate depletion, uremia, and moderate hypercholesterolemia. Anesthesia with neutralized M.S. 222 (pH 7) or benzocaine prevented these changes and significantly reduced the variability in plasma glucose, cholesterol, and cortisol, indicating that the stress of anesthesia with M.S. 222 is due to the low pK of the sulfonic acid moiety.

Cross-sectional examination of metabolites and metabolic phenotypes in uremia.

PubMed

Kalim, Sahir; Clish, Clary B; Deferio, Joseph J; Ortiz, Guillermo; Moffet, Alexander S; Gerszten, Robert E; Thadhani, Ravi; Rhee, Eugene P

2015-07-07

Although metabolomic approaches have begun to document numerous changes that arise in end stage renal disease (ESRD), how these alterations relate to established metabolic phenotypes in uremia is unknown. In 200 incident hemodialysis patients we used partial least squares discriminant analysis to identify which among 166 metabolites could best discriminate individuals with or without diabetes, and across tertiles of body mass index, serum albumin, total cholesterol, and systolic blood pressure. Our data do not recapitulate metabolomic signatures of diabetes and obesity identified among individuals with normal renal function (e.g. elevations in branched chain and aromatic amino acids) and highlight several potential markers of diabetes status specific to ESRD, including xanthosine-5-phosphate and vanillylmandelic acid. Further, our data identify significant associations between elevated tryptophan and long-chain acylcarnitine levels and both decreased total cholesterol and systolic blood pressure in ESRD. Higher tryptophan levels were also associated with higher serum albumin levels, but this may reflect tryptophan's significant albumin binding. Finally, an examination of the uremic retention solutes captured by our platform in relation to 24 clinical phenotypes provides a framework for investigating mechanisms of uremic toxicity. In sum, these studies leveraging metabolomic and metabolic phenotype data acquired in a well-characterized ESRD cohort demonstrate striking differences from metabolomics studies in the general population, and may provide clues to novel functional pathways in the ESRD population.

Bilateral rectal sheath hematomas after low-molecular weight heparin treatment in uremia.

PubMed

Xu, Lu; Liu, Lei; Li, Xinjian

2017-11-01

Rectus sheath hematomas (RSHs) are uncommon. They are usually unilateral and rarely bilateral. In this paper, we report the first case of spontaneous bilateral RSHs in a uremic patient after the administration of the first dose of low-molecular weight heparin during hemodialysis. The most interesting aspect of this case is that the main symptom of RSH in our patient was urinary bladder irritation. We highlight the importance of the prompt diagnosis and management of this medical emergency.

Noninvasive diagnosis of uremic osteodystrophy: uses and limitations.

PubMed

Heaf, J G; Joffe, P; Pødenphant, J; Andersen, J R

1987-01-01

45 bone biopsies from patients with chronic uremia were reviewed to define which noninvasive investigations were of value in predicting the histological diagnosis and to quantify the spectrum of uremic bone disease at a center that has consistently used an aluminum-free dialysis bath. 17 biopsies were taken postmortem. 15 patients received conservative treatment, the rest were on maintenance dialysis. 13 patients had symptomatic bone disease. Virtually all patients with a uremia duration greater than 3 years had uremic osteodystrophy. All patients with clinical bone disease, hypercalcemia or raised alkaline phosphatase activity had osteodystrophy, but the specific histology was not indicated. Greatly raised parathyroid levels suggested secondary hyperparathyroidism, but the test was only 100% specific when 20 times normal. Total aluminum consumption was highly indicative of bone aluminum concentration (p less than 0.0001) and aluminum-related osteomalacia (5 cases), suggesting that a considerable proportion of uremic bone disease is iatrogenic. Serum aluminum was of some use in the diagnosis of aluminum-related osteomalacia, but was not wholly reliable. Bone mineral content (BMC) using both forearm measurements and total body bone mineral levels (TBBM) were assessed in 32 patients and were found to be reduced in 12, with a preponderance of secondary hyperparathyroidism. BMC and TBBM were negatively correlated to resorbing surfaces and bone formation rate, suggesting that secondary hyperparathyroidism is the uremic bone disease that represents the greatest threat to bone mass. It is concluded that while noninvasive investigations give considerable information, reliable diagnosis requires the use of histological methods.

Defining end-stage renal disease in clinical trials: a framework for adjudication.

PubMed

Agarwal, Rajiv

2016-06-01

Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m(2) itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease. Published by Oxford University Press on behalf of ERA-EDTA 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD.

PubMed

Kortman, Guus A M; Reijnders, Dorien; Swinkels, Dorine W

2017-06-01

Patients with chronic kidney disease (CKD) and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to "uremia," an increased concentration of uremic retention solutes (toxins) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. There is a high prevalence of anemia in patients with CKD, for which patients are often treated with oral or intravenous iron. Recent in vivo and in vitro studies have reported adverse effects of oral iron supplementation on the gut microbiota composition, gut metabolome, and intestinal health, which in turn may result in an increased production of uremic toxins. It may also affect circulating levels of other microbe-derived molecules, that can act as mediators of immune regulation. Changes in body iron levels have also been reported to exert subtle effects on host immune function by modulating immune cell proliferation and differentiation, and by directly regulating cytokine formation and antimicrobial immune effector mechanisms. Based on the foregoing it is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection. Future studies are needed to confirm these hypotheses and to assess whether, compared to IV iron supplementation, oral iron supplementation negatively impacts on morbidity of CKD, and whether these adverse effects depend on the iron bioavailability of the iron formulation to the microbiota. © 2017 International Society for Hemodialysis.

Analysis of the energetic metabolism in cyclic Bedouin goats (Capra hircus): Nychthemeral and seasonal variations of some haematochemical parameters in relation with body and ambient temperatures.

PubMed

Malek, Mouna; Amirat, Zaina; Khammar, Farida; Khaldoun, Mounira

2016-08-01

Several studies have examined changes in some haematochemical parameters as a function of the different physiological status (cyclic, pregnant and lactating) of goats, but no relevant literature has exhaustively investigated these variations from anestrous to estrous stages in cyclic goats. In this paper, we report nychthemeral and seasonal variations in ambient and body temperatures, and in some haematochemical parameters (glycemia, cholesterolemia, triglyceridemia, creatininemia and uremia) measured during summer, winter and spring, in seven (7) experimental cyclic female Bedouin goats (Capra hircus) living in the Béni-Abbès region (Algerian Sahara desert). Cosinor rhythmometry procedure was used to determine the rhythmic parameters of ambient temperature and haematochemical parameters. To determine the effect of time of day on the rhythmicity of the studied parameters, as well as their seasonality, repeated measure analysis of variance (ANOVA) was applied. The results showed that in spite of the nychthemeral profile presented by the ambient temperature for each season, the body temperature remained in a narrow range, thus indicating a successful thermoregulation. The rhythmometry analysis showed a circadian rhythmicity of ambient temperature and haematochemical parameters with diurnal acrophases. A statistically significant effect of the time of day was shown on all studied haematochemical parameters, except on creatininemia. It was also found that only uremia, cholesterolemia and triglyceridemia followed the seasonal sexual activity of the studied ruminant. This study demonstrated the good physiological adaptation developed by this breed in response to the harsh climatic conditions of its natural environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Emperor Napoleon Bonaparte: did he have seizures? Psychogenic or epileptic or both?

PubMed

Hughes, John R

2003-12-01

Napoleon Bonaparte was a general in the French army at 24 years of age, later conquering most of Europe. He was one of the greatest military geniuses the world has ever known, but also an extremely intelligent individual. Did he have seizures? The evidence shows that he had both psychogenic and epileptic attacks. The psychogenic attacks were likely related to the tremendous stress in his life, and the epileptic seizures were the result of chronic uremia from a severe urethral stricture caused by gonorrhea that was transmitted from his wife, Empress Josephine.

Development of resin adsorbents for blood purification at Nankai University in China.

PubMed

Wang, Yong-Jian; Yu, Yao-Ting

2011-04-01

Various types of porous resin adsorbents based on polystyrene, agarose, and cellulose as matrixes coupling with DNA, amino acids and other biological active molecules as ligands were extensively studied in China. Molecular recognition between the ligand and pathogenic molecule was investigated. Several commercialized products are now widely used in hospitals all over China. Whole blood hemoperfusion is used to treat patients suffering from autoimmune diseases, uremia acute intoxication, and hyperbilirubinemia. Clinical performances of hundreds and thousands of patients treated by whole blood sorption therapy show that the therapy is safe, efficient, and cost-effective.

The imaging spectrum of posterior reversible encephalopathy syndrome: A pictorial review.

PubMed

Brady, Emily; Parikh, Neal S; Navi, Babak B; Gupta, Ajay; Schweitzer, Andrew D

Posterior reversible encephalopathy syndrome (PRES) is characterized by the acute onset of neurologic symptoms (headache, altered mental status, visual changes, seizures) with accompanying vasogenic edema on brain imaging. Risk factors for PRES include infection, uremia, malignancy, autoimmune disorders, the peripartum state and hypertension. PRES is classically described as being posterior (i.e. parieto-occipital) but radiologic variants are increasingly recognized. This pictorial review demonstrates the heterogeneity of the different radiologic presentations of PRES in reference to lesion distribution, hemorrhage, diffusion restriction, contrast enhancement, and other associated findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Insulin binding and glycolytic activity in erythrocytes from dialyzed and nondialyzed uremic patients.

PubMed

Weisinger, J R; Contreras, N E; Cajias, J; Bellorin-Font, E; Amair, P; Guitierrez, L; Sylva, V; Paz-Martínez, V

1988-01-01

Insulin resistance in uremia has been attributed to impaired hormone-receptor binding or to postbinding defects. Oral glucose tolerance tests, insulin binding, and in vitro glycolytic activity were studied in purified red blood cells from normal control subjects (C) and from uremic patients belonging to three groups: nondialyzed (U), on chronic hemodialysis (HD), and on continuous ambulatory peritoneal dialysis (CAPD). Glucose intolerance and hyperinsulinemia were demonstrated in all groups of patients. Maximal specific binding of 125I-insulin to erythrocytes, kinetically derived receptor numbers per cell, and affinity constants for insulin binding did not differ between control and patient groups. No correlation was found between the degree of glucose intolerance and insulin binding parameters. Basal lactate production by erythrocytes incubated in vitro was significantly higher in U and HD patients than in C, whereas CAPD patients did not differ from C in this respect. Addition of 1 mM dibutyryl-cAMP and 0.5 mM isobutyl-methyl-xanthine during incubation of erythrocytes caused an increase in the rate of lactate production that was similar in magnitude in the U, HD and C groups, whereas cells from CAPD subjects showed a significantly larger absolute response to these compounds after 1 h of incubation. There was no evidence of impairment of glycolytic capacity in red blood cells from uremic patients. In addition, no correlation was found between the degree of glucose intolerance and basal or stimulated lactate production by erythrocytes. Our results obtained in human erythrocytes suggest that the insulin resistance observed in uremia does not involve a defect in hormone binding or in the intracellular capacity to utilize glucose through glycolysis.

Diagnosis and management of sleep apnea syndrome and restless legs syndrome in dialysis patients.

PubMed

Novak, Marta; Mendelssohn, David; Shapiro, Colin M; Mucsi, Istvan

2006-01-01

Sleep complaints are very common in patients with end-stage renal disease (ESRD) and contribute to their impaired quality of life. Both obstructive and central sleep apnea syndromes are reported more often in patients on dialysis than in the general population. Impaired daytime functioning, sleepiness, and fatigue, as well as cognitive problems, are well known in patients with sleep apnea. Increasing evidence supports the pathophysiological role of sleep apnea in cardiovascular disorders, which are the leading cause of death in ESRD patients. Uremic factors may be involved in the pathogenesis of sleep apnea in this patient population and optimal dialysis may reduce disease severity. Furthermore, treatment with continuous positive airway pressure may improve quality of life and may help to manage hypertension in these patients. Secondary restless legs syndrome is highly prevalent in patients on maintenance dialysis. The pathophysiology of the disorder may also involve uremia-related factors, iron deficiency, and anemia, but genetic and lifestyle factors might also play a role. The treatment of restless legs syndrome involves various pharmacologic approaches and might be challenging in severe cases. In this article we review the diagnosis and treatment of sleep apnea and restless legs syndrome, with a focus on dialysis patients. We also briefly review current data regarding sleep problems after transplantation, since these studies may indirectly shed light on the possible pathophysiological role of uremia or dialysis in the etiology of sleep disorders. Considering the importance of sleep disorders, more awareness among professionals involved in the care of patients on dialysis is necessary. Appropriate management of sleep disorders could improve the quality of life and possibly even impact upon survival of renal patients.

Contingent negative variation before and after hemodialysis among patients with end-stage renal disease.

PubMed

Bae, Jong Seok; Park, Sung Sik

2008-04-15

To investigate changes in contingent negative variation (CNV) induced by uremia and to study the effects of hemodialysis. Fifteen right-handed healthy subjects and 12 patients with end-stage renal disease (ESRD) were studied. CNV was recorded from the Fz, Cz and Pz (using the International 10-20 System) referenced to linked ear lobes, using an S1 (click)-S2 (flashes)-key press paradigm. The amplitude of initial CNV (iCNV) was calculated as the average amplitude at 550-750 ms after S1. The amplitude of late CNV (lCNV) was the mean amplitude of the last 200 ms before S2. Testing was repeated for the patient group at pre- and post-hemodialysis observations. Neuropsychological measurements, a trail making test (TMT) and mini-mental state examination (MMSE), were conducted at each time. The mean amplitudes of iCNV and lCNV at the vertex (Cz) were both significantly lower in the patient group than in the control group (P<0.05). TMT were also significantly different between patient and control groups (P<0.05)), however MMSE showed no significant difference. There were no significant correlations between the values of neuropsychological tests and the parameters of CNV. Both iCNV and lCNV were not significantly different between the pre- and post-dialysis tests. CNV negativity in patients with ESRD reflects diffuse nonlocalizing neurological symptoms of uremia rather than a selective involvement of the frontal lobes. It is likely to reflect dysfunction in the frontal-subcortical circuit. In addition, hemodialysis seemed to have no significant effect on executive brain function in these patients with ESRD.

Effects of growth hormone treatment on the pituitary expression of GHRH receptor mRNA in uremic rats.

PubMed

Ferrando, Susana; Rodríguez, Julián; Santos, Fernando; Weruaga, Ana; Fernández, Marta; Carbajo, Eduardo; García, Enrique

2002-09-01

A decreased ability of pituitary cells to secrete growth hormone (GH) in response to growth hormone releasing hormone (GHRH) stimulation has been shown in young uremic rats. The aim of the current study was to examine the effect of uremia and GH treatment on pituitary GHRH receptor expression. Pituitary GHRH receptor mRNA levels were analyzed by RNase protection assay in young female rats made uremic by subtotal nephrectomy, either untreated (UREM) or treated with 10 IU/kg/day of GH (UREM-GH), and normal renal function animals fed ad libitum (SAL) or pair-fed with the UREM group (SPF). Rats were sacrificed 14 days after the second stage nephrectomy. Renal failure was confirmed by concentrations (X +/- SEM) of serum urea nitrogen (mmol/L) and creatinine (micromol/L) in UREM (20 +/- 1 and 89.4 +/- 4.5) and UREM-GH (16 +/- 1 and 91.4 +/- 6.9) that were much higher (P < 0.001) than those of sham animals (SAL, 3 +/- 0 and 26.5 +/- 2.2; SPF, 4 +/- 0 and 26.5 +/- 2.1). UREM rats became growth retarded as shown by a daily longitudinal tibia growth rate below (P < 0.05) that observed in SAL animals (156 +/- 3 vs. 220 +/- 5 microm/day). GH treatment resulted in significant growth rate acceleration (213 +/- 6 microm/day). GHRH receptor mRNA levels were no different among the SAL (0.43 +/- 0.03), SPF (0.43 +/- 0.08) and UREM (0.44 +/- 0.04) groups, whereas UREM-GH rats had significantly higher values (0.72 +/- 0.07). The status of pituitary GHRH receptor is not modified by nutritional deficit or by severe uremia causing growth retardation. By contrast, the growth promoting effect of GH administration is associated with stimulated GHRH receptor gene expression.

Urea transporters and sweat response to uremia.

PubMed

Keller, Raymond W; Bailey, James L; Wang, Yanhua; Klein, Janet D; Sands, Jeff M

2016-06-01

In humans, urea is excreted in sweat, largely through the eccrine sweat gland. The urea concentration in human sweat is elevated when compared to blood urea nitrogen. The sweat urea nitrogen (UN) of patients with end-stage kidney disease (ESRD) is increased when compared with healthy humans. The ability to produce sweat is maintained in the overwhelming majority of ESRD patients. A comprehensive literature review found no reports of sweat UN neither in healthy rodents nor in rodent models of chronic kidney disease (CKD). Therefore, this study measured sweat UN concentrations in healthy and uremic rats. Uninephrectomy followed by renal artery ligation was used to remove 5/6 of renal function. Rats were then fed a high-protein diet to induce uremia. Pilocarpine was used to induce sweating. Sweat droplets were collected under oil. Sweat UN was measured with a urease assay. Serum UN was measured using a fluorescent ortho-pthalaldehyde reaction. Immunohistochemistry (IHC) was accomplished with a horseradish peroxidase and diaminobenzidine technique. Sweat UN in uremic rats was elevated greater than two times compared to healthy pair-fed controls (220 ± 17 and 91 ± 15 mmol/L, respectively). Post hoc analysis showed a significant difference between male and female uremic sweat UN (279 ± 38 and 177 ± 11 mmol/L, respectively.) IHC shows, for the first time, the presence of the urea transporters UT-B and UT-A2 in both healthy and uremic rat cutaneous structures. Future studies will use this model to elucidate how rat sweat UN and other solute excretion is altered by commonly prescribed diuretics. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Association between hippuric acid and left ventricular hypertrophy in maintenance hemodialysis patients.

PubMed

Yu, Teng-Hung; Tang, Wei-Hua; Lu, Yung-Chuan; Wang, Chao-Ping; Hung, Wei-Chin; Wu, Cheng-Ching; Tsai, I-Ting; Chung, Fu-Mei; Houng, Jer-Yiing; Lan, Wen-Chun; Lee, Yau-Jiunn

2018-05-22

Left ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end-stage renal disease. Hippuric acid (HA), a harmful uremic toxin, is known to be elevated in patients with uremia, and serum HA levels are associated with neurological symptoms, metabolic acidosis, and accelerated renal damage associated with chronic kidney disease. However, the pathophysiological role of HA in patients with uremia remains unclear. We investigated the association between serum HA levels and echocardiographic measurements in patients undergoing hemodialysis (HD) treatment. Eighty consecutive patients treated at a single HD center (44 males, 36 females; mean age 66 y, mean HD duration 6 y) were included in this study. Comprehensive echocardiography was performed after HD. Blood samples were obtained before HD. Pearson's correlation analysis revealed that serum HA levels were positively correlated with diastolic blood pressure, serum creatinine, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-diastolic diameter, left ventricular end systolic diameter, end systolic left ventricular posterior wall thickness, and left atrium diameter, and negatively correlated with age. Furthermore, the HD patients with LVH had higher median serum HA levels than those without LVH (34.2 vs. 18.1 μg/ml, p = 0.003). Multiple logistic regression analysis revealed that HA was independently associated with LVH even after adjusting for known biomarkers. Moreover, the receiver operator characteristics curve of HA showed that a HA level of >26.9 μg/ml was associated with LVH. HA was significantly associated with LVH. HA could be a novel biomarker of left ventricular overload, which is closely associated with an increased risk of death in HD patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Natriuretic factor, a lasting enigma.

PubMed

Licht, A; Fine, L G; Bourgoignie, J J

1978-01-01

A gel filtration fraction of urine from patients with chronic uremia (natriuretic factor) decreases potential difference, net sodium flux and lumen to peritubular flux of sodium across the isolated rabbit cortical collecting tubule. These effects are consistent with the possibility that natriuretic factor represents a modulator of sodium excretion in the mammalian nephron. Natriuretic factor induces a dose-dependent inhibition of short-circuit current in the isolated toad bladder. By comparing the effects of natriuretic factor to those of a standard unit of reference, it may be possible to develop a quantitative assay for natriuretic factor. The acidic nature of natriuretic factor was confirmed by cation exchange column in a high pressure liquid chromatography system.

Profound metabolic acidosis from pyroglutamic acidemia: an underappreciated cause of high anion gap metabolic acidosis.

PubMed

Green, Thomas J; Bijlsma, Jan Jaap; Sweet, David D

2010-09-01

The workup of the emergency patient with a raised anion gap metabolic acidosis includes assessment of the components of “MUDPILES” (methanol; uremia; diabetic ketoacidosis; paraldehyde; isoniazid, iron or inborn errors of metabolism; lactic acid; ethylene glycol; salicylates). This approach is usually sufficient for the majority of cases in the emergency department; however, there are many other etiologies not addressed in this mnemonic. Organic acids including 5-oxoproline (pyroglutamic acid) are rare but important causes of anion gap metabolic acidosis. We present the case of a patient with profound metabolic acidosis with raised anion gap, due to pyroglutamic acid in the setting of malnutrition and chronic ingestion of acetaminophen.

Production of recombinant human beta2-microglobulin for scintigraphic diagnosis of amyloidosis in uremia and hemodialysis.

PubMed

Linke, R P; Schäeffer, J; Gielow, P; Lindner, P; Lottspeich, F; Plückthun, A; Weiss, E H

2000-02-01

Amyloid of beta2-microglobulin (beta2m) origin can be diagnosed using 131I-radiolabelled-beta2m scintigraphy in patients with uremia and hemodialysis treatment. As the tracer beta2m is isolated from another patient, it carries the common risks, including viral infections such as Hepatitis B, C and HIV, which are associated with human plasma products. In order to exclude these risks we have produced recombinant human beta2m (rhbeta2m) in Escherichia coli. The expression vector pASK40DeltaLbeta2m(His)5 contains a C-terminal (His)5-tag for purification via immobilized metal ion affinity chromatography (IMAC). Size exclusion chromatography on a Superose 12 column represents the second step of purification. The isolated rhbeta2mH5 reacted in an immunochemically identical manner to native human beta2m, and showed a single band of approximately 11.8 kDa in Western blot analysis and revealed a single spot in two-dimensional gel electrophoresis. Mass spectrometry analysis revealed a single peak at the expected molecular mass of 12 415.8 Da. Uniformity was further proven by crystallization and N-terminal amino-acid sequence analysis. The rhbeta2mH5 protein was then produced under conditions that allow the intravenous use in humans. Intraveneously applied indium-111-labelled rhbeta2mH5 was monitored in hemodialysed patients with and without known beta2m-amyloidosis. The tracer was localized specifically to particular areas known to contain amyloid. Thus, this rhbeta2mH5 preparation is suitable for detecting amyloid-containing organs of the beta2m-class in vivo and fulfils the requirements of a tracer for common use. Finally, the use of indium-111 instead of iodine-131 has reduced the radioactive load and resulted in higher resolution.

Effect of variations in dietary Pi intake on intestinal Pi transporters (NaPi-IIb, PiT-1, and PiT-2) and phosphate-regulating factors (PTH, FGF-23, and MEPE).

PubMed

Aniteli, Tatiana Martins; de Siqueira, Flávia Ramos; Dos Reis, Luciene Machado; Dominguez, Wagner Vasques; de Oliveira, Elizabeth Maria Costa; Castelucci, Patrícia; Moysés, Rosa Maria Affonso; Jorgetti, Vanda

2018-04-01

Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (P i ) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent P i absorption is modulated by dietary P i . Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary P i concentration over 2 days would alter hormones involved in P i metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine. The animals were divided into groups receiving different levels of dietary phosphate: low (Nx/LP i ), normal (Nx/NP i ), and high (Nx/HP i ). Serum phosphate, fractional excretion of phosphate, intact serum fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were significantly higher and ionized calcium was significantly lower in the Nx/HP i group than in the Nx/LP i group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LP i group compared with the Nx/HP i group. Modification of P i concentration in the diet affected the apoptosis of enterocytes, particularly with P i overload. MEPE expression was higher in the Nx/HP i group than in the Nx/NP i . These data reveal the importance of early control of P i in uremia to prevent an increase in serum PTH and FGF-23. Uremia may be a determining factor that explains the expressional modulation of the cotransporters in the small intestine segments.

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.

Diminished parathyroid gland responsiveness to hypocalcemia in diabetic patients with uremia.

PubMed

Heidbreder, E; Götz, R; Schafferhans, K; Heidland, A

1986-01-01

The parathyroid gland responsiveness to hypocalcemia induced by short-term calcium-free hemodialysis in patients with insulin-dependent diabetes mellitus was investigated in comparison with 10 nondiabetic uremic patients and compared with test results from the autonomic nervous system. Diabetic patients had lower C-terminal parathyroid hormone (cPTH) levels before hemodialysis than uremic control patients and showed a significantly smaller increase in cPTH during hypocalcemia. The neurological tests revealed severe disturbances of the autonomic functions in the diabetic group. In conclusion, the disturbances observed in the parathyroid secretory pattern are probably caused by gland dysfunction; it is hypothesized that the defective autonomic nervous system has an additional effect on the development of this hormonal dysfunction.

Recent progress in the analysis of uremic toxins by mass spectrometry.

PubMed

Niwa, Toshimitsu

2009-09-01

Mass spectrometry (MS) has been successfully applied for the identification and quantification of uremic toxins and uremia-associated modified proteins. This review focuses on recent progress in the analysis of uremic toxins by using MS. Uremic toxins include low-molecular-weight compounds (e.g., indoxyl sulfate, p-cresol sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, asymmetric dimethylarginine), middle-molecular-weight peptides, and proteins modified with advanced glycation and oxidation. These uremic toxins are considered to be involved in a variety of symptoms which may appear in patients with stage 5 chronic kidney disease. Based on MS analysis of these uremic toxins, the pathogenesis of the uremic symptoms will be elucidated to prevent and manage the symptoms.

The effect of zinc on cellular immunity in chronic uremia.

PubMed

Antoniou, L D; Shalhoub, R J; Schechter, G P

1981-09-01

Delayed hypersensitivity to mumps was examined in 25 apparently well-nourished men receiving regular hemodialysis, each of whom had a history of mumps. A positive reaction was observed in eight of nine patients already under therapy with zinc added to the dialysis bath. In contrast, 11 of 16 untreated patients were anergic. Four of the anergic patients were subsequently treated with zinc resulting in restoration of sensitivity in three patients. There were no significant differences in lymphocyte, monocyte, or T-cell counts between the two groups of patients. Consequently, zinc probably acts by improving the function of one or more of these cell types. Protracted zinc deficiency may be a major cause of impaired cellular immunity in chronic renal failure.

Shrinking pleuritis with lobar atelectasis, a morphologic variant of round atelectasis

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

Chung-Park, M.; Tomashefski, J.F. Jr.; Cohen, A.M.

1989-04-01

Round atelectasis (shrinking pleuritis) is typically a localized process characterized by focal pleural scarring and subjacent peripheral atelectasis. We report three patients, studied at autopsy, with an unusual variant of round atelectasis, termed shrinking pleuritis with lobar atelectasis, which is characterized by lobar atelectasis, visceral pleural fibrosis involving multiple lobes, interlobar fibrous cords, pleural effusion, and nonspecific, persistent infiltrates on chest radiogram. The possible causes of shrinking pleuritis with lobar atelectasis in our patients were multiple and included environmental dust exposure, infection, uremia, and recurrent pleural effusions. Our findings support both the folding (pleural effusion) and fibrosing (pleural injury) theoriesmore » of pathogenesis of round atelectasis and emphasize the spectrum of morphologic variability in this condition.« less

Bone and mineral disorders after kidney transplantation: therapeutic strategies

PubMed Central

Molnar, Miklos Z.; Naser, Mohamed S.; Rhee, Connie M.; Kalantar-Zadeh, Kamyar; Bunnapradist, Suphamai

2017-01-01

Mineral and bone diseases (MBD) are common in patients with chronic kidney disease who undergo kidney transplantation. The incidence, types and severity of MBD varies according to the duration of chronic kidney disease, presence of comorbid conditions and intake of certain medications. Moreover, multiple types of pathology may be responsible for MBD. After successful reversal of uremia by kidney transplantation, many bone and mineral disorders improve, while immunosuppression, other medications, and new and existing comorbidities may result in new or worsening MBD. Chronic kidney disease is also common after kidney transplantation and may impact bone and mineral disease. In this article, we reviewed the prevalence, pathophysiology, and impact of MBD on post-transplant outcomes. We also discussed the diagnostic approach; immunosuppression management and potential treatment of MBD in kidney transplant recipients. PMID:24462303

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.

Algorithm for optimal dialysis access timing.

PubMed

Heaf, J G

2007-02-01

Acute initiation of dialysis is associated with increased morbidity due to access and uremia complications. It is frequent despite early referral and regular out-patient control. We studied factors associated with end-stage renal disease (ESRD) progression in order to optimize the timing of dialysis access (DA). In a retrospective longitudinal study (Study 1), the biochemical and clinical course of 255 dialysis and 64 predialysis patients was registered to determine factors associated with dialysis-free survival (DFS). On the basis of these results an algorithm was developed to predict timely DA, defined as >6 weeks and <26 weeks before dialysis initiation, with too late placement weighted twice as harmful as too early. The algorithm was validated in a prospective study (Study 2) of 150 dialysis and 28 predialysis patients. Acute dialysis was associated with increased 90-day hospitalization (17.9 vs. 9.0 days) and mortality (14% vs. 6%). P-creatinine and p-urea were poor indicators of DFS. At any level of p-creatinine, DFS was shorter with lower creatinine clearance and vice versa. Patients with systemic renal disease had a significantly shorter DFS than primary renal disease, due to faster GFR loss and earlier dialysis initiation. Short DFS was seen with hypoalbuminemia and cachexia; these patients were recommended early DA. The following algorithm was used to time DA (units: 1iM and ml/min/1.73 m2): P-Creatinine - 50 x GFR + (100 if Systemic Renal Disease) >200. Use of the algorithm was associated with earlier dialysis placement and a fall in acute dialysis requirements from 50% to 23%. The incidence of too early DA was unchanged (7% vs. 9%), and was due to algorithm non-application. The algorithm failed to predict imminent dialysis in 10% of cases, primarily due to acute exacerbation of stable uremia. Dialysis initiation was advanced by approximately one month. A predialysis program based on early dialysis planning and GFR-based DA timing may reduce the requirement for acute dialysis initiation and patient morbidity and mortality, at the cost of slightly earlier dialysis initiation.

Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients.

PubMed

Libetta, C; Rampino, T; Dal Canton, A

2001-08-01

T-helper (Th) lymphocytes consist of Th1 and Th2 subsets. Th1 cells are effectors of cell-mediated immunity and secrete interferon-gamma (IFN-gamma), which recruits new Th1 cells in cooperation with interleukin-12 (IL-12; produced by monocytes) and inhibits Th2 differentiation. Th2 cells produce IL-4 and IL-10, which inhibit IFN-gamma secretion and cell immunity. We investigated whether the impaired immune response in uremia is associated with an altered balance of Th1/Th2. Peripheral-blood mononuclear cells (PBMCs) were collected from patients with chronic renal failure (CRF) on conservative treatment (CRF patients), patients with end-stage renal disease (ESRD) on regular hemodialysis therapy (ESRD-HD patients), and healthy controls (CON). CD4(+) cells were isolated from PBMCs by negative selection using a magnetic labeling system. PBMCs and purified CD4(+) cells were cultured in Iscove's medium and Iscove's medium plus mitogens (phytohemagglutinin and lipopolysaccharide). IFN-gamma, IL-12, IL-4, and IL-10 were measured in supernatant. The constitutive release of IL-4 and IL-10 by PBMCs and CD4(+) cells of CRF and ESRD-HD patients was increased by five to eight times in comparison with CON (P < 0.001). Constitutive IFN-gamma release by PBMCs of ESRD-HD patients was undetectable, although they secreted an increased amount of IL-12. Mitogen-stimulated release of IFN-gamma by PBMCs and CD4(+) cells of CRF and ESRD-HD patients was blunted (average PBMCs: CON, 115.8 pg/2 x10(6) cells; CRF, 81.8 pg/2 x10(6) cells; ESRD-HD, 9.3 pg/2 x10(6) cells; CD4(+) cells: CON, 358.0 pg/5 x 10(5) cells; CRF, 165.4 pg/5 x 10(5) cells; ESRD-HD, 43.5 pg/5 x 10(5) cells). The ability of PBMCs of ESRD-HD patients to secrete IFN-gamma was recovered after IL-4 and IL-10 neutralization. Uremia is associated with a prevalence of Th1 over Th2 cells and a configuration of cytokine network that depresses cell-mediated immunity.

Effects of end-stage renal disease and dialysis modalities on blood ammonia level

PubMed Central

VAZIRI, Nosratola D.; KHAZAELI, Mahyar; NUNES, Ane C. F.; HARLEY, Kevin T.; SAID, Hyder; ALIPOUR, Omeed; LAU, Wei Ling; PAHL, Madeleine V.

2018-01-01

Introduction Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 1 0-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Methods Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. Findings No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P<0.001) which was paradoxically accompanied by a modest but significant (P<0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre- and post-hemodialysis correlated with change in serum bicarbonate levels (r=0.61, P<0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r=0.88, P<0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124±8vs.136±6mmHg respectively, P=0.27). Discussion Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure. PMID:27804262

Effects of end-stage renal disease and dialysis modalities on blood ammonia level.

PubMed

Vaziri, Nosratola D; Khazaeli, Mahyar; Nunes, Ane C F; Harley, Kevin T; Said, Hyder; Alipour, Omeed; Lau, Wei Ling; Pahl, Madeleine V

2017-07-01

Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P < 0.001) which was paradoxically accompanied by a modest but significant (P < 0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre- and post-hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P < 0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P < 0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27). Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure. © 2016 International Society for Hemodialysis.

Pathways of the Maillard reaction under physiological conditions.

PubMed

Henning, Christian; Glomb, Marcus A

2016-08-01

Initially investigated as a color formation process in thermally treated foods, nowadays, the relevance of the Maillard reaction in vivo is generally accepted. Many chronic and age-related diseases such as diabetes, uremia, atherosclerosis, cataractogenesis and Alzheimer's disease are associated with Maillard derived advanced glycation endproducts (AGEs) and α-dicarbonyl compounds as their most important precursors in terms of reactivity and abundance. However, the situation in vivo is very challenging, because Maillard chemistry is paralleled by enzymatic reactions which can lead to both, increases and decreases in certain AGEs. In addition, mechanistic findings established under the harsh conditions of food processing might not be valid under physiological conditions. The present review critically discusses the relevant α-dicarbonyl compounds as central intermediates of AGE formation in vivo with a special focus on fragmentation pathways leading to formation of amide-AGEs.

[What you should know of the arterial blood gases during the watch].

PubMed

Márquez-González, Horacio; Pámanes-González, Jesús; Márquez-Flores, Horacio; Gómez-Negrete, Alonso; Muñoz-Ramírez, Mireya C; Villa-Romero, Antonio Rafael

2012-01-01

Gasometry is the measurement of dissolved gases in the blood, by measuring pH, carbon dioxide pressure (pCO(2)), serum bicarbonate (HCO(3-)), and lactate and serum electrolytes: sodium, potassium and chlorine you can make a diagnosis, etiology and treatment in the critically ill patient. The aim is to provide five steps for the interpretation of blood gases by: 1. The definition of acidemia or acidosis, or alkalemia or alkalosis. 2. Defining the metabolic component or respiratory. 3. To determine the anion gap; levels above 15 ± 2 determine other likely causes of excess anions (methanol, uremia, diabetic ketoacidosis, paraldehyde, ionized, lactic acidosis, ethylene glycol and salicylates. 4. Compensation, using the Winter formula. 5. The delta gap, with the formula for determining intrinsic and metabolic alkalosis. When anion gap is normal, is calculated urinary anion gap; the value is negative if the loss is extrarenal, contrary to the positive result is renal etiology.

McKittrick-Wheelock syndrome - a rare cause of acute renal failure.

PubMed

Popescu, Alina; Orban-Schiopu, Ana-Maria; Becheanu, Gabriel; Diculescu, Mircea

2005-03-01

Fluid and electrolyte hypersecretion in the villous adenoma of the rectum is presented in the case of a 74 year old man presenting with a severe fluid imbalance. The patient had a 2-year history of mucous diarrhea and, on admission, presented prerenal uremia, hyponatremia and severe hypokalemia. At sigmoidoscopy, a 6/4 cm villous adenoma of the rectum was found. The increased loss of volume, followed by exhaustion of the physiological compensation mechanisms, led to a life-threatening hypokalemia, as well as to acute renal failure. Conservative treatment was followed by a temporary improvement of the renal function. Alternative treatment was: endocavitary irradiation, endoscopic resection and radical tumor surgery. The surgical removal of the adenoma led to complete recovery of the symptoms. The McKittrick-Wheelock syndrome can be a problem of difficult diagnosis, both for the gastroenterologist and also for the nephrologist. The patient may develop severe complications, which require a sustained treatment.

The impact of gut microbiota on kidney function and pathogenesis.

PubMed

Mahmoodpoor, Fariba; Rahbar Saadat, Yalda; Barzegari, Abolfazl; Ardalan, Mohammadreza; Zununi Vahed, Sepideh

2017-09-01

Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Rejection of isolated pancreatic allografts in patients with with diabetes.

PubMed

Groth, C G; Lundgren, G; Arner, P; Collste, H; Hårdstedt, C; Lewander, R; Ostman, J

1976-12-01

Four patients with diabetes mellitus of juvenile onset but without uremia have been treated with segmental transplantation of the body and tail of pancreas. The indications were hyperlabile diabetes or progressive loss of vision. The grafts were procured from cadaveric donors four to 16 minutes after circulary arrest and were subsequently stored in the cold for approximately four hours. In one patient, the pancreatic duct was ligated, while in the other three, drainage was attained by suturing the transected end of the pancreas into a jejunal Roux-en-Y loop. Three of the grafts failed within six weeks as a result of irreversible refection, and one graft failed because of the early onset of venous thrombosis. The first sign of graft rejection was an increase in the postprandial blood sugar level, an increase in the fasting blood sugar level occurring several days later. Neither hyperamylasemia nor fever was observed. Radioisotope scans and angiograms were of great value in establishing the diagnosis of graft rejection. All of the patients survived after graft removal.

Feline congenital erythropoietic porphyria associated with severe anemia and renal disease. Clinical, morphologic, and biochemical studies.

PubMed Central

Giddens, W. E.; Labbe, R. F.; Swango, L. J.; Padgett, G. A.

1975-01-01

A feline erythropoietic porphyria was studied in an affected female Siamese cat and 2 male offspring. The principal elevated porphyrins were Type I isomers of uroporphyrin and coproporphyrin; the porphyrin precursors, porphobilinogen and sigma-aminolevulinic acid, were also detected. Porphyrins were present in the blood and in all the viscera, teeth, bones, and excreta. There was severe macrocytic hypochromic anemia, hepatomegaly, splenomegaly, and uremia associated with a renal disease characterized by mesangial hypercellularity and proliferation (resulting in narrowing of glomerular capillaries) and ischemic tubular injury. There was thickening of tubular basement membranes and tubular epithelial lipidosis, degeneration, and necrosis. Electron microscopic studies of bone marrow and kidney revealed the presence of membrane-enclosed lamellar bodies 150 to 1000 nm in diameter in cytoplasmic and extracellular locations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:1231563

Nephron sparing by partial median nephrectomy for treatment of renal hemangioma in a dog.

PubMed

Mott, J C; McAnulty, J F; Darien, D L; Steinberg, H

1996-04-15

A 6-year-old neutered male Golden Retriever was admitted for evaluation of intermittent hematuria of 2 months' duration. A 3-cm heterogeneous mass causing distortion of the caudomedial aspect of the left kidney was detected via ultrasonography. Histologic examination of a renal tissue sample obtained by ultrasound-guided biopsy revealed a telangiectatic vascular plexus of unknown origin. Low glomerular filtration rate was identified by a modified exogenous creatinine clearance test. Excretory urography revealed a filling defect in the medial aspect of the caudal pole of the kidney, near the hilus. Because total renal function was low, a decision was made to perform nephron-sparing surgery involving resection of centrally located renal parenchymal and pelvic tissue by en bloc resection in the median plane, instead of radical nephrectomy. After surgery, the hematuria resolved and further decrease in renal function was not evident. Nephron-sparing surgery is a viable option for dogs with compromised renal function when there is concern that radical nephrectomy may precipitate uremia.

Disseminated toxoplasmosis in a patient with advanced acquired immunodeficiency syndrome

PubMed Central

Pastorello, Ricardo Garcia; Costa, Anderson da Costa Lino; Sawamura, Marcio Valente Yamada; Nicodemo, Antonio Carlos

2018-01-01

Extracerebral toxoplasmosis, with pulmonary involvement and shock, is a rare form of toxoplasmosis in patients with advanced AIDS. It can mimic pneumocystosis, histoplasmosis, and disseminated tuberculosis, and should be considered in the differential diagnosis of causes of respiratory failure and fulminant disease in this group of individuals, especially in areas where the Toxoplasma gondii infection is highly prevalent and in those without proper use of antimicrobial prophylaxis. We report the case of a 46-year-old male patient who presented to the emergency department with uremia, requiring urgent dialysis. During the laboratorial investigation, the patient had confirmed HIV infection, with a low CD4+ peripheral T-cell count (74 cells/µL). During hospitalization, the patient presented drug-induced hepatitis due to trimethoprim/sulfamethoxazole in a prophylactic dose, requiring interruption of this medication. On the 55th day of hospitalization, the patient developed refractory shock and died. At the autopsy, disseminated toxoplasmosis with encephalitis and severe necrotizing pneumonia were diagnosed, with numerous tachyzoites in the areas of pulmonary necrosis. PMID:29588907

Endothelial Progenitor Cells and Kidney Diseases.

PubMed

Ozkok, Abdullah; Yildiz, Alaattin

2018-05-10

Endothelial progenitor cells (EPC) are bone marrow derived or tissue-resident cells that play major roles in the maintenance of vascular integrity and repair of endothelial damage. Although EPCs may be capable of directly engrafting and regenerating the endothelium, the most important effects of EPCs seem to be depended on paracrine effects. In recent studies, specific microvesicles and mRNAs have been found to mediate the pro-angiogenic and regenerative effects of EPCs on endothelium. EPC counts have important prognostic implications in cardiovascular diseases (CVD). Uremia and inflammation are associated with lower EPC counts which probably contribute to increased CVD risks in patients with chronic kidney disease. Beneficial effects of the EPC therapies have been shown in studies performed on different models of CVD and kidney diseases such as acute and chronic kidney diseases and glomerulonephritis. However, lack of a clear definition and specific marker of EPCs is the most important problem causing difficulties in interpretation of the results of the studies investigating EPCs. © 2018 The Author(s). Published by S. Karger AG, Basel.

Etiology of the protein-energy wasting syndrome in chronic kidney disease: a consensus statement from the International Society of Renal Nutrition and Metabolism (ISRNM).

PubMed

Carrero, Juan Jesús; Stenvinkel, Peter; Cuppari, Lilian; Ikizler, T Alp; Kalantar-Zadeh, Kamyar; Kaysen, George; Mitch, William E; Price, S Russ; Wanner, Christoph; Wang, Angela Y M; ter Wee, Pieter; Franch, Harold A

2013-03-01

Protein-energy wasting (PEW), a term proposed by the International Society of Renal Nutrition and Metabolism (ISRNM), refers to the multiple nutritional and catabolic alterations that occur in chronic kidney disease (CKD) and associate with morbidity and mortality. To increase awareness, identify research needs, and provide the basis for future work to understand therapies and consequences of PEW, ISRNM provides this consensus statement of current knowledge on the etiology of PEW syndrome in CKD. Although insufficient food intake (true undernutrition) due to poor appetite and dietary restrictions contribute, other highly prevalent factors are required for the full syndrome to develop. These include uremia-induced alterations such as increased energy expenditure, persistent inflammation, acidosis, and multiple endocrine disorders that render a state of hypermetabolism leading to excess catabolism of muscle and fat. In addition, comorbid conditions associated with CKD, poor physical activity, frailty, and the dialysis procedure per se further contribute to PEW. Published by Elsevier Inc.

In vivo imaging of advanced glycation end products (AGEs) of albumin: first observations of significantly reduced clearance and liver deposition properties in mice.

PubMed

Tsutsui, Ayumi; Ogura, Akihiro; Tahara, Tsuyoshi; Nozaki, Satoshi; Urano, Sayaka; Hara, Mitsuko; Kojima, Soichi; Kurbangalieva, Almira; Onoe, Hirotaka; Watanabe, Yasuyoshi; Taniguchi, Naoyuki; Tanaka, Katsunori

2016-06-15

Advanced glycation end products (AGEs) are associated with various diseases, especially during aging and the development of diabetes and uremia. To better understand these biological processes, investigation of the in vivo kinetics of AGEs, i.e., analysis of trafficking and clearance properties, was carried out by molecular imaging. Following the preparation of Cy7.5-labeled AGE-albumin and intravenous injection in BALB/cA-nu/nu mice, noninvasive fluorescence kinetics analysis was performed. In vivo imaging and fluorescence microscopy analysis revealed that non-enzymatic AGEs were smoothly captured by scavenger cells in the liver, i.e., Kupffer and other sinusoidal cells, but were unable to be properly cleared from the body. Overall, these results highlight an important link between AGEs and various disorders associated with them, which may serve as a platform for future research to better understand the processes and mechanisms of these disorders.

[Hemodialysis in patients with chronic renal insufficiency].

PubMed

Canaud, Bernard; Leray-Moragués, Hélène; Chenine-Koualef, Leila; Patrier, Laure

2012-01-01

Hemodialysis is the most advanced form of artificial renal support. It ensures the survival of almost 2 million patients wordwide. Considerable progress has been made in recent years thanks to a better understanding of uremia, optimization of treatment modalities and more personalized treatment schedules. Increase of uremic toxins removal, improvement of hemodynamic tolerance of the sessions, reduction of proinflammatory reactions due to the bioincompatibility system are major advances that may explain the reduction of morbidity and mortality in dialysis patients. New technologies (nanotechnology, biotechnology, microelectronics) are now expected to introduce further progresses by miniaturizing devices and providing them with an "artificial intelligence" capable of interacting with the patient. The main obstacle remains ageing of uremic patients, increasing prevalence of comorbidities and shortage of social resources that are not conducive to innovation. By promoting a more physiological, longer and more effective hemodialysis performed at home with help of teledialysis monitoring that would probably be an interesting option to evaluate on a medico-economical point of view.

Grape seed proanthocyanidin extract protects human umbilical vein endothelial cells from indoxyl sulfate-induced injury via ameliorating mitochondrial dysfunction.

PubMed

Lu, Zhaoyu; Lu, Fuhua; Zheng, Yanqun; Zeng, Yuqun; Zou, Chuan; Liu, Xusheng

2016-01-01

To investigate the effects of grape seed proanthocyanidin extract (GSPE) on indoxyl sulfate-induced Human Umbilical Vein Endothelial Cells (HUVECs) injury in vitro and study its mechanism. HUVECs were incubated with indoxyl sulfate at concentrations in the range found in uremic patients. Then we determined the effect of indoxyl sulfate on endothelial phenotype, endothelial function, ROS (reactive oxygen species), cell apoptosis and mitochondrial function. In addition, we detected whether GSPE can suppress the injury of HUVECs induced by indoxyl sulfate and probe the mechanism underlying the protective effects of GSPE by analyzing mitochondrial dysfunction. GSPE treatment significantly attenuated indoxyl sulfate-induced HVUECs injury in a dose- and time-dependent manner. GSPE-enhanced eNOS and VE-cadherin expression, inhibited intracellular ROS level and cell apoptosis, adjust mitochondrial membrane potential and reduced 8-hydroxy-desoxyguanosine (8-OHdG) level induced by indoxyl sulfate. These results suggest that GSPE prevents HUVECs from indoxyl sulfate-induced injury by ameliorating mitochondrial dysfunction and may be a promising agent for treating uremia toxin-induced injury.

Protective effect of grape seed and skin extract against diabetes-induced oxidative stress and renal dysfunction in virgin and pregnant rat.

PubMed

Oueslati, Nourhene; Charradi, Kamel; Bedhiafi, Takwa; Limam, Ferid; Aouani, Ezzedine

2016-10-01

The present work deal with the effect of alloxan-induced diabetes on kidney oxidative stress and dysfunction of virgin and pregnant rat as well as the protection that may be afforded by high dosage GSSE (4g/kg) treatment. Diabetes affected negatively several kidney function parameters as creatinemia, uremia, uricemia and proteinuria without affecting kidney index. Diabetes also induced an oxidative stress characterized by increased lipid and protein oxidation, a drop in antioxidant enzyme defenses as catalase, superoxide-dismutase, glutathione-peroxidase, an alteration in transition metals as free iron, copper, selenium and associated enzymes and an increase in calpain and acetyl-cholinesterase activities. Tremendously, GSSE treatment protected efficiently against all the deleterious effects of diabetes-induced kidney dysfunction in both virgin and pregnant animals. High dosage GSSE is a safe and potent anti-oxidant that may be further tested in clinical trials for the long-term preservation of kidney function especially in multiple pregnancies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Cyclooxygenase 2 Promotes Parathyroid Hyperplasia in ESRD

PubMed Central

Zhang, Qian; Qiu, Junsi; Li, Haiming; Lu, Yanwen; Wang, Xiaoyun; Yang, Junwei; Wang, Shaoqing; Zhang, Liyin; Gu, Yong; Hao, Chuan-Ming

2011-01-01

Hyperplasia of the PTG underlies the secondary hyperparathyroidism (SHPT) observed in CKD, but the mechanism underlying this hyperplasia is incompletely understood. Because aberrant cyclooxygenase 2 (COX2) expression promotes epithelial cell proliferation, we examined the effects of COX2 on the parathyroid gland in uremia. In patients with ESRD who underwent parathyroidectomy, clusters of cells within the parathyroid glands had increased COX2 expression. Some COX2-positive cells exhibited two nuclei, consistent with proliferation. Furthermore, nearly 78% of COX2-positive cells expressed proliferating cell nuclear antigen (PCNA). In the 5/6-nephrectomy rat model, rats fed a high-phosphate diet had significantly higher serum PTH levels and larger parathyroid glands than sham-operated rats. Compared with controls, the parathyroid glands of uremic rats exhibited more PCNA-positive cells and greater COX2 expression in the chief cells. Treatment with COX2 inhibitor celecoxib significantly reduced PCNA expression, attenuated serum PTH levels, and reduced the size of the glands. In conclusion, COX2 promotes the pathogenesis of hyperparathyroidism in ESRD, suggesting that inhibiting the COX2 pathway could be a potential therapeutic target. PMID:21335517

Nutritional status, functional capacity and exercise rehabilitation in end-stage renal disease.

PubMed

Mercer, T H; Koufaki, P; Naish, P F

2004-05-01

A significant percentage of patients with end-stage renal disease are malnourished and/or muscle wasted. Uremia is associated with decreased protein synthesis and increased protein degradation. Fortunately, nutritional status has been shown to be a modifiable risk factor in the dialysis population. It has long been proposed that exercise could positively alter the protein synthesis-degradation balance. Resistance training had been considered as the only form of exercise likely to induce anabolism in renal failure patients. However, a small, but growing, body of evidence indicates that for some dialysis patients, favourable improvements in muscle atrophy and fibre hypertrophy can be achieved via predominantly aerobic exercise training. Moreover, some studies tentatively suggest that nutritional status, as measured by SGA, can also be modestly improved by modes and patterns of exercise training that have been shown to also increase muscle fibre cross-sectional area and improve functional capacity. Functional capacity tests can augment the information content of basic nutritional status assessments of dialysis patients and as such are recommended for routine inclusion as a feature of all nutritional status assessments.

Anxiety in Patients Treated with Hemodialysis.

PubMed

Cohen, Scott D; Cukor, Daniel; Kimmel, Paul L

2016-12-07

Anxiety is a common yet frequently overlooked psychiatric symptom in patients with ESRD treated with hemodialysis (HD). Anxiety is characterized by disruptive feelings of uncertainty, dread, and fearfulness. A variety of common medical complaints may be manifestations of an anxiety disorder, including palpitations, tremors, indigestion, numbness/tingling, nervousness, shortness of breath, diaphoresis, and fear. It is essential for the clinician to rule out specific medical conditions, including cardiovascular, pulmonary, and neurologic diseases, before ascribing these symptoms to an anxiety disorder. In addition, there is considerable overlap between the symptoms of anxiety and those of depression and uremia. This psychiatric condition has a significant adverse impact on patients' perception of quality of life. Little is known regarding the prevalence and impact of anxiety disorders in patients with ESRD treated with HD; however, many of the seemingly irrational behaviors of patients, or behaviors which place them in conflict with staff and physicians, such as behavioral noncompliance, may be the expression of an underlying anxiety disorder. In this review, we present three clinical vignettes, highlighting the impact of anxiety disorders in patients with ESRD treated with HD. Copyright © 2016 by the American Society of Nephrology.

Colitis induced by sodium polystyrene sulfonate in sorbitol: A report of six cases.

PubMed

Jacob, Sheba S K; Parameswaran, Ashok; Parameswaran, Sarojini Ashok; Dhus, Ubal

2016-03-01

Drug-related injury has been noted in virtually all organ systems, and recognition of the patterns of injury associated with medication enables modification of treatment and reduces the morbidity associated with the side effects of drugs. With the large number of new drugs being developed, documentation of the morphology of the changes seen as an adverse effect becomes important to characterize the pattern of injury. The pathologist is often the first to identify these abnormalities and correlate them with a particular drug. Kayexalate or sodium polystyrene sulfonate (SPS), a linear polymer derived from polystyrene containing sulfonic acid and sulfonate functional groups is used to treat hyperkalemia. It is usually administered with an osmotic laxative sorbitol orally or as retention enema. This combination has been implicated in causing damage to different parts of the gastrointestinal (GI) tract especially the colon and causes an established pattern of injury, recognizable by the presence of characteristic crystals, is presented to create a greater awareness of the Kayexalate colitis. This entity should be included in the differential diagnosis of lower GI mucosal injury in a setting of uremia and hyperkalemia.

Integrative Examination of Motor Abilities in Dialysis Patients and Selection of Tests for a Standardized Physical Function Assessment.

PubMed

Bučar Pajek, Maja; Leskošek, Bojan; Vivoda, Tjaša; Svilan, Katarina; Čuk, Ivan; Pajek, Jernej

2016-06-01

To reduce the need for a large number of executed physical function tests we examined inter-relations and determined predictive power for daily physical activity of the following tests: 6-min walk, 10 repetition sit-to-stand, time up-and-go, Storke balance, handgrip strength, upper limb tapping and sitting forward bend tests. In 90 dialysis and 140 healthy control subjects we found high correlations between all tests, especially those engaging lower extremities. Sit-to-stand, forward bend and handgrip strength were selected for the test battery and composite motor performance score. Sit-to-stand test was superior in terms of sensitivity to uremia effects and association with daily physical function in adjusted analyses. There was no incremental value in calculating the composite performance score. We propose to standardize the physical function assessment of dialysis patients for cross-sectional and longitudinal observations with three simple, cheap, well-accessible and easily performed test tools: sit-to-stand test, handgrip strength and Human Activity Profile questionnaire. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

Demonstration of 2-hydroxybenzoylglycine as a drug binding inhibitor in newborn infants.

PubMed Central

Suh, B; Wadsworth, S J; Lichtenwalner, D M

1987-01-01

Newborn infants have drug binding defects that share similarities to those of uremic subjects. Since 2-hydroxybenzoylglycine has been chemically defined to be a major drug binding inhibitor in uremia, a search for the presence of a similar compound in the sera of newborn infants was made. An organic substance that has the characteristics of 2-hydroxybenzoylglycine as supported by the retardation factor values on thin-layer chromatograms, retention times of high performance liquid chromatograms, fluorescence emission spectra, and mass spectrum has been demonstrated to be present in the majority of the neonatal sera studied. A strong positive correlation between the levels of the binding inhibitor and the extent of binding defects for nafcillin has been observed. The substance could effectively reduce the total bilirubin concentration when added to the cord sera specimens. It is concluded that 2-hydroxybenzoylglycine plays an important role in drug binding defects observed in the newborn, and the inhibitor may also play a part in the precipitation of bilirubin-induced neurotoxicity in neonates when the substance is abnormally elevated. Images PMID:3654972

Potentials and limitations of microorganisms as renal failure biotherapeutics

PubMed Central

Jain, Poonam; Shah, Sapna; Coussa, Razek; Prakash, Satya

2009-01-01

Renal insufficiency leads to uremia, a complicated syndrome. It thus becomes vital to reduce waste metabolites and regulate water and electrolytes in kidney failure. The most common treatment of this disease is either dialysis or transplantation. Although these treatments are very effective, they are extremely costly. Recently artificial cells, microencapsulated live bacterial cells, and other cells have been studied to manage renal failure metabolic wastes. The procedure for microencapsulation of biologically active material is well documented and offers many biomedical applications. Microencapsulated bacteria have been documented to efficiently remove urea and several uremic markers such as ammonia, creatinine, uric acid, phosphate, potassium, magnesium, sodium, and chloride. These bacteria also have further potential as biotherapeutic agents because they can be engineered to remove selected unwanted waste. This application has enormous potential for removal of waste metabolites and electrolytes in renal failure as well as other diseases such as liver failure, phenylketonuria, and Crohn’s disease, to name a few. This paper discusses the various options available to date to manage renal failure metabolites and focuses on the potential of using encapsulated live cells as biotherapeutic agents to control renal failure waste metabolites and electrolytes. PMID:19707412

Proteomic Investigations into Hemodialysis Therapy

PubMed Central

Bonomini, Mario; Sirolli, Vittorio; Pieroni, Luisa; Felaco, Paolo; Amoroso, Luigi; Urbani, Andrea

2015-01-01

The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane’s performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane’s bio(in)compatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research. PMID:26690416

Effects of chronic kidney disease on liver transport: quantitative intravital microscopy of fluorescein transport in the rat liver.

PubMed

Ryan, Jennifer C; Dunn, Kenneth W; Decker, Brian S

2014-12-15

Clinical studies indicate that hepatic drug transport may be altered in chronic kidney disease (CKD). Uremic solutes associated with CKD have been found to alter the expression and/or activity of hepatocyte transporters in experimental animals and in cultured cells. However, given the complexity and adaptability of hepatic transport, it is not clear whether these changes translate into significant alterations in hepatic transport in vivo. To directly measure the effect of CKD on hepatocyte transport in vivo, we conducted quantitative intravital microscopy of transport of the fluorescent organic anion fluorescein in the livers of rats following 5/6th nephrectomy, an established model of CKD. Our quantitative analysis of fluorescein transport showed that the rate of hepatocyte uptake was reduced by ∼20% in 5/6th nephrectomized rats, consistent with previous observations of Oatp downregulation. However, the overall rate of transport into bile canaliculi was unaffected, suggesting compensatory changes in Mrp2-mediated secretion. Our study suggests that uremia resulting from 5/6th nephrectomy does not significantly impact the overall hepatic clearance of an Oatp substrate. Copyright © 2014 the American Physiological Society.

Technical note. The serum concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine is increased in uremia.

PubMed

Degenhardt, T P; Grass, L; Reddy, S; Thorpe, S R; Diamandis, E P; Baynes, J W

1997-10-01

Advanced glycation end products (AGEs) such as pentosidine and N epsilon-(carboxymethyl)lysine (CML) have been traditionally quantified by HPLC or gas chromatography--mass spectrometry (GC/MS). Enzyme-linked immunosorbent assays (ELISA) have been introduced as a convenient alternative to simplify the detection and measurement of AGEs in proteins and tissues, but some of these studies are limited by the lack of information on the structure of the epitopes recognized by antibodies to AGE-proteins. In this work we demonstrate that an antibody used in a previous study, reporting increased levels of AGEs in patients with diabetes or on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD), recognizes CML as its major epitope. We also show that there is a significant correlation between the concentration of AGEs in serum measured by ELISA and a GC/MS assay for CML in serum proteins. Both analyses yielded comparable results, with patients on CAPD and HD having about threefold higher AGE- or CML-concentrations in their serum. Our data suggest that ELISA assays for CML should be useful for the clinical measurement of AGEs in serum proteins.

Captain Lord's uremia.

PubMed

Wyner, Lawrence Michael

2013-06-01

The hundredth anniversary of the worst ever civilian maritime disaster was also the fiftieth anniversary of the death of arguably its most controversial character, Captain Stanley Lord, skipper of the Californian, a "tramp" steamer that became entrapped in ice just off the Grand Banks of Newfoundland on April 14, 1912. Although Lord was faulted in two widely publicized inquiries for failing to respond to Titanic's distress signals, there may have actually been a medical reason for his behavior because he suffered from chronic renal disease and most likely had some secondary cognitive impairment due to this disease. An assessment of Lord's health history shows that he fractured his leg as a young man; suffered from poor eyesight, which led to his premature retirement from the sea by the age of 50; and eventually died from renal failure. Furthermore, his death certificate alludes to previous uremic episodes, perhaps encompassing the time period of the Titanic accident. Lord may have been under some pressure not to reveal his infirmity because doing so could have further jeopardized his career. The literature abounds with evidence that renal insufficiency negatively affects cognition, often years before progression to end-stage renal disease. Captain Lord's failure to act in a crisis situation may serve as a case in point.

Current status of the microbiome in renal transplantation.

PubMed

Ahmad, Sarwat; Bromberg, Jonathan S

2016-11-01

An imbalance between pathogenic and protective microbiota characterizes dysbiosis. Presence of dysbiosis may affect immunity, tolerance, or disease depending on a variety of conditions. In the transplant patient population, the need for immunosuppression and widespread use of prophylactic and therapeutic antimicrobial agents create new posttransplant microbiota communities that remain to be fully defined. Studies in mice have demonstrated significant bidirectional interactions between microbiota-derived products and host immune cells. The stimulation of regulatory T cell and T helper cell type 17 cells by specific products leads to maintenance of immune homeostasis versus activation of inflammation, respectively. Dysbiosis may lead to development of antigen cross-reactivity, which may affect alloreactivity. Certain immunologic sequelae of microbiota are pronounced in chronic kidney disease, because of uremia and renal metabolism of microbiota metabolites. Dietary modifications, probiotics, and fecal microbiota transplant have been investigated for alteration of microbiota in humans. Researchers have begun to identify dysbioses associated with clinical conditions, including chronic kidney disease, posttransplant infection, and rejection. This information will allow clinicians not only to select at-risk patients for early intervention, but also to develop therapies that restore the microbiota to a state of homeostasis or tolerance.

Influence of salt intake, ANG II synthesis and SFO lesion on thirst and blood pressure during sodium depletion. Subfornical organ.

PubMed

Starbuck, E M; Fitts, D A

1998-12-01

Water intake was elevated in sodium-depleted rats during a daytime salt appetite test, but other rats drank a similar amount of water when saline was not available for drinking during the test. This water intake stimulated by sodium depletion was blocked by an inhibition of angiotensin (ANG) II synthesis with a high dose of captopril (100 mg/kg, sc). Captopril did not reduce water intake by causing hypotensive shock or uremia, because water and saline intakes were increased rather than decreased after a low dose of captopril (5 mg/kg) that also reduced blood pressure and elevated blood urea nitrogen. The water intake, but not salt appetite, induced by sodium depletion was greatly reduced by a lesion of the subfornical organ (SFO) in one-bottle tests, and this was not clearly related to any effects of the lesion on blood pressure. A physiological role for ANG II in water intake induced by sodium depletion has recently been disputed, but the simplest explanation for the data remains that elevated levels of circulating ANG II bind to receptors in the SFO to generate daytime water drinking during sodium depletion.

Parathyroid diseases and animal models.

PubMed

Imanishi, Yasuo; Nagata, Yuki; Inaba, Masaaki

2012-01-01

CIRCULATING CALCIUM AND PHOSPHATE ARE TIGHTLY REGULATED BY THREE HORMONES: the active form of vitamin D (1,25-dihydroxyvitamin D), fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH). PTH acts to stimulate a rapid increment in serum calcium and has a crucial role in calcium homeostasis. Major target organs of PTH are kidney and bone. The oversecretion of the hormone results in hypercalcemia, caused by increased intestinal calcium absorption, reduced renal calcium clearance, and mobilization of calcium from bone in primary hyperparathyroidism. In chronic kidney disease, secondary hyperparathyroidism of uremia is observed in its early stages, and this finally develops into the autonomous secretion of PTH during maintenance hemodialysis. Receptors in parathyroid cells, such as the calcium-sensing receptor, vitamin D receptor, and FGF receptor (FGFR)-Klotho complex have crucial roles in the regulation of PTH secretion. Genes such as Cyclin D1, RET, MEN1, HRPT2, and CDKN1B have been identified in parathyroid diseases. Genetically engineered animals with these receptors and the associated genes have provided us with valuable information on the patho-physiology of parathyroid diseases. The application of these animal models is significant for the development of new therapies.

Kidney-Heart Interactions in Acute Kidney Injury.

PubMed

Doi, Kent

2016-01-01

Acute kidney injury (AKI) is a common complication in critically ill patients treated in intensive care units. Renal replacement therapy (RRT)-requiring AKI occurs in approximately 5-10% patients in intensive care unit and their mortality rate is unacceptably high (50-60%), despite sufficient control of uremia using remarkably advanced modern RRT techniques. This suggests that there are unrecognized organ interactions following AKI that could worsen the outcomes. Cardiorenal syndrome has been defined based on clinical observations that acute and chronic heart failure causes kidney injury and AKI and that chronic kidney disease worsens heart diseases. Possible pathways that connect these 2 organs have been suggested; however, the precise mechanisms are yet to be clarified, particularly in AKI-induced cardiac dysfunction. This review focuses on acute cardiac dysfunction in the setting of AKI. A recent animal study demonstrated the dysregulation of mitochondrial dynamics caused by an increased dynamin-related protein 1 expression and cellular apoptosis of the heart in a renal ischemia reperfusion model. Although the precise mechanisms that induce cardiac mitochondrial injury in AKI remain unclear, cardiac mitochondria injury could be a novel candidate of drug targets against high mortality in severe AKI. © 2016 S. Karger AG, Basel.

Ferrokinetics in Patients on CAPD: Influence of CAPD on the Anemia of Uremia*

PubMed Central

Lee, Hi Bahl; Koh, Seong Won; Park, Hee Sook

1986-01-01

Ferrokinetic studies were performed with 59Fe-citrate to evaluate erythropoietic activity in CAPD patients and to investigate the mechanism(s) by which the hematocrit increases in CAPD patients. Plasma iron disappearance rate (PID), plasma iron turnover rate (PIT), red cell iron utilization (RCIU), red cell iron turnover rate (RCIT) and marrow transit time (MTT) were all “normal” in uremic patients not yet on dialysis (Hct 23.8±3.4%), CAPD patients with persistently low hematocrit (Hct 24.9±1.8%) and CAPD patients with improved hematocrit (Hct 32.4±3.1%). Compared to these uremic patients, patients with iron deficiency anemia and normal renal function (Hct 28.0±5.1 %) had significantly faster PID and MTT and significantly higher RCIU and RCIT. Plasma volume was significantly reduced (to normal level) in CAPD patients with improved hematocrits. The results of this study suggest that erythropoietic activity is inadequate for the degree of anemia in CAPD patients as well as uremic patients not on dialysis and further suggest that the hematocrit increases in CAPD as a result of decreased plasma volume. PMID:15759377

Effect of the conditions of isolation on the physicochemical properties of human serum albumin in the norm and with pathology

NASA Astrophysics Data System (ADS)

Ivanov, A. I.; Zhbankov, R. G.; Korolenko, E. A.; Korolik, E. V.; Meleshchenko, L. A.; Sarnatskaya, V. V.; Nikolaev, V. G.; Nikolaichik, V. V.; Yushko, L. A.

1997-01-01

Differential scanning calorimetry and IR spectrosocopy were used to investigate the effect of the procedure of isolation of human serum albumin on its physicochemical characteristics. It is shown that fractionation of blood plasma with ethylene glycol followed by ion exchange chromatography can be used to obtain albumin of normal donors that is similar to the albumin in the nonfractionated plasma according to melting thermograms. Endotherms of human serum albumin samples that were obtained by affinity chromatography and preparative electrophoresis are bimodal, unlike the monophasic for albumin obtained by polyethylene glycol precipitation. These changes result from a higher content of nonetherified fatty acids in the albumin samples obtained by affinity chromatography and from modification of the secondary protein structure in the samples obtained by electrophoresis. Analysis of melting thermograms of serum albumin from patients with uremia, chronic hepatitis, and peritonitis shows that fractionation of blood with polyethylene glycol preserves the thermodynamic characteristics of the various pathological serum albumins to the greatest extent. The present results demonstrate the advantage of polyethylene glycol fractionation for isolation of native preparations of normal and “pathological” human serum albumin.

Delayed recovery from anesthesia: A postgraduate educational review.

PubMed

Misal, Ullhas Sudhakarrao; Joshi, Suchita Annasaheb; Shaikh, Mudassir Mohd

2016-01-01

Delayed awakening from anesthesia remains one of the biggest challenges that involve an anesthesiologist. With the general use of fast-acting anesthetic agents, patients usually awaken quickly in the postoperative period. The time to emerge from anesthesia is affected by patient factors, anesthetic factors, duration of surgery, and painful stimulation. The principal factors responsible for delayed awakening following anesthesia are anesthetic agents and medications used in the perioperative period. Nonpharmacological causes may have a serious sequel, hence recognizing these organic conditions is important. Certain underlying metabolic disorders such as hypoglycemia, severe hyperglycemia, and electrolyte imbalance, especially hypernatremia, hypoxia, hypercapnia, central anticholinergic syndrome, chronic hypertension, liver disease, hypoalbuminemia, uremia, and severe hypothyroidism may also be responsible for delayed recovery following anesthesia. Unexpected delayed emergence after general anesthesia may also be due to intraoperative cerebral hypoxia, hemorrhage, embolism, or thrombosis. Accurate diagnosis of the underlying cause is the key for the institution of appropriate therapy, but primary management is to maintain airway, breathing, and circulation. This comprehensive review discusses the risk factors, causes, evaluation and management of delayed recovery based on our clinical experience, and literature search on the internet, supported by the standard textbooks of anesthesiology.

[Bad breath--etiological, diagnostic and therapeutic problems].

PubMed

Reiss, M; Reiss, G

2000-01-01

Oral malodor has many etiologies and is a clinical problem for many people. This paper reviews the causes and management of oral malador. In the majority of cases the problem has been shown to originate in the oral cavity. Oral malodor, a generic descriptor term for foul smells emanating from the mouth, encompasses ozostomia, stomatodysodia, halitosis (both pathological halitosis and physiological halitosis) and fetor oris or fetor ex ore. These latter terms, in turn, denote different sources of oral malodor. All conditions that favour the retention of anaerobic, mainly gram-negative, bacteria will predispose for the development of bad breath. In addition to periodontal pockets, the most important retention site is the dorsum of the tongue with its numerous papillae. During the night and between meals the conditions are optimal for odour production. Systemic pathological states, such as diabetes mellitus, uremia and hepatic diseases, induce metabolic products that are detectable as oral smells. It is always easy to recognize halitosis, but identifying the exact cause is more complex. The clinical labelling and interpretation of different oral malodors both contribute to the diagnosis and treatment of underlying disease. Treatment is directed at the underlying cause.

Oxidative stress in hepatitis C infected end-stage renal disease subjects

PubMed Central

Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Filiz F; Aslan, Mehmet; Koylu, Ahmet O; Selek, Sahbettin; Erel, Ozcan

2006-01-01

Background Both uremia and hepatitis C infection is associated with increased oxidative stress. In the present study, we aimed to find out whether hepatitis C infection has any impact on oxidative stress in hemodialysis subjects. Methods Sixteen hepatitis C (+) hemodialysis subjects, 24 hepatitis C negative hemodialysis subjects and 24 healthy subjects were included. Total antioxidant capacity, total peroxide level and oxidative stress index were determined in all subjects. Results Total antioxidant capacity was significantly higher in controls than hemodialysis subjects with or without hepatitis C infection (all p < 0.05/3), while total peroxide level and oxidative stress index were significantly lower (all p < 0.05/3). Hepatitis C (-) hemodialysis subjects had higher total antioxidant capacity compared to hepatitis C (+) hemodialysis subjects (all p < 0.05/3). Total peroxide level and oxidative stress index was comparable between hemodialysis subjects with or without hepatitis C infection (p > 0.05/3). Conclusion Oxidative stress is increased in both hepatitis C (+) and hepatitis C (-) hemodialysis subjects. However, hepatitis C infection seems to not cause any additional increase in oxidative stress in hemodialysis subjects and it may be partly due to protective effect of dialysis treatment on hepatitis C infection. PMID:16842626

Oxidative stress in hepatitis C infected end-stage renal disease subjects.

PubMed

Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Filiz F; Aslan, Mehmet; Koylu, Ahmet O; Selek, Sahbettin; Erel, Ozcan

2006-07-14

Both uremia and hepatitis C infection is associated with increased oxidative stress. In the present study, we aimed to find out whether hepatitis C infection has any impact on oxidative stress in hemodialysis subjects. Sixteen hepatitis C (+) hemodialysis subjects, 24 hepatitis C negative hemodialysis subjects and 24 healthy subjects were included. Total antioxidant capacity, total peroxide level and oxidative stress index were determined in all subjects. Total antioxidant capacity was significantly higher in controls than hemodialysis subjects with or without hepatitis C infection (all p < 0.05/3), while total peroxide level and oxidative stress index were significantly lower (all p < 0.05/3). Hepatitis C (-) hemodialysis subjects had higher total antioxidant capacity compared to hepatitis C (+) hemodialysis subjects (all p < 0.05/3). Total peroxide level and oxidative stress index was comparable between hemodialysis subjects with or without hepatitis C infection (p > 0.05/3). Oxidative stress is increased in both hepatitis C (+) and hepatitis C (-) hemodialysis subjects. However, hepatitis C infection seems to not cause any additional increase in oxidative stress in hemodialysis subjects and it may be partly due to protective effect of dialysis treatment on hepatitis C infection.

Bioassay of procoagulant albumin in human plasma.

PubMed

Grosset, A; Liu, L; Parker, C J; Rodgers, G M

1994-09-01

Procoagulant albumin (P-Al) is present in normal human plasma and increases monocyte and endothelial cell expression of tissue factor activity. To develop a bioassay for P-Al, we partially purified plasma from healthy volunteers and several patient groups using BaCl2 and (NH4)2SO4 precipitation. The samples were assayed for tissue factor (TF) inducing activity, expressed as a percentage increase compared to a serum-free media control. Over six months, the assay was reproducible in stored samples and in serial samples from normal volunteers. The plasma P-Al activities of 35 volunteers averaged 141 +/- 8.2% (SEM). There was no diurnal variation. There was no difference in the P-Al activity after a 12 hour fast and 2 hours after a large meal in 4 healthy volunteers. There was no increase in activity (r = 0.16) with the subject's age. The average activity from 16 poorly-controlled diabetics was 131 +/- 11% (SEM). No alteration in activity was seen with samples from patients with uremia, liver dysfunction, hemophilia, thrombotic events, or adenocarcinoma. These results indicate that P-Al activity can be bioassayed in individual patient samples; however, pathologic states associated with abnormal P-Al-induced tissue factor activity presently remain unidentified.

Antioxidant and Antifatigue Properties of the Aqueous Extract of Moringa oleifera in Rats Subjected to Forced Swimming Endurance Test.

PubMed

Lamou, Bonoy; Taiwe, Germain Sotoing; Hamadou, André; Abene; Houlray, Justin; Atour, Mahamat Mey; Tan, Paul Vernyuy

2016-01-01

The effects of the aqueous extract of Moringa oleifera on swimming performance and related biochemical parameters were investigated in male Wistar rats (130-132 g). Four groups of rats (16 per group) were fed a standard laboratory diet and given distilled water, 100, 200, or 400 mg/kg of extract, respectively, for 28 days. On day 28, 8 rats from each group were subjected to the forced swimming test with tail load (10% of body weight). The remaining 8 rats per group were subjected to the 90-minute free swim. Maximum swimming time, glycemia, lactamia, uremia, triglyceridemia, hepatic and muscle glycogen, hematological parameters, and oxidative stress parameters (superoxide dismutase, catalase, reduced glutathione, and malondialdehyde) were measured. Results. M. oleifera extract increased maximum swimming time, blood hemoglobin, blood glucose, and hepatic and muscle glycogen reserves. The extract also increased the activity of antioxidant enzymes and decreased the blood concentrations of malondialdehyde. Furthermore, it decreased blood concentrations of lactate, triglycerides, and urea. In conclusion, the antifatigue properties of M. oleifera extract are demonstrated by its ability to improve body energy stores and tissue antioxidant capacity and to reduce the tissue build-up of lactic acid.

Congenital nephrotic syndrome.

PubMed

Hamed, Radi Ma

2003-01-01

The congenital nephrotic syndrome (CNS) is an uncommon disorder with onset of the nephrotic syndrome usually in the first three months of life. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The clinical course is marked by failure to thrive, recurrent life threatening bacterial infections, and early death from sepsis and/or uremia. A characteristic phenotype may be seen in children with CNS. The majority of reported cases of CNS are of the Finnish type (CNF). Although the role of the glomerular basement membrane has been emphasized as the barrier for retaining plasma proteins, recent studies have clearly shown that the slit diaphragm is the structure most likely to be the barrier in the glomerular capillary wall. The gene (NPHS1) was shown to encode a novel protein that was termed nephrin, due to its specific location in the kidney filter barrier, where it seems to form a highly organized filter structure. Nephrin is a transmembrane protein that probably forms the main building block of an isoporous zipper-like slit diaphragm filter structure. Defects in nephrin lead to the abnormal or absent slit diaphragm resulting in massive proteinuria and renal failure.

Antioxidant and Antifatigue Properties of the Aqueous Extract of Moringa oleifera in Rats Subjected to Forced Swimming Endurance Test

PubMed Central

Lamou, Bonoy; Taiwe, Germain Sotoing; Hamadou, André; Abene; Houlray, Justin; Atour, Mahamat Mey; Tan, Paul Vernyuy

2016-01-01

The effects of the aqueous extract of Moringa oleifera on swimming performance and related biochemical parameters were investigated in male Wistar rats (130–132 g). Four groups of rats (16 per group) were fed a standard laboratory diet and given distilled water, 100, 200, or 400 mg/kg of extract, respectively, for 28 days. On day 28, 8 rats from each group were subjected to the forced swimming test with tail load (10% of body weight). The remaining 8 rats per group were subjected to the 90-minute free swim. Maximum swimming time, glycemia, lactamia, uremia, triglyceridemia, hepatic and muscle glycogen, hematological parameters, and oxidative stress parameters (superoxide dismutase, catalase, reduced glutathione, and malondialdehyde) were measured. Results. M. oleifera extract increased maximum swimming time, blood hemoglobin, blood glucose, and hepatic and muscle glycogen reserves. The extract also increased the activity of antioxidant enzymes and decreased the blood concentrations of malondialdehyde. Furthermore, it decreased blood concentrations of lactate, triglycerides, and urea. In conclusion, the antifatigue properties of M. oleifera extract are demonstrated by its ability to improve body energy stores and tissue antioxidant capacity and to reduce the tissue build-up of lactic acid. PMID:26904162

Protein carbamylation predicts mortality in ESRD.

PubMed

Koeth, Robert A; Kalantar-Zadeh, Kamyar; Wang, Zeneng; Fu, Xiaoming; Tang, W H Wilson; Hazen, Stanley L

2013-04-01

Traditional risk factors fail to explain the increased risk for cardiovascular morbidity and mortality in ESRD. Cyanate, a reactive electrophilic species in equilibrium with urea, posttranslationally modifies proteins through a process called carbamylation, which promotes atherosclerosis. The plasma level of protein-bound homocitrulline (PBHCit), which results from carbamylation, predicts major adverse cardiac events in patients with normal renal function, but whether this relationship is similar in ESRD is unknown. We quantified serum PBHCit in a cohort of 347 patients undergoing maintenance hemodialysis with 5 years of follow-up. Kaplan-Meier analyses revealed a significant association between elevated PBHCit and death (log-rank P<0.01). After adjustment for patient characteristics, laboratory values, and comorbid conditions, the risk for death among patients with PBHCit values in the highest tertile was more than double the risk among patients with values in the middle tertile (adjusted hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.5-3.9) or the lowest tertile (adjusted HR, 2.3; 95% CI, 1.5-3.7). Including PBHCit significantly improved the multivariable model, with a net reclassification index of 14% (P<0.01). In summary, serum PBHCit, a footprint of protein carbamylation, predicts increased cardiovascular risk in patients with ESRD, supporting a mechanistic link among uremia, inflammation, and atherosclerosis.

A Case Report Describing a Rare Presentation of Simultaneous Occurrence of MPO-ANCA-Associated Vasculitis and Rheumatoid Arthritis.

PubMed

Foray, Nathalie; Hudali, Tamer; Papireddy, Muralidhar; Gao, John

2016-01-01

Background . Renal-limited myeloperoxidase vasculitis with simultaneous rheumatoid arthritis is reported as a rare occurrence. Review of literature suggests that most patients had a diagnosis of rheumatoid arthritis for several years prior to presenting with renal failure from myeloperoxidase vasculitis. Case Presentation . A 58-year-old Caucasian male presented to the hospital experiencing malaise, fevers, decreased oral intake, nausea, and vomiting for one week duration. His past medical history consisted of newly diagnosed but untreated rheumatoid arthritis, hypertension, and non-insulin-dependent diabetes mellitus. He was found to have acute renal failure, proteinuria, and hypoglycemia. Standard therapy, including intravenous fluids, did not improve his acute renal failure. A vasculitis workup resulted in a positive myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). Renal biopsy revealed crescentic glomerulonephritis (GN) pauci-immune type, suggestive of MPO-ANCA-associated vasculitis (MPO-AAV). Treatment consisted of prednisone, cyclophosphamide, and seven cycles of plasmapheresis, in addition to hemodialysis for uremia. Upon discharge, he received hemodialysis for another week and continued treatment with cyclophosphamide and prednisone. Conclusion . Patients with longstanding rheumatoid arthritis may develop renal failure due to nonsteroidal anti-inflammatory medication use and AA type amyloidosis; however, necrotizing glomerulonephritis with crescent formation has been rarely reported. This stresses the importance of early recognition and swift initiation of treatment.

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease

PubMed Central

Hickson, LaTonya J.; Eirin, Alfonso; Lerman, Lilach O.

2016-01-01

Chronic kidney disease (CKD) is a global healthcare burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including pro-angiogenic, anti-inflammatory, and anti-fibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. PMID:26924058

Challenges and opportunities for stem cell therapy in patients with chronic kidney disease.

PubMed

Hickson, LaTonya J; Eirin, Alfonso; Lerman, Lilach O

2016-04-01

Chronic kidney disease (CKD) is a global health care burden affecting billions of individuals worldwide. The kidney has limited regenerative capacity from chronic insults, and for the most common causes of CKD, no effective treatment exists to prevent progression to end-stage kidney failure. Therefore, novel interventions, such as regenerative cell-based therapies, need to be developed for CKD. Given the risk of allosensitization, autologous transplantation of cells to boost regenerative potential is preferred. Therefore, verification of cell function and vitality in CKD patients is imperative. Two cell types have been most commonly applied in regenerative medicine. Endothelial progenitor cells contribute to neovasculogenesis primarily through paracrine angiogenic activity and partly by differentiation into mature endothelial cells in situ. Mesenchymal stem cells also exert paracrine effects, including proangiogenic, anti-inflammatory, and antifibrotic activity. However, in CKD, multiple factors may contribute to reduced cell function, including older age, coexisting cardiovascular disease, diabetes, chronic inflammatory states, and uremia, which may limit the effectiveness of an autologous cell-based therapy approach. This Review highlights current knowledge on stem and progenitor cell function and vitality, aspects of the uremic milieu that may serve as a barrier to therapy, and novel methods to improve stem cell function for potential transplantation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Captain Lord’s uremia

PubMed Central

Wyner, Lawrence Michael

2013-01-01

The hundredth anniversary of the worst ever civilian maritime disaster was also the fiftieth anniversary of the death of arguably its most controversial character, Captain Stanley Lord, skipper of the Californian, a “tramp” steamer that became entrapped in ice just off the Grand Banks of Newfoundland on April 14, 1912. Although Lord was faulted in two widely publicized inquiries for failing to respond to Titanic’s distress signals, there may have actually been a medical reason for his behavior because he suffered from chronic renal disease and most likely had some secondary cognitive impairment due to this disease. An assessment of Lord’s health history shows that he fractured his leg as a young man; suffered from poor eyesight, which led to his premature retirement from the sea by the age of 50; and eventually died from renal failure. Furthermore, his death certificate alludes to previous uremic episodes, perhaps encompassing the time period of the Titanic accident. Lord may have been under some pressure not to reveal his infirmity because doing so could have further jeopardized his career. The literature abounds with evidence that renal insufficiency negatively affects cognition, often years before progression to end-stage renal disease. Captain Lord’s failure to act in a crisis situation may serve as a case in point. PMID:26328096

A fatal outcome after unintentional overdosing of rivastigmine patches.

PubMed

Lövborg, Henrik; Jönsson, Anna K; Hägg, Staffan

2012-02-01

Rivastigmine is an acetylcholine esterase inhibitor used in the treatment of dementia. Patches with rivastigmine for transdermal delivery have been used to increase compliance and to reduce side effects. We describe an 87-year old male with dementia treated with multiple rivastigmine patches (Exelon 9,5 mg/24 h) who developed nausea, vomiting and renal failure with disturbed electrolytes resulting in death. The symptoms occurred after six rivastigmine patches had concomitantly been erroneously applied by health care personnel on two consecutive days. The terminal cause of death was considered to be uremia from an acute tubular necrosis that was assessed as a result of dehydration through vomiting. The rivastigmine intoxication was assessed as having caused or contributed to the dehydrated condition. The medication error occurred at least partly due to ambiguous labeling. The clinical signs were not initially recognized as adverse effects of rivastigmine. The presented case is a description of a rivastigmine overdose due to a medication error involving patches. This case indicates the importance of clear and unambiguous instructions to avoid administration errors with patches and to be vigilant to adverse drug reactions for early detection and correction of drug administration errors. In particular, instructions clearly indicating that only one patch should be applied at a time are important.

Nightly high dose lactulose infusion could be a cost-effective treatment for hepatic encephalopathy, renal insufficiency and heart failure.

PubMed

Alisky, Joseph Martin

2007-01-01

Lactulose is an established remedy for hepatic encephalopathy and shows efficacy for chronic renal insufficiency, reducing volume overload, uremia and hyperkalemia. Potentially lactulose could also be used for non-diuretic treatment of congestive heart failure. However, use of lactulose is limited by diarrhea and flatulence. Chronic lactulose administration might be tolerable if it was accomplished by nocturnal infusion through a percutaneous duodenostomy tube, also placing a rectal foley each night following a clearing enema so that large volumes of liquid stool could be passed while patients sleep. Each morning the duodenostomy would be clamped and the foley removed. For acute patients without duodenostomies, a temporary dobhoff feeding tube with accompanying rectal foley could be employed. Patients who did not want a rectal foley could elect to have a permanent colostomy. Clinical trials could establish the relationship between lactulose infusion and clearance of water, salt, potassium, hydrogen, urea and other wastes, and compare efficacy, cost and tolerability with that of peritoneal dialysis and ultrafiltration. Lactulose could potentially allow inexpensive home-based therapy for hepatic encephalopathy, chronic renal failure and congestive heart failure, and might be life-saving in countries where renal replacement in any form is currently unavailable.

Factors influencing wound dehiscence.

PubMed

Riou, J P; Cohen, J R; Johnson, H

1992-03-01

Thirty-one abdominal fascial wound dehiscences occurred in 2,761 patients undergoing major abdominal surgery during a 5-year period (1%). Twenty-two specific local and systemic risk factors were analyzed and compared with the risk factors of a control group of 38 patients undergoing similar procedures without dehiscence. Through multivariate analysis, each factor was assessed as an independent statistical variable. Significant factors (p less than 0.05) were found to include age over 65, wound infection, pulmonary disease, hemodynamic instability, and ostomies in the incision. Additional systemic risk factors that were found to be significant included hypoproteinemia, systemic infection, obesity, uremia, hyperalimentation, malignancy, ascites, steroid use, and hypertension. Risk factors not found to be important independent variables included sex, type of incision, type of closure, foreign body in the wound, anemia, jaundice, and diabetes. When dehiscence and control groups were combined, 30% of patients with at least five significant risk factors developed dehiscence, and all the patients with more than eight risk factors developed a wound dehiscence. There was an overall mortality of 29%, which was directly related to the number of significant risk factors. The co-existence of 9 risk factors portended death in one third of the patients, and all the patients with more than 10 risk factors died.

Bone changes in hypercalcemia of malignancy in dogs.

PubMed

Norrdin, R W; Powers, B E

1983-08-15

Bone was collected for trabecular bone morphometry from 6 dogs with hypercalcemia of malignancy. Five of the dogs had lymphosarcoma and 1 had an anal sac apocrine gland carcinoma with vertebral metastases. Parathyroid gland weights varied around normal, with those for 1 dog being slightly low and those for another dog being moderately increased. As a group, the dogs had decreased bone volume, with increased resorption surfaces and increased numbers of osteoclasts. In 4 dogs, osteoid seams and osteoblasts were limited in extent and this distinguished them from dogs with hyperparathyroidism. Although most dogs had received corticosteroids, chemotherapy, or radiation treatment, the bone changes in these dogs were similar to 1 dog that had not received treatment. Also, the changes could not be related to uremia or renal mineralization that had developed in 2 of the dogs. Two of the dogs had somewhat greater amounts of osteoid-covered surface and slightly widened osteoid seams, ie, findings more like those of hyperparathyroidism. One of these dogs had anal sac apocrine gland carcinoma and the other had lymphosarcoma in which there was invasion of the bone cortex at the sampling site. It was concluded that bone remodeling changes do occur in hypercalcemia of malignancy and that these changes are varied and often are not those of hyperparathyroidism.

Treatment with pyrophosphate inhibits uremic vascular calcification

PubMed Central

O’Neill, W. Charles; Lomashvili, Koba A.; Malluche, Hartmut H.; Faugere, Marie-Claude; Riser, Bruce L.

2011-01-01

Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone. PMID:21124302

Treatment with pyrophosphate inhibits uremic vascular calcification.

PubMed

O'Neill, W Charles; Lomashvili, Koba A; Malluche, Hartmut H; Faugere, Marie-Claude; Riser, Bruce L

2011-03-01

Pyrophosphate, which may be deficient in advanced renal failure, is a potent inhibitor of vascular calcification. To explore its use as a potential therapeutic, we injected exogenous pyrophosphate subcutaneously or intraperitoneally in normal rats and found that their plasma pyrophosphate concentrations peaked within 15 min. There was a single exponential decay with a half-life of 33 min. The kinetics were indistinguishable between the two routes of administration or in anephric rats. The effect of daily intraperitoneal pyrophosphate injections on uremic vascular calcification was then tested in rats fed a high-phosphate diet containing adenine for 28 days to induce uremia. Although the incidence of aortic calcification varied and was not altered by pyrophosphate, the calcium content of calcified aortas was significantly reduced by 70%. Studies were repeated in uremic rats given calcitriol to produce more consistent aortic calcification and treated with sodium pyrophosphate delivered intraperitoneally in a larger volume of glucose-containing solution to prolong plasma pyrophosphate levels. This maneuver significantly reduced both the incidence and amount of calcification. Quantitative histomorphometry of bone samples after double-labeling with calcein indicated that there was no effect of pyrophosphate on the rates of bone formation or mineralization. Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone.

Fibroblast Growth Factor-23: A Novel Biomarker for Cardiovascular Disease in Chronic Kidney Disease Patients.

PubMed

Papagianni, Aikaterini

2017-09-01

Fibroblast Growth Factor (FGF)-23 increase is considered one of the earliest biochemical abnormalities in chronic kidney disease-mineral bone disorder (CKD-MBD). Furthermore, accumulating data have provided evidence of a link between increased FGF-23 levels and cardiovascular morbidity and mortality in CKD patients as well as in several other populations including cardiology patients and general population. The cellular and molecular mechanisms underlying the deleterious effect of FGF-23 on the cardiovascular system are not yet completely defined and are the focus of intense research. However, animal and human studies have demonstrated important actions of FGF-23 in the heart and vessels through which could promote the development of cardiovascular complications in uremia. Moreover, significant interactions have been reported between FGF-23 and other well recognized cardiovascular risk factors such as renin-angiotensin system and inflammation which could account, at least in part, for the observed associations between FGF-23 and adverse clinical outcomes. Further studies are needed to clarify the mechanisms responsible for the pleiotropic actions of FGF-23 and moreover to identify whether it is a modifiable risk factor and a potential target of therapeutic interventions which could probably help to reduce the unacceptably high cardiovascular morbidity and mortality of CKD patients.

Prevalence of cysts in seminal tract and abnormal semen parameters in patients with autosomal dominant polycystic kidney disease.

PubMed

Torra, Roser; Sarquella, Joaquim; Calabia, Jordi; Martí, Jordi; Ars, Elisabet; Fernández-Llama, Patricia; Ballarin, Jose

2008-05-01

Autosomal dominant polycystic kidney disease is a systemic disorder with a wide range of extrarenal involvement. The scope of this study was to analyze the prevalence of seminal cysts and to correlate these findings with the sperm parameters in patients with autosomal dominant polycystic kidney disease. A prospective study enrolled 30 adult men with autosomal dominant polycystic kidney disease. Of these 30 patients, 22 agreed to provide a semen sample for analysis, and 28 of 30 agreed to undergo an ultrasound rectal examination. Data obtained from the semen tests and from the ultrasound study were compared. Cysts in the seminal tract were present in 10 (43.47%) of 28 individuals. Twenty of 22 patients showed abnormal semen parameters, with asthenozoospermia as the most common finding. No correlation between ultrasound findings and sperm abnormalities was observed. The presence of cysts in the seminal tract is remarkably high (43.47%); however, this finding does not correlate with sperm abnormalities, which are also a frequent finding, especially asthenozoospermia. This semen abnormality is probably related to the abnormal function of polycystins. More attention should be paid to reproductive aspects in the initial evaluation of patients with autosomal dominant polycystic kidney disease before their ability to conceive is further impaired by uremia.

The 50th anniversary of long-term hemodialysis: University of Washington Hospital, March 9th, 1960.

PubMed

Blagg, Christopher R

2011-01-01

The first 6 months of 1960 saw the development of the shunt that first made long-term hemodialysis possible for patients dying from chronic kidney failure. A brief account of hemodialysis for acute kidney failure prior to 1960 is followed by a description of the work of Belding Scribner, Wayne Quinton and David Dillard at the University of Washington in Seattle. Scribner had the idea of a shunt connecting indwelling arterial and venous cannulas in the forearm between dialyses, to maintain patency of the cannulas, Quinton used Teflon tubing to make the device, and Dillard was the surgeon who implanted the first shunt on March 9th, 1960. The patient, Clyde Shields, was a 39-year-old man dying from uremia secondary to chronic glomerulonephritis. The shunt worked, and Clyde lived a further 11 years on dialysis. Scribner took Quinton and Clyde to the American Society for Artificial Internal Organs (ASAIO) meeting in April and showed Clyde to physicians interested in dialysis, and Quinton demonstrated fabrication of the shunt. In June 1960, 2 landmark papers describing cannulation and the treatment were published in the Transactions of the ASAIO. Today there are some 2 million patients with end-stage renal disease living worldwide.

[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.

Modulation of the cationic amino acid transport system y+L by surface potential, ouabain and thrombin in human platelets: effects of uremia.

PubMed

Alves de Sá Siqueira, Mariana; Martins, Marcela Anjos; Rodrigues Pereira, Natália; Bandeira Moss, Monique; Santos, Sérgio F F; Mann, Giovanni E; Mendes-Ribeiro, Antônio C; Brunini, Tatiana M C

2007-01-01

Nitric oxide (NO), a key endogenous mediator involved in the maintenance of platelet function, is synthesized from the amino acid L-arginine. We have shown that L-arginine transport in platelets is rate-limiting for NO synthesis. A disturbance in the L-arginine-NO pathway in platelets was previously described in chronic renal failure (CRF) patients. Detailed kinetic studies were performed in platelets from controls (n = 60) and hemodialysis patients (n = 26). The transport of L-arginine in platelets is mediated via system y+L, which is competitively inhibited by L-leucine in the presence of Na+ and by the irreversible inhibitor pCMB. In platelets, system y+L is markedly stimulated by an Na+/K+-ATPase inhibitor, ouabain, and by changes in surface potential, while it is downregulated by intraplatelet amino acid depletion (zero-trans) and by thrombin. In CRF patients, activation of L-arginine transport was limited to well-nourished patients compared to malnourished patients and controls, where it was reduced and did not differ significantly among the groups under zero-trans conditions. Our results provide the first evidence that system y+L in platelets is modulated by zero-trans conditions, surface potential, thrombin and intraplatelet Na+ concentration. Our findings suggest that enhanced transport in CRF involves increased L-arginine exchange with intraplatelet neutral amino acids.

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.

A chronic hemodialysis patient with isolated pulmonary valve infective endocarditis caused by non-albicans Candida: a rare case and literature review.

PubMed

Chang, Chih-Hao; Huang, Myo-Ming; Yeih, Dong-Feng; Lu, Kuo-Cheng; Hou, Yi-Chou

2017-09-06

Isolated pulmonary valve infective endocarditis caused by Candida is rare in chronic hemodialysis patients. The 2009 Infectious Diseases Society of America guidelines suggest the combined use of surgery and antibiotics to treat candidiasis; however, successful nonsurgical treatment of Candida endocarditis has been reported. A 63-year-old woman with end-stage kidney disease was admitted to our hospital after experiencing disorientation for 5 days. The patient was permanently bedridden because of depression, and denied active intravenous drug use. She received maintenance hemodialysis through a tunneled-cuffed catheter. An initial blood culture grew Candida guilliermondii without other bacteria. Subsequent blood cultures and tip culture of tunneled-cuffed catheter also grew C. guilliermondii, even after caspofungin replaced fluconazole. A 1.2-cm mobile mass was observed on the pulmonary valve. Surgical intervention was suggested, but the family of the patient declined because of her multiple comorbidities. The patient was discharged with a prescription of fluconazole, but she died soon after. Our patient is the first case with isolated pulmonary valve endocarditis caused by C. guilliermondii in patients with uremia. Hematologic disorders, in addition to long-term central venous catheter use, prolonged antibiotic intravenous injection, and congenital cardiac anomaly, predispose to the condition. The diagnosis "isolated" pulmonary IE is difficult, and combing surgery with antifungal antibiotics is the appropriate therapeutic management for Candida related pulmonary IE.

Blastocystis sp. and other intestinal parasites in hemodialysis patients.

PubMed

Kulik, Rose Anne; Falavigna, Dina Lúcia Morais; Nishi, Letícia; Araujo, Silvana Marques

2008-08-01

Chronic renal insufficiency disease (CRI) leads to uremia in hemodialysis patients and induces a state of immunodepression that results in higher frequencies of infections and diarrhea. Hemodialysis patients resident in the city of Campo Mourão, Paraná, Brazil were analyzed from April 2006 through September 2007 for Blastocystis sp. and other intestinal parasites and for associated diarrhea. Fecal samples from 86 hemodialysis patients and 146 healthy (reference) persons were examined by standard methods for detecting ova, larvae and cysts, which included preservation in 10% formalin and the Kinyoun method. Thirty-three hemodialysis patients (45.1%) and 36 reference individuals (25.7%) were found to be parasitized. The differences in the percentages of parasitism and polyparasitism between the reference group and the chronic renal patients was significant (p= 0.0318 and 0.0019, respectively). Blastocystis sp. (18%-20.1%), Endolimax nana (14%-16.3%), Cryptosporidium sp. (4%-4.7%) and Entamoeba coli (4%-4.7%) were the most frequent protozoa found in the hemodialysis patients. Parasitism was not significantly associated with diarrhea (p=0.9947) or with decreased white blood cell counts (p=0.7046) in these individuals. Because parasitic infections may be an important comorbidity factor in hemodialysis patients, we suggest that parasitological stool examinations, especially for Blastocystis sp. and Cryptosporidium sp., be included in routine medical follow-up examinations of these patients.

Dyslipidemia in chronic kidney disease: are statins still indicated in reduction cardiovascular risk in patients on dialysis treatment?

PubMed

Scarpioni, Roberto; Ricardi, Marco; Melfa, Luigi; Cristinelli, Luciano

2010-12-01

Chronic kidney disease (CKD) is an increasingly health disease all around the world with a high burden of mortality and cardiovascular (CV) morbidity rate. Even when renal replacement therapy is reached, more than half patients die, mainly for CV causes due either to uremia-related cardiovascular risk factors (such as anemia, hyperhomocysteinemia, mineral bone disease-CKD with hyperparathyroidism, oxidative stress, hypoalbuminemia, chronic inflammation, prothrombotic factors) or to traditional ones (age, male gender, diabetes, obesity, hypertension, smoking, insulin levels, family history, dyslipidemia). Among the latter causes dyslipidemia represents one of the major, potentially correctable risk factor. Statins have demonstrated to effectively and safely reduce cholesterol levels in CKD patients. Here we will examine the effects of statins on CV risk factors in CKD patients and particularly in patients on dialysis treatment, in the light of the unfavorable results of the large trials 4D and AURORA, recently published, underlining the role of malnutrition/inflammation as confounding factor. Probably it will be that only with a real prevention, starting statins even in the early stages of CKD, as indicated by post hoc analysis of large trials, that we will reach results in reducing the mortality rate in CKD patients. In the meanwhile, all the other remediable CV risk factors have to be at the same time corrected. © 2010 Blackwell Publishing Ltd.

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency.

PubMed

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. SXND may antagonize the renin-angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

Role of kidney injury in sepsis.

PubMed

Doi, Kent

2016-01-01

Kidney injury, including acute kidney injury (AKI) and chronic kidney disease (CKD), has become very common in critically ill patients treated in ICUs. Many epidemiological studies have revealed significant associations of AKI and CKD with poor outcomes of high mortality and medical costs. Although many basic studies have clarified the possible mechanisms of sepsis and septic AKI, translation of the obtained findings to clinical settings has not been successful to date. No specific drug against human sepsis or AKI is currently available. Remarkable progress of dialysis techniques such as continuous renal replacement therapy (CRRT) has enabled control of "uremia" in hemodynamically unstable patients; however, dialysis-requiring septic AKI patients are still showing unacceptably high mortality of 60-80 %. Therefore, further investigations must be conducted to improve the outcome of sepsis and septic AKI. A possible target will be remote organ injury caused by AKI. Recent basic studies have identified interleukin-6 and high mobility group box 1 (HMGB1) as important mediators for acute lung injury induced by AKI. Another target is the disease pathway that is amplified by pre-existing CKD. Vascular endothelial growth factor and HMGB1 elevations in sepsis were demonstrated to be amplified by CKD in CKD-sepsis animal models. Understanding the role of kidney injury as an amplifier in sepsis and multiple organ failure might support the identification of new drug targets for sepsis and septic AKI.

Inflammation and premature aging in advanced chronic kidney disease.

PubMed

Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

2017-10-01

Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

Uremia Induces Dental Pulp Ossification but Reciprocally Inhibits Adjacent Alveolar Bone Osteogenesis.

PubMed

Yang, Chih-Yu; Chang, Zee-Fen; Chau, Yat-Pang; Chen, Ann; Lee, Oscar Kuang-Sheng; Yang, An-Hang

2015-11-01

Uremic patients are predisposed to atrophy of the alveolar bone and narrowing of the dental pulp chamber. Such pulp chamber changes have only been diagnosed radiologically; however, this has not been supported by any pathological evidence. We used a uremic rat model with secondary hyperparathyroidism induced by 5/6 nephrectomy surgery and high-phosphate diet to examine the dental pulp and adjacent alveolar bone pathology. In addition, we collected pulp tissues for real-time PCR. We found an opposite histopathological presentation of the ossified dental pulp and the osteomalacic adjacent alveolar bone. Furthermore, pulp cells with positive staining for Thy-1, a surrogate stem cell marker, were significantly reduced in the pulp of uremic rats compared to the controls, indicating a paucity of stem cells. This was further evidenced by the reduced pulp expression of dickkopf-1 (Dkk-1), a Wnt/β-catenin signaling inhibitor produced by mesenchymal stem cells. In contrast, expressions of receptor activator of nuclear factor κB ligand (RANKL) and RANK in uremic pulp were up-regulated, probably to counteract the ossifying process of uremic pulp. In conclusion, uremic pulp ossifications were associated with a paucity of stem cells and dysregulated Dkk-1 and RANKL signaling systems, further shifting the imbalance toward osteogenesis. Strategies to counteract such an imbalance may offer a potential therapeutic target to improve dental health in uremic patients, which warrants further interventional studies.

Quantification of carbamylated albumin in serum based on capillary electrophoresis.

PubMed

Delanghe, Sigurd; Moerman, Alena; Pletinck, Anneleen; Schepers, Eva; Glorieux, Griet; Van Biesen, Wim; Delanghe, Joris R; Speeckaert, Marijn M

2017-09-01

Protein carbamylation, a nonenzymatic posttranslational modification promoted during uremia, is linked to a poor prognosis. In the present study, carbamylation of serum albumin was assayed using the symmetry factor on a capillary electrophoresis instrument (Helena V8). The symmetry factor has been defined as the distance from the center line of the peak to the back slope, divided by the distance from the center line of the peak to the front slope, with all measurements made at 10% of the maximum peak height. Serum albumin, creatinine, and urea concentrations were assayed using routine methods, whereas uremic toxins were determined using HPLC. In vitro carbamylation induced a marked albumin peak asymmetry. Reference values for the albumin symmetry factor were 0.69-0.92. In kidney patients, albumin peak asymmetry corresponded to the chronic kidney disease stage (p < 0.0001). The symmetry factor correlated well with serum urea (r = -0.5595, p < 0.0001) and creatinine (r = -0.5986, p < 0.0001) concentrations. Several protein-bound uremic toxins showed a significant negative correlation with the symmetry factor. Morphology of the albumin fraction was not affected by presence of glycated albumin and protein-bound antibiotics. In conclusion, the presented method provides a simple, practical way for monitoring protein carbamylation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hazardous factors besides infection in hypoglycemia.

PubMed

Su, Yu-Jang; Lai, Yen-Chun; Liao, Chia-Jung

2017-04-01

Hypoglycemia is one of the most common issues encountered in daily emergency practice. In addition to the treatment of hypoglycemia, certain other situations concomitant with hypoglycemia require further treatment. The aim of the present study was to compare demographic and clinical characteristics of infected [urinary tract infection (UTI), pneumonia or biliary tract infection (BTI)] vs. non-infected hypoglycemic patients to establish which hypoglycemic patients required further observation or hospitalization. This was a retrospective cross-sectional study of hypoglycemic (<60 mg/dl) hospitalized patients. The patients were divided into two groups: Those with hypoglycemia and concurrent infection (UTIs, pneumonia or BTIs; n=103) and non-infected hypoglycemic patients (n=83). Student's t-test was performed to analyze continuous data and the χ 2 test was used to analyze categorical data. Infections included 62 UTI, 43 pneumonia and 5 BTI. Comparing between the infected and non-infected groups, no significant differences were identified between mean glucose or body temperature, concurrent diagnosis (liver cirrhosis, uremia, acute renal failure, stroke or cancer) or mortality rate. Compared with the non-infected subjects, the infected patients were significantly older and had a significantly higher female ratio, as well as increased heart rates, white blood cell count and C-reactive protein levels. The present study proposes that characteristics, including concurrent stroke, liver cirrhosis and cancer are a point of focus in the initial management of hospitalized hypoglycemic patients.

{sup 99m}Tc DTPA aerosol clearances in the assessment of radiation injury top the lung

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

Halkar, R.K.; Raghab, A.; Higazi, E.

1994-05-01

In a prospective study, 36 patients with inoperable lung Ca. (sq. cells-24, adeno-5, largecell-2, unknown-5) underwent pre and post radiation {sup 99m}Tc DTPA aerosol clearance studies. The aim was to evaluate the value of aerosol clearance in the prediction of radiation injury to the regions other than the radiation field. Aerosol study was done using a commercially available nebulizer, dynamic images were obtained (30 sec/frame) in the posterior projection for a duration of 45 min. ROIs were drawn on upper, mid and lower zones on either lung, and time activity curves were generated. Using a linear fit, clearance half timemore » (t{sub 1/2}) was calculated, for all six curves. The difference between pre and post radiation (t{sub 1/2}) was compared to the clinical follow up of each patient and a difference of more than 15 minutes was considered positive. Of the 36 patients 12 had a t{sub 1/2} difference of more than 15 minutes. Of these 5 patients had radiation pulmonlitis and the remaining 7 had respiratory failure due to infection and uremia. 24 patients had a t{sub 1/2} difference of less than 15 minutes and their clinical follow-up did not reveal any evidence of pulmonary radiation injury during this period. The results indicate that the clearance of Tc-99m DTPA aerosols is effective for excluding radiation pulmonlitis.« less

Future research directions to improve fistula maturation and reduce access failure

PubMed Central

Hu, Haidi; Patel, Sandeep; Hanisch, Jesse J.; Santana, Jeans M.; Hashimoto, Takuya; Bai, Hualong; Kudze, Tambudzai; Foster, Trenton R.; Guo, Jianming; Yatsula, Bogdan; Tsui, Janice; Dardik, Alan

2016-01-01

With the increasing prevalence of end stage renal disease there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes, in the setting of uremia, systemic inflammation, oxidative stress and preexistent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis, as well as development of neointimal hyperplasia (NIH) that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to NIH involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure, based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure requires a multidisciplinary approach involving nephrologists, vascular surgeons and interventional radiologists, allowing careful patient selection and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy. PMID:28779782

Future research directions to improve fistula maturation and reduce access failure.

PubMed

Hu, Haidi; Patel, Sandeep; Hanisch, Jesse J; Santana, Jeans M; Hashimoto, Takuya; Bai, Hualong; Kudze, Tambudzai; Foster, Trenton R; Guo, Jianming; Yatsula, Bogdan; Tsui, Janice; Dardik, Alan

2016-12-01

With the increasing prevalence of end-stage renal disease, there is a growing need for hemodialysis. Arteriovenous fistulae (AVF) are the preferred type of vascular access for hemodialysis, but maturation and failure continue to present significant barriers to successful fistula use. AVF maturation integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes in the setting of uremia, systemic inflammation, oxidative stress, and pre-existent vascular pathology. AVF can fail due to both failure to mature adequately to support hemodialysis and development of neointimal hyperplasia that narrows the AVF lumen, typically near the fistula anastomosis. Failure due to neointimal hyperplasia involves vascular cell activation and migration and extracellular matrix remodeling with complex interactions of growth factors, adhesion molecules, inflammatory mediators, and chemokines, all of which result in maladaptive remodeling. Different strategies have been proposed to prevent and treat AVF failure based on current understanding of the modes and pathology of access failure; these approaches range from appropriate patient selection and use of alternative surgical strategies for fistula creation, to the use of novel interventional techniques or drugs to treat failing fistulae. Effective treatments to prevent or treat AVF failure require a multidisciplinary approach involving nephrologists, vascular surgeons, and interventional radiologists, careful patient selection, and the use of tailored systemic or localized interventions to improve patient-specific outcomes. This review provides contemporary information on the underlying mechanisms of AVF maturation and failure and discusses the broad spectrum of options that can be tailored for specific therapy. Published by Elsevier Inc.

Oxidative stress in uremia: nature, mechanisms, and potential consequences.

PubMed

Vaziri, Nosratola D

2004-09-01

Oxidative stress has emerged as a constant feature of chronic renal failure (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance of lipid, carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients and animals. We recently have shown that oxidative stress in CRF animals is associated with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase (SOD). The functional significance of these findings was confirmed by favorable response to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays an important role in the pathogenesis of the associated hypertension (oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension, and autoimmune diseases, which independently increase production of reactive oxygen intermediates, and frequently are associated with CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane and dialysate impurities), acute and chronic infections (blood access infection, hepatitis, and so forth), and excessive parenteral iron administration intensify CRF-associated oxidative stress and its adverse consequences in patients with end-stage renal disease. The problem is compounded by limited intake of fresh fruits and vegetables (K(+) restriction), which contain numerous natural phytochemicals and antioxidant vitamins.

Uremic Conditions Drive Human Monocytes to Pro-Atherogenic Differentiation via an Angiotensin-Dependent Mechanism

PubMed Central

Trojanowicz, Bogusz; Ulrich, Christof; Seibert, Eric; Fiedler, Roman; Girndt, Matthias

2014-01-01

Aims Elevated expression levels of monocytic-ACE have been found in haemodialysis patients. They are not only epidemiologically linked with increased mortality and cardiovascular disease, but may also directly participate in the initial steps of atherosclerosis. To further address this question we tested the role of monocytic-ACE in promotion of atherosclerotic events in vitro under conditions mimicking those of chronic renal failure. Methods and Results Treatment of human primary monocytes or THP-1 cells with uremic serum as well as PMA-induced differentiation led to significantly up-regulated expression of ACE, further increased by additional treatment with LPS. Functionally, these monocytes revealed significantly increased adhesion and transmigration through endothelial monolayers. Overexpression of ACE in transfected monocytes or THP-1 cells led to development of more differentiated, macrophage-like phenotype with up-regulated expression of Arg1, MCSF, MCP-1 and CCR2. Expression of pro-inflammatory cytokines TNFa and IL-6 were also noticeably up-regulated. ACE overexpression resulted in significantly increased adhesion and transmigration properties. Transcriptional screening of ACE-overexpressing monocytes revealed noticeably increased expression of Angiotensin II receptors and adhesion- as well as atherosclerosis-related ICAM-1 and VCAM1. Inhibition of monocyte ACE or AngII-receptor signalling led to decreased adhesion potential of ACE-overexpressing cells. Conclusions Taken together, these data demonstrate that uremia induced expression of monocytic-ACE mediates the development of highly pro-atherogenic cells via an AngII-dependent mechanism. PMID:25003524

[Skin and chronic kidney disease].

PubMed

Rizzo, Raffaella; Mancini, Elena; Santoro, Antonio

2014-01-01

Kidneys and skin are seldom considered associated, but their relationship is more closer than generally believed. In some immunological diseases (SLE...) and genetic syndromes (tuberous sclerosis, Fabrys disease...) the cutaneous manifestations are integral parts of the clinical picture. In advanced uremia, besides the well-known itching skin lesions, calciphylaxis may appear, a typical example of cutaneous involvement secondary to the metabolic complications (calcium-phosphate imbalance) of the renal disease. Nephrogenic systemic fibrosis appears only in patients with renal failure and it has a very severe prognosis due to the systemic organ involvement. Moreover, there is a heterogeneous group of metabolic diseases, with renal involvement, that may be accompanied by skin lesions, either related to the disease itself or to its complications (diabetes mellitus, porphyrias). In systemic amyloidosis, fibrils may deposit even in dermis leading to different skin lesions. In some heroin abusers, in the presence of suppurative lesions in the sites of needle insertion, renal amyloidosis should be suspected, secondary to the chronic inflammation. Atheroembolic disease is nowadays frequently observed, as a consequence of the increasing number of invasive intravascular manoeuvres. Skin manifestations like livedo reticularis or the blue toe syndrome are the most typical signs, but often renal dysfunction is also present. In all these conditions, the skin lesion may be a first sign, a warning, that should arouse the suspicion of a more complex pathology, even with renal involvement. Being aware of this relationship is fundamental to accelerate the diagnostic process.

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.

Serum Predictors of Percent Lean Mass in Young Adults.

PubMed

Lustgarten, Michael S; Price, Lori L; Phillips, Edward M; Kirn, Dylan R; Mills, John; Fielding, Roger A

2016-08-01

Lustgarten, MS, Price, LL, Phillips, EM, Kirn, DR, Mills, J, and Fielding, RA. Serum predictors of percent lean mass in young adults. J Strength Cond Res 30(8): 2194-2201, 2016-Elevated lean (skeletal muscle) mass is associated with increased muscle strength and anaerobic exercise performance, whereas low levels of lean mass are associated with insulin resistance and sarcopenia. Therefore, studies aimed at obtaining an improved understanding of mechanisms related to the quantity of lean mass are of interest. Percent lean mass (total lean mass/body weight × 100) in 77 young subjects (18-35 years) was measured with dual-energy x-ray absorptiometry. Twenty analytes and 296 metabolites were evaluated with the use of the standard chemistry screen and mass spectrometry-based metabolomic profiling, respectively. Sex-adjusted multivariable linear regression was used to determine serum analytes and metabolites significantly (p ≤ 0.05 and q ≤ 0.30) associated with the percent lean mass. Two enzymes (alkaline phosphatase and serum glutamate oxaloacetate aminotransferase) and 29 metabolites were found to be significantly associated with the percent lean mass, including metabolites related to microbial metabolism, uremia, inflammation, oxidative stress, branched-chain amino acid metabolism, insulin sensitivity, glycerolipid metabolism, and xenobiotics. Use of sex-adjusted stepwise regression to obtain a final covariate predictor model identified the combination of 5 analytes and metabolites as overall predictors of the percent lean mass (model R = 82.5%). Collectively, these data suggest that a complex interplay of various metabolic processes underlies the maintenance of lean mass in young healthy adults.

Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis

PubMed Central

Liappas, Georgios; González-Mateo, Guadalupe Tirma; Sánchez-Díaz, Raquel; Lazcano, Juan José; Lasarte, Sandra; Matesanz-Marín, Adela; Zur, Rafal; Ferrantelli, Evelina; Ramírez, Laura García; Aguilera, Abelardo; Fernández-Ruiz, Elena; Beelen, Robert H.J.; Selgas, Rafael; Sánchez-Madrid, Francisco

2016-01-01

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69−/− and Rag2−/−γc−/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69−/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation. PMID:27151919

Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency

PubMed Central

Yang, Xuejun; Zhou, Hua; Qu, Huiyan; Liu, Weifang; Huang, Xiaojin; Shun, Yating; He, Liqun

2014-01-01

Objective: To observe the efficacy of Shenxinning Decoction (SXND) in ventricular remodeling in AT1 receptor-knockout (AT1-KO) mice with chronic renal insufficiency (CRI). Materials and Methods: AT1-KO mice modeled with subtotal (5/6) nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN), serum creatinine (SCr), brain natriuretic peptide (BNP), echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF), collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1) of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice's BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin–angiotensin system (RAS) and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1. PMID:25097276

Serum Mannose-binding Lectin in Patients on Peritoneal Dialysis Compared With Healthy Individuals.

PubMed

Akbari, Roghayeh; Najafi, Iraj; Maleki, Suzan; Alizadeh-Navaei, Reza

2016-01-01

The increased susceptibility to infection in patients with end-stage renal disease is probably secondary to the impaired immune defense in uremia. Mannose-binding lectin (MBL) has an important role in host defense through activation of the lectin complement pathway. The aim of this study was to measure serum MBL level in peritoneal dialysis patients and compare it with a healthy group. Seventy peritoneal dialysis patients and 70 healthy individuals were enrolled in this study. Serum MBL levels were measured by an enzyme-linked immunosorbent assay kit using the mannan molecule. In addition, serum C-reactive protein and albumin levels were measured to determine whether there is a correlation between serum MBL level and these two parameters. The mean serum MBL level was 2.32 ± 2.54 µg/mL (range, zero to 6.93 µg/mL) in the patients group and 1.80 ± 2.14 µg/mL (range, zero to 6.97µg/mL) in the control group (P = .19). No significant correlation was detected between age and serum MBL level in either the groups. In the patients group, no significant correlation was found between serum MBL and C-reactive protein levels or MBL and albumin levels. There were no correlation between duration of peritoneal dialysis and MBL or dialysis adequacy and MBL, either. This study did not find MBL deficiency in peritoneal dialysis patients as compared to the healthy individuals.

Experimental animal models of encapsulating peritoneal sclerosis.

PubMed

Hoff, Catherine M

2005-04-01

Encapsulating peritoneal sclerosis (EPS) is an infrequent, but extremely serious complication of long-term peritoneal dialysis. The cause of EPS is unclear, but the low incidence suggests that it is most likely multifactorial. The elucidation of developmental pathways and predictive markers of EPS would facilitate the identification and management of high-risk patients. Animal models are often used to define pathways of disease progression and to test strategies for treatment and prevention in the patient population. Ideally such models could help to define the cause of EPS and its developmental pathways, to facilitate the identification of contributing factors and predictive markers, and to provide a system to test therapeutic strategies. Researchers have studied several rodent models of EPS that rely on chronic chemical irritation (for example, bleach, low-pH solution, chlorhexidine gluconate) to induce peritoneal sclerosis and abdominal encapsulation. Development in all models is progressive, with inflammation giving way to peritoneal fibrosis or sclerosis with accumulating membrane damage, culminating in cocoon formation. Microscopic findings are similar to those proposed as diagnostic criteria for clinical EPS: an initial inflammatory infiltrate and submesothelial thickening, collagen deposition, and activation and proliferation of peritoneal fibroblasts. The potential to block progression of peritoneal sclerosis in these models by anti-inflammatory, antifibrotic, and anti-angiogenic agents, and by inhibitors of the renin-angiotensin system have been demonstrated. Animal models based on clinically relevant risk factors (for example, uremia, peritonitis, and long-term exposure to dialysis solutions) now represent the next step in model development.

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

PubMed

Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

2012-01-01

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.

Current status of the measurement of blood hepcidin levels in chronic kidney disease.

PubMed

Macdougall, Iain C; Malyszko, Jolanta; Hider, Robert C; Bansal, Sukhvinder S

2010-09-01

Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.

Enhanced Sensitivity of Gas Sensor Based on Poly(3-hexylthiophene) Thin-Film Transistors for Disease Diagnosis and Environment Monitoring

PubMed Central

Cavallari, Marco R.; Izquierdo, José E. E.; Braga, Guilherme S.; Dirani, Ely A. T.; Pereira-da-Silva, Marcelo A.; Rodríguez, Estrella F. G.; Fonseca, Fernando J.

2015-01-01

Electronic devices based on organic thin-film transistors (OTFT) have the potential to supply the demand for portable and low-cost gadgets, mainly as sensors for in situ disease diagnosis and environment monitoring. For that reason, poly(3-hexylthiophene) (P3HT) as the active layer in the widely-used bottom-gate/bottom-contact OTFT structure was deposited over highly-doped silicon substrates covered with thermally-grown oxide to detect vapor-phase compounds. A ten-fold organochloride and ammonia sensitivity compared to bare sensors corroborated the application of this semiconducting polymer in sensors. Furthermore, P3HT TFTs presented approximately three-order higher normalized sensitivity than any chemical sensor addressed herein. The results demonstrate that while TFTs respond linearly at the lowest concentration values herein, chemical sensors present such an operating regime mostly above 2000 ppm. Simultaneous alteration of charge carrier mobility and threshold voltage is responsible for pushing the detection limit down to units of ppm of ammonia, as well as tens of ppm of alcohol or ketones. Nevertheless, P3HT transistors and chemical sensors could compose an electronic nose operated at room temperature for a wide range concentration evaluation (1–10,000 ppm) of gaseous analytes. Targeted analytes include not only biomarkers for diseases, such as uremia, cirrhosis, lung cancer and diabetes, but also gases for environment monitoring in food, cosmetic and microelectronics industries. PMID:25912354

Acute and subacute oral toxicity of periodate salts in rats.

PubMed

Lent, Emily May; Crouse, Lee C B; Eck, William S

2017-02-01

Periodate salts are being developed as potential replacements for perchlorate due to potential health hazards associated with exposure to perchlorate. The aim of this study was to investigate acute and subacute effects of periodate salts in rats. Acute oral toxicity of potassium and sodium periodate was determined using the Sequential Stage-Wise Probit method. The LD 50 for potassium periodate was 732 (95% CI = 539-838, slope = 13.4) and 685 mg/kg (95% CI = 580-809, slope = 10.6) for females and males, respectively. The LD 50 for sodium periodate was 318 (95% CI = 292-347, slope = 24.3) and 741 mg/kg (95% CI = 704-779, slope = 31.2) for females and males, respectively. In the subacute study, rats were administered sodium periodate at five doses (1/16 LD 50 up to LD 50 ) or distilled water for 14-days via oral gavage. Female rats in the 318 mg/kg-day group and male rats in the 185, 370, and 741 mg/kg-day groups exhibited moribundity, kidney toxicity, uremia, and a stress response. BMDL 10 s of 17.2 and 33.7 mg/kg-day were derived for females and males, respectively. Comparison with the NOAEL for perchlorate-induced thyroid toxicity in rats (0.009 mg/kg-day) suggests sodium periodate is less toxic than perchlorate on a subacute basis. Copyright © 2016. Published by Elsevier Inc.

Treating hypertension in hemodialysis improves symptoms seemingly unrelated to volume excess.

PubMed

Agarwal, Rajiv

2016-01-01

Among hemodialysis patients, probing dry weight is an effective strategy for improving control of hypertension. Whether controlling hypertension improves or worsens symptoms among such patients remains unclear. The purpose of the study was to develop a tool to evaluate symptoms and examine the relationship of the change in these symptoms with blood pressure (BP) control. Among patients participating in the Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) randomized controlled trial, a confirmatory factor analysis (CFA) was performed to establish the relationship between symptoms and organ systems. Next, the change in symptom scores pertaining to organ systems was analyzed using a mixed model. Finally, the independent effect of lowering home BP on change in symptoms was evaluated. Among 133 participants where symptoms were available at baseline, CFA revealed four level 1 domains: gastrointestinal symptoms, dialysis-related symptoms, cardiovascular symptoms and general symptoms. All except dialysis-related symptoms were ascribed to uremia (level 2 domain). Uremic symptoms improved over 6 months and then increased. Dialysis-related symptoms (fatigue, cramps and orthostatic dizziness) did not worsen despite lowering home BP. Probing dry weight was independently associated with an improvement in cardiovascular symptoms such as shortness of breath. Reducing BP through the use of a strategy that includes volume control and medication improves symptoms seemingly unrelated to volume excess. In long-term hemodialysis patients, treating hypertension using home BP measurements may improve well-being. Published by Oxford University Press on behalf of ERA-EDTA 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

PubMed Central

Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

2015-01-01

Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

The impact of peripheral serotonin on leptin-brain serotonin axis, bone metabolism and strength in growing rats with experimental chronic kidney disease.

PubMed

Pawlak, Dariusz; Domaniewski, Tomasz; Znorko, Beata; Oksztulska-Kolanek, Ewa; Lipowicz, Paweł; Doroszko, Michał; Karbowska, Malgorzata; Pawlak, Krystyna

2017-12-01

Chronic kidney disease (CKD) results in decreased bone strength. Serotonin (5-HT) is one of the critical regulators of bone health, fulfilling distinct functions depending on its synthesis site: brain-derived serotonin (BDS) favors osteoblast proliferation, whereas gut-derived serotonin (GDS) inhibits it. We assessed the role of BDS and peripheral leptin in the regulation of bone metabolism and strength in young rats with 5/6 nephrectomy. BDS synthesis was accelerated during CKD progression. Decreased peripheral leptin in CKD rats was inversely related to BDS content in the hypothalamus, brainstem and frontal cortex. Serotonin in these brain regions affected bone strength and metabolism in the studied animals. The direct effect of circulating leptin on bone was not shown in uremia. At the molecular level, there was an inverse association between elevated GDS and the expression of cAMP responsive element-binding protein (Creb) gene in bone of CKD animals. In contrast, increased expression of activating transcription factor 4 (Atf4) was shown, which was associated with GDS-dependent transcription factor 1 (Foxo1), clock gene - Cry-1, cell cycle genes: c-Myc, cyclins, and osteoblast differentiation genes. These results identified a previously unknown molecular pathway, by which elevated GDS can shift in Foxo1 target genes from Creb to Atf4-dependent response, disrupting the leptin-BDS - dependent gene pathway in the bone of uremic rats. Thus, in the condition of CKD the effect of BDS and GDS on bone metabolism and strength can't be distinguished. Copyright © 2017 Elsevier Inc. All rights reserved.

The Frequency of Prediabetes and Contributing Factors in Patients with Chronic Kidney Disease

PubMed Central

Razeghi, Effat; Heydarian, Peimaneh; Heydari, Mahshid

2011-01-01

AIMS: Uremia is a prediabetic state, but abnormal glucose metabolism and relative risk factors in non-diabetic chronic kidney disease (CKD) patients are not studied extensively. This study aimed to evaluate prediabetes and contributing factors in patients with CKD. METHODS: We studied the frequency of prediabetes (defined as fasting plasma glucose 100-125 mg/dl and 2-h plasma glucose 140-199 mg/dl) and contributing risk factors in 91 (34 women and 57 men) non-diabetic CKD (GFR < 60) patients who were referred to Sina Hospital between November 2010 and November 2011. Impaired fasting glucose and impaired glucose tolerance were regarded as prediabetic state. RESULTS: Thirty-eight patients (41.8%), 28 male and 10 female, with mean age of 57.4 ± 17.1 yr, had prediabetes. Among these, 18.7% had impaired fasting glucose, 7.7% impaired glucose tolerance, and 15.4% combined impaired fasting glucose and impaired glucose tolerance. CKD patients with impaired glucose tolerance had more frequently hypertriglyceridemia (85.7% vs. 42.0%, p = 0.001), hypertension (66.6% vs. 31.4%, p = 0.004), and metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III (52.3% vs. 25.7%, p = 0.02). Also, mean systolic blood pressure (134.2 ± 13.9 vs. 124.5 ± 20.0, p = 0.004) was higher in CKD patients with impaired glucose tolerance compared to CKD patients with normal glucose. CONCLUSIONS: Prediabetes is a frequent condition in CKD patients. Also, hypertriglyceridemia and hypertension are more prevalent in prediabetic CKD patients than in non-diabetic CKD patients. PMID:22189551

The dialysis orders objective structured clinical examination (OSCE): a formative assessment for nephrology fellows.

PubMed

Prince, Lisa K; Campbell, Ruth C; Gao, Sam W; Kendrick, Jessica; Lebrun, Christopher J; Little, Dustin J; Mahoney, David L; Maursetter, Laura A; Nee, Robert; Saddler, Mark; Watson, Maura A; Yuan, Christina M

2018-04-01

Few quantitative nephrology-specific simulations assess fellow competency. We describe the development and initial validation of a formative objective structured clinical examination (OSCE) assessing fellow competence in ordering acute dialysis. The three test scenarios were acute continuous renal replacement therapy, chronic dialysis initiation in moderate uremia and acute dialysis in end-stage renal disease-associated hyperkalemia. The test committee included five academic nephrologists and four clinically practicing nephrologists outside of academia. There were 49 test items (58 points). A passing score was 46/58 points. No item had median relevance less than 'important'. The content validity index was 0.91. Ninety-five percent of positive-point items were easy-medium difficulty. Preliminary validation was by 10 board-certified volunteers, not test committee members, a median of 3.5 years from graduation. The mean score was 49 [95% confidence interval (CI) 46-51], κ = 0.68 (95% CI 0.59-0.77), Cronbach's α = 0.84. We subsequently administered the test to 25 fellows. The mean score was 44 (95% CI 43-45); 36% passed the test. Fellows scored significantly less than validators (P < 0.001). Of evidence-based questions, 72% were answered correctly by validators and 54% by fellows (P = 0.018). Fellows and validators scored least well on the acute hyperkalemia question. In self-assessing proficiency, 71% of fellows surveyed agreed or strongly agreed that the OSCE was useful. The OSCE may be used to formatively assess fellow proficiency in three common areas of acute dialysis practice. Further validation studies are in progress.

[Assessment of epidemiological profile of patients and their difficulties for the first query in the screening ambulatory of Nephrology UNIFESP-EPM].

PubMed

Padovani, Cícera Sebastiana da Silva

2012-01-01

The aim of this study was to evaluate the epidemiologic profile of patients and difficulties of patients referred by basic health units (UBS) or other hospitals, outpatient screening of the Division of Nephrology, Hospital São Paulo (UNIFESP) for evaluation and treatment kidney disease. From February to September 2009, has been evaluated 341 patients referred from UBS in São Paulo and other parts of the Country. Of these patients, 26% (86/341) required for new tests to confirm the diagnosis doubtful for referrals, incomplete, or because of the waiting period for the care and exams, which ranged from one week to three years, and part of them did not bring any kind of examination for the evaluation, 12% (45/341) returned for follow-up at the unit location, 13% (46/341) were referred for treatment site closest to their residence, 47% (164/341) for our sub-specialty Clinics of Nephrology (HSP): 24% (82/341) uremia, 8% (27/341) with polycystic kidney disease, 7% (23/341) for hypertension, 4% (16/341) renal Lithiasis and 4% (16/341) nephritis. Our results suggest investments investment in infrastructure in the training of officials of UBS and HSP, reorganization of central references for better management and referral of patients, humanization of care and training of health professionals for outpatient care at UBS in preventive work and basic monitoring of patients, particularly those with diabetes mellitus and hypertension, which can lead to the development of chronic kidney disease (CKD).

Uremic Toxins Affect the Imbalance of Redox State and Overexpression of Prolyl Hydroxylase 2 in Human Adipose Tissue-Derived Mesenchymal Stem Cells Involved in Wound Healing.

PubMed

Khanh, Vuong Cat; Ohneda, Kinuko; Kato, Toshiki; Yamashita, Toshiharu; Sato, Fujio; Tachi, Kana; Ohneda, Osamu

2017-07-01

Chronic kidney disease (CKD) results in a delay in wound healing because of its complications such as uremia, anemia, and fluid overload. Mesenchymal stem cells (MSCs) are considered to be a candidate for wound healing because of the ability to recruit many types of cells. However, it is still unclear whether the CKD-adipose tissue-derived MSCs (CKD-AT-MSCs) have the same function in wound healing as healthy donor-derived normal AT-MSCs (nAT-MSCs). In this study, we found that uremic toxins induced elevated reactive oxygen species (ROS) expression in nAT-MSCs, resulting in the reduced expression of hypoxia-inducible factor-1α (HIF-1α) under hypoxic conditions. Consistent with the uremic-treated AT-MSCs, there was a definite imbalance of redox state and high expression of ROS in CKD-AT-MSCs isolated from early-stage CKD patients. In addition, a transplantation study clearly revealed that nAT-MSCs promoted the recruitment of inflammatory cells and recovery from ischemia in the mouse flap model, whereas CKD-AT-MSCs had defective functions and the wound healing process was delayed. Of note, the expression of prolyl hydroxylase domain 2 (PHD2) is selectively increased in CKD-AT-MSCs and its inhibition can restore the expression of HIF-1α and the wound healing function of CKD-AT-MSCs. These results indicate that more studies about the functions of MSCs from CKD patients are required before they can be applied in the clinical setting.

Endogenous carboxyhemoglobin concentrations in the assessment of severity in patients with community-acquired pneumonia.

PubMed

Corbacioglu, Seref Kerem; Kilicaslan, Isa; Bildik, Fikret; Guleryuz, Atacan; Bekgoz, Burak; Ozel, Ayca; Keles, Ayfer; Demircan, Ahmet

2013-03-01

Previous studies have shown that carbon monoxide, which is endogenously produced, is increased in community-acquired pneumonia (CAP). However, it has not been studied enough whether severity of pneumonia is correlated with increased carboxyhemoglobin (COHb) concentrations in CAP. The aim of this study was to determine whether endogenous carbon monoxide levels in patients with CAP were higher compared with the control group and, if so, to determine whether COHb concentrations could predict severity in CAP. Eighty-two patients with CAP were evaluated in this cross-sectional study during a 10-month period. Demographic data, pneumonia severity index and confusion, uremia, rate respiratory, pressure blood, age>65 (CURB-65) scores, hospital admission or discharge decisions, and 30-day hospital mortality rate were recorded. In addition, 83 control subjects were included to study. The COHb concentration was measured in arterial blood sample. The levels of COHb in patients with CAP were 1.70% (minimum-maximum, 0.8-3.2), whereas those in control subjects, 1.40% (minimum-maximum, 0.8-2.9). The higher COHb concentrations in patients with CAP were statistically significant (P < .05). Concentration of COHb correlated with pneumonia severity index (P = .04, r = 0.187); however, it did not correlate with CURB-65 (P = .218, r = 0.112). Although COHb concentrations show an increase in patients with pneumonia, it was concluded that this increase did not act as an indicator in diagnosis process or prediction of clinical severity for the physicians. Copyright © 2013 Elsevier Inc. All rights reserved.

Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter.

PubMed

Schophuizen, Carolien M S; Wilmer, Martijn J; Jansen, Jitske; Gustavsson, Lena; Hilgendorf, Constanze; Hoenderop, Joost G J; van den Heuvel, Lambert P; Masereeuw, Rosalinde

2013-12-01

Several organic cations, such as guanidino compounds and polyamines, have been found to accumulate in plasma of patients with kidney failure due to inadequate renal clearance. Here, we studied the interaction of cationic uremic toxins with renal organic cation transport in a conditionally immortalized human proximal tubule epithelial cell line (ciPTEC). Transporter activity was measured and validated in cell suspensions by studying uptake of the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium-iodide (ASP(+)). Subsequently, the inhibitory potencies of the cationic uremic toxins, cadaverine, putrescine, spermine and spermidine (polyamines), acrolein (polyamine breakdown product), guanidine, and methylguanidine (guanidino compounds) were determined. Concentration-dependent inhibition of ASP(+) uptake by TPA, cimetidine, quinidine, and metformin confirmed functional endogenous organic cation transporter 2 (OCT2) expression in ciPTEC. All uremic toxins tested inhibited ASP(+) uptake, of which acrolein required the lowest concentration to provoke a half-maximal inhibition (IC50 = 44 ± 2 μM). A Dixon plot was constructed for acrolein using three independent inhibition curves with 10, 20, or 30 μM ASP(+), which demonstrated competitive or mixed type of interaction (K i = 93 ± 16 μM). Exposing the cells to a mixture of cationic uremic toxins resulted in a more potent and biphasic inhibitory response curve, indicating complex interactions between the toxins and ASP(+) uptake. In conclusion, ciPTEC proves a suitable model to study cationic xenobiotic interactions. Inhibition of cellular uptake transport was demonstrated for several uremic toxins, which might indicate a possible role in kidney disease progression during uremia.

Management of hypercalcaemic crisis in adults: Current role of renal replacement therapy.

PubMed

Bentata, Yassamine; El Maghraoui, H; Benabdelhak, M; Haddiya, I

2018-06-01

Neoplasms and hematologic diseases are the predominant etiologies of hypercalcemic crisis in adults and the immediate treatment is mainly medical and symptomatic. The use of renal replacement therapy (RRT) is often necessary to correct the hypercalcemia, uremia and electrolyte disturbances related to Acute Kidney Injury (AKI). The aim of this work was to determine the etiologies and the place of RRT in treating patients with hypercalcaemic crisis. We conducted a retrospective study for 36months at the Nephrology Unit, University Hospital, Oujda, eastern of Morocco. We included all adult patients diagnosed with hypercalcemic crisis that was defined as corrected total serum calcium of >3.5mmol/l. 12 patients were collected. All patients were female and 5 patients were elderly (≥65years). Three patients had a serum calcium value of >4mmol/l and the highest calcium value was 5.8mmol/l. Electrocardiographic abnormalities were observed in 8 cases. AKI was observed in 8 cases. Three patients had chronic kidney disease on hemodialysis. Neoplasm was noted in 9 cases. All patients received venous rehydration, glucocorticoids and biphosphonates. The use of RRT with low calcium dialysate was performed in 11 cases. Three patients died during the first 24h of hospitalization. RRT must play its full role as first line treatment of hypercalcemia crisis. Improvements in hemodialysis techniques and the use of low calcium or calcium-free dialysates currently allows this therapeutic measure to be prescribed safely, and the benefit-risk balance is positive for the great benefit provided by dialysis. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia.

PubMed

De Schutter, Tineke M; Behets, Geert J; Geryl, Hilde; Peter, Mirjam E; Steppan, Sonja; Gundlach, Kristina; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Neven, Ellen

2013-06-01

Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.

Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia

PubMed Central

De Schutter, Tineke M; Behets, Geert J; Geryl, Hilde; Peter, Mirjam E; Steppan, Sonja; Gundlach, Kristina; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Neven, Ellen

2013-01-01

Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification. PMID:23486515

Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease

PubMed Central

El Machhour, Fala; Keuylian, Zela; Kavvadas, Panagiotis; Dussaule, Jean-Claude

2015-01-01

Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. PMID:25421557

Tear drops of kidney: a historical overview of Polycystic Kidney Disease.

PubMed

Balat, Ayse

2016-02-01

Polycystic kidneydisease (PKD) is one of the most common inheritedkidneydiseases causing end stage renal disease. Although it has been in existence with humanity, it was defined in 18th century. The most detailed observations on PKD have been written after the disease of Stephen Bathory, the King of Poland. He had fatigue and chest pain accompanied by unconsciousness within a few days after a hunting trip, and died within 9 days, at the age of 53 years in 1586. Surgeon Jan Zigulitz described the cysts in his kidneys as large like those of a bull, with an uneven and bumpy surface during the mummification. Based on available information, 347 years later, a group of physicians and historians in Krakow concluded that the probable cause of Kings death was PKD and uremia. Unfortunately, PKD did not attracted the interest of physicians until the 18th century. In late 18th century, Matthew Baillie noted that these vesicular cysts in kidney were different from hydatid cysts, and described them as "false hydatids of kidney". In 1888, Flix Lejars used the term of "polycystic kidney" for the first time, and stressed that these cysts were bilateral, and causing clinically identifiable symptoms. At the end of 19th century, the basic clinical signs, and genetic basis of the disease have been better defined. However, the inheritance pattern could only be understood long years later. In this study, the history of PKD, i.e., the tear drops (cysts) of kidney will try to be explained by the light of old and current knowledge.

The relationship between coping with stress and employment in patients receiving maintenance hemodialysis.

PubMed

Takaki, Jiro; Yano, Eiji

2006-07-01

The goal of this study was to assess the relationship between emotion- and task-oriented coping (EOC/TOC) with stress and employment in patients undergoing maintenance hemodialysis. Individuals aged 18 to 64 yr who had uremia and had been undergoing hemodialysis regularly for at least three months were evaluated according to sociodemographic and clinical factors. Work status was defined using the most recent International Labour Organization definitions. Patients were requested to complete the following questionnaires: the Japanese version of the Coping Inventory for Stressful Situations, the Short Form-36 Health Survey, an item on itchiness, the Self-Efficacy on Health-Related Behavior Scale, the Japanese version of the Health Locus of Control Scale, the Social Support Scale, and the Japanese version of the Hospital Anxiety and Depression Scale. A total of 317 individuals participated in this study. Among men, age, physical functioning, EOC, and depression differed significantly (p<0.05) depending on employment. Among women, marital status, household composition, EOC, depression, and anxiety differed significantly (p<0.05) depending on employment. TOC was not significantly associated with employment in either sex. Multiple logistic regression analyses, including possible confounders, indicated that when EOC increased by 10 points, the associated adjusted odds ratio of an unemployed or economically inactive status changed by 1.48 (95% confidence interval, 1.04-2.11; p=0.030) in men and by 1.88 (95% confidence interval, 1.02-3.46; p=0.042) in women. These results suggest that EOC is associated with employment in patients receiving maintenance hemodialysis.

Metabolic Changes in Summer Active and Anuric Hibernating Free-Ranging Brown Bears (Ursus arctos)

PubMed Central

Stenvinkel, Peter; Fröbert, Ole; Anderstam, Björn; Palm, Fredrik; Eriksson, Monica; Bragfors-Helin, Ann-Christin; Qureshi, Abdul Rashid; Larsson, Tobias; Friebe, Andrea; Zedrosser, Andreas; Josefsson, Johan; Svensson, My; Sahdo, Berolla; Bankir, Lise; Johnson, Richard J.

2013-01-01

The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during this time ingests no food or water and remains anuric and inactive. Despite these extreme conditions, bears do not develop azotemia and preserve their muscle and bone strength. To date most renal studies have been limited to small numbers of bears, often in captive environments. Sixteen free-ranging bears were darted and had blood drawn both during hibernation in winter and summer. Samples were collected for measurement of creatinine and urea, markers of inflammation, the calcium-phosphate axis, and nutritional parameters including amino acids. In winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in urea, indicating a remarkable ability to recycle urea nitrogen during hibernation. During hibernation serum calcium remained constant despite a decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged inactivity and reduced renal function, inflammation does not ensue and bears seem to have enhanced antioxidant defense mechanisms during hibernation. Nutrition parameters showed high fat stores, preserved amino acids and mild hyperglycemia during hibernation. While total, essential, non-essential and branched chain amino acids concentrations do not change during hibernation anorexia, changes in individual amino acids ornithine, citrulline and arginine indicate an active, although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid and serum fructose levels were elevated in summer and changes between seasons were positively correlated. Further studies to understand how bears can prevent the development of uremia despite minimal renal function during hibernation could provide new therapeutic avenues for the treatment of human kidney disease. PMID:24039826

Effect of intensive plasma exchange (PE) in rapidly progressive crescentic glomerulonephritis (RPCGN).

PubMed

D'Amico, G; Sinico, R; Fornasieri, A; Ferrario, F; Colasanti, G; Porri, M T; Paracchini, M L; Gibelli, A

1983-07-01

Ten adult patients with RPCGN (crescents in greater than 70% of glomeruli), primary in 6 and associated with systemic diseases in 4, were treated with PE, associated with oral steroids (P) and cyclophosphamide (C) in all cases and with intravenous methylprednisolone pulses (MP) in 7 cases. Four out of ten patients were anuric and needed dialysis treatment at the start of treatment. Therapeutic benefit, i.e. reversal of the trend to further deterioration and substantial improvement of GFR, was achieved in 8 out of 10 patients (80%), including 2 of 4 anuric patients, and in 7 of those (8) who had still active cellular crescents (87.5%). Similar therapeutic benefit had been achieved only in 10% of a comparable population of 10 patients with RPCGN treated before 1980 with P and C, without PE or MP pulses. It is difficult to establish whether the better therapeutic results in the more recently treated group were due to PE or to MP pulses of to both the new approaches, even though the clinical improvement obtained in all the 3 patients treated with PE without concomitant MP suggest a specific beneficial role for PE. RPCGN is a catastrophic illness characterized by progressive deterioration of kidney function, resulting in oliguria and uremia, usually within weeks or months. The most consistent histopathologic finding is the presence of extensive glomerular crescents resulting from proliferation of the extracapillary epithelial cell lining of Bowman's capsule. It is apparent that RPCGN is not a homogeneous entity, clinically, histologically or immunohistologically, but rather a clinicopathologic syndrome, the features of which may be seen in a variety of systemic disorders, including SLE, polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura, cryoglobulinemia, and subacute bacterial endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

PubMed Central

Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W.

2017-01-01

The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions. PMID:28775711

Metabolic changes in summer active and anuric hibernating free-ranging brown bears (Ursus arctos).

PubMed

Stenvinkel, Peter; Fröbert, Ole; Anderstam, Björn; Palm, Fredrik; Eriksson, Monica; Bragfors-Helin, Ann-Christin; Qureshi, Abdul Rashid; Larsson, Tobias; Friebe, Andrea; Zedrosser, Andreas; Josefsson, Johan; Svensson, My; Sahdo, Berolla; Bankir, Lise; Johnson, Richard J

2013-01-01

The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during this time ingests no food or water and remains anuric and inactive. Despite these extreme conditions, bears do not develop azotemia and preserve their muscle and bone strength. To date most renal studies have been limited to small numbers of bears, often in captive environments. Sixteen free-ranging bears were darted and had blood drawn both during hibernation in winter and summer. Samples were collected for measurement of creatinine and urea, markers of inflammation, the calcium-phosphate axis, and nutritional parameters including amino acids. In winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in urea, indicating a remarkable ability to recycle urea nitrogen during hibernation. During hibernation serum calcium remained constant despite a decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged inactivity and reduced renal function, inflammation does not ensue and bears seem to have enhanced antioxidant defense mechanisms during hibernation. Nutrition parameters showed high fat stores, preserved amino acids and mild hyperglycemia during hibernation. While total, essential, non-essential and branched chain amino acids concentrations do not change during hibernation anorexia, changes in individual amino acids ornithine, citrulline and arginine indicate an active, although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid and serum fructose levels were elevated in summer and changes between seasons were positively correlated. Further studies to understand how bears can prevent the development of uremia despite minimal renal function during hibernation could provide new therapeutic avenues for the treatment of human kidney disease.

Advanced glycation end product free adducts are cleared by dialysis.

PubMed

Agalou, S; Ahmed, N; Thornalley, P J; Dawnay, A

2005-06-01

Plasma advanced glycation end product (AGE) free adducts are increased up to 50-fold among patients on dialysis. We examined the ability of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) to clear these compounds. The AGE free adducts Nepsilon-carboxymethyl-lysine (CML) and Nepsilon-(1-carboxyethyl)lysine (CEL) and the hydroimidazolones derived from glyoxal (G-H1), methylglyoxal (MG-H1), and 3-deoxyglucosone (3DG-H) were determined by LC-MS/MS and pentosidine by HPLC with fluorimetric detection in ultrafiltrates of plasma, urine, or PD effluent as appropriate from patients on HD (n = 8) or PD (n = 8), and from healthy controls (n = 8). Among patients on HD, all free AGEs predialysis were significantly higher than in controls and were decreased with dialysis. The removal of MG-H1 and 3DG-H was comparable to that of urea, whereas that of CML and pentosidine was some 20% higher; in contrast, the removal of CEL and G-H1 was 25% lower. Among patients on CAPD, free AGEs in PD effluent increased with increasing dwell time. The combined renal and peritoneal 24-h excretion rates of CML (4.7 micromol), CEL (6.5 micromol), 3DG-H (16.6 micromol), and pentosidine (0.08 micromol) were twofold higher than the amount excreted in healthy controls, whereas MG-H1 was ninefold higher (59 micromol); the combined clearances of all free AGEs except pentosidine were lower than in healthy controls. Impaired renal clearance contributes to increased plasma free AGEs in uremia, but the increased excretion rate among patients on PD demonstrates that there was also an increased synthesis of free AGEs. Both HD and PD are able to remove free AGEs.

Keto analogue and amino acid supplementation and its effects on ammonemia and performance under thermoneutral conditions.

PubMed

Camerino, Saulo Rodrigo Alves e Silva; Lima, Rafaela Carvalho Pereira; França, Thássia Casado Lima; Herculano, Edla de Azevedo; Rodrigues, Daniela Souza Araújo; Gouveia, Marcos Guilherme de Sousa; Cameron, L C; Prado, Eduardo Seixas

2016-02-01

Alterations of cerebral function, fatigue and disturbance in cognitive-motor performance can be caused by hyperammonemia and/or hot environmental conditions during exercise. Exercise-induced hyperammonemia can be reduced through supplementation with either amino acids or combined keto analogues and amino acids (KAAA) to improve exercise tolerance. In the present study, we evaluated KAAA supplementation on ammonia metabolism and cognitive-motor performance after high-intensity exercise under a low heat stress environment. Sixteen male cyclists received a ketogenic diet for 2 d and were divided into two groups, KAAA (KEx) or placebo (CEx) supplementation. The athletes performed a 2 h cycling session followed by a maximum test (MAX), and blood samples were obtained at rest and during exercise. Cognitive-motor tasks were performed before and after the protocol, and the exhaustion time was used to evaluate physical performance. The hydration status was also evaluated. The CEx group showed a significant increase (∼ 70%) in ammonia concentration at MAX, which did not change in the KEx group. The non-supplemented group showed a significant increase in uremia. Both the groups had a significant increase in blood urate concentrations at 120 min, and an early significant increase from 120 min was observed in the CEx group. There was no change in the glucose concentrations of the two groups. A significant increase in lactate was observed at the MAX moment in both groups. There was no significant difference in the exhaustion times between the groups. No changes were observed in the cognitive-motor tasks after the protocol. We suggest that KAAA supplementation decreases ammonia concentration during high-intensity exercise but does not affect physical or cognitive-motor performances under a low heat stress environment.

Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy1234

PubMed Central

Kovesdy, Csaba P; Kopple, Joel D; Kalantar-Zadeh, Kamyar

2013-01-01

Protein-energy wasting (PEW), characterized by a decline in body protein mass and energy reserves, including muscle and fat wasting and visceral protein pool contraction, is an underappreciated condition in early to moderate stages of chronic kidney disease (CKD) and a strong predictor of adverse outcomes. The prevalence of PEW in early to moderate CKD is ≥20–25% and increases as CKD progresses, in part because of activation of proinflammatory cytokines combined with superimposed hypercatabolic states and declines in appetite. This anorexia leads to inadequate protein and energy intake, which may be reinforced by prescribed dietary restrictions and inadequate monitoring of the patient's nutritional status. Worsening uremia also renders CKD patients vulnerable to potentially deleterious effects of uncontrolled diets, including higher phosphorus and potassium burden. Uremic metabolites, some of which are anorexigenic and many of which are products of protein metabolism, can exert harmful effects, ranging from oxidative stress to endothelial dysfunction, nitric oxide disarrays, renal interstitial fibrosis, sarcopenia, and worsening proteinuria and kidney function. Given such complex pathways, nutritional interventions in CKD, when applied in concert with nonnutritional therapeutic approaches, encompass an array of strategies (such as dietary restrictions and supplementations) aimed at optimizing both patients’ biochemical variables and their clinical outcomes. The applicability of many nutritional interventions and their effects on outcomes in patients with CKD with PEW has not been well studied. This article reviews the definitions and pathophysiology of PEW in patients with non-dialysis-dependent CKD, examines the current indications for various dietary modification strategies in patients with CKD (eg, manufactured protein-based supplements, amino acids and their keto acid or hydroxyacid analogues), discusses the rationale behind their potential use in patients with PEW, and highlights areas in need of further research. PMID:23636234

[Coagulation factor VII levels in uremic patients and theirs influence factors].

PubMed

Fang, Jun; Xia, Ling-Hui; Wei, Wen-Ning; Song, Shan-Jun

2004-12-01

This study was aimed to investigate coagulation factor VII level in uremic patients with chronic renal failure and to explore theirs influence factors. The plasma levels of coagulation factor VII were detected in 30 uremic patients with chronic renal failure before and after hemodialysis for 1 month, the factor VII activity (FVII:C) was determined by one-stage coagulation method, while activated factor VII (FVIIa) was measured by one-stage coagulation method using recombinant soluble tissue factor, and factor VII antigen was detected by ELISA. The results showed that: (1) The FVIIa, FVII:C and FVIIAg levels in chronic uremic patients before hemodialysis were 4.00 +/- 0.86 microg/L, (148.5 +/- 40.4)% and (99.8 +/- 21.1)% respectively, which were significantly increased, as compared with healthy controls [2.77 +/- 1.02 microg/L, (113.1 +/- 33.0)% and (73.7 +/- 18.3)% respectively, P < 0.05]. (2) After hemodialysis the FVIIa, FVII:C and FVIIAg levels in uremic patients significantly enhanced to 5.56 +/- 1.45 microg/L, (200.8 +/- 68.7)% and (124.1 +/- 19.3)% respectively (P < 0.05). (3) The abnormal increase of coagulation factor VII was positively correlated with levels of blood uria nitrogen and serum creatinine before hemodialysis but not after hemodialysis. It is concluded that the enhanced levels of coagulation factor VII in chronic uremic patients suggested abnormal activated state, herperactivity and elevated production of factor VII which correlated with renal functional injury. The abnormality of factor VII in uremia may be aggravated by hemodialysis. Coagulation factor (FVII) may be a risk factor for cardiovascular events in uremic patients who especially had been accepted long-term hemodialysis.

Vitamin D receptor agonist VS-105 improves cardiac function in the presence of enalapril in 5/6 nephrectomized rats

PubMed Central

Chen, Yung-wu; Wessale, Jerry L.

2014-01-01

Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). Patients with CKD experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRA therapy may be associated with cardio-renal protective and survival benefits in patients with CKD. The 5/6 nephrectomized (NX) Sprague-Dawley rat with established uremia exhibits elevated serum parathyroid hormone (PTH), hypertension, and abnormal cardiac function. Treatment of 5/6 NX rats with VS-105, a novel VDRA (0.05 and 0.5 μg/kg po by gavage), once daily for 8 wk in the presence or absence of enalapril (30 mg/kg po via drinking water) effectively suppressed serum PTH without raising serum calcium. VS-105 alone reduced systolic blood pressure (from 174 ± 6 to 145 ± 9 mmHg, P < 0.05) as effectively as enalapril (from 174 ± 6 to 144 ± 7 mmHg, P < 0.05). VS-105 improved cardiac functional parameters such as E/A ratio, ejection fraction, and fractional shortening with or without enalapril. Enalapril or VS-105 alone significantly reduced left ventricular hypertrophy (LVH); VS-105 plus enalapril did not further reduce LVH. VS-105 significantly reduced both cardiac and renal fibrosis. The lack of hypercalcemic toxicity of VS-105 is due to its lack of effects on stimulating intestinal calcium transport and inducing the expression of intestinal calcium transporter genes such as Calb3 and TRPV6. These studies demonstrate that VS-105 is a novel VDRA that may provide cardiovascular benefits via VDR activation. Clinical studies are required to confirm the cardiovascular benefits of VS-105 in CKD. PMID:25503724

Expression pattern of salt tolerance-related genes in Aegilops cylindrica.

PubMed

Arabbeigi, Mahbube; Arzani, Ahmad; Majidi, Mohammad Mahdi; Sayed-Tabatabaei, Badraldin Ebrahim; Saha, Prasenjit

2018-02-01

Aegilops cylindrica , a salt-tolerant gene pool of wheat, is a useful plant model for understanding mechanism of salt tolerance. A salt-tolerant USL26 and a salt-sensitive K44 genotypes of A. cylindrica , originating from Uremia Salt Lake shores in Northwest Iran and a non-saline Kurdestan province in West Iran, respectively, were identified based on screening evaluation and used for this work. The objective of the current study was to investigate the expression patterns of four genes related to ion homeostasis in this species. Under treatment of 400 mM NaCl, USL26 showed significantly higher root and shoot dry matter levels and K + concentrations, together with lower Na + concentrations than K44 genotype. A. cylindrica HKT1;5 ( AecHKT1;5 ), SOS1 ( AecSOS1 ), NHX1 ( AecNHX1 ) and VP1 ( AecVP1 ) were partially sequenced to design each gene specific primer. Quantitative real-time PCR showed a differential expression pattern of these genes between the two genotypes and between the root and shoot tissues. Expressions of AecHKT1;5 and AecSOS1 was greater in the roots than in the shoots of USL26 while AecNHX1 and AecVP1 were equally expressed in both tissues of USL26 and K44. The higher transcripts of AecHKT1;5 in the roots versus the shoots could explain both the lower Na + in the shoots and the much lower Na + and higher K + concentrations in the roots/shoots of USL26 compared to K44. Therefore, the involvement of AecHKT1;5 in shoot-to-root handover of Na + in possible combination with the exclusion of excessive Na + from the root in the salt-tolerant genotype are suggested.

Quantification of Internal Filtration in Hollow Fiber Hemodialyzers with Medium Cut-Off Membrane.

PubMed

Lorenzin, Anna; Neri, Mauro; Lupi, Andrea; Todesco, Martina; Santimaria, Monica; Alghisi, Alberta; Brendolan, Alessandra; Ronco, Claudio

2018-06-08

Inadequate removal of molecules between 5 and 50 KDa may cause long-term complication in chronic hemodialysis. Medium cut-off (MCO) is a new class of membranes with enhanced sieving properties and negligible albumin loss. MCO membrane makes it possible to perform expanded hemodialysis (HDx), a technique based on high internal filtration (IF).The present study is designed to quantify IF in 2 MCO dialyzers (Theranova 400 and 500, Baxter, Deerfield, USA) using a nuclear imaging technique previously validated. Blood and dialysate compartment pressure drop along with transmembrane pressure; they were measured in a closed in vitro circuit with human blood (blood flow [QB] = 300 and 400 mL/min; dialysate flow 500 mL/min; net ultrafiltration rate 0 mL/min). A non-diffusible marker molecule (albumin macro-aggregates labeled with 99Tc metastable) was injected in the blood compartment and nuclear emission was recorded by a gamma camera. Relative variations in the concentration of the marker molecule along the length of the filter were used to calculate local cross filtration. Based on marker concentration profiles, IF was estimated. For Theranova 400, IF were 29.7 and 41.6 mL/min for QB of 300 and 400 mL/min. For Theranova 500, IF were 31.6 and 53.1 mL/min for QB of 300 and 400 mL/min respectively. MCO membrane provides significant amounts of IF due to the particular combination between hydraulic permeability of the membrane and reduced inner diameter of the fibers. High IF combined with enhanced sieving profile of MCO membrane leads to improved removal of a wider spectrum of uremia retention molecules in HDx, without requiring complex equipment. © 2018 S. Karger AG, Basel.

Exposure to potentially toxic hydrocarbons and halocarbons released from the dialyzer and tubing set during hemodialysis.

PubMed

Lee, Hyun Ji Julie; Meinardi, Simone; Pahl, Madeleine V; Vaziri, Nostratola D; Blake, Donald R

2012-10-01

Although much is known about the effect of chronic kidney failure and dialysis on the composition of solutes in plasma, little is known about their impact on the composition of gaseous compounds in exhaled breath. This study was designed to explore the effect of uremia and the hemodialysis (HD) procedure on the composition of exhaled breath. Breath samples were collected from 10 dialysis patients immediately before, during, and after a dialysis session. To determine the potential introduction of gaseous compounds from dialysis components, gasses emitted from dialyzers, tubing set, dialysate, and water supplies were collected. Prospective cohort study. 10 HD patients and 10 age-matched healthy individuals. Predictors include the dialyzers, tubing set, dialysate, and water supplies before, during, and after dialysis. Changes in the composition of exhaled breath. A 5-column/detector gas chromatography system was used to measure hydrocarbon, halocarbon, oxygenate, and alkyl nitrate compounds. Concentrations of 14 hydrocarbons and halocarbons in patients' breath rapidly increased after the onset of the HD treatment. All 14 compounds and 5 others not found in patients' breath were emitted from the dialyzers and tubing sets. Contrary to earlier reports, exhaled breath ethane concentrations in our dialysis patients were virtually unchanged during the HD treatment. Single-center study with a small sample size may limit the generalizability of the findings. The study documented the release of several potentially toxic hydrocarbons and halocarbons to patients from the dialyzer and tubing sets during the HD procedure. Because long-term exposure to these compounds may contribute to the morbidity and mortality in dialysis population, this issue should be considered in the manufacturing of the new generation of dialyzers and dialysis tubing sets. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of αCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades.

PubMed

Kim, Jong Wan; Ha, Gyoung Yim; Jung, Yong Wook

2014-09-01

N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propinoic acid (AMPA) receptors bound to postsynaptic density-95 (PSD-95) and α isoform of calcium/calmodulin-dependent protein kinase II (αCaMKII) is fundamentally involved in the regulation of working memory. The aim of present study was to investigate the alterations of NMDA and AMPA receptors responsible for hippocampal synaptic dysfunction and selective neuronal cell death after chronic renal failure (CRF) which may be associated with impairment of working memory. Altered interactions between NMDA and AMPA receptors and PSD-95 and αCaMKII were analyzed in the cornu ammonis (CA) 1 and CA3/dentate gyrus (DG) subfields of the uremic rat hippocampi using the immunoblotting and immunoprecipitation methods. Uremia induced by CRF produced necrotic cell death and decreased neuronal nucleoli protein levels in the hippocampal CA1 subfield, but not in the CA3/DG subfields. The CA1 subfields of CRF rats exhibited significant decreases and increases, respectively, in the expressions of PSD-95/NR2B and αCaMKII/NR2A synaptic complex. Moreover, increased phosphorylation of glutamate receptor type 1 (GluR1) AMPA receptor at ser831 was observed in the CA1 subfield after CRF. These hippocampal CA1 neuronal vulnerability may be responsible for memory dysfunction after CRF as mediated by an increase in NR2A-containing NMDA receptors bound to αCaMKII and subsequent activation of GluR1-containing AMPA receptors caused by the phosphorylation of GluR1 at ser831.

The dialysis orders objective structured clinical examination (OSCE): a formative assessment for nephrology fellows

PubMed Central

Prince, Lisa K; Campbell, Ruth C; Gao, Sam W; Kendrick, Jessica; Lebrun, Christopher J; Little, Dustin J; Mahoney, David L; Maursetter, Laura A; Nee, Robert; Saddler, Mark; Watson, Maura A

2018-01-01

Abstract Background Few quantitative nephrology-specific simulations assess fellow competency. We describe the development and initial validation of a formative objective structured clinical examination (OSCE) assessing fellow competence in ordering acute dialysis. Methods The three test scenarios were acute continuous renal replacement therapy, chronic dialysis initiation in moderate uremia and acute dialysis in end-stage renal disease-associated hyperkalemia. The test committee included five academic nephrologists and four clinically practicing nephrologists outside of academia. There were 49 test items (58 points). A passing score was 46/58 points. No item had median relevance less than ‘important’. The content validity index was 0.91. Ninety-five percent of positive-point items were easy–medium difficulty. Preliminary validation was by 10 board-certified volunteers, not test committee members, a median of 3.5 years from graduation. The mean score was 49 [95% confidence interval (CI) 46–51], κ = 0.68 (95% CI 0.59–0.77), Cronbach’s α = 0.84. Results We subsequently administered the test to 25 fellows. The mean score was 44 (95% CI 43–45); 36% passed the test. Fellows scored significantly less than validators (P < 0.001). Of evidence-based questions, 72% were answered correctly by validators and 54% by fellows (P = 0.018). Fellows and validators scored least well on the acute hyperkalemia question. In self-assessing proficiency, 71% of fellows surveyed agreed or strongly agreed that the OSCE was useful. Conclusions The OSCE may be used to formatively assess fellow proficiency in three common areas of acute dialysis practice. Further validation studies are in progress. PMID:29644053

Challenges in device closure of a large patent ductus arteriosus in infants weighing less than 6 kg.

PubMed

Vijayalakshmi, I B; Chitra, Narasimhan; Praveen, Jayan; Prasanna, Simha Rao

2013-02-01

Transcatheter closure of patent ductus arteriosus (PDA) has replaced surgery in most institutions. Despite improvements in techniques and the devices available, closure of large PDA in very small infants remains a challenge. To assess the challenges, feasibility, and efficacy of device closure of large PDA, in infants weighing ≤6 kg. Analysis of device closure of a PDA was done in 61 infants ≤6 kg. Their ages, ranged from 9 days-12 months (mean 8.9 months), weight ranged from 2.2 to 6 kg (mean 5.3 kg), and PDA measured 3.2-8.7 mm (mean 4.8 mm). The fluoroscopy time was 3-18 minutes. The largest device used was 12 × 10 mm. Successful device placement was achieved in 60/61 infants (98.4%). Mild aortic obstruction occurred in 2 cases (3.3%), as the device got displaced towards the aorta after release. The device embolized in 2 cases (3.3%). In one it was retrieved by a novel method like fastening the screw in the aorta and was closed with a 4 × 6 ADO II. In the other infant, with a single kidney, died of uremia after device retrieval. Mild left pulmonary artery (LPA) obstruction occurred in one case (1.6%). Four cases (6.6%) had minor vascular complications. The postprocedure weight gain after 3 months was between 2.5 kg ± 250 mg. Device closure of large PDA in infants weighing ≤6 kg with left ventricular failure is challenging but possible, safe and effective. Retrieval of embolized device could be tricky. © 2012, Wiley Periodicals, Inc.

Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease

PubMed Central

Sureshbabu, Angara; Doty, Steve B.; Zhu, Yuan-Shan; Patino, Edwin; Cunningham-Rundles, Susanna; Choi, Mary E.; Boskey, Adele; Rivella, Stefano

2016-01-01

Growth delay is common in children with chronic kidney disease (CKD), often associated with poor quality of life. The role of anemia in uremic growth delay is poorly understood. Here we describe an induction of uremic growth retardation by a 0.2% adenine diet in wild-type (WT) and hepcidin gene (Hamp) knockout (KO) mice, compared with their respective littermates fed a regular diet. Experiments were started at weaning (3 wk). After 8 wk, blood was collected and mice were euthanized. Adenine-fed WT mice developed CKD (blood urea nitrogen 82.8 ± 11.6 mg/dl and creatinine 0.57 ± 0.07 mg/dl) and were 2.1 cm shorter compared with WT controls. WT adenine-fed mice were anemic and had low serum iron, elevated Hamp, and elevated IL6 and TNF-α. WT adenine-fed mice had advanced mineral bone disease (serum phosphorus 16.9 ± 3.1 mg/dl and FGF23 204.0 ± 115.0 ng/ml) with loss of cortical and trabecular bone volume seen on microcomputed tomography. Hamp disruption rescued the anemia phenotype resulting in improved growth rate in mice with CKD, thus providing direct experimental evidence of the relationship between Hamp pathway and growth impairment in CKD. Hamp disruption ameliorated CKD-induced growth hormone-insulin-like growth factor 1 axis derangements and growth plate alterations. Disruption of Hamp did not mitigate the development of uremia, inflammation, and mineral and bone disease in this model. Taken together, these results indicate that an adenine diet can be successfully used to study growth in mice with CKD. Hepcidin appears to be related to pathways of growth retardation in CKD suggesting that investigation of hepcidin-lowering therapies in juvenile CKD is warranted. PMID:27440777

Management of a child with vomiting.

PubMed

Singhi, Sunit C; Shah, Ravi; Bansal, Arun; Jayashree, M

2013-04-01

Vomiting is a protective reflex that results in forceful ejection of stomach contents up to and out of the mouth. It is a common complaint and may be the presenting symptom of several life-threatening conditions. It can be caused by a variety of organic and nonorganic disorders; gastrointestinal (GI) or outside of GI. Acute gastritis and gastroenteritis (AGE) are the leading cause of acute vomiting in children. Important life threatening causes in infancy include congenital intestinal obstruction, atresia, malrotation with volvulus, necrotizing enterocolitis, pyloric stenosis, intussusception, shaken baby syndrome, hydrocephalus, inborn errors of metabolism, congenital adrenal hypoplasia, obstructive uropathy, sepsis, meningitis and encephalitis, and severe gastroenteritis, and in older children appendicitis, intracranial mass lesion, diabetic ketoacidosis, Reye's syndrome, toxic ingestions, uremia, and meningitis. Initial evaluation is directed at assessment of airway, breathing and circulation, assessment of hydration status and red flag signs (bilious or bloody vomiting, altered sensorium, toxic/septic/apprehensive look, inconsolable cry or excessive irritability, severe dehydration, concern for symptomatic hypoglycemia, severe wasting, Bent-over posture). The history and physical examination guides the approach in an individual patient. The diverse nature of causes of vomiting makes a "routine" laboratory or radiologic screen impossible. Investigations (Serum electrolytes and blood gases,renal and liver functions and radiological studies) are required in any child with dehydration or red flag signs, to diagnose surgical causes. Management priorities include treatment of dehydration, stoppage of oral fluids/feeds and decompression of the stomach with nasogastric tube in patients with bilious vomiting. Antiemetic ondansetron(0.2 mg/kg oral; parenteral 0.15 mg/kg; maximum 4 mg) is indicated in children unable to take orally due to persistent vomiting, post-operative vomiting, chemotherapy induced vomiting, cyclic vomiting syndrome and acute mountain sickness.

Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease.

PubMed

El Machhour, Fala; Keuylian, Zela; Kavvadas, Panagiotis; Dussaule, Jean-Claude; Chatziantoniou, Christos

2015-07-01

Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. Copyright © 2015 by the American Society of Nephrology.

Effect of hemodialysis and peritoneal dialysis on redox status in chronic renal failure patients: a comparative study.

PubMed

Mekki, Khedidja; Taleb, Warda; Bouzidi, Nassima; Kaddous, Abbou; Bouchenak, Malika

2010-09-03

To investigate the effects of hemodialysis (HD) and periotoneal dialysis (PD) on oxidative stress in chronic renal failure patients (CRF). 20 HD patients (M/F: 8/12, 36 ± 12 years) and 20 PD patients (M/F: 10/10, 40 ± 8 years) were compared with 20 end stage renal failure patients (CRF) (M/F: 4/16, 61 ± 13 years). Thiobarbituric acid reactive substances (TBARS) values were elevated in HD and decreased in PD compared to CRF (P < 0.05). TBARS-VLDL and TBARS-HDL2 were decreased in HD and PD, compared to CRF (p < 0.05). TBARS-LDL were higher in HD compared to CRF (p < 0.05). No significant difference in TBARS-HDL3 values between the three groups. Carbonyls were increased in HD (p < 0.05) and PD (p < 0.01) compared to CRF. Plasma superoxide dismutase activity (SOD) was decreased in HD compared to CRF and PD (P < 0.05). Glutathion peroxidase activity (GSH-Px) was decreased in HD and PD (P < 0.005), compared to CRF. Decrease in catalase activity was noted only in PD compared to CRF (P < 0.05). An increase in nitric oxide was noted in HD compared to CRF (p < 0.05). Albumin concentrations were higher in HD and PD compared to CRF (P < 0.001). Whereas uric acid concentrations were decreased in HD (P < 0.001) compared to CRF and PD. Bilirubin values were similar in all groups. Increased values of iron were noted in HD and PD, compared to PD (p < 0.001). HD and PD aggravate oxidative stress generated by uremia. HD accentuates lipid and protein peroxidation, while PD aggravates protein oxidation. However, the activity of antioxidant enzymes was altered by both dialysis treatments.

Basic mechanisms and clinical implications of peritoneal fibrosis.

PubMed

Margetts, Peter J; Bonniaud, Philippe

2003-01-01

We have stressed the role of certain growth factors and cytokines in peritoneal fibrosis, including TGFbeta, TIMP-1, and inflammatory cytokines, especially IL-1beta. Recent research highlights the myofibroblast-like transformation of mesothelial cells as a central initiating event in peritoneal fibrosis. The induction, survival, and apoptosis of the myofibroblast cell population likely dictate the nature of the fibrogenic response. The accumulation of collagen occurs in a nondegradative environment, and collagenases and their inhibitors have a role in the maintenance of fibrosis. Fibrosis appears to be a ubiquitous response of peritoneal tissues to the damaging effects of uremia, bioincompatible dialysate, recurrent infection, and inflammation. Recent research has focused on the induction of angiogenesis, as this appears to correlate with increased solute transport and peritoneal membrane ultrafiltration failure. Fibrosis may play an integral part in peritoneal membrane dysfunction in several aspects. Angiogenesis may be induced as part of the fibrotic response, as many key fibrogenic cytokines are also strongly angiogenic. Fibrotic tissue may support and preserve angiogenesis. Changes in the interstitium may have a direct effect on the hydrodynamic properties of the peritoneum and may directly influence fluid movement. In its most extreme form, fibrosis manifests as the rare but devastating EPS. Peritoneal biopsy studies have identified a high prevalence of peritoneal fibrosis in PD patients. Research into peritoneal fibrosis will be enhanced by new animal models where the role of various cytokines and growth factors, cellular processes, and matrix interactions can be studied. With these models, the role of fibrosis in alteration of peritoneal membrane function can be better assessed. Clinical trials to assess the role of prevention of peritoneal injury using biocompatible solutions and treatments targeted directly at peritoneal fibrosis will be important, but challenging to design and carry out.

Effects of Rapid Intravenous Rehydration in Children With Mild-to-Moderate Dehydration.

PubMed

Janet, Sophie; Molina, Juan Carlos; Marañón, Rafael; García-Ros, Marta

2015-08-01

New guidelines for "rapid or ultrarapid" intravenous rehydration are being developed in different emergency departments. These new guidelines propose a faster administration of fluids and electrolytes than in traditional protocols. However, there is still insufficient evidence to establish a standard protocol. Our objective was to determine the effects of an outpatient rapid intravenous rehydration regimen based on the administration of 0.9% saline + 2.5% dextrose, at a rate of 20 mL/kg per hour for 2 hours, in children with mild-to-moderate isonatremic dehydration resulting from acute gastroenteritis. We performed a 2-institution, prospective, observational, descriptive study. Eighty-three patients were included in the study. All patients underwent a first evaluation, including physical examination, laboratory tests, and assessment of clinical degree of dehydration. After this initial evaluation, all children received our intravenous rehydration regimen. A second evaluation including the same items as in the first one was made after in all the children. Intravenous rehydration was successful in 69 patients (83.1%). It failed in 14 patients (16.8%), who required hospitalization because of persistent vomiting in 9 patients and poor general appearance in 5 patients. After intravenous rehydration, we observed a statistically significant decrease in the levels of ketonemia and uremia and in the Gorelick scale score. However, no significant changes were observed in sodium, chloride, potassium, and osmolarity values. We conclude that, in children with mild-to-moderate dehydration, the administration of 20 mL/kg per hour for 2 hours of 0.9% saline solution + 2.5% glucose improved clinical scores and may be used as an alternative and safe way for intravenous rehydration.

Higher versus lower protein intake in formula-fed low birth weight infants.

PubMed

Fenton, Tanis R; Premji, Shahirose S; Al-Wassia, Heidi; Sauve, Reg S

2014-04-21

The ideal quantity of dietary protein for formula-fed low birth weight infants is still a matter of debate. Protein intake must be sufficient to achieve normal growth without negative effects such as acidosis, uremia, and elevated levels of circulating amino acids. To determine whether higher (≥ 3.0 g/kg/d) versus lower (< 3.0 g/kg/d) protein intake during the initial hospital stay of formula-fed preterm infants or low birth weight infants (< 2.5 kilograms) results in improved growth and neurodevelopmental outcomes without evidence of short- and long-term morbidity.To examine the following distinctions in protein intake. 1. Low protein intake if the amount was less than 3.0 g/kg/d. 2. High protein intake if the amount was equal to or greater than 3.0 g/kg/d but less than 4.0 g/kg/d. 3. Very high protein intake if the amount was equal to or greater than 4.0 g/kg/d.If the reviewed studies combined alterations of protein and energy, subgroup analyses were to be carried out for the planned categories of protein intake according to the following predefined energy intake categories. 1. Low energy intake: less than 105 kcal/kg/d. 2. Medium energy intake: greater than or equal to 105 kcal/kg/d and less than or equal to 135 kcal/kg/d. 3. High energy intake: greater than 135 kcal/kg/d.As the Ziegler-Fomon reference fetus estimates different protein requirements for infants based on birth weight, subgroup analyses were to be undertaken for the following birth weight categories. 1. < 800 grams. 2. 800 to 1199 grams. 3. 1200 to 1799 grams. 4. 1800 to 2499 grams. The standard search methods of the Cochrane Neonatal Review Group were used. MEDLINE, CINAHL, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library) were searched. Randomized controlled trials contrasting levels of formula protein intake as low (< 3.0 g/kg/d), high (≥ 3.0 g/kg/d but < 4.0 g/kg/d), or very high (≥ 4.0 g/kg/d) in formula-fed hospitalized neonates weighing less than 2.5 kilograms were included. Studies were excluded if infants received partial parenteral nutrition during the study period or were fed formula as a supplement to human milk. Studies in which nutrients other than protein also varied were added in a post-facto analysis. The standard methods of the Cochrane Neonatal Review Group were used. Five studies compared low versus high protein intake. Improved weight gain and higher nitrogen accretion were demonstrated in infants receiving formula with higher protein content while other nutrients were kept constant. No significant differences were seen in rates of necrotizing enterocolitis, sepsis, or diarrhea.One study compared high versus very high protein intake during and after an initial hospital stay. Very high protein intake promoted improved gain in length at term, but differences did not remain significant at 12 weeks corrected age. Three of the 24 infants receiving very high protein intake developed uremia.A post-facto analysis revealed further improvement in all growth parameters in infants receiving formula with higher protein content. No significant difference in the concentration of plasma phenylalanine was noted between high and low protein intake groups. However, one study (Goldman 1969) documented a significantly increased incidence of low intelligence quotient (IQ) scores among infants of birth weight less than 1300 grams who received a very high protein intake (6 to 7.2 g/kg). Higher protein intake (≥ 3.0 g/kg/d but < 4.0 g/kg/d) from formula accelerates weight gain. However, limited information is available regarding the impact of higher formula protein intake on long-term outcomes such as neurodevelopmental abnormalities. Available evidence is not adequate to permit specific recommendations regarding the provision of very high protein intake (> 4.0 g/kg/d) from formula during the initial hospital stay or after discharge.

Comorbidity Analysis According to Sex and Age in Hypertension Patients in China

PubMed Central

Liu, Jiaqi; Ma, James; Wang, Jiaojiao; Zeng, Daniel Dajun; Song, Hongbin; Wang, Ligui; Cao, Zhidong

2016-01-01

Background: Hypertension, an important risk factor for the health of human being, is often accompanied by various comorbidities. However, the incidence patterns of those comorbidities have not been widely studied. Aim: Applying big-data techniques on a large collection of electronic medical records, we investigated sex-specific and age-specific detection rates of some important comorbidities of hypertension, and sketched their relationships to reveal the risk for hypertension patients. Methods: We collected a total of 6,371,963 hypertension-related medical records from 106 hospitals in 72 cities throughout China. Those records were reported to a National Center for Disease Control in China between 2011 and 2013. Based on the comprehensive and geographically distributed data set, we identified the top 20 comorbidities of hypertension, and disclosed the sex-specific and age-specific patterns of those comorbidities. A comorbidities network was constructed based on the frequency of co-occurrence relationships among those comorbidities. Results: The top four comorbidities of hypertension were coronary heart disease, diabetes, hyperlipemia, and arteriosclerosis, whose detection rates were 21.71% (21.49% for men vs 21.95% for women), 16.00% (16.24% vs 15.74%), 13.81% (13.86% vs 13.76%), and 12.66% (12.25% vs 13.08%), respectively. The age-specific detection rates of comorbidities showed five unique patterns and also indicated that nephropathy, uremia, and anemia were significant risks for patients under 39 years of age. On the other hand, coronary heart disease, diabetes, arteriosclerosis, hyperlipemia, and cerebral infarction were more likely to occur in older patients. The comorbidity network that we constructed indicated that the top 20 comorbidities of hypertension had strong co-occurrence correlations. Conclusions: Hypertension patients can be aware of their risks of comorbidities based on our sex-specific results, age-specific patterns, and the comorbidity network. Our findings provide useful insights into the comorbidity prevention, risk assessment, and early warning for hypertension patients. PMID:26941567

[Prevalence of histological types of bone disease in a hemodialysis center limiting the oral intake of aluminum hydroxide].

PubMed

Belbrik, S; Marie, A; Boudailliez, B; Morinière, P; Sébert, J L; Solal, M C; Westeel, P F; Roche, D; Fournier, A

1990-01-01

To assess the prevalence of histologic bone disease in our center where Al(OH)3 intake is restricted, we reviewed 42 bone biopsies performed between 1975 and 1985 in patients dialyzed more than 29 months. Bone biopsies were performed systematically (2/3 of the cases) or because of a mild hypercalcemia (1/3 of the cases). Seventeen of these patients had been dialyzed before 1978 with softened water moderately contaminated by aluminum. Fifteen had always been dialyzed with reverse osmosis treated water and 10 had been exclusively treated by hemofiltration. The prevalence of osteitis fibrosa was 76%, that of osteomalacia null and that of adynamic bone disease 24% (but only 9.5% with positive Aluminon staining). When the 17 patients dialyzed with aluminum contaminated water before 1978 were excluded, only one patient among 25 had an aluminum adynamic bone disease (4%). This low prevalence can probably be explained by the restricted intake of Al(OH)3 thanks to the systematic administration of Ca CO3 and in a few cases of Mg (OH). The adynamic bone disease group has lower serum concentration of PTH and shorter duration on dialysis whereas the serum levels of calcium, phosphorus, magnesium and aluminum and daily dose of Ca CO3, Mg (OH)2 and Al(OH)3 do not differ. The frequency of the positivity of aluminum staining is not statistically different in the 2 groups. In 4 cases, adynamic bone disease without aluminum or iron intoxications is found, associated with a relative hypoparathyroidism. It is not explained by previous parathyroidectomy, diabetes or steroid therapy. 1) Restriction of aluminum intake and dialysis with reverse osmosis treated water lead to a low prevalence of aluminum bone disease. 2) A new bone disease in uremia is described: the idiopathic adynamic bone disease associated with a relative hypoparathyroidism.

Adipose tissue-derived mesenchymal stem cells in long-term dialysis patients display downregulation of PCAF expression and poor angiogenesis activation.

PubMed

Yamanaka, Shuichiro; Yokote, Shinya; Yamada, Akifumi; Katsuoka, Yuichi; Izuhara, Luna; Shimada, Yohta; Omura, Nobuo; Okano, Hirotaka James; Ohki, Takao; Yokoo, Takashi

2014-01-01

We previously demonstrated that mesenchymal stem cells (MSCs) differentiate into functional kidney cells capable of urine and erythropoietin production, indicating that they may be used for kidney regeneration. However, the viability of MSCs from dialysis patients may be affected under uremic conditions. In this study, we isolated MSCs from the adipose tissues of end-stage kidney disease (ESKD) patients undergoing long-term dialysis (KD-MSCs; mean: 72.3 months) and from healthy controls (HC-MSCs) to compare their viability. KD-MSCs and HC-MSCs were assessed for their proliferation potential, senescence, and differentiation capacities into adipocytes, osteoblasts, and chondrocytes. Gene expression of stem cell-specific transcription factors was analyzed by PCR array and confirmed by western blot analysis at the protein level. No significant differences of proliferation potential, senescence, or differentiation capacity were observed between KD-MSCs and HC-MSCs. However, gene and protein expression of p300/CBP-associated factor (PCAF) was significantly suppressed in KD-MSCs. Because PCAF is a histone acetyltransferase that mediates regulation of hypoxia-inducible factor-1α (HIF-1α), we examined the hypoxic response in MSCs. HC-MSCs but not KD-MSCs showed upregulation of PCAF protein expression under hypoxia. Similarly, HIF-1α and vascular endothelial growth factor (VEGF) expression did not increase under hypoxia in KD-MSCs but did so in HC-MSCs. Additionally, a directed in vivo angiogenesis assay revealed a decrease in angiogenesis activation of KD-MSCs. In conclusion, long-term uremia leads to persistent and systematic downregulation of PCAF gene and protein expression and poor angiogenesis activation of MSCs from patients with ESKD. Furthermore, PCAF, HIF-1α, and VEGF expression were not upregulated by hypoxic stimulation of KD-MSCs. These results suggest that the hypoxic response may be blunted in MSCs from ESKD patients.

Dendritic cell co-stimulatory and co-inhibitory markers in chronic HCV: An Egyptian study

PubMed Central

Fouad, Hanan; Raziky, Maissa Saeed El; Aziz, Rasha Ahmed Abdel; Sabry, Dina; Aziz, Ghada Mahmoud Abdel; Ewais, Manal; Sayed, Ahmed Reda

2013-01-01

AIM: To assess co-stimulatory and co-inhibitory markers of dendritic cells (DCs) in hepatitis C virus (HCV) infected subjects with and without uremia. METHODS: Three subject groups were included in the study: group 1 involved 50 control subjects, group 2 involved 50 patients with chronic HCV infection and group 3 involved 50 HCV uremic subjects undergoing hemodialysis. CD83, CD86 and CD40 as co-stimulatory markers and PD-L1 as a co-inhibitory marker were assessed in peripheral blood mononuclear cells by real-time polymerase chain reaction. Interleukin-10 (IL-10) and hyaluronic acid (HA) levels were also assessed. All findings were correlated with disease activity, viral load and fibrogenesis. RESULTS: There was a significant decrease in co-stimulatory markers; CD83, CD86 and CD40 in groups 2 and 3 vs the control group. Co-stimulatory markers were significantly higher in group 3 vs group 2. There was a significant elevation in PD-L1 in both HCV groups vs the control group. PD-L1 was significantly lower in group 3 vs group 2. There was a significant elevation in IL-10 and HA levels in groups 2 and 3, where IL-10 was higher in group 3 and HA was lower in group 3 vs group 2. HA level was significantly correlated with disease activity and fibrosis grade in group 2. IL-10 was significantly correlated with fibrosis grade in group 2. There were significant negative correlations between co-stimulatory markers and viral load in groups 2 and 3, except CD83 in dialysis patients. There was a significant positive correlation between PD-L1 and viral load in both HCV groups. CONCLUSION: A significant decrease in DC co-stimulatory markers and a significant increase in a DC co-inhibitory marker were observed in HCV subjects and to a lesser extent in dialysis patients. PMID:24282359

Effect of antioxidant therapy with dl-alpha-tocopherol on cardiovascular structure in experimental renal failure.

PubMed

Amann, Kerstin; Törnig, Johannes; Buzello, Mareike; Kuhlmann, Alexander; Gross, Marie-Luise; Adamczak, Marcin; Buzello, Moriz; Ritz, Eberhard

2002-09-01

Chronic renal failure is characterized by remodeling of the structure of the heart and the vasculature, for example, left ventricular hypertrophy, myocardial fibrosis, capillary/myocyte mismatch, as well as thickening of intramyocardial arteries and of peripheral arteries and veins. Furthermore, uremia is a state of increased oxygen stress. It was the purpose of this study to examine whether these findings are interrelated. To investigate whether antioxidative therapy with dl-alpha-tocopherol (Toco; vitamin E) interferes with the development of abnormal cardiovascular structure in experimental renal failure, 28 male Sprague-Dawley rats were subjected to partial renal ablation (subtotal nephrectomy, SNX) or to sham operation (sham). SNX were either left untreated or received the antioxidant Toco (2 x 1500 IE/kg BW/week in the pellets). Blood pressure was measured using tail plethysmography. The experiment was terminated after 12 weeks. Heart and left ventricular weight were determined and the following parameters were measured using morphometry and stereology: volume densities of cardiomyocytes, capillaries and non-vascular interstitium; length density and total length of cardiac capillaries, wall thickness of intramyocardial arterioles and of the aorta. Systolic blood pressure and body weight were comparable in all groups. Treatment with Toco led to significantly increased plasma concentrations of Toco. Left ventricular weight and wall thickness of intramyocardial arteries were significantly higher in both SNX groups compared to sham controls. Volume density of the cardiac interstitial tissue was significantly higher in untreated SNX than in Toco treated SNX and sham control rats. Length density of capillaries was significantly lower in untreated SNX than in control rats; however, the values were significantly higher, and even higher than in sham controls, when SNX were treated with Toco. Treatment with the antioxidant dl-alpha-tocopherol prevented cardiomyocyte/capillary mismatch, and to some extent also myocardial fibrosis in rats with renal failure. The results point to a role of oxidative stress in the genesis of myocardial interstitial fibrosis and capillary deficit of the heart.

Cardiovascular risk in peritoneal dialysis - a Portuguese multicenter study.

PubMed

Neves, Marta; Machado, Susana; Rodrigues, Luís; Borges, Andreia; Maia, Pedro; Campos, Mário

2014-01-01

Cardiovascular (CV) disease is the major cause of mortality in patients undergoing renal replacement therapy. The primary aim of the study was to evaluate the CV risk profile and prevalence of CV disease in patients on peritoneal dialysis (PD) in Portugal. The secondary goal was to establish parameters most associated with CV disease. Retrospective, multicenter study of the prevalent adult population on PD. Six hundred patients were included (56.7% male; mean age 53.5 ± 15.3 years), on PD for 25.6 ± 21.9 months. Patients were divided into two groups: group 1 (n=166) with CV disease and group 2 (n=434) without CV disease. Comparisons were made regarding traditional CV risk factors and those associated with uremia and PD itself, and a multivariate analysis was performed to determine variables independently associated with CV disease. At the end of the study, the prevalence of CV disease was 28%. At univariate analysis, group 1 presented a higher frequency of males (p<.01), older patients (p<.01), diabetics (p<.01), occurrence of left ventricular hypertrophy (LVH) (p<.01), mean C-reactive protein (CRP) (p=.04), lower mean parathormone level (p=.014), lower serum phosphorus (p=.02), lower daily urine output (p=.04), lower weekly Kt/V (p=.008), increased use of icodextrin and hypertonic glucose-based PD solutions (p<.001 and p=.006, respectively) and more were under continuous ambulatory PD (CAPD) (p=.014) and had a high peritoneal transport status (p=.02). Multivariate analysis provided a significant discriminatory influence pertaining to age >50 years, CRP>0.6 mg/dl, male gender, diabetes, LVH, CAPD and anuria, when comparing group 1 and group 2. Risk factors most related to the development of CV disease in PD in Portugal are age >50 years, CRP>0.6 mg/dL, male gender, diabetes, LVH, CAPD and anuria.

Effect of protein leaking BK-F PMMA-based hemodialysis on plasma pentosidine levels.

PubMed

Tessitore, Nicola; Lapolla, Annunziata; Aricò, Nadia Concetta; Poli, Albino; Gammaro, Linda; Bassi, Antonella; Bedogna, Valeria; Corgnati, Angela; Reitano, Rachele; Fedele, Domenico; Lupo, Antonio

2004-01-01

Advanced glycation end-products (AGEs) are now considered to contribute to the middle molecule toxicity of uremia and, because they are not cleared by conventional low-flux hemodialysis, alternative strategies are needed to improve their removal. In a prospective cross-over trial involving 18 adult chronic hemodialysis subjects, we evaluated the intradialytic removal and the long-term effect on predialysis levels of Protein-bound (PBPe) and Free (FPe) pentosidine by high-pore, protein-leaking BK-F Polymethylmethacrylate-based hemodialysis (BK-F-HD), by comparing it to hemodialysis using low-flux dialyzers (LF-HD). A single BK-F-HD session removed more PBPe, but not FPe, than LF-HD. Long-term BK-F-HD was associated with a significant decrease in pre-dialysis PBPe, FPe, and albumin (17.7 +/- 20.8, 25.3 +/- 17.3 and 8.0 +/- 3.3%, p<0.01) and no change in body mass index and protein catabolic rate, compared to LF-HD. Multiple stepwise regression analysis identified C-reactive Protein (CRP) (standardized beta coefficient=-0.629), pre-dialysis levels in LF-HD (beta=0.452) and dialysis vintage (beta=0.428) as significant determinants of BK-F-induced changes in predialysis PBPe, and predialysis FPe and PBPe levels in LF-HD as significant determinants of BK-F-induced changes in predialysis FPe (beta=0.720 and 0.286, respectively). Our study shows that long-term standard diffusive hemodialysis with BK-F membrane reduces predialysis PBPe and FPe levels by comparison with LF-HD, largely due to a greater intradialytic clearance of PBPe. Serum albumin is also reduced without any associated changes in nutritional status markers. The study also suggests that the effect of BK-F-HD in lowering PBPe levels is modulated by the body burden of pentosidine and is blunted or even lost in the presence of elevated CRP levels.

Adipose Tissue-Derived Mesenchymal Stem Cells in Long-Term Dialysis Patients Display Downregulation of PCAF Expression and Poor Angiogenesis Activation

PubMed Central

Yamanaka, Shuichiro; Yokote, Shinya; Yamada, Akifumi; Katsuoka, Yuichi; Izuhara, Luna; Shimada, Yohta; Omura, Nobuo; Okano, Hirotaka James; Ohki, Takao; Yokoo, Takashi

2014-01-01

We previously demonstrated that mesenchymal stem cells (MSCs) differentiate into functional kidney cells capable of urine and erythropoietin production, indicating that they may be used for kidney regeneration. However, the viability of MSCs from dialysis patients may be affected under uremic conditions. In this study, we isolated MSCs from the adipose tissues of end-stage kidney disease (ESKD) patients undergoing long-term dialysis (KD-MSCs; mean: 72.3 months) and from healthy controls (HC-MSCs) to compare their viability. KD-MSCs and HC-MSCs were assessed for their proliferation potential, senescence, and differentiation capacities into adipocytes, osteoblasts, and chondrocytes. Gene expression of stem cell-specific transcription factors was analyzed by PCR array and confirmed by western blot analysis at the protein level. No significant differences of proliferation potential, senescence, or differentiation capacity were observed between KD-MSCs and HC-MSCs. However, gene and protein expression of p300/CBP-associated factor (PCAF) was significantly suppressed in KD-MSCs. Because PCAF is a histone acetyltransferase that mediates regulation of hypoxia-inducible factor-1α (HIF-1α), we examined the hypoxic response in MSCs. HC-MSCs but not KD-MSCs showed upregulation of PCAF protein expression under hypoxia. Similarly, HIF-1α and vascular endothelial growth factor (VEGF) expression did not increase under hypoxia in KD-MSCs but did so in HC-MSCs. Additionally, a directed in vivo angiogenesis assay revealed a decrease in angiogenesis activation of KD-MSCs. In conclusion, long-term uremia leads to persistent and systematic downregulation of PCAF gene and protein expression and poor angiogenesis activation of MSCs from patients with ESKD. Furthermore, PCAF, HIF-1α, and VEGF expression were not upregulated by hypoxic stimulation of KD-MSCs. These results suggest that the hypoxic response may be blunted in MSCs from ESKD patients. PMID:25025381

Comorbidity Analysis According to Sex and Age in Hypertension Patients in China.

PubMed

Liu, Jiaqi; Ma, James; Wang, Jiaojiao; Zeng, Daniel Dajun; Song, Hongbin; Wang, Ligui; Cao, Zhidong

2016-01-01

Hypertension, an important risk factor for the health of human being, is often accompanied by various comorbidities. However, the incidence patterns of those comorbidities have not been widely studied. Applying big-data techniques on a large collection of electronic medical records, we investigated sex-specific and age-specific detection rates of some important comorbidities of hypertension, and sketched their relationships to reveal the risk for hypertension patients. We collected a total of 6,371,963 hypertension-related medical records from 106 hospitals in 72 cities throughout China. Those records were reported to a National Center for Disease Control in China between 2011 and 2013. Based on the comprehensive and geographically distributed data set, we identified the top 20 comorbidities of hypertension, and disclosed the sex-specific and age-specific patterns of those comorbidities. A comorbidities network was constructed based on the frequency of co-occurrence relationships among those comorbidities. The top four comorbidities of hypertension were coronary heart disease, diabetes, hyperlipemia, and arteriosclerosis, whose detection rates were 21.71% (21.49% for men vs 21.95% for women), 16.00% (16.24% vs 15.74%), 13.81% (13.86% vs 13.76%), and 12.66% (12.25% vs 13.08%), respectively. The age-specific detection rates of comorbidities showed five unique patterns and also indicated that nephropathy, uremia, and anemia were significant risks for patients under 39 years of age. On the other hand, coronary heart disease, diabetes, arteriosclerosis, hyperlipemia, and cerebral infarction were more likely to occur in older patients. The comorbidity network that we constructed indicated that the top 20 comorbidities of hypertension had strong co-occurrence correlations. Hypertension patients can be aware of their risks of comorbidities based on our sex-specific results, age-specific patterns, and the comorbidity network. Our findings provide useful insights into the comorbidity prevention, risk assessment, and early warning for hypertension patients.

Determination of glycated nucleobases in human urine by a new monoclonal antibody specific for N2-carboxyethyl-2'-deoxyguanosine.

PubMed

Schneider, Marc; Thoss, Gerlinde; Hübner-Parajsz, Christa; Kientsch-Engel, Rose; Stahl, Peter; Pischetsrieder, Monika

2004-10-01

Sugars and sugar degradation products react in vivo readily with proteins (glycation) resulting in the formation of a heterogeneous group of reaction products, which are called advanced glycation end products (AGEs). AGEs notably change the structure and function of proteins so that extended protein-AGE formation is linked to complications such as nephropathy, atherosclerosis, and cataract. DNA can be glycated in vitro in a similar way as proteins, and the two diastereomers of N(2)-carboxyethyl-2'-deoxyguanosine (CEdG(A,B)) were identified as major DNA AGEs. It was postulated that DNA AGEs play an important role in aging, diabetes, and uremia. However, at the moment, sensitive methods to measure the extent and impact of DNA AGEs in vivo do not exist. In this study, we developed a monoclonal antibody, which recognized CEdG(A,B) with high affinity and specificity (MAb M-5.1.6). The I(50) value for CEdG(A,B) was 2.1 ng/mL, whereas other modified nuclueobases and AGE proteins showed negligible cross-reactivity. Unmodified 2'-deoxyguanosine was only weakly recognized with an I(50) value > 600,000 ng/mL, which is the limit of solubility. MAb M-5.1.6 was then used to measure the urinary excretion of AGE-modified nucleobases in a competitive enzyme-linked immunosorbent assay. The recovery of CEdG(A,B) from human urine was between 87.4 and 99.7% with coefficients of variations between 8.0 and 22.2%. The detection limit was 0.06 ng/mL, and the determination limit was 0.15 ng/mL with a linear range between 0.3 and 100 ng/mL. CEdG equivalents were analyzed in urine samples from 121 healthy volunteers, and concentrations between 1.2 and 117 ng CEdG equiv/mg creatinine were detected.

Clade 8 and Clade 6 Strains of Escherichia coli O157:H7 from Cattle in Argentina have Hypervirulent-Like Phenotypes

PubMed Central

Amigo, Natalia; Mercado, Elsa; Bentancor, Adriana; Singh, Pallavi; Vilte, Daniel; Gerhardt, Elisabeth; Zotta, Elsa; Ibarra, Cristina; Manning, Shannon D.; Larzábal, Mariano; Cataldi, Angel

2015-01-01

The hemolytic uremic syndrome (HUS) whose main causative agent is enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a disease that mainly affects children under 5 years of age. Argentina is the country with the highest incidence of HUS in the world. Cattle are a major reservoir and source of infection with E. coli O157:H7. To date, the epidemiological factors that contribute to its prevalence are poorly understood. Single nucleotide polymorphism (SNP) typing has helped to define nine E. coli O157:H7 clades and the clade 8 strains were associated with most of the cases of severe disease. In this study, eight randomly selected isolates of EHEC O157:H7 from cattle in Argentina were studied as well as two human isolates. Four of them were classified as clade 8 through the screening for 23 SNPs; the two human isolates grouped in this clade as well, while two strains were closely related to strains representing clade 6. To assess the pathogenicity of these strains, we assayed correlates of virulence. Shiga toxin production was determined by an ELISA kit. Four strains were high producers and one of these strains that belonged to a novel genotype showed high verocytotoxic activity in cultured cells. Also, these clade 8 and 6 strains showed high RBC lysis and adherence to epithelial cells. One of the clade 6 strains showed stronger inhibition of normal water absorption than E. coli O157:H7 EDL933 in human colonic explants. In addition, two of the strains showing high levels of Stx2 production and RBC lysis activity were associated with lethality and uremia in a mouse model. Consequently, circulation of such strains in cattle may partially contribute to the high incidence of HUS in Argentina. PMID:26030198

Impact of Gate 99mTc DTPA GFR, Serum Creatinine and Urea in Diagnosis of Patients with Chronic Kidney Failure

PubMed Central

Miftari, Rame; Nura, Adem; Topçiu-Shufta, Valdete; Miftari, Valon; Murseli, Arbenita; Haxhibeqiri, Valdete

2017-01-01

Aim: The aim of this study was determination of validity of 99mTcDTPA estimation of GFR for early detection of chronic kidney failure Material and methods: There were 110 patients (54 males and 56 females) with kidney disease referred for evaluation of renal function at UCC of Kosovo. All patients were included in two groups. In the first group were included 30 patients confirmed with renal failure, whereas in the second group were included 80 patients with other renal disease. In study were included only patients with ready results of creatinine, urea and glucose in the blood serum. For estimation of GFR we have used the Gate GFR DTPA method. The statistical data processing was conducted using statistical methods such as arithmetic average, the student t-test, percentage or rate, sensitivity, specificity and accuracy of the test. Results: The average age of all patients was 36 years old. The average age of female was 37 whereas of male 35. Patients with renal failure was significantly older than patients with other renal disease (p<0.005). Renal failure was found in 30 patients (27.27%). The concentration of urea and creatinine in blood serum of patients with renal failure were significantly higher than in patients with other renal disease (P< 0.00001). GFR in patients with renal failure were significantly lower than in patients with other renal disease, 51.75 ml/min (p<0.00001). Sensitivity of uremia and creatininemia for detection of renal failure were 83.33%, whereas sensitivity of 99mTcDTPA GFR was 100%. Specificity of uraemia and creatininemia were 63% whereas specificity of 99mTcDTPA GFR was 47.5%. Diagnostic accuracy of blood urea and creatinine in detecting of renal failure were 69%, whereas diagnostic accuracy of 99mTcDTPA GFR was 61.8%. Conclusion: Gate 99mTc DTPA scintigraphy in collaboration with biochemical tests are very sensitive methods for early detection of patients with chronic renal failure. PMID:28883673

[Permanent cardiac pacing for chronic symptomatic atrioventricular block in uremic hemodialysed patients. A prospective study].

PubMed

Arsenescu, Cătălina; Georgescu, G I M; Covic, A; Briotă, Laura

2002-01-01

Though sudden cardiac death accounts for as much as 15% of all cause mortality in uremia, reports concerning advanced A-V block, requiring permanent cardiac pacing in end-stage renal disease (ESRD) hemodialysed (HD) patients are very few. This is the first long term prospective study reporting on systematic permanent pacemaker implantation, in a cohort of ESRD patients from a single HD unit. Between 01/06/1997 and 30/12/2001, 396 pacemakers were inserted for advanced, symptomatic A-V block in our institution, including 5 in ESRD, HD patients (M/F--4/1, age 47-73, M +/- SD--61 +/- 12 years) from a single dialysis center, treating 137 patients during the study period. Thus, the incidence and prevalence of A-V defects treated by permanent pacing in uremic patients was 0.81% and 3.65% respectively. Conversely, the incidence and prevalence of ESRD treated by hemodialysis, among patients with advanced A-V conduction disturbances, requiring permanent pacing were 0.28% and 1.26%. Mitral valve calcifications were present in all patients; 3 subjects also had extensive aortic valve calcifications. Left ventricular hypertrophy (echocardiographic Framingham criteria) was present in 4 patients, but the systolic function (ejection fraction and fractional shortening index) was normal in all cases, although a clinical picture of chronic heart failure was seen in 3 subjects preoperatively. A-V conduction defects were attributed to extensive metastatic calcifications, involving the cardiac squeleton, consecutive to severe hyperparathyroidism and inadvertent use of calcitriol and calcium carbonate as phosphate binders. No technical difficulties, short or long-term complications related to pacemaker implantation (4 VVI and 1 VVD devices) were encountered. Acute threshold and sensing values were similar with those of non-uremic patients. During follow-up, one patients died from a non cardiac death. If optimal hemodialysis is provided, benefits of permanent pacing are equal in uremic or non uremic patients and pacemaker implantation should be instituted as a prompt life-saving method in all dialysis patients with chronic symptomatic advanced A-V blocks.

Lectins in fruits having gastrointestinal activity: their participation in the hemagglutinating property of Escherichia coli O157:H7.

PubMed

Coutiño-Rodríguez, R; Hernández-Cruz, P; Giles-Ríos, H

2001-01-01

In fruits with therapeutic properties for antidiarrheal and laxative uses, the presence of lectins may be the bioactive properties that interfere with bacterial adhesion, thought to be competition for glycoside signal sites in the attachment. This study identifies lectins in crude extracts from fruits such as Tamarindus indica (tamarind), Spontia vulgaris (plum), Psidium guava (guava), Mangifera indica (mango), Cydonia vulgaris (quince), and Crataegus mexicanus (tejocote). To verify the procedures, extracts from Ricinus communis (castor bean), Glycine max (soybean), Phaseolus vulgaris (beans), Vicia fava (fava bean), and Solanum tuberosum (potato) were used as controls for lectin activity. Both sources of lectins were analyzed to determine their participation in the host-parasite interaction, using as a model the hemagglutinating properties of Escherichia coli O157:H7 (EHA). All extracts showed hemagglutination to group O erythrocytes test (HA) with the exception of mango. Two new galactose-specific lectins were identified from tamarind and guava. When analyzed for participation in EHA, only guava lectins inhibited this, while soybean lectin induced hemolysis; as both lectins bind to galactose, it is probable that their recognition occurs in different domains. Sugars involved in the attachment between Escherichia coli O157:H7 and red cells were identified and again, galactose in addition to mannose was found to be related in EHA. On the other hand, guava lectins also agglutinated E. coli O157:H7, perhaps due to the same galactose-specific lectin or to another type of lectin. In summary, guava has a galactose-specific lectin that prevents adhesion of E. coli O157:H7 to red cells; this lectin is mediated by galactose. Prevention could also be due to their capacity of agglutinating E. coli by guava lectins. Soybean lectin induced hemolysis only when bacteria was present, but not with floating secretions. This finding showed that guava is a source of lectin that can be explored to prevent adhesion of E. coli to epithelial intestinal cells; contrariwise, soya must be studied to see its participation in the uremia caused during E. coli O157:H7 pathogenesis.

Functional genomic analysis identifies indoxyl sulfate as a major, poorly dialyzable uremic toxin in end-stage renal disease.

PubMed

Jhawar, Sachin; Singh, Prabhjot; Torres, Daniel; Ramirez-Valle, Francisco; Kassem, Hania; Banerjee, Trina; Dolgalev, Igor; Heguy, Adriana; Zavadil, Jiri; Lowenstein, Jerome

2015-01-01

Chronic renal failure is characterized by progressive renal scarring and accelerated arteriosclerotic cardiovascular disease despite what is considered to be adequate hemodialysis or peritoneal dialysis. In rodents with reduced renal mass, renal scarring has been attributed to poorly filtered, small protein-bound molecules. The best studied of these is indoxyl sulfate (IS). We have attempted to establish whether there are uremic toxins that are not effectively removed by hemodialysis. We examined plasma from patients undergoing hemodialysis, employing global gene expression in normal human renal cortical cells incubated in pre- and post- dialysis plasma as a reporter system. Responses in cells incubated with pre- and post-dialysis uremic plasma (n = 10) were compared with responses elicited by plasma from control subjects (n = 5). The effects of adding IS to control plasma and of adding probenecid to uremic plasma were examined. Plasma concentrations of IS were measured by HPLC (high pressure liquid chromatography). Gene expression in our reporter system revealed dysregulation of 1912 genes in cells incubated with pre-dialysis uremic plasma. In cells incubated in post-dialysis plasma, the expression of 537 of those genes returned to baseline but the majority of them (1375) remained dysregulated. IS concentration was markedly elevated in pre- and post-dialysis plasma. Addition of IS to control plasma simulated more than 80% of the effects of uremic plasma on gene expression; the addition of probenecid, an organic anion transport (OAT) inhibitor, to uremic plasma reversed the changes in gene expression. These findings provide evidence that hemodialysis fails to effectively clear one or more solutes that effect gene expression, in our reporter system, from the plasma of patients with uremia. The finding that gene dysregulation was simulated by the addition of IS to control plasma and inhibited by addition of an OAT inhibitor to uremic plasma identifies IS as a major, poorly dialyzable, uremic toxin. The signaling pathways initiated by IS and possibly other solutes not effectively removed by dialysis may participate in the pathogenesis of renal scarring and uremic vasculopathy.

Overview of developmental, reproductive, and behavioral/ neurological effects of mercury exposures in wildlife

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.; Klimstra, J.; Stebbins, K.

2007-01-01

We review wildlife/mercury literature and our own research findings that demonstrate the relevance of wildlife toxicity data in protecting human health. Methylmercury affects wildlife through reduced adult survival and reproduction, aberrant behavior, immune system effects, and teratogenic effects. Methylmercury can readily cross the blood-brain barrier, is excreted into eggs in birds, and is transferred to young mammals across the placenta and in milk. Its principal effect on wildlife is on neurological functions. Wild mink (Mustela vison) and otter (Lutra canadensis) have died from methylmercury poisoning, with signs of poisoning including anorexia, loss of weight, incoordination, tremors, and convulsions, which are symptoms similar to those experienced by mercury-poisoned humans. Mammals also may experience tonic and clonic convulsions and an increase in fetal anomalies, again paralleling toxic problems in people. Antibody-producing cells can be suppressed by methylmercury. Microscopically, the most notable lesions are in the cerebrum. Extensive vacuolation of hepatocytes in the liver and necrosis and other changes in the appearance of the proximal convoluted tubules of the kidneys are often noted. When harp seals (Pagophilus groenlandicus) were dosed with methylmercury chloride the number of circulating erythrocytes decreased and white blood cell counts greatly increased. The poisoned seals also suffered from uremia, hyperproteinemia, hypercholesterolemia, hyperbilirubinemia, and elevations in lactic dehydrogenase and alkaline phosphatase. In birds, signs of methylmercury poisoning included emaciation and weakness in the extremities, which progressed until the birds died. Mercury poisoning in birds and mammals can be diagnosed from a combination of the signs of poisoning if the animal is still alive, the pathological effects seen in a gross necropsy, the histopathological effects seen with a microscope, and the concentrations of mercury in various tissues. Our studies with mallards (Anas platyrhynchos) suggest that the dietary concentrations of mercury that cause toxicity are lower than those set in fish consumption advisories to protect humans. Because wild mammals and birds are so sensitive to methylmercury poisoning and cannot escape dietary exposure the way humans can, guidelines set to protect wild birds and mammals may very well provide a margin of safety for human health.

Middle molecules and small-molecular-weight proteins in ESRD: properties and strategies for their removal.

PubMed

Clark, William R; Winchester, James F

2003-10-01

Molecular weight has traditionally been the parameter most commonly used to classify uremic toxins, with a value of approximately 500 Da frequently used as a demarcation point below which the molecular weights of small nitrogenous waste products fall. This toxin group, the most extensively studied from a clinical perspective, is characterized by a high degree of water solubility and the absence of protein binding. However, uremia is mediated by the retention of a plethora of other compounds having characteristics that differ significantly from those of the previously mentioned group. As opposed to the relative homogeneity of the nitrogenous metabolite class, other uremic toxins collectively are a very heterogeneous group, not only with respect to molecular weight but also other characteristics, such as protein binding and hydrophobicity. A recently proposed classification scheme by the European Uraemic Toxin Work Group subdivides the remainder of molecules into 2 categories: protein-bound solutes and middle molecules. For the latter group, the Work Group proposes a molecular weight range (500-60,000 Da) that incorporates many toxins identified since the original middle molecule hypothesis, for which the upper molecular weight limit was approximately 2,000 Da. In fact, low-molecular-weight peptides and proteins (LMWPs) comprise nearly the entire middle molecule category in the new scheme. The purpose of this article is to provide an overview of the middle molecule class of uremic toxins, with the focus on LMWPs. A brief review of LMWP metabolism under conditions of normal (and in a few cases, abnormal) renal function will be presented. The physical characteristics of several LMWPs will also be presented, including molecular weight, conformation, and charge. Specific LMWPs to be covered will include beta 2-microglobulin, complement proteins (C3a and Factor D), leptin, and proinflammatory cytokines. The article will also include a discussion of the treatment-related factors influencing dialytic removal of middle molecules. Once these factors, which include membrane characteristics, protein-membrane interactions, and solute removal mechanisms, are discussed, an overview of the different therapeutic strategies used to enhance clearance of these compounds is provided.

Effect of cross-linked chitosan iron (III) on vascular calcification in uremic rats.

PubMed

de Castro, Barbara Bruna Abreu; do Carmo, Wander Barros; de Albuquerque Suassuna, Paulo Giovani; Carminatti, Moises; Brito, Julia Bianchi; Dominguez, Wagner Vasques; de Oliveira, Ivone Braga; Jorgetti, Vanda; Custodio, Melani Ribeiro; Sanders-Pinheiro, Helady

2018-05-01

Cross-linked chitosan iron (III) is a chitin-derived polymer with a chelating effect on phosphorus, but it is untested in vascular calcification. We evaluated this compound's ability to reduce hyperphosphatemia and its effect on vascular calcification in uremic rats using an adenine-based, phosphorus-rich diet for seven weeks. We used a control group to characterize the uremia. Uremic rats were divided according the treatment into chronic kidney disease, CKD-Ch-Fe(III)CL (CKD-Ch), CKD-calcium carbonate, or CKD-sevelamer groups. We measured creatinine, phosphorus, calcium, alkaline phosphatase, phosphorus excretion fraction, parathyroid hormone, and fibroblast growth factor 23. Vascular calcification was assessed using the aortic calcium content, and a semi-quantitative analysis was performed using Von Kossa and hematoxylin-eosin staining. At week seven, rats in the chronic kidney disease group had higher creatinine, phosphorus, phosphorus excretion fraction, calcium, alkaline phosphatase, fibroblast growth factor 23, and aortic calcium content than those in the Control group. Treatments with cross-linked chitosan iron (III) and calcium carbonate prevented phosphorus increase (20%-30% reduction). The aortic calcium content was lowered by 88% and 85% in the CKD-Ch and CKD-sevelamer groups, respectively. The prevalence of vascular changes was higher in the chronic kidney disease and CKD-calcium carbonate (62.5%) groups than in the CKD-Ch group (37.5%). In conclusion, cross-linked chitosan iron (III) had a phosphorus chelating effect similar to calcium carbonate already available for clinical use, and prevented calcium accumulation in the aorta. Impact statement Vascular calcification (VC) is a common complication due to CKD-related bone and mineral disorder (BMD) and is characterized by deposition of calcium in vessels. Effective therapies are not yet available but new phosphorus chelators can prevent complications from CV. We tested the effect of chitosan, a new phosphorus chelator, on the VC of uremic animals. It has recently been proposed that chitosan treatment may be effective in the treatment of hyperphosphataemia. However, its action on vascular calcification has not been investigated yet. In this study, we demonstrated that chitosan reduced the calcium content in the aorta, suggesting that this may be a therapeutic approach in the treatment of hyperphosphatemia by preventing CV.

Pharmacological effects of Vitamin C & E on Diclofenac Sodium intoxicated Rats.

PubMed

El-Shafei, Reham A; Saleh, Rasha M

2016-12-01

The aim of this study was to evaluate the probable protective effect of vitamin C and vitamin E on diclofenac-induced acute nephrotoxicity using biochemical, molecular and histopathological examination in rats following administration of diclofenac sodium (50mg/kg, I.M). Ninety male Wister rats were allotted in six equal groups. Rats in the 1st group (control group) were injected with physiological saline, while rats in the 2nd group (C-group) were given vitamin C (100mg/kg orally via stomach tube) for 5 successive days. The 3rd group (E-group) was given vitamin E (250mg/kg orally in diet) for 5 successive days. Rats in the 4th group (D-group) were injected by diclofenac sodium (50mg/kg, I.M) for 5 successive days. The 5th group (DvC-group) was given diclofenac sodium (50mg/kg, I.M) and vitamin C (100mg/kg orally via stomach tube) for 5 successive days. Rats in the 6th group (DvE-group) were given diclofenac sodium (50mg/kg, I.M) and vitamin E (250mg/kg orally in diet) for 5 successive days. Blood samples were collected two days post treatment (1st week of experiment), 2nd and 4th week of the experiment for assessment of urea, creatinine, malondialdehyde, nitric oxide and superoxide dismutase activities. At the end of 4th week, rats were sacrificed and kidneys were excised for biochemical analyses, histopathological evaluation and determination of kidney interleukin-1β, interleukin-18, demsin and nepherin expressions in by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that, diclofenac induced severe kidney damage as indicated by histopathological changes and increased serum oxidative stress parameters. Behavioral changes were monitored; a significant increase in uremia in intoxicated animals was also noted indicating that diclofenac sodium provoked kidney damage in rats. Application of vitamin C (DvC-group) and vitamin E (DvE-group) were found to improve the abovementioned abnormalities. The present data suggest that, vitamin C and vitamin E might play an important role in reducing oxidative stress and kidney damage induced by diclofenac sodium. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Timing of Initiation of Maintenance Dialysis

PubMed Central

Wong, Susan P. Y.; Vig, Elizabeth K.; Taylor, Janelle S.; Burrows, Nilka R.; Liu, Chuan-Fen; Williams, Desmond E.; Hebert, Paul L.; O’Hare, Ann M.

2016-01-01

IMPORTANCE There is often considerable uncertainty about the optimal time to initiate maintenance dialysis in individual patients and little medical evidence to guide this decision. OBJECTIVE To gain a better understanding of the factors influencing the timing of initiation of dialysis in clinical practice. DESIGN, SETTING, AND PARTICIPANTS A qualitative analysis was conducted using the electronic medical records from the Department of Veterans Affairs (VA) of a national random sample of 1691 patients for whom the decision to initiate maintenance dialysis occurred in the VA between January 1, 2000, and December 31, 2009. Data analysis took place from June 1 to November 30, 2014. MAIN OUTCOMES AND MEASURES Central themes related to the timing of initiation of dialysis as documented in patients’ electronic medical records. RESULTS Of the 1691 patients, 1264 (74.7%) initiated dialysis as inpatients and 1228 (72.6%) initiated dialysis with a hemodialysis catheter. Cohort members met with a nephrologist during an outpatient clinic visit a median of 3 times (interquartile range, 0–6) in the year prior to initiation of dialysis. The mean (SD) estimated glomerular filtration rate at the time of initiation for cohort members was 10.4 (5.7) mL/min/1.73m2. The timing of initiation of dialysis reflected the complex interplay of at least 3 interrelated and dynamic processes. The first was physician practices, which ranged from practices intended to prepare patients for dialysis to those intended to forestall the need for dialysis by managing the signs and symptoms of uremia with medical interventions. The second process was sources of momentum. Initiation of dialysis was often precipitated by clinical events involving acute illness or medical procedures. In these settings, the imperative to treat often seemed to override patient choice. The third process was patient-physician dynamics. Interactions between patients and physicians were sometimes adversarial, and physician recommendations to initiate dialysis sometimes seemed to conflict with patient priorities. CONCLUSIONS AND RELEVANCE The initiation of maintenance dialysis reflects the care practices of individual physicians, sources of momentum for initiation of dialysis, interactions between patients and physicians, and the complex interplay of these dynamic processes over time. Our findings suggest opportunities to improve communication between patients and physicians and to better align these processes with patients’ values, goals, and preferences. PMID:26809745

Peritoneal Morphology After Long-Term Peritoneal Dialysis with Biocompatible Fluid: Recent Clinical Practice in Japan

PubMed Central

Ayuzawa, Nobuhiro; Ishibashi, Yoshitaka; Takazawa, Yutaka; Kume, Haruki; Fujita, Toshiro

2012-01-01

♦ Background: Morphology changes of the peritoneal membrane after long-term peritoneal dialysis (PD) consist of denudation of peritoneal mesothelial cells, interstitial sclerosis, and hyalinizing vasculopathy. Those changes are considered to be the result of uremia and bioincompatible effects of conventional acidic lactate-buffered dialysate with glucose degradation products (GDPs). In the last decade, biocompatible dialysate with neutral pH and low GDPs has become widely used. Clinical practice has been modified in Japan, especially for anuric patients, and now includes the use of hybrid therapy. The impact on peritoneal morphology has not been well reported. ♦ Objective: The aim of the present study was to investigate the long-term effect on peritoneal morphology and function of biocompatible fluid use and current clinical practice in Japan, including hybrid dialysis therapy. ♦ Methods: We evaluated peritoneal biopsy specimens from patients who had undergone PD for more than 3 years. We used the average peritoneal thickness (APT) of the submesothelial compact zone as a marker of interstitial sclerosis and the lumen/vessel diameter ratio (L/V ratio) at postcapillary venules as a marker of hyalinizing vasculopathy. Demography and other data for the patients, including dialysate-to-plasma (D/P) ratio of creatinine, were obtained at baseline and every 6 months by peritoneal equilibration test. ♦ Results: Between 2002 and 2009, 110 patients started PD therapy with biocompatible dialysate at Tokyo University Hospital. Among them, 11 patients (8 men, 3 women; age: 54.2 ± 11.8 years; 1 with diabetes mellitus) were enrolled into this morphology study. The mean duration of PD in this group was 61 ± 11.3 months, and the mean time to peritoneal biopsy was 58 ± 15.1 months. The median APT was 180 μm (96 – 1424 μm), and the median L/V ratio was 0.66 (0.46 – 0.74). No obvious correlations between APT, L/V ratio, and PD duration were detected. The D/P creatinine of the 11 patients was maintained at a favorably low value, comparable with that of the other 99 patients. ♦ Conclusions: Peritoneal dialysis therapy using biocompatible dialysate in conjunction with modification of clinical practice may minimize the progression of peritoneal interstitial sclerosis and hyalinizing vasculopathy, preserving favorable peritoneal function for more than 3 years. PMID:21804136

Expression of beta2-microglobulin and c-fos mRNA: is there an influence of high- or low-flux dialyzer membranes?

PubMed

Haufe, C C; Eismann, U; Deppisch, R M; Stein, G

2001-02-01

Dialysis-related amyloidosis is an important complication of long-term hemodialysis (HD) therapy with several pathogenetic factors. One of them is the influence of the dialyzer membrane type on the synthesis of beta2-microglobulin (beta2m). In vitro results are controversial. Thus, the hypothesis of whether in vivo beta2m generation is induced by the HD procedure and whether this induction depends on the type of the used dialyzer membrane should be tested. The aim of the present study was to investigate the influence of "biocompatible" high-flux versus "bioincompatible" low-flux HD on in vivo beta2m generation as well as the induction of the early activation gene c-fos in peripheral blood cells. Six nondiabetic HD patients [mean age 46 (21 to 69) years; Kt/V> 1.2] were included in a randomized crossover study using either a low-flux (cellulosic/cuprophan) or a high-flux (polyamide) dialyzer membrane. At the end of a four-week run-in period for each membrane, whole blood samples were taken before, immediately at, and four hours after the end of the dialysis session. MRNA was extracted, and after transcription to cDNA, quantitative polymerase chain reaction was performed for the beta2m gene, the early response gene c-fos, and the GAP-DH housekeeping gene. Based on the applied method for detection of specific mRNA, the results were given as ratio of beta2m or c-fos cDNA per GAP-DH cDNA. General cell activation during HD was indicated by increasing mRNA expression of c-fos related to the time course of the dialysis session, whereas beta2m did not change significantly. However, no difference was found when comparing the low-flux and the high-flux dialyzer membranes. Despite the evidence for activation of peripheral blood cells, as indicated by increasing c-fos message, no sign of beta2m mRNA induction during HD procedure with different dialyzer membranes was seen. Our results suggest that there is post-transcriptional regulation of beta2m generation and/or release as well as the influence of the dialyzer membrane type on post-translational processes, that is, advance glycation end products (AGE) or conformational modification of the beta2m protein. Furthermore, our data demonstrate that gene expression patterns during dialysis and/or uremia are not homogenous and need to be investigated further, especially with respect to the proinflammatory role of early leukocyte activation signals.

Detection of noncarboxymethyllysine and carboxymethyllysine advanced glycation end products (AGE) in serum of diabetic patients.

PubMed Central

Takeuchi, M.; Makita, Z.; Yanagisawa, K.; Kameda, Y.; Koike, T.

1999-01-01

BACKGROUND: The advanced stage of the Maillard reaction, which leads to the formation of advanced glycation end products (AGE), plays an important role in the pathogenesis of angiopathy in diabetic patients and in the aging process. N(epsilon)-(carboxymethyl)lysine (CML) is thought to be an important epitope for many of currently available AGE antibodies. However, recent findings have indicated that a major source of CML may be by pathways other than glycation. A distinction between CML and non-CML AGE may increase our understanding of AGE formation in vivo. In the present study, we prepared antibodies directed against CML and non-CML AGE. MATERIALS AND METHODS: AGE-rabbit serum albumin prepared by 4, 8, and 12 weeks of incubation with glucose was used to immunize rabbits, and a high-titer AGE-specific antiserum was obtained without affinity for the carrier protein. To separate CML and non-CML AGE antibodies, the anti-AGE antiserum was subjected to affinity chromatography on a column coupled with AGE-BSA and CML-BSA. Two different antibodies were obtained, one reacting specifically with CML and the other reacting with non-CML AGE. Circulating levels of CML and non-CML AGE were measured in 66 type 2 diabetic patients without uremia by means of the competitive ELISA. Size distribution and clearance by hemodialysis detected by non-CML AGE and CML were assessed in serum from diabetic patients on hemodialysis. RESULTS: The serum non-CML AGE level in type 2 diabetic patients was significantly correlated with the mean fasting blood glucose level over the previous 2 months (r = 0.498, p < 0.0001) or the previous 1 month (r = 0.446, p = 0. 0002) and with HbA(1c) (r = 0.375, p = 0.0019), but the CML AGE level was not correlated with these clinical parameters. The CML and non-CML AGE were detected as four peaks with apparent molecular weights of 200, 65, 1.15, and 0.85 kD. The hemodialysis treatment did not affect the high-molecular-weight protein fractions. Although the low-molecular-weight peptide fractions (absorbance at 280 nm and fluorescence) were decreased by hemodialysis, there was no difference before and after dialysis in the non-CML AGE- and CML-peptide fractions (1.15 and 0.85 kD fractions). CONCLUSIONS: We propose that both CML and non-CML AGE are present in the blood and that non-CML AGE rather than CML AGE should be more closely evaluated when investigating the pathophysiology of AGE-related diseases. PMID:10415164

Chronic sustained inflammation links to left ventricular hypertrophy and aortic valve sclerosis: a new link between S100/RAGE and FGF23.

PubMed

Yan, Ling; Bowman, Marion A Hofmann

Cardiovascular disease including left ventricular hypertrophy, diastolic dysfunction and ectopic valvular calcification are common in patients with chronic kidney disease (CKD). Both S100A12 and fibroblast growth factor 23 (FGF23) have been identified as biomarkers of cardiovascular morbidity and mortality in patients with CKD. We tested the hypothesis that human S100/calgranulin would accelerate cardiovascular disease in mice subjected to CKD. This review paper focuses on S100 proteins and their receptor for advanced glycation end products (RAGE) and summarizes recent findings obtained in novel developed transgenic hBAC-S100 mice that express S100A12 and S100A8/9 proteins. A bacterial artificial chromosome of the human S100/calgranulin gene cluster containing the genes and regulatory elements for S100A8, S100A9 and S100A12 was expressed in C57BL/6J mice (hBAC-S100). CKD was induced by ureteral ligation, and hBAC-S100 mice and WT mice were studied after 10 weeks of chronic uremia. hBAC-S100 mice with CKD showed increased FGF23 in the heart, left ventricular hypertrophy (LVH), diastolic dysfunction, focal cartilaginous metaplasia and calcification of the mitral and aortic valve annulus together with aortic valve sclerosis. This phenotype was not observed in WT mice with CKD or in hBAC-S100 mice lacking RAGE with CKD, suggesting that the inflammatory milieu mediated by S100/RAGE promotes pathological cardiac hypertrophy in CKD. In vitro, inflammatory stimuli including IL-6, TNFα, LPS, or serum from hBAC-S100 mice up regulated FGF23 mRNA and protein in primary murine neonatal and adult cardiac fibroblasts. Taken together, our study shows that myeloid-derived human S100/calgranulin is associated with the development of cardiac hypertrophy and ectopic cardiac calcification in a RAGE dependent manner in a mouse model of CKD. We speculate that FGF23 produced by cardiac fibroblasts in response to cytokines may act in a paracrine manner to accelerate LVH and diastolic dysfunction in hBAC-S100 mice with CKD. We suggest that S100/RAGE-mediated chronic sustained systemic inflammation is linked to pathological cardiac remodeling via direct up regulation of FGF23 in cardiac fibroblasts, thereby providing a new mechanistic understanding for the common association between CKD, diabetes, metabolic syndrome, or hypertension with left ventricular hypertrophy with diastolic dysfunction.

Effect of concentrate level on feeding behavior and rumen and blood parameters in dairy goats: relationships between behavioral and physiological parameters and effect of between-animal variability.

PubMed

Giger-Reverdin, S; Rigalma, K; Desnoyers, M; Sauvant, D; Duvaux-Ponter, C

2014-07-01

This work aimed first to compare 2 diets differing in their percentage of concentrate [low (LO): 30% concentrate vs. High (HI): 60% concentrate] by measuring simultaneously feeding behavior, rumen parameters, blood and plasma parameters, and milk yield and composition in 8 mid-lactation goats. The second aim was to study the interrelationships between these variables and to analyze the between-animal variability to better understand the between-animal differences in acidosis susceptibility. All of the animals received the 2 diets ad libitum as total mixed ration according to a crossover design of two 4-wk periods. Mean daily DMI was similar between the 2 diets but the variability was higher for the HI than for the LO diet. Goats produced more milk when fed the HI diet compared with the LO diet but with a lower fat:protein ratio (0.81 vs. 0.99). They ate more rapidly the HI than the LO diet but stopped eating sooner after the afternoon feed allowance, and spent less time chewing. The increase in concentrate percentage modified rumen parameters: the pH and acetate:propionate ratio decreased and total VFA, ammonia, and soluble carbohydrate concentrations increased. Hematocrit, plasma NEFA, and blood K and Ca concentrations decreased but glycemia and uremia increased. Other parameters were not modified: milk fat content, blood pH, and bicarbonate and Na concentrations. A large between-animal variability was detected for all the measured parameters, especially for feeding behavior, with important consequences on rumen and blood parameters. This work confirmed the effects of a high percentage of concentrate on feeding behavior, rumen and blood parameters, and milk production, and some known relationships such as the positive link between rumen pH and chewing index. It also pointed out other relationships between parameters seldom measured at the same time, such as rumen redox potential or blood pH and chewing index, or the negative link between blood and rumen pH. When the animals spent a lot of time chewing, they probably produced a lot of saliva that buffered the rumen pH and prevented them from suffering from subacute ruminal acidosis. However, they used part of their blood bicarbonates reserve, which might have induced metabolic acidosis, as rumen and blood pH were inversely related. This could explain why some animals suffer from acidosis and others do not in a herd receiving the same diet, and why some animals seem to suffer more from subacute ruminal acidosis and others from metabolic acidosis. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Glyoxalase I deficiency is associated with an unusual level of advanced glycation end products in a hemodialysis patient.

PubMed

Miyata, T; van Ypersele de Strihou, C; Imasawa, T; Yoshino, A; Ueda, Y; Ogura, H; Kominami, K; Onogi, H; Inagi, R; Nangaku, M; Kurokawa, K

2001-12-01

Advanced glycation of proteins and their attendant advanced glycation end products (AGEs) contribute to the complications associated with diabetes mellitus or uremia. Regulatory mechanisms of AGE formation in vivo remain an issue of particular interest. We investigated a role of the glyoxalase detoxification system of precursor reactive carbonyl compounds (RCOs) in the in vivo AGE formation. Plasma levels of AGEs [pentosidine and Nepsilon-carboxymethyllysine (CML)], their RCO precursors, d-lactate (the final product resulting from the glyoxalase detoxification pathway), as well as of various compounds known to generate AGE precursors and surrogate markers for oxidative stress (antioxidant enzymes and glutathione), were measured in both hemodialysis (HD) patients and normal subjects. The activity and protein expression of glyoxalase I, an enzyme essential for the detoxification of alpha-oxoaldehydes, in red blood cells (RBC) were also examined. In one 69-year-old lady who had been on hemodialysis (HD) for three years and had suffered from recurrent cardiovascular complications despite the absence of significant risk factors, plasma levels of pentosidine (77.3 +/- 2.4 pmol/mg protein) and CML (330.8 +/- 8.2 pmol/mg protein) were markedly elevated as compared to other HD patients (N = 20: 26.6 +/- 11.8 pmol/mg protein for pentosidine and 224.4 +/- 51.7 pmol/mg protein for CML). The plasma level of RCO precursors for pentosidine and CML was also higher in this patient than in other HD patients. Further investigation disclosed a very low activity in RBC of glyoxalase I (1.5 +/- 0.4 mU/106 RBC), as compared to other HD patients (3.9 +/- 0.6 mU/106 RBC) or normal subjects (4.0 +/- 0.6 mU/106 RBC). The glyoxalase I protein level, assessed in RBC by immunoblot analysis with a specific antibody, was markedly lower than that observed in HD patients and normal subjects. The causes of this deficiency remain unknown. Nucleotide sequencing of the products of reverse transcription-polymerase chain reaction from the patient's mononuclear cells revealed no genetic mutation within the coding region of the glyoxalase I gene. Plasma d-lactate level was also in the lower range (0.18 +/- 0.03 mg/dL) of the values measured in the other HD patients (0.27 +/- 0.09 mg/dL) and normal subjects (0.35 +/- 0.12 mg/dL). The plasma levels of various compounds known to generate AGE precursors (glucose, lipids and ascorbic acid) were either normal or low. The surrogate markers for oxidative stress such as antioxidant enzymes (glutathione peroxidases and superoxide dismutase) and glutathione were all within the range observed in the other HD patients. The unusually high levels of AGEs in this patient implicate a deficient glyoxalase detoxification of RCO precursors. The present clinical observation implicates, to our knowledge for the first time, the glyoxalase detoxification system and, in particular, glyoxalase in the actual level of AGEs in a uremic patient.

Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients.

PubMed

Janssen, M J; van der Kuy, A; ter Wee, P M; van Boven, W P

1996-02-01

Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used. Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium acetate and calcium carbonate-treated patients (1.28 +/- 0.15 g versus 1.09 +/- 0.19 g; n.s.). The incidence of hypercalcemic episodes (albumin-corrected serum calcium levels above 2.80 mmol/l) in the calcium acetate-treated group was 18% versus 31% in the calcium carbonate-treated group (p < 0.005). None of the aluminum hydroxide-treated patients experienced hypercalcemic episodes. Mean serum concentrations of alkaline phosphatase, intact parathormone, and aluminum did not differ between the groups. In chronic intermittent hemodialysis patients, per gram administered elemental calcium phosphate binding with either calcium acetate or calcium carbonate is equivalent, provided that calcium carbonate is taken on an empty stomach a few minutes before meals. The number of capsules calcium carbonate, but also the total amount in grams, necessary to keep serum phosphate and intact parathormone levels into an acceptable range then is significantly less. This might improve patient compliance.

Enhanced expression of glucose transporter-1 in vascular smooth muscle cells via the Akt/tuberous sclerosis complex subunit 2 (TSC2)/mammalian target of rapamycin (mTOR)/ribosomal S6 protein kinase (S6K) pathway in experimental renal failure.

PubMed

Lin, Chih-Yuan; Hsu, Shih-Che; Lee, Herng-Sheng; Lin, Shih-Hua; Tsai, Chien-Sung; Huang, Shih-Ming; Shih, Chun-Che; Hsu, Yu-Juei

2013-02-01

Chronic renal failure (CRF) is associated with increased cardiovascular mortality, and medial vascular smooth muscle cell (VSMC) hypertrophy, proliferation, and calcification play a pivotal role in uremic vasculopathy. Glucose transporter-1 (GLUT1) facilitates the transport of glucose into VSMCs, and GLUT1 overexpression associated with high glucose influx leads to a stimulation of VSMC proliferation. However, the role of GLUT1 in uremic vasculopathy remains unclear. This study aimed to identify changes in the expression of GLUT1 in VSMCs in the setting of experimental uremia and investigate whether Akt/tuberous sclerosis complex subunit 2 (TSC2)/mammalian target of rapamycin (mTOR)/ribosomal S6 protein kinase (S6K) signaling, which plays a crucial role in VSMC proliferation and glucose metabolism, is involved in the regulation of GLUT1 expression. In vivo experimental CRF was induced in Wistar rats by 5/6 nephrectomy, and the GLUT1 expression in aortic tissue was determined by the reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemical staining. Indoxyl sulfate (IS) is a uremic retention solute proven with pro-proliferative effect on rat VSMCs, and we further studied the expression of GLUT1 in rat A7r5 rat embryonic aortic cells stimulated by IS in the presence or absence of phloretin, a GLUT1 inhibitor, to explore the pathogenic role of GLUT1 in uremic vasculopathy. The contribution of Akt/TSC2/mTOR/S6K signaling in modifying the GLUT1 expression was also assessed. Eight weeks after 5/6 nephrectomy, aortic tissue obtained from CRF rats exhibited increased wall thickness and VSMC hypertrophy, hyperplasia, and degeneration. Compared with the sham-operated control group, the messenger (m)RNA and protein abundance of GLUT1 were both markedly increased in CRF rats. In vitro, IS induced a significant increase in expression of GLUT1 protein as well as pro-proliferative cyclin D1 and p21 mRNA and a modest increase in expression of antiapoptotic p53 mRNA in A7r5 cells, whereas inhibition of GLUT1 mediated glucose influx reduced the pro-proliferative and antiapoptotic effects of IS. In addition to increased GLUT1 expression, IS significantly suppressed Akt and TSC2 phosphorylation after 6-hour and 12-hour treatment, but increased S6K phosphorylation after 3-hour treatment. Inactivation of mTOR downstream signaling by rapamycin treatment inhibited S6K phosphorylation and abolished the stimulatory effect of IS on GLUT1 expression. In vivo and in vitro experimental CRF displayed prominent GLUT1 upregulation in VSMCs. The uremic toxin IS stimulated proliferation of VSMCs possibly through induction of GLUT1 expression. The Akt/TSC/mTOR/S6K signaling pathway may be one of the mechanisms underlying the upregulation of GLUT1 expression in uremic VSMCs. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Safety and effectiveness of low-protein diet supplemented with ketoacids in diabetic patients with chronic kidney disease.

PubMed

Bellizzi, Vincenzo; Calella, Patrizia; Hernández, Julia Nava; González, Verónica Figueroa; Lira, Silvia Moran; Torraca, Serena; Arronte, Rocio Urbina; Cirillo, Pietro; Minutolo, Roberto; Montúfar Cárdenas, Rafael A

2018-05-09

The impact of the low-protein diet on nutrition in CKD diabetics is uncertain. The metabolic and nutritional effects of a low-protein (0.5-0.6 g/kg/d), normal-high energy (30-35 kcal/kg/d) diet supplemented with ketoacids (LPD-KA) were prospectively evaluated in CKD patients with (DM) and without (non-DM) diabetes mellitus. 197 patients on CKD stages 3-5 were enrolled. DM (n = 81) and non-DM (n = 116) were comparable for gender (Male 58 vs 55%), age (66 ± 9 vs 63 ± 18 years), renal function (eGFR 23 ± 13 vs 24 ± 13 mL/min). After 6-month, serum urea (DM: 131 ± 58 to 105 ± 49 mg/dl, p < 0.05; non-DM: 115 ± 52 to 88 ± 36, p < 0.05) and phosphate (DM: 4.5 ± 1.3 to 4.1 ± 1.2 mg/dl, p = 0.06; non-DM: 4.3 ± 1.0 to 3.7 ± 0.8, p < 0.05) declined. Fasting glucose decreased in DM (126 ± 52 to 103 ± 29 mg/dl, p < 0.05) without insulin dose increase. These effects were preserved after 3-year. Serum albumin did not change after 6 months (DM: 3.7 ± 0.6 to 3.8 ± 0.4 mg/dl; non-DM: 4.0 ± 0.6 to 4.0 ± 0.4) and in the long-term. Body weight (BW) declined after the diet start (DM: 68.9 ± 14.3 to 65.1 ± 12.1 kg, p < 0.05; non-DM: 66.6 ± 15.1 to 64.1 ± 15.1, p < 0.05) and was stable at 6 months and 3 years. Muscle strength at baseline was reduced in all patients and remained stable during the diet period. Changes of nutritional markers during the study were similar among groups and diabetes was not associated to any nutritional change at the multivariate analysis. As attain wasting, lower BMI (< 23 kg/m 2 ) and albumin (< 3.8 g/dl) levels were present in 1/3 patients at start and along 3 years, cholesterol never dropped below the lower threshold (< 100 mg/dl) and poorer FM (< 10%) was less than 10% during the study in both groups. In diabetic CKD patients a low-protein diet supplemented with ketoacids improves uremia and diabetes, causes sudden decline of body weight which remains stable over time and has not a negative effect on wasting and muscle mass and fitness. In diabetic CKD patients the LPD-KA is safe and the nutritional impact is the same as in non-diabetics CKD.

Trace Metals' abnormalities in hemodialysis patients: relationship with medications.

PubMed

Lee, S H; Huang, J W; Hung, K Y; Leu, L J; Kan, Y T; Yang, C S; Chung Wu, D; Huang, C L; Chen, P Y; Chen, J S; Chen, W Y

2000-11-01

A multicenter collaborative study was performed to investigate the prevalence of abnormal blood contents of 6 trace metals, copper (Cu), zinc (Zn), aluminum (Al), lead (Pb), cadmium (Cd), and mercury (Hg), in hemodialysis (HD) patients and to analyze their relationship with the medications, such as CaCO3, Ca acetate, Al containing phosphate-binding agents, 1,25-dihydroxy vitD3, 1-hydroxy vitD3, and erythropoietin (EPO), as well as hematocrit level, by chi-square statistics. From 6 medical centers in Taiwan, we included 456 patients in maintenance HD for more than 4 months for this study, and they had continued the previously mentioned medications for at least 3 months. Blood samples were collected before initiating HD, and atomic absorption spectrophotometry was used to measure plasma levels of Cu, Zn, and Al as well as whole blood levels of Pb, Cd, and Hg. Three hundred seventy-five (78%) of the HD patients had low plasma Zn levels, that is, <800 microg/L, and the mean (+/-SD) concentration was 705.8 (+/-128.23) microg/L in all subjects. One hundred forty-one (31%) of the HD patients had high plasma Al, that is, >50 microg/L, and the mean (+/-SD) was 44.30 (+/-28.28) microg/L in all subjects. Three hundred thirty-three (73%) of the dialysis patients had high Cd levels, that is, >2.5 microg/L, and the mean (+/-SD) was 3.32 (+/-1.49) microg/L in all subjects. The majority of HD patients had normal blood levels of Cu, PB, and Hg. Only 21 (4. 6%), 5 (1.1%), and 3 (0.06%) patients had elevated blood levels of Cu, Pb, and Hg, respectively. Their mean (+/-SD) blood concentration of Cu, Pb, and Hg were 1,049.78 (+/-233.25) microg/L, 7.45 (+/-3.95) microg/dL, and 3.17 (+/-25.56) microg/L, respectively. Three patients had elevated plasma Hg concentrations, that is, 546, 12.6, and 24.0 microg/L, respectively. In the 152 normal healthy age and sex matched control group, the blood levels of Al, Cd, and Pb were all significantly lower than the HD patients. However, the levels of Cu and Zn were higher in the control group. The Hg level was not significantly different in both groups. There was no statistical difference between patients with normal and abnormal blood levels of trace metals in various medications except Al containing phosphate binder. The Al containing phosphate binder users had significantly higher plasma Al levels (54.71 +/- 26.70 versus 41.15 +/- 28.03 microg/L, p < 0.001) and hematocrit levels (29.61 +/- 4.61 versus 27. 81 +/- 3.91, p < 0.0005). There was no statistical correlation between erythropoietin (EPO) dose and hematocrit level in these patients. In conclusion, the blood level of trace metals of these HD patients except Al was not related to their medications. However, caution must be exercised in interpreting this result as dose and duration of medication; efficiency of HD and water treatment may play an important role. Otherwise, environmental factors, diet, and the aging process may contribute to the trace metal burden in uremia. Thus, Zn and Cu are abundant in seafood, and Cd is abundant in contaminated plants such as rice.

Total allowable concentrations of monomeric inorganic aluminum and hydrated aluminum silicates in drinking water.

PubMed

Willhite, Calvin C; Ball, Gwendolyn L; McLellan, Clifton J

2012-05-01

Maximum contaminant levels are used to control potential health hazards posed by chemicals in drinking water, but no primary national or international limits for aluminum (Al) have been adopted. Given the differences in toxicological profiles, the present evaluation derives total allowable concentrations for certain water-soluble inorganic Al compounds (including chloride, hydroxide, oxide, phosphate and sulfate) and for the hydrated Al silicates (including attapulgite, bentonite/montmorillonite, illite, kaolinite) in drinking water. The chemistry, toxicology and clinical experience with Al materials are extensive and depend upon the particular physical and chemical form. In general, the water solubility of the monomeric Al materials depends on pH and their water solubility and gastrointestinal bioavailability are much greater than that of the hydrated Al silicates. Other than Al-containing antacids and buffered aspirin, food is the primary source of Al exposure for most healthy people. Systemic uptake of Al after ingestion of the monomeric salts is somewhat greater from drinking water (0.28%) than from food (0.1%). Once absorbed, Al accumulates in bone, brain, liver and kidney, with bone as the major site for Al deposition in humans. Oral Al hydroxide is used routinely to bind phosphate salts in the gut to control hyperphosphatemia in people with compromised renal function. Signs of chronic Al toxicity in the musculoskeletal system include a vitamin D-resistant osteomalacia (deranged membranous bone formation characterized by accumulation of the osteoid matrix and reduced mineralization, reduced numbers of osteoblasts and osteoclasts, decreased lamellar and osteoid bands with elevated Al concentrations) presenting as bone pain and proximal myopathy. Aluminum-induced bone disease can progress to stress fractures of the ribs, femur, vertebrae, humerus and metatarsals. Serum Al ≥100 µg/L has a 75-88% positive predictive value for Al bone disease. Chronic Al toxicity is also manifest in the hematopoietic system as an erythropoietin-resistant microcytic hypochromic anemia. Signs of Al toxicity in the central nervous system (speech difficulty to total mutism to facial grimacing to multifacial seizures and dyspraxia) are related to Al accumulation in the brain and these symptoms can progress to frank encephalopathy. There are four groups of people at elevated risk of systemic Al intoxication after repeated ingestion of monomeric Al salts: the preterm infant, the infant with congenital uremia and children and adults with kidney disease. There is a dose-dependent increase in serum and urinary Al in people with compromised renal function, and restoration of renal function permits normal handling of systemically absorbed Al and resolution of Al bone disease. Clinical experience with 960 mg/day of Al(OH)(3) (~5 mg Al/kg-day) given by mouth over 3 months to men and women with compromised renal function found subclinical reductions in hemoglobin, hematocrit and serum ferritin. Following adult males and females with reduced kidney function found that ingestion of Al(OH)(3) at 2.85 g/day (~40 mg/kg-day Al) over 7 years increased bone Al, but failed to elicit significant bone toxicity. There was one report of DNA damage in cultured lymphocytes after high AlCl(3) exposure, but there is no evidence that ingestion of common inorganic Al compounds presents an increased carcinogenic risk or increases the risk for adverse reproductive or developmental outcomes. A number of studies of Al exposure in relation to memory in rodents have been published, but the results are inconsistent. At present, there is no evidence to substantiate the hypothesis that the pathogenesis of Alzheimer's Disease is caused by Al found in food and drinking water at the levels consumed by people living in North America and Western Europe. Attapulgite (palygorskite) has been used for decades at oral doses (recommended not to exceed two consecutive days) of 2,100 mg/day in children of 3-6 years, 4,200 mg/day in children of 6-12 years, and 9,000 mg/day in adults. Chronic ingestion of insoluble hydrated Al silicates (in kg) can result in disturbances in iron and potassium status, primarily as a result of clay binding to intestinal contents and enhanced fecal iron and zinc elimination. Sufficiently high doses of ingested Al silicates (≥50 g/day) over prolonged periods of time can elicit a deficiency anemia that can be corrected with oral Fe supplements. There is essentially no systemic Al uptake after ingestion of the hydrated Al silicates. Rats fed up to 20,000 ppm Ca montmorillonite (equivalent to 1,860 ppm total Al as the hydrated Al silicate) for 28 weeks failed to develop any adverse signs. The results of dietary Phase I and II clinical trials conducted in healthy adult volunteers over 14 days and 90 days with montmorillonite found no adverse effects after feeding up to 40 mg/kg-day as Al. Since the Al associated with ingestion of hydrated Al silicates is not absorbed into the systemic circulation, the hydrated Al silicates seldom cause medical problems unless the daily doses consumed are substantially greater than those used clinically or as dietary supplements. A no-observable-adverse-effect-level (NOAEL) of 13 mg/kg-day as total Al can be identified based on histologic osteomalacia seen in adult hemodialysis patients given Al hydroxide for up to 7 years as a phosphate binder. Following U.S. EPA methods for calculation of an oral reference dose (RfD), an intraspecies uncertainty factor of 10x was applied to that value results in a chronic oral reference dose (RfD) of 1.3 mg Al/kg-day; assuming a 70-kg adult consumes 2 L of drinking water per day and adjusting for a default 20% relative source contribution that value corresponds to a drinking water maximum concentration of 9 mg/L measured as total Al. A chronic NOAEL for montmorillonite as representative of the hydrated Al silicates was identified from the highest dietary concentration (20,000 ppm) fed in a 28-week bioassay with male and female Sprague-Dawley rats. Since young rats consume standard laboratory chow at ~23 g/day, this concentration corresponds to 56 mg Al/kg-day. Application of 3x interspecies uncertainty factor and a 3x factor to account for study duration results in a chronic oral RfD of 6 mg Al/kg-day. Of note, this RfD is 5-10 fold less than oral doses of Al silicates consumed by people who practice clay geophagy and it corresponds to a maximum drinking water concentration of 40 mg Al/L. To utilize the values derived here, the risk manager must recognize the particular product (e.g., alum) or source (e.g., groundwater, river water, clay or cement pipe) of the Al found in tap water, apply the appropriate analytical methods (atomic absorption, energy dispersive X-ray diffraction, infrared spectral analysis and/or scanning transmission electron microscopy) and compare the results to the most relevant standard. The drinking water concentrations derived here are greater than the U.S. EPA secondary maximum contaminant level (MCL) for total Al of 0.05-0.2 mg/L [40 CFR 143.3]. As such, domestic use of water with these concentrations is likely self-limiting given that its cloudy appearance will be greater than the maximum permitted (0.5-5.0 nephalometric turbidity units; 40 CFR Parts 141 and 142). Therefore, the organoleptic properties of Al materials in water determine public acceptance of potable water as contrast to any potential health hazard at the concentrations ordinarily present in municipal drinking water.