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Sample records for affect kidney function

  1. Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III-V, and ESRD.

    PubMed

    Saad, Marc; Karam, Boutros; Faddoul, Geovani; Douaihy, Youssef El; Yacoub, Harout; Baydoun, Hassan; Boumitri, Christine; Barakat, Iskandar; Saifan, Chadi; El-Charabaty, Elie; Sayegh, Suzanne El

    2016-01-01

    logistics regression. Cardiac catheterization on the other hand carried the strongest association among all studied variables (P<0.001). This association was maintained after adjusting for other comorbidities. The length of stay for the three cohorts (non-CKD, CKD stage III-V, and ESRD on hemodialysis) was 16, 17, and 15 days, respectively and was not statistically different. Many observations have reported discrimination of care for patients with CKD considered suboptimal candidates for aggressive management of their cardiac disease. In our study, medical therapy was achieved at high percentage and was comparable among groups of different kidney function. However, kidney disease seems to affect the management of patients with acute MI; percutaneous coronary angiography is not uniformly performed in patients with CKD and ESRD when compared with patients with normal kidney function.

  2. Endocrine tumour in kidney affecting small bowel structure, motility, and absorptive function 1

    PubMed Central

    Gleeson, M. H.; Bloom, S. R.; Polak, J. M.; Henry, K.; Dowling, R. H.

    1971-01-01

    A 44-year-old woman is described with an endocrine tumour arising in the kidney. There were associated abnormalities of small intestinal morphology, motility, and absorptive function. These abnormalities reversed on removal of the tumour. Detailed studies showed that the tumour contained, and was secreting, glucagon. It is postulated that the intestinal abnormalities may have resulted from glucagon itself or another, as yet unidentified, hormone. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6 PMID:4941684

  3. The use of contrast media in deceased kidney donors does not affect initial graft function or graft survival.

    PubMed

    Vigneau, C; Fulgencio, J-P; Godier, A; Chalem, Y; El Metaoua, S; Rondeau, E; Tuppin, P; Bonnet, F

    2006-09-01

    Patients receiving cadaveric kidney transplants often experience delayed graft function. As iodinated contrast media injection (ICMI), necessary for cerebral angiography, which is often used to diagnose brain death, can be nephrotoxic, we compared renal function recovery (RFR) and 1-year and long-term graft survival according to the method used to diagnose brain death. Data from 9921 cadaveric kidneys, transplanted between 1 January 1998 and 31 December 2003, were retrieved from the French National Registry for organ donation. We defined RFR as the number of days for the recipient to reach a plasma creatinine less than 250 mumol/l, and/or a 24-h urine output greater than 1000 ml. RFR and 1-year and long-term graft survival were compared between four different donor groups (according to ICMI and diabetes mellitus). A total of 41.5% of deceased donors received ICMI before organ procurement and 1.95% of them were diabetic. History of ICMI or diabetes in the donor did not influence RFR or 1-year graft survival. Long-term graft survival was decreased in the group of patients transplanted with a diabetic graft as compared to patients transplanted with a non-diabetic graft (P=0.001). History of ICMI in the donor did not affect long-term graft survival in the non-diabetic donor group (P=0.2); however, in the diabetic group, ICMI tended to decrease long-term graft survival (P=0.056). ICMI did not affect RFR or graft survival in non-diabetic deceased donors. However, its use in diabetic deceased donors requires further study.

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

    PubMed Central

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

    2015-01-01

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

  5. Kidney function tests

    MedlinePlus

    Oh MS. Evaluation of renal function, water, electrolytes and acid-base balance. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods . 22nd ed. Philadelphia, PA: Elsevier Saunders; ...

  6. Renal function in single-kidney rats.

    PubMed

    Provoost, A P; De Keijzer, M H; Wessel, J N; Molenaar, J C

    1989-01-01

    Can a single kidney survive for a normal life span? This is the type of question frequently asked by patients and especially by parents of children who lose one kidney in early childhood. Based on our wide experience with single-kidney rats, we will try to give an answer to this question. After the removal of its counterpart, the single remaining kidney will rapidly adapt to the new situation by a compensatory increase in the glomerular filtration rate (GFR) and renal mass. This is true not only for intact kidneys but also for damaged ones. The GFR level obtained by damaged kidneys will be less than that of intact single kidneys, however, depending on the degree of initial damage. The GFR is stable for a certain period of time, which is longer for intact single kidneys than for damaged kidneys and also depends on the daily protein intake; after that renal function will deteriorate. This decline in GFR is preceded by a marked increase in urinary protein excretion. Although the follow-up period is not completed yet, the survival time of single intact kidneys in rats on a normal diet is expected to be 15%-20% less than the normal rat life span. In rats on a lifelong high protein intake the kidney survival time drops to 40% below the normal rat life span. In rats on a moderately reduced protein intake, however, single intact kidneys may survive for a normal life span. The situation is worse for single damaged kidneys. Depending on the severity of the initial damage, kidney survival time will be much less than a normal life span. We studied rats with an initial recovery to 75% of renal function. Despite this initial recovery, the animals died of renal failure within 50% of the expected life span. A low-protein diet prolonged the renal survival by about 12%, a high-protein diet shortened it by the same percentage.

  7. Reflex anuria affecting both kidneys following hysterectomy.

    PubMed

    Gholyaf, Mahmoud; Afzali, Saeed; Babolhavaegi, Hoshang; Rahimi, Abolfazl; Wagharseyedayn, Seyed A

    2009-01-01

    In situations when there is unilateral ureteral obstruction, the contralateral kidney retains its normal function. In rare instances however, it has been reported that unilateral ureteral obstruction can lead to reflex anuria (RA) and acute renal failure (ARF). Even more unusually, RA with ARF can occur without organic obstruction due to ureteric manipulation during pelvic surgery. We report a 78- year-old woman, who underwent hysterectomy because of endometrial carcinoma. She developed ARF evidenced by anuria of 120-hours duration, and gradual rise of serum creatinine levels to 11.8 mg/dL on the fifth day after hysterectomy. Ultrasound study of the urinary tract revealed bilateral moderate hydronephrosis. Detailed evaluation did not reveal any organic obstruction. She was managed with hemodialysis, control of hypertension and correction of fluid and electrolyte imbalances. By the sixth day, diuresis was established, and the blood urea and serum creatinine levels decreased to normal by the sixteenth day. The patient was finally discharged on the eighteenth day. Our case suggests that urologists and nephrologists should consider RA as one of the causes of anuria and ARF.

  8. Allopurinol and kidney function: An update.

    PubMed

    Stamp, Lisa K; Chapman, Peter T; Palmer, Suetonia C

    2016-01-01

    Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.

  9. Superparamagnetic iron oxide polyacrylic acid coated γ-Fe{sub 2}O{sub 3} nanoparticles do not affect kidney function but cause acute effect on the cardiovascular function in healthy mice

    SciTech Connect

    Iversen, Nina K.; Frische, Sebastian; Thomsen, Karen; Laustsen, Christoffer; Pedersen, Michael; Hansen, Pernille B.L.; Bie, Peter; Fresnais, Jérome; Berret, Jean-Francois; Baatrup, Erik; Wang, Tobias

    2013-01-15

    This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe{sub 2}O{sub 3} NPs (10 mg kg{sup −1}) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1 h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid–base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46 ± 0.02 and 7.41 ± 0.02 in mice 0.5 h after injections of saline or NP, and did not change over the next 12 h. In addition, the injections of NP did not affect arterial PCO{sub 2} or [HCO{sub 3}{sup −}] either. Twenty-four and 96 h after NP injections, the GFR averaged 0.35 ± 0.04 and 0.35 ± 0.01 ml min{sup −1} g{sup −1}, respectively, values which were statistically comparable with controls (0.29 ± 0.02 and 0.33 ± 0.1 ml{sup –1} min{sup –1} 25 g{sup –1}). Mean arterial blood pressure (MAP) decreased 12–24 h after NP injections (111.1 ± 11.5 vs 123.0 ± 6.1 min{sup −1}) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterize endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure. -- Highlights: ► PAA coated γ-Fe{sub 2}O{sub 3} nanoparticles were injected intravenously into healthy mice. ► We examine the distribution and physiological effects of

  10. Biomarkers in chronic kidney disease, from kidney function to kidney damage

    PubMed Central

    Lopez-Giacoman, Salvador; Madero, Magdalena

    2015-01-01

    Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD. PMID:25664247

  11. Kidney Function, β-Cell Function and Glucose Tolerance in Older Men

    PubMed Central

    Jia, Ting; Risérus, Ulf; Xu, Hong; Lindholm, Bengt; Ärnlöv, Johan; Sjögren, Per; Cederholm, Tommy; Larsson, Tobias E.; Ikizler, Talat Alp

    2015-01-01

    Context: Kidney dysfunction induces insulin resistance, but it is unknown if β cell function is affected. Objective: To investigate insulin release (β cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata. Setting and Design: Community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM). Participants and Main Outcome Measure: Included were 1015 nondiabetic Swedish men aged 70–71 years. All participants underwent OGTT and euglycaemic hyperinsulinaemic clamp (HEGC) tests, allowing determination of insulin sensitivity, β cell function, and glucose tolerance. Kidney function was estimated by cystatin C-algorithms. Mixed models were used to identify determinants of insulin secretion after the hyperglycemic load. Results: As many as 466 (46%) of participants presented moderate-advanced kidney disease. Insulin sensitivity (by HEGC) decreased across decreasing kidney function quartiles. After the OGTT challenge, however, β cell function indices (area under the curve for insulin release, the estimated first phase insulin release, and the insulinogenic index) were incrementally higher. Neither the oral disposition index nor the 2-h postload glucose tolerance differed across the kidney function strata. Mixed models showed that dynamic insulin release during the OGTT was inversely associated with kidney function, despite the correction for each individual's insulin sensitivity or its risk factors. Conclusions: In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved. PMID:25429626

  12. Biologically active extracts with kidney affections applications

    NASA Astrophysics Data System (ADS)

    Pascu (Neagu), Mihaela; Pascu, Daniela-Elena; Cozea, Andreea; Bunaciu, Andrei A.; Miron, Alexandra Raluca; Nechifor, Cristina Aurelia

    2015-12-01

    This paper is aimed to select plant materials rich in bioflavonoid compounds, made from herbs known for their application performances in the prevention and therapy of renal diseases, namely kidney stones and urinary infections (renal lithiasis, nephritis, urethritis, cystitis, etc.). This paper presents a comparative study of the medicinal plant extracts composition belonging to Ericaceae-Cranberry (fruit and leaves) - Vaccinium vitis-idaea L. and Bilberry (fruit) - Vaccinium myrtillus L. Concentrated extracts obtained from medicinal plants used in this work were analyzed from structural, morphological and compositional points of view using different techniques: chromatographic methods (HPLC), scanning electronic microscopy, infrared, and UV spectrophotometry, also by using kinetic model. Liquid chromatography was able to identify the specific compounds of the Ericaceae family, present in all three extracts, arbutosid, as well as specific components of each species, mostly from the class of polyphenols. The identification and quantitative determination of the active ingredients from these extracts can give information related to their therapeutic effects.

  13. Environmental and stressful factors affecting the occurrence of kidney stones and the kidney colic.

    PubMed

    Kalaitzidis, Rigas G; Damigos, Dimitrios; Siamopoulos, Kostas C

    2014-09-01

    The first renal disease described from Hippocrates is nephrolithiasis with renal colic, which is the pain of stone passage and is also a common renal problem with easily recognizable characteristics. There has been much written about dietary factors, which have unequivocally been proved to play an important role in the formation of kidney stones. In this regard, it is of interest that the contribution of factors such as stressful events, life style, or occupation in the formation of kidney stones has not been well studied. This review examines the clinical evidence of the stressful events and other environmental factors affecting the occurrence of kidney stones. PMID:24927933

  14. Emerging functions of autophagy in kidney transplantation.

    PubMed

    Pallet, N; Livingston, M; Dong, Z

    2014-01-01

    In response to ischemic, toxic or immunological insults, the more frequent injuries encountered by the kidney, cells must adapt to maintain vital metabolic functions and avoid cell death. Among the adaptive responses activated, autophagy emerges as an important integrator of various extracellular and intracellular triggers (often related to nutrients availability or immunological stimuli), which, as a consequence,may regulate cell viability, and also immune functions,both innate or adaptive. The aim of this review is to make the synthesis of the recent literature on the implications of autophagy in the kidney transplantation field and to discuss the future directions for research. PMID:24369023

  15. Interactions between thyroid and kidney function in pathological conditions of these organ systems: a review.

    PubMed

    van Hoek, Ingrid; Daminet, Sylvie

    2009-02-01

    Thyroidal status affects kidney function already in the embryonic stage. Thyroid hormones influence general tissue growth as well as tubular functions, electrolyte handling and neural input. Hyper- and hypo-functioning of the thyroid influences mature kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, electrolyte pumps, the secretory and absorptive capacity of the tubuli, and the structure of the kidney. Hyperthyroidism accelerates several physiologic processes, a fact which is reflected in the decreased systemic vascular resistance, increased cardiac output (CO), increased renal blood flow (RBF), hypertrophic and hyperplastic tubuli, and increased glomerular filtration rate (GFR). Renal failure can progress due to glomerulosclerosis, proteinuria and oxidative stress. Hypothyroidism has a more negative influence on kidney function. Peripheral vascular resistance is increased with intrarenal vasoconstriction, and CO is decreased, causing decreased RBF. The influence on the different tubular functions is modest, although the transport capacity is below normal. The GFR is decreased up to 40% in hypothyroid humans. Despite the negative influences on glomerular and tubular kidney function, a hypothyroid state has been described as beneficial in kidney disease. Kidney disease is associated with decreased thyroid hormone concentrations caused by central effects and by changes in peripheral hormone metabolism and thyroid hormone binding proteins. Geriatric cats form an animal model of disease because both hyperthyroidism and chronic kidney disease (CKD) have high prevalence among them, and the link between thyroid and kidney affects the evaluation of clinical wellbeing and the possible treatment options. PMID:19133263

  16. Kidney function decline and physical function in women

    PubMed Central

    Lin, Julie; Curhan, Gary C.

    2008-01-01

    Background. Cross-sectional analyses of kidney function and physical function have identified profound quality of life impairments in people with advanced kidney dysfunction. No data are currently available, however, on how kidney function decline may be associated with physical function. Methods. We undertook a study of kidney function decline and physical function in 2544 women participating in the Nurses’ Health Study. Glomerular filtration rates (GFR) were estimated using the four-variable MDRD equation from plasma creatinine measured in blood collected in 1989 and 2000. Physical function was assessed by the Physical Function Sub-Scale (PFS) score of the Short Form 36 (SF-36) in a questionnaire administered in the year 2000. PFS scores have been shown to correlate well with direct measures of physical function. Results. In the year 2000, the median age was 67 years, median body mass index (BMI) was 25.6 kg/m2, 48.5% had hypertension and 5.8% had diabetes. There were 427 women (16.8%) who experienced an ≥25% decline in eGFR between 1989 and 2000. Median PFS in 2000 for those with an eGFR decline of ≥25% was 80 compared to a PFS score of 85 for those without (P < 0.001). In fully adjusted models, the presence of an eGFR decline of ≥25% was independently associated with a 3.5-point lower PFS score (95% CI −5.4 to −1.5). Also, an eGFR decline of ≥25% was independently associated with an increased odds ratio of being in the lowest quartile of PFS score (OR 1.37; 95% CI 1.04–1.81). Conclusions. We conclude that an eGFR decline of ≥25% over 11 years is independently associated with lower physical function in women. PMID:18398018

  17. Genetic loci influencing kidney function and chronic kidney disease in man

    PubMed Central

    Chambers, John C; Zhang, Weihua; Lord, Graham M; van der Harst, Pim; Lawlor, Debbie A; Sehmi, Joban S; Gale, Daniel P; Wass, Mark N; Ahmadi, Kourosh R; Bakker, Stephan JL; Beckmann, Jacqui; Bilo, Henk JG; Bochud, Murielle; Brown, Morris J; Caulfield, Mark J; Connell, John M C; Cook, Terence; Cotlarciuc, Ioana; Smith, George Davey; de Silva, Ranil; Deng, Guohong; Devuyst, Olivier; Dikkeschei, Lambert D.; Dimkovic, Nada; Dockrell, Mark; Dominiczak, Anna; Ebrahim, Shah; Eggermann, Thomas; Farrall, Martin; Ferrucci, Luigi; Floege, Jurgen; Forouhi, Nita G; Gansevoort, Ron T; Han, Xijin; Hedblad, Bo; van der Heide, Jaap J Homan; Hepkema, Bouke G; Hernandez-Fuentes, Maria; Hypponen, Elina; Johnson, Toby; de Jong, Paul E; Kleefstra, Nanne; Lagou, Vasiliki; Lapsley, Marta; Li, Yun; Loos, Ruth J F; Luan, Jian'an; Luttropp, Karin; Maréchal, Céline; Melander, Olle; Munroe, Patricia B; Nordfors, Louise; Parsa, Afshin; Penninx, Brenda W.; Perucha, Esperanza; Pouta, Anneli; Prokopenko, Inga; Roderick, Paul J; Ruokonen, Aimo; Samani, Nilesh; Sanna, Serena; Schalling, Martin; Schlessinger, David; Schlieper, Georg; Seelen, Marc AJ; Shuldiner, Alan R; Sjögren, Marketa; Smit, Johannes H.; Snieder, Harold; Soranzo, Nicole; Spector, Timothy D; Stenvinkel, Peter; Sternberg, Michael JE; Swaminathan, Ramasamyiyer; Tanaka, Toshiko; Ubink-Veltmaat, Lielith J.; Uda, Manuela; Vollenweider, Peter; Wallace, Chris; Waterworth, Dawn; Zerres, Klaus; Waeber, Gerard; Wareham, Nicholas J; Maxwell, Patrick H; McCarthy, Mark I; Jarvelin, Marjo-Riitta; Mooser, Vincent; Abecasis, Goncalo R; Lightstone, Liz; Scott, James; Navis, Gerjan; Elliott, Paul; Kooner., Jaspal S

    2013-01-01

    Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD. PMID:20383145

  18. Biosignals analysis for kidney function effect analysis of fennel aromatherapy.

    PubMed

    Kim, Bong-Hyun; Cho, Dong-Uk; Seo, Ssang-Hee

    2015-01-01

    Human effort in order to enjoy a healthy life is diverse. IT technology to these analyzes, the results of development efforts, it has been applied. Therefore, I use the care and maintenance diagnostic health management and prevention than treatment. In particular, the aromatherapy treatment easy to use without the side effects there is no irritation, are widely used in modern society. In this paper, we measured the aroma effect by applying a biosignal analysis techniques; an experiment was performed to analyze. In particular, we design methods and processes of research based on the theory aroma that affect renal function. Therefore, in this paper, measuring the biosignals and after fennel aromatherapy treatment prior to the enforcement of the mutual comparison, through the analysis, studies were carried out to analyze the effect of fennel aromatherapy therapy on kidney function.

  19. Biosignals analysis for kidney function effect analysis of fennel aromatherapy.

    PubMed

    Kim, Bong-Hyun; Cho, Dong-Uk; Seo, Ssang-Hee

    2015-01-01

    Human effort in order to enjoy a healthy life is diverse. IT technology to these analyzes, the results of development efforts, it has been applied. Therefore, I use the care and maintenance diagnostic health management and prevention than treatment. In particular, the aromatherapy treatment easy to use without the side effects there is no irritation, are widely used in modern society. In this paper, we measured the aroma effect by applying a biosignal analysis techniques; an experiment was performed to analyze. In particular, we design methods and processes of research based on the theory aroma that affect renal function. Therefore, in this paper, measuring the biosignals and after fennel aromatherapy treatment prior to the enforcement of the mutual comparison, through the analysis, studies were carried out to analyze the effect of fennel aromatherapy therapy on kidney function. PMID:25977696

  20. [Unilateral catheterless determination of kidney function in hydronephrosis].

    PubMed

    Müller, P; Schönberger, B; Strangfeld, D; Siewert, H

    1983-04-01

    Whereas the value of quantitative separate determination of kidney functioning is undisputed for most urological and nephrological problems, its value for the judgement of hydronephrotic kidneys is doubted by various working groups. Using 15 mongrel dogs, the nuclide excretion at certain times, various calculation intervals and the results of separate functional analysis of hydronephrotic and non-hydronephrotic kidneys were compared. Due to the early nuclide excretion with an advanced secretion peak it is no longer acceptable to use a 2-minute calculation interval for hydronephrotic kidneys in dogs. If the upper limit of the calculation interval is prior to the secretion peak, there will be no overestimation of the hydronephrotic kidneys. PMID:6868840

  1. Sperm function in affective illness.

    PubMed

    Amsterdam, J; Winokur, A; Levin, R

    1981-04-01

    There is evidence for functional changes in the hypothalamic-pituitary-gonadal axis of patients with affective disorders. Little is known concerning spermatogenesis or sperm function in depressed men. We systematically evaluated the sperm indices in a group of depressed males complaining of diminished libido, and a healthy control group. No differences were noted in sperm parameters between the groups.

  2. Novel in vivo techniques to visualize kidney anatomy and function.

    PubMed

    Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

    2015-07-01

    Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped track the fate and function (e.g., cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic, rather than static, nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting-edge area of kidney research.

  3. Structural and Functional Changes With the Aging Kidney.

    PubMed

    Denic, Aleksandar; Glassock, Richard J; Rule, Andrew D

    2016-01-01

    Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.

  4. Do kidney histology lesions predict long-term kidney function after liver transplantation?

    PubMed

    Kamar, Nassim; Maaroufi, Chakib; Guilbeau-Frugier, Céline; Servais, Aude; Meas-Yedid, Vannary; Tack, Ivan; Thervet, Eric; Cointault, Olivier; Esposito, Laure; Guitard, Joelle; Lavayssière, Laurence; Panterne, Clarisse; Muscari, Fabrice; Bureau, Christophe; Rostaing, Lionel

    2012-01-01

    Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60±48 months post-transplant, were included in this follow-up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109±48 months after liver transplantation. eGFR decreased from 92±33 mL/min at transplantation to 63±19 mL/min after six months, to 57±17 mL/min at the kidney biopsy, to 54±24 mL/min at last follow-up (p<0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR≥60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions.

  5. Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals.

    PubMed

    Yanik, Elizabeth L; Clarke, Christina A; Snyder, Jon J; Pfeiffer, Ruth M; Engels, Eric A

    2016-05-01

    Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin's lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin's lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin's lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention. PMID:26563384

  6. Spontaneous bilateral kidney rupture during autologous stem cell transplantation in a patient affected by amyloidosis

    PubMed Central

    Ferrannini, Michele; Vischini, Gisella; De Angelis, Gottardo; Giannakakis, Konstantinos; Arcese, William

    2011-01-01

    Kidney spontaneous rupture is not a recognized complication neither for amyloidosis nor of autologous stem cell transplantation (ASCT). A 46-year-old white woman, affected by nephrotic syndrome, was diagnosed as AL amyloidosis by renal biopsy. We report the singular case of a bilateral spontaneous kidney rupture during ASCT for AL with renal rescue. PMID:25984105

  7. Musculoskeletal Health, Kidney and Liver Function in Retired Jockeys.

    PubMed

    Cullen, S; Donohoe, A; McGoldrick, A; McCaffrey, N; Davenport, C; Byrne, B; Donaghy, C; Tormey, W; Smith, D; Warrington, G

    2015-11-01

    The long-term implications of making-weight daily on musculoskeletal health and functioning of the kidney and liver remain unknown. This study aimed to investigate musculoskeletal health and kidney and liver function in a group of retired jockeys. 28 retired male jockeys (age 50-70 years) provided fasting blood samples for markers of bone metabolism and kidney and liver function. A dual-energy x-ray absorptiometry (DXA) scan was performed for the assessment of bone mineral density (BMD). Established reference ranges were used for interpretation of results. Comparisons were made between retired jockeys based on the professional racing licence held: Flat, National Hunt or Dual. Mean whole-body osteopenia was reported, with no differences between groups. Bone markers, micronutrients, electrolytes and associated hormones, and markers for kidney and liver function were within clinical normative ranges. No differences existed between groups. Results indicate the retired jockeys in this study do not demonstrate compromised bone health or kidney and liver function. However, the retired jockeys may not have undergone chronic weight cycling in the extreme manner evident in present-day jockeys, indicating the next generation of jockeys may face more of a problem. Jockeys should be tracked longitudinally throughout their racing career and beyond. PMID:26212243

  8. Kidney Function in Severely Obese Adolescents Undergoing Bariatric Surgery

    PubMed Central

    Xiao, Nianzhou; Jenkins, Todd M; Nehus, Edward; Inge, Thomas H; Michalsky, Marc P; Harmon, Carroll M.; Helmrath, Michael A.; Brandt, Mary L.; Courcoulas, Anita; Moxey-Mims, Marva; Mitsnefes, Mark M

    2014-01-01

    Objective To describe objective measures of kidney function and analyze factors associated with kidney dysfunction in severely obese adolescents undergoing weight loss surgery. Design and Methods We analyzed cross-sectional data from 242 adolescent participants in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study before weight loss surgery. Kidney status was assessed by measuring urine albumin creatinine ratio to determine microalbuminuria and by calculating serum cystatin C-based estimated glomerular filtration rate (eGFR) to assess kidney function. Results Mean age and median body mass index (BMI) were 17.1 years and 50.5kg/m2, respectively; 76% were females and 65% were non-Hispanic white race. Fourteen percent of the cohort had microalbuminuria, and 3% had macroalbuminuria; 3% had eGFR <60 ml/min/1.73m2, and 7.1% had eGFR >150 ml/min/1.73m2. In adjusted analyses, female gender and increasing ferritin levels were significantly associated with the presence of microalbuminuria/macroalbuminuria. Increasing BMI and HOMA-IR values were significantly associated with lower eGFR. Conclusions A significant number of severely obese adolescents undergoing weight loss surgery have evidence of early kidney dysfunction. Longitudinal studies following weight loss surgery in these individuals are needed to determine whether these kidney abnormalities are reversible following weight loss therapy. PMID:25376399

  9. Calciphylaxis in Patients With Preserved Kidney Function.

    PubMed

    Maroz, Natallia; Mohandes, Samer; Field, Halle; Kabakov, Zlata; Simman, Richard

    2014-04-01

    Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a devastating disease typically seen in patients with end stage renal disease. It manifests as extremely painful symmetrical wounds resistant to surgical and medical interventions. The prevalence of CUA among hemodialysis dependent patients was found to be as high as 4.1%. The management of patients with CUA requires a multidisciplinary approach by the medical team, yet often results in a low rate of successful outcomes. Recently, non-uremic calciphylaxis (NUC) has been described in the absence of kidney disease. Limited knowledge exists on the management of NUC and the outcomes of this condition. Herein we describe three clinical scenarios of patients diagnosed with NUC in the absence of permanent or prolonged acute renal pathology. The reporting of successful and fruitless therapeutic interventions for wound management in NUC is important for compiling the evidence of effective therapeutic strategies.

  10. Calciphylaxis in Patients With Preserved Kidney Function

    PubMed Central

    Maroz, Natallia; Mohandes, Samer; Field, Halle; Kabakov, Zlata; Simman, Richard

    2015-01-01

    Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a devastating disease typically seen in patients with end stage renal disease. It manifests as extremely painful symmetrical wounds resistant to surgical and medical interventions. The prevalence of CUA among hemodialysis dependent patients was found to be as high as 4.1%. The management of patients with CUA requires a multidisciplinary approach by the medical team, yet often results in a low rate of successful outcomes. Recently, non-uremic calciphylaxis (NUC) has been described in the absence of kidney disease. Limited knowledge exists on the management of NUC and the outcomes of this condition. Herein we describe three clinical scenarios of patients diagnosed with NUC in the absence of permanent or prolonged acute renal pathology. The reporting of successful and fruitless therapeutic interventions for wound management in NUC is important for compiling the evidence of effective therapeutic strategies. PMID:26442208

  11. Associations of deceased donor kidney injury with kidney discard and function after transplantation

    PubMed Central

    Hall, Isaac E.; Schröppel, Bernd; Doshi, Mona D.; Ficek, Joseph; Weng, Francis L.; Hasz, Rick D.; Thiessen-Philbrook, Heather; Reese, Peter P.; Parikh, Chirag R.

    2015-01-01

    Deceased-donor kidneys with acute kidney injury (AKI) are often discarded due to fear of poor outcomes. We performed a multicenter study to determine associations of AKI (increasing admission-to-terminal serum creatinine by AKI Network stages) with kidney discard, delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). In 1632 donors, kidney discard risk increased for AKI stages 1, 2 and 3 (compared to no AKI) with adjusted relative risks of 1.28 (1.08–1.52), 1.82 (1.45–2.30) and 2.74 (2.0–3.75), respectively. Adjusted relative risk for DGF also increased by donor AKI stage: 1.27 (1.09–1.49), 1.70 (1.37–2.12) and 2.25 (1.74–2.91), respectively. Six-month eGFR, however, was similar across AKI categories but was lower for recipients with DGF (48 [interquartile range: 31–61] vs. 58 [45–75] ml/min/1.73m2 for no DGF, P<0.001). There was significant favorable interaction between donor AKI and DGF such that 6-month eGFR was progressively better for DGF kidneys with increasing donor AKI (46 [29–60], 49 [32–64], 52 [36–59] and 58 [39–71] ml/min/1.73m2 for no AKI, stage 1, 2 and 3, respectively; interaction P=0.05). Donor AKI is associated with kidney discard and DGF, but given acceptable 6-month allograft function, clinicians should consider cautious expansion into this donor pool. PMID:25762442

  12. Association of metabolic syndrome with kidney function and histology in living kidney donors.

    PubMed

    Ohashi, Y; Thomas, G; Nurko, S; Stephany, B; Fatica, R; Chiesa, A; Rule, A D; Srinivas, T; Schold, J D; Navaneethan, S D; Poggio, E D

    2013-09-01

    The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

  13. Effects of Dietary Calcium Supplementation on Bone Metabolism, Kidney Mineral Concentrations, and Kidney Function in Rats Fed a High-Phosphorus Diet.

    PubMed

    Katsumata, Shinichi; Matsuzaki, Hiroshi; Uehara, Mariko; Suzuki, Kazuharu

    2015-01-01

    We investigated the effects of dietary calcium (Ca) supplementation on bone metabolism, kidney mineral concentrations, and kidney function in rats fed a high-phosphorus (P) diet. Wistar strain rats were randomly divided into 4 dietary groups and fed their respective diets for 21 d: a diet containing 0.3% P and 0.5% Ca (C), a diet containing 1.5% P and 0.5% Ca (HP), a diet containing 0.3% P and 1.0% Ca (HCa), or a diet containing 1.5% P and 1.0% Ca (HPCa). Compared to the C group, the high-P diet increased serum parathyroid hormone concentration, markers of bone turnover, receptor activator of NF-κB ligand mRNA expression of the femur, kidney Ca and P concentrations, urinary N-acetyl-β-D-glucosaminidase activity, and urinary β2-microglobulin excretion, and decreased bone mineral content and bone mineral density of the femur and tibia. Dietary Ca supplementation improved the parameters of bone metabolism and kidney function in rats fed the high-P diet, while there were no significant differences in kidney Ca or P concentrations between the HP and HPCa groups. These results suggest that dietary Ca supplementation prevented the bone loss and decline in kidney function induced by a high-P diet, whereas dietary Ca supplementation did not affect kidney mineral concentrations in rats fed the high-P diet.

  14. Berberine Improves Kidney Function in Diabetic Mice via AMPK Activation

    PubMed Central

    Zhao, Long; Sun, Li-Na; Nie, Hui-Bin; Wang, Xue-Ling; Guan, Guang-Ju

    2014-01-01

    Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPKα2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice. PMID:25409232

  15. Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children.

    PubMed

    Rodieux, Frederique; Wilbaux, Melanie; van den Anker, Johannes N; Pfister, Marc

    2015-12-01

    Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood has an impact not only on renal clearance but also on absorption, distribution, metabolism and nonrenal clearance of drugs. 'Omics'-based technologies, such as proteomics and metabolomics, can be leveraged to uncover novel markers for kidney function during normal development, acute kidney injury, and chronic diseases. Pharmacometric modeling and simulation can be applied to simplify the design of pediatric investigations, characterize the effects of kidney function on drug exposure and response, and fine-tune dosing in pediatric patients, especially in those with impaired kidney function. One case study of amikacin dosing in neonates with reduced kidney function is presented. Collaborative efforts between clinicians and scientists in academia, industry, and regulatory agencies are required to evaluate new renal biomarkers, collect and share prospective pharmacokinetic, genetic and clinical data, build integrated pharmacometric models for key drugs, optimize and standardize dosing strategies, develop bedside decision tools, and enhance labels of drugs utilized in neonates, infants, and children.

  16. Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium

    PubMed Central

    Köttgen, Anna; Pattaro, Cristian; Böger, Carsten A.; Fuchsberger, Christian; Olden, Matthias; Glazer, Nicole L.; Parsa, Afshin; Gao, Xiaoyi; Yang, Qiong; Smith, Albert V.; O’Connell, Jeffrey R.; Li, Man; Schmidt, Helena; Tanaka, Toshiko; Isaacs, Aaron; Ketkar, Shamika; Hwang, Shih-Jen; Johnson, Andrew D.; Dehghan, Abbas; Teumer, Alexander; Paré, Guillaume; Atkinson, Elizabeth J.; Zeller, Tanja; Lohman, Kurt; Cornelis, Marilyn C.; Probst-Hensch, Nicole M.; Kronenberg, Florian; Tönjes, Anke; Hayward, Caroline; Aspelund, Thor; Eiriksdottir, Gudny; Launer, Lenore; Harris, Tamara B.; Rapmersaud, Evadnie; Mitchell, Braxton D.; Boerwinkle, Eric; Struchalin, Maksim; Cavalieri, Margherita; Singleton, Andrew; Giallauria, Francesco; Metter, Jeffery; de Boer, Ian; Haritunians, Talin; Lumley, Thomas; Siscovick, David; Psaty, Bruce M.; Zillikens, M. Carola; Oostra, Ben A.; Feitosa, Mary; Province, Michael; Levy, Daniel; de Andrade, Mariza; Turner, Stephen T.; Schillert, Arne; Ziegler, Andreas; Wild, Philipp S.; Schnabel, Renate B.; Wilde, Sandra; Muenzel, Thomas F.; Leak, Tennille S; Illig, Thomas; Klopp, Norman; Meisinger, Christa; Wichmann, H.-Erich; Koenig, Wolfgang; Zgaga, Lina; Zemunik, Tatijana; Kolcic, Ivana; Minelli, Cosetta; Hu, Frank B.; Johansson, Åsa; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Schreiber, Stefan; Aulchenko, Yurii S; Rivadeneira, Fernando; Uitterlinden, Andre G; Hofman, Albert; Imboden, Medea; Nitsch, Dorothea; Brandstätter, Anita; Kollerits, Barbara; Kedenko, Lyudmyla; Mägi, Reedik; Stumvoll, Michael; Kovacs, Peter; Boban, Mladen; Campbell, Susan; Endlich, Karlhans; Völzke, Henry; Kroemer, Heyo K.; Nauck, Matthias; Völker, Uwe; Polasek, Ozren; Vitart, Veronique; Badola, Sunita; Parker, Alexander N.; Ridker, Paul M.; Kardia, Sharon L. R.; Blankenberg, Stefan; Liu, Yongmei; Curhan, Gary C.; Franke, Andre; Rochat, Thierry; Paulweber, Bernhard; Prokopenko, Inga; Wang, Wei; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Shlipak, Michael G.; van Duijn, Cornelia M.; Borecki, Ingrid; Krämer, Bernhard K.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Witteman, Jacqueline C.; Pramstaller, Peter P.; Rettig, Rainer; Hastie, Nick; Chasman, Daniel I.; Kao, W. H.; Heid, Iris M.; Fox, Caroline S.

    2010-01-01

    Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 Caucasian individuals from 20 population-based studies to identify new susceptibility loci for reduced renal function, estimated by serum creatinine (eGFRcrea), cystatin C (eGFRcys), and CKD (eGFRcrea <60 ml/min/1.73m2; n = 5,807 CKD cases). Follow-up of the 23 genome-wide significant loci (p<5×10−8) in 22,982 replication samples identified 13 novel loci for renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2, and SLC7A9) and 7 creatinine production and secretion loci (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72, BCAS3). These results further our understanding of biologic mechanisms of kidney function by identifying loci potentially influencing nephrogenesis, podocyte function, angiogenesis, solute transport, and metabolic functions of the kidney. PMID:20383146

  17. Hydration status affects osteopontin expression in the rat kidney.

    PubMed

    Lee, Su-Youn; Lee, Sae-Jin; Piao, Hong-Lin; Yang, Suk-Young; Weiner, I David; Kim, Jin; Han, Ki-Hwan

    2016-09-30

    Osteopontin (OPN) is a secretory protein that plays an important role in urinary stone formation. Hydration status is associated with the development of urolithiasis. This study was conducted to examine the effects of dehydration and hydration on OPN expression in the rat kidney. Animals were divided into three groups, control, dehydrated, and hydrated. Kidney tissues were processed for light and electron microscope immunocytochemistry, in situhybridization, and immunoblot analysis. Dehydration induced a significant increase in OPN protein expression, whereas increased fluid intake induced a decrease in protein expression. Under control conditions, OPN protein and mRNA expression were only detected in the descending thin limb (DTL). Dehydration induced increased expression in the DTL and the development of detectable expression in the thick ascending limb (TAL). In contrast, OPN expression levels declined to less than the controls in the DTL after hydration, while no expression of either protein or mRNA was detectable in the TAL. Immunoelectron microscopy demonstrated that hydration status altered tubular ultrastructure and intracellular OPN expression in the Golgi apparatus and secretory cytoplasmic vesicles. These data confirm that changes in oral fluid intake can regulate renal tubular epithelial cell OPN expression.

  18. Hydration status affects osteopontin expression in the rat kidney

    PubMed Central

    Lee, Su-Youn; Lee, Sae-Jin; Piao, Hong-Lin; Yang, Suk-Young; Weiner, I. David; Kim, Jin

    2016-01-01

    Osteopontin (OPN) is a secretory protein that plays an important role in urinary stone formation. Hydration status is associated with the development of urolithiasis. This study was conducted to examine the effects of dehydration and hydration on OPN expression in the rat kidney. Animals were divided into three groups, control, dehydrated, and hydrated. Kidney tissues were processed for light and electron microscope immunocytochemistry, in situ hybridization, and immunoblot analysis. Dehydration induced a significant increase in OPN protein expression, whereas increased fluid intake induced a decrease in protein expression. Under control conditions, OPN protein and mRNA expression were only detected in the descending thin limb (DTL). Dehydration induced increased expression in the DTL and the development of detectable expression in the thick ascending limb (TAL). In contrast, OPN expression levels declined to less than the controls in the DTL after hydration, while no expression of either protein or mRNA was detectable in the TAL. Immunoelectron microscopy demonstrated that hydration status altered tubular ultrastructure and intracellular OPN expression in the Golgi apparatus and secretory cytoplasmic vesicles. These data confirm that changes in oral fluid intake can regulate renal tubular epithelial cell OPN expression. PMID:26645343

  19. Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation.

    PubMed

    Malyszko, Jolanta; Lukaszyk, Ewelina; Glowinska, Irena; Durlik, Magdalena

    2015-01-01

    Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness. PMID:26175216

  20. A patient with heart failure and worsening kidney function.

    PubMed

    Sarnak, Mark J

    2014-10-01

    There is high prevalence of CKD, defined by reduced GFR, in patients with heart failure. Reduced kidney function is associated with increased morbidity and mortality in this patient population. The cardiorenal syndrome (CRS) involves a bidirectional relationship between the heart and kidneys whereby dysfunction in either may exacerbate the function of the other, but this syndrome has been difficult to precisely define because it has many complex physiologic, biochemical, and hormonal abnormalities. The pathophysiology of CRS is not completely understood, but potential mechanisms include reduced kidney perfusion due to decreased forward flow, increased right ventricular and venous pressure, and neurohormonal adaptations. Treatment options include inotropic medications; diuretics; ultrafiltration; and medications, such as β-blockers, inhibitors of the renin-angiotensin-aldosterone system, and more novel treatments that focus on unique aspects of the pathophysiology. Recent observational studies suggest that treatments that result in a decrease in venous pressure and lead to hemoconcentration may be associated with improved outcomes. Patients with CRS that is not responsive to medical interventions should be considered for ventricular assist devices, heart transplantation, or combined heart and kidney transplantation.

  1. Interconnected network motifs control podocyte morphology and kidney function.

    PubMed

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

    2014-02-01

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

  2. Renal Artery Stenting in Patients with a Solitary Functioning Kidney

    SciTech Connect

    Cioni, Roberto; Vignali, Claudio; Petruzzi, Pasquale; Neri, Emanuele; Caramella, Davide; Vagli, Paola; Bargellini, Irene; Napoli, Vinicio; Pinto, Stefania; Bartolozzi, Carlo

    2001-12-15

    Purpose: To retrospectively evaluate the results of renal artery stenting in patients with renovascular disease and a solitary functioning kidney.Methods: Palmazstents were placed in 16 patients with a solitary functioning kidney,renal artery stenosis, hypertension and renal failure. Stenoses were evaluated with color Doppler ultrasound, MR angiography and digital subtraction angiography (DSA). Indications for stenting were: recoil after percutaneous transluminal renal angioplasty (PTRA) (63%),arterial dissection after PTRA (13%) and primary stenting (25%).Immediate results were evaluated by DSA. On follow-up (6-36 months),patients underwent periodical evaluation of clinical conditions (blood pressure and serum creatinine level) and stent patency, by means of color Doppler ultrasound.Results: Stent placement was successful in all patients (100%). Cumulative primary patency rate was: 100% at 1 day, 93.75% at 6 months, 81.25% at 12 months and 75% at 24 months. A significant reduction in diastolic blood pressure occurred (mean {+-} SD 104 {+-} 6 vs 92 {+-} 3;p < 0.05); renal function improved or stabilized in over 80% of patients. However, there was no significant difference in the creatinine values before and after treatment (mean {+-} SD 200 {+-} 142 mmol/l vs 197 {+-} 182 mmol/l; p> 0.05).Conclusion: Renal artery stenting, both after PTRA and as primary stenting, represents a safe procedure, able to preserve renal function in patients with a solitary functioning kidney.

  3. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients.

    PubMed

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-03-01

    Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages.Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I.Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = -0.76, BUN: r = -0.72, and cystatin C: r = -0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603-0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746-0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P = 0.811, and e

  4. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

    PubMed Central

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-01-01

    Abstract Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = −0.76, BUN: r = −0.72, and cystatin C: r = −0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603–0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746–0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P

  5. Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.

    PubMed

    McCormack, K M; Kluwe, W M; Sanger, V L; Hook, J B

    1978-04-01

    Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function. PMID:209969

  6. In vitro function of cyst epithelium from human polycystic kidney.

    PubMed Central

    Perrone, R D

    1985-01-01

    It is thought that cysts in polycystic kidneys originate from nephron segments and function in a manner similar to the segment or origin. The indirect evidence for this derives from studies of microanatomy and cyst fluid composition. Cysts with low Na+ have been classified as distal, whereas cysts with high Na+ have been classified as proximal. In order to directly determine the transport characteristics of cyst epithelium, cysts from a human polycystic kidney were studied in vitro using Ussing chamber techniques. Composition of cyst fluid was determined in parallel with these studies. Cysts with low Na+ (gradient cysts) demonstrate characteristics consistent with distal nephron origin including elevated potential difference (PD), short-circuit current (Isc), and low conductance. PD and Isc of gradient cysts were amiloride sensitive. Nongradient cysts, however, require additional characterization. At least two types of nongradient cysts were identified, one with characteristics consistent with proximal nephron origin and another apparently without function. These studies are the first direct evidence for active transport of cysts from human polycystic kidney and provide strong evidence to support the concept that cysts function in the same manner as the nephron segment of origin. PMID:4056045

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

    PubMed

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

    2009-10-01

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

  8. Dietary Fiber, Kidney Function, Inflammation, and Mortality Risk

    PubMed Central

    Xu, Hong; Huang, Xiaoyan; Risérus, Ulf; Krishnamurthy, Vidya M.; Cederholm, Tommy; Ärnlöv, Johan; Lindholm, Bengt; Sjögren, Per

    2014-01-01

    Background and objectives In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population. Design, setting, participants, & measurements Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70–71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991–1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years. Results Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m2 per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m2) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m2 (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01). Conclusions High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also

  9. Changes in kidney function among Nicaraguan sugarcane workers

    PubMed Central

    Laws, Rebecca L; Brooks, Daniel R; Amador, Juan José; Weiner, Daniel E; Kaufman, James S; Ramírez-Rubio, Oriana; Riefkohl, Alejandro; Scammell, Madeleine K; López-Pilarte, Damaris; Sánchez, José Marcel; Parikh, Chirag R; McClean, Michael D

    2015-01-01

    Background: There is an epidemic of chronic kidney disease (CKD) of unknown etiology in Central American workers. Objectives: To investigate changes and job-specific differences in kidney function over a 6-month sugarcane harvest season, explore the potential role of hydration, and measure proteinuria. Methods: We recruited 284 Nicaraguan sugarcane workers performing seven distinct tasks. We measured urine albumin and serum creatinine and estimated glomerular filtration rate (eGFR). Results: eGFR varied by job and decreased during the harvest in seed cutters (−8.6 ml/min/1.73 m2), irrigators (−7.4 ml/min/1.73 m2), and cane cutters (−5.0 ml/min/1.73 m2), as compared to factory workers. The number of years employed at the company was negatively associated with eGFR. Fewer than 5% of workers had albumin-to-creatinine ratio (ACR) >30 mg/g. Conclusions: The decline in kidney function during the harvest and the differences by job category and employment duration provide evidence that one or more risk factors of CKD are occupational. PMID:25631575

  10. Estimating Kidney Function in the Critically Ill Patients

    PubMed Central

    Seller-Pérez, Gemma; Herrera-Gutiérrez, Manuel E.; Maynar-Moliner, Javier; Sánchez-Izquierdo-Riera, José A.; do Pico, José Luis

    2013-01-01

    Glomerular filtration rate (GFR) is an accepted measure for assessment of kidney function. For the critically ill patient, creatinine clearance is the method of reference for the estimation of the GFR, although this is often not measured but estimated by equations (i.e., Cockroft-Gault or MDRD) not well suited for the critically ill patient. Functional evaluation of the kidney rests in serum creatinine (Crs) that is subjected to multiple external factors, especially relevant overhydration and loss of muscle mass. The laboratory method used introduces variations in Crs, an important fact considering that small increases in Crs have serious repercussion on the prognosis of patients. Efforts directed to stratify the risk of acute kidney injury (AKI) have crystallized in the RIFLE or AKIN systems, based in sequential changes in Crs or urine flow. These systems have provided a common definition of AKI and, due to their sensitivity, have meant a considerable advantage for the clinical practice but, on the other side, have introduced an uncertainty in clinical research because of potentially overestimating AKI incidence. Another significant drawback is the unavoidable period of time needed before a patient is classified, and this is perhaps the problem to be overcome in the near future. PMID:23862059

  11. History of fluid balance and kidney function in space.

    PubMed

    Drummer, Christian; Cirillo, Massimo; De Santo, Natale G

    2004-01-01

    During the last four decades, about 400 people have been in Space, since Yuri Gagarin was sent in 1961 as the first human into Earth orbit. From the very beginning, the circulatory system of astronauts (meaning heart, vascular system, body fluid distribution and balance, and the kidney) was central to the medical concerns of Space physiologists and physicians because of its gravity-dependence. The present manuscript puts emphasize on some key scientists who worked in the field of body fluid regulation and kidney function in the USA, in Russia and in Europe during recent decades. The manuscript in particular summarizes the outcome of this research and describes the present understanding of how the body fluid regulatory system adapts to the extreme environment of Space. PMID:15151277

  12. Tissue Kidney Injury Molecule-1 Expression in the Prediction of Renal Function for Several Years after Kidney Biopsy

    PubMed Central

    Simic Ogrizovic, Sanja; Basta-Jovanovic, Gordana; Radojevic, Sanja; Pavlovic, Jelena; Kotur Stevuljevic, Jelena; Dopsaj, Violeta; Naumovic, Radomir

    2013-01-01

    Objectives. Retrospective study was designed to examine the importance of tissue kidney injury molecule-1 (KIM-1) expression in predicting kidney function in sixty patients (27 males) aged 34.15 ± 12.23 years with different kidney diseases over three years after kidney biopsy. Materials and Methods. Tissue KIM-1 expression was determined immunohistochemically and KIM-1 staining was scored semiquantitatively, as well as tubulointerstitialis (TIN), inflammation, atrophy, and fibrosis. Kidney function (MDRD formula) and proteinuria/day were evaluated at the time of biopsy (GFR0) and 6, 12, 24, and 36 months later. Results. Significantly positive correlations between tissue KIM-1 expression and age (r = 0.313), TIN inflammation (r = 0.456), fibrosis (r = 0.317), and proteinuria at 6 months (r = 0.394) as well as negative correlations with GFR0 (r = −0.572), GFR6 (r = −0.442), GFR24 (r = −0.398), and GFR36 (r = −0.412) were found. Meanwhile, TIN inflammation was the best predictor of all measured kidney functions during three years, while tissue KIM-1 expression (P = 0.016) was a predictor only at 6 months after biopsy. Conclusion. Tissue KIM-1 expression significantly predicts kidney function solely at 6 months after biopsy, when the effects of immune and nonimmune treatments are the strongest. PMID:24282337

  13. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status

    PubMed Central

    Zhou, Hai Ying; Chen, Tian Wu; Zhang, Xiao Ming

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR) imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper. PMID:26925411

  14. Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.

    PubMed

    Mahajan, Anubha; Rodan, Aylin R; Le, Thu H; Gaulton, Kyle J; Haessler, Jeffrey; Stilp, Adrienne M; Kamatani, Yoichiro; Zhu, Gu; Sofer, Tamar; Puri, Sanjana; Schellinger, Jeffrey N; Chu, Pei-Lun; Cechova, Sylvia; van Zuydam, Natalie; Arnlov, Johan; Flessner, Michael F; Giedraitis, Vilmantas; Heath, Andrew C; Kubo, Michiaki; Larsson, Anders; Lindgren, Cecilia M; Madden, Pamela A F; Montgomery, Grant W; Papanicolaou, George J; Reiner, Alex P; Sundström, Johan; Thornton, Timothy A; Lind, Lars; Ingelsson, Erik; Cai, Jianwen; Martin, Nicholas G; Kooperberg, Charles; Matsuda, Koichi; Whitfield, John B; Okada, Yukinori; Laurie, Cathy C; Morris, Andrew P; Franceschini, Nora

    2016-09-01

    We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans. PMID:27588450

  15. 99Tcm-MAG3 renogram deconvolution in normal subjects and in normal functioning kidney grafts.

    PubMed

    González, A; Puchal, R; Bajén, M T; Mairal, L; Prat, L; Martin-Comin, J

    1994-09-01

    This study provides values of transit times obtained by 99Tcm- mercaptoacetyl triglycine (99Tcm-MAG3) renogram deconvolution for both normal subjects and kidney graft recipients. The analysis included 50 healthy kidney units from 25 volunteers and 28 normal functioning kidney grafts. The parameters calculated for the whole kidney (WK) and for the renal parenchyma (P) were: mean transit time (MTT) and times at 20% (T20) and 80% (T80) of renal retention function initial height. For healthy kidneys the WK MTT was 174 +/- 27 s and P MTT 148 +/- 22 s. The WK T20 values were 230 +/- 33 s and P T20 231 +/- 34 s. The WK T80 was 108 +/- 19 s and P T80 106 +/- 12 s. Whole kidney and parenchymal values of transit times for normal functioning kidney grafts do not present significant differences with respect to healthy kidneys. PMID:7816379

  16. Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

    PubMed Central

    Wang, Hao; Guan, Yuxia; Karamercan, Mehmet Akif; Ye, Lan; Bhatti, Tricia; Becker, Lance B.; Baur, Joseph A.; Sims, Carrie A.

    2015-01-01

    Objective Hemorrhagic shock may contribute to acute kidney injury by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin-1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Method Using a decompensated hemorrhagic shock model, male Long-Evans rats (n=6 per group) were sacrificed prior to hemorrhage (Sham), at severe shock, and following either lactated Ringer’s (LR) Resuscitation or LR+RSV Resuscitation (RSV: 30mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen (BUN) and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (CI, CII, and CIV) using high-resolution respirometry. Total mitochondria reactive oxygen species (ROS) were measured using fluorometry and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. qPCR was used quantify mRNA from PGC1-α, SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Results RSV supplementation during resuscitation restored mitochondrial respiratory capacity, decreased mitochondrial ROS and lipid peroxidation. Compared to standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both SOD2 and catalase expression. Although RSV was associated with decreased lactate production, pH, BUN and serum creatinine values did not differ between resuscitation strategies. Conclusions Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock. PMID:25895148

  17. Image Registration for Quantitative Analysis of Kidney Function using MRI

    NASA Astrophysics Data System (ADS)

    Sance, Rosario; Ledesma-Carbayo, María J.; Lundervold, Arvid; Santos, Andrés

    2006-10-01

    The aim of the present study is to analyze the possibilities of registration algorithms to compensate respiratory motion and deformation in abdominal DCE-MRI 3D temporary series. The final objective is that from registered data, appropriate intensity curves of local renal activity along the time could be represented for each kidney voxel. Assuming a relation between the voxel intensity and the contrast media concentration, this non-invasive renographic method could be used to evaluate the local renal function, and to calculate typical renal parameters like glomerular filtration rate.

  18. Elevated depressive affect is associated with adverse cardiovascular outcomes among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    This study was designed to examine the impact of elevated depressive affect on health outcomes among participants with hypertensive chronic kidney disease in the African-American Study of Kidney Disease and Hypertension (AASK) Cohort Study. Elevated depressive affect was defined by Beck Depression Inventory II (BDI-II) thresholds of 11 or more, above 14, and by 5-Unit increments in the score. Cox regression analyses were used to relate cardiovascular death/hospitalization, doubling of serum creatinine/end-stage renal disease, overall hospitalization, and all-cause death to depressive affect evaluated at baseline, the most recent annual visit (time-varying), or average from baseline to the most recent visit (cumulative). Among 628 participants at baseline, 42% had BDI-II scores of 11 or more and 26% had a score above 14. During a 5-year follow-up, the cumulative incidence of cardiovascular death/hospitalization was significantly greater for participants with baseline BDI-II scores of 11 or more compared with those with scores <11. The baseline, time-varying, and cumulative elevated depressive affect were each associated with a significant higher risk of cardiovascular death/hospitalization, especially with a time-varying BDI-II score over 14 (adjusted HR 1.63) but not with the other outcomes. Thus, elevated depressive affect is associated with unfavorable cardiovascular outcomes in African Americans with hypertensive chronic kidney disease. PMID:21633409

  19. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

    PubMed

    Mohamed, Fahim; Buckley, Nicholas A; Jayamanne, Shaluka; Pickering, John W; Peake, Philip; Palangasinghe, Chathura; Wijerathna, Thilini; Ratnayake, Indira; Shihana, Fathima; Endre, Zoltan H

    2015-09-01

    Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning. PMID:26071311

  20. Placebo Sleep Affects Cognitive Functioning

    ERIC Educational Resources Information Center

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  1. Kidney Function Can Improve in Patients with Hypertensive CKD

    PubMed Central

    Gadegbeku, Crystal; Lipkowitz, Michael S.; Rostand, Stephen; Lewis, Julia; Wright, Jackson T.; Appel, Lawrence J.; Greene, Tom; Gassman, Jennifer; Astor, Brad C.

    2012-01-01

    The typical assumption is that patients with CKD will have progressive nephropathy. Methodological issues, such as measurement error and regression to the mean, have made it difficult to document whether kidney function might improve in some patients. Here, we used data from 12 years of follow-up in the African American Study of Kidney Disease and Hypertension to determine whether some patients with CKD can experience a sustained improvement in GFR. We calculated estimated GFR (eGFR) based on serum creatinine measurements during both the trial and cohort phases. We defined clearly improved patients as those with positive eGFR slopes that we could not explain by random measurement variation under Bayesian mixed-effects models. Of 949 patients with at least three follow-up eGFR measurements, 31 (3.3%) demonstrated clearly positive eGFR slopes. The mean slope among these patients was +1.06 (0.12) ml/min per 1.73 m2 per yr, compared with −2.45 (0.07) ml/min per 1.73 m2 per yr among the remaining patients. During the trial phase, 24 (77%) of these 31 patients also had clearly positive slopes of 125I-iothalamate–measured GFR during the trial phase. Low levels of proteinuria at baseline and randomization to the lower BP goal (mean arterial pressure ≤92 mmHg) associated with improved eGFR. In conclusion, the extended follow-up from this study provides strong evidence that kidney function can improve in some patients with hypertensive CKD. PMID:22402803

  2. Smell and taste function in children with chronic kidney disease.

    PubMed

    Armstrong, Jessica E; Laing, David G; Wilkes, Fiona J; Kainer, Gad

    2010-08-01

    Loss of appetite and poor growth are common in children with chronic kidney disease (CKD), and changes in smell and/or taste function may be responsible, but the hypothesis has not been proven. This aims of this prospective age- and gender-controlled study were to determine whether: (1) changes in smell and taste function occur in children with CKD; (2) smell or taste dysfunction are associated with estimated glomerular filtration rate (eGFR); (3) there is an association between smell or taste loss and body mass index (BMI). The study cohort consisted of 72 children of whom 20 were CKD stage 3-5 patients, 12 were CKD stage 2 patients, 20 were clinical controls (CC) and 20 were healthy children (HC). The CKD patients and clinical controls were recruited from Sydney Children's Hospital and The Children's Hospital, Westmead, and healthy controls were recruited from a local school. Scores for each group from taste and smell chemosensory function tests were compared, and their relationship with renal function and BMI investigated. The CKD stage 3-5 group had a significantly lower taste identification score (85.6%, P < 0.001) than the CC (94.8%) and HC (94.8%) groups, with almost one third of the children in the CKD stage 3-5 group exhibiting taste loss. Decreased taste function was associated with decreased eGFR (r = 0.43, P < 0.01), but no association between BMI and taste function was found (r = 0.001, P > 0.9). Odour identification scores were not different; however, there was a positive relationship with BMI (r = 0.427, P = 0.006). We conclude that a loss of taste can occur in children with CKD and that when it occurs, it worsens as eGFR declines and is found early in kidney disease.

  3. Sociodemographic factors contribute to the depressive affect among African Americans with chronic kidney disease

    PubMed Central

    Fischer, Michael J.; Kimmel, Paul L.; Greene, Tom; Gassman, Jennifer J.; Wang, Xuelei; Brooks, Deborah H.; Charleston, Jeanne; Dowie, Donna; Thornley-Brown, Denyse; Cooper, Lisa A.; Bruce, Marino A.; Kusek, John W.; Norris, Keith C.; Lash, James P.

    2011-01-01

    Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score of 11.0 varied with the estimated glomerular filtration rate (eGFR) from 10.7 (eGFR 50–60) to 16.0 (eGFR stage 5); however, there was no significant independent association between these. Unemployment, low income, and lower quality and satisfaction with life scale scores were independently and significantly associated with a higher Beck Depression score. Thus, our study shows that an increased depressive affect is highly prevalent in African Americans with chronic kidney disease, is infrequently treated with antidepressants, and is associated with poorer quality of life. Sociodemographic factors have especially strong associations with this increased depressive affect. Because this study was conducted in an African-American cohort, its findings may not be generalized to other ethnic groups. PMID:20200503

  4. Mechanosensory function of microvilli of the kidney proximal tubule

    PubMed Central

    Du, Zhaopeng; Duan, Yi; Yan, QingShang; Weinstein, Alan M.; Weinbaum, Sheldon; Wang, Tong

    2004-01-01

    Normal variations in glomerular filtration induce proportional changes in proximal tubule Na+ reabsorption. This “glomerulotubular balance” derives from flow dependence of Na+ uptake across luminal cell membranes; however, the underlying physical mechanism is unknown. Our hypothesis is that flow-dependent reabsorption is an autoregulatory mechanism that is independent of neural and hormonal systems. It is signaled by the hydrodynamic torque (bending moment) on epithelial microvilli. Such signals need to be transmitted to the terminal web to modulate Na+-H+-exchange activity. To investigate this hypothesis, we examined Na+ transport and tubular diameter in response to different flow rates during the microperfusion of isolated S2 proximal tubules from mouse kidneys. The data were analyzed by using a mathematical model to estimate the microvillous torque as function of flow. In this model, increases in luminal diameter have the effect of blunting the impact of flow velocity on microvillous shear stress and, thus, microvillous torque. We found that variations in microvillous torque produce nearly identical fractional changes in Na+ reabsorption. Furthermore, the flow-dependent Na+ transport is increased by increasing luminal fluid viscosity, diminished in Na+-H+ exchanger isoform 3 knockout mice, and abolished by nontoxic disruption of the actin cytoskeleton. These data support our hypothesis that the “brush-border” microvilli serve a mechanosensory function in which fluid dynamic torque is transmitted to the actin cytoskeleton and modulates Na+ absorption in kidney proximal tubules. PMID:15319475

  5. Pretransplant transcriptome profiles identify among kidneys with delayed graft function those with poorer quality and outcome.

    PubMed

    Mas, Valeria R; Scian, Mariano J; Archer, Kellie J; Suh, Jihee L; David, Krystle G; Ren, Qing; Gehr, Todd W B; King, Anne L; Posner, Marc P; Mueller, Thomas F; Maluf, Daniel G

    2011-01-01

    Robust biomarkers are needed to identify donor kidneys with poor quality associated with inferior early and longer-term outcome. The occurrence of delayed graft function (DGF) is most often used as a clinical outcome marker to capture poor kidney quality. Gene expression profiles of 92 preimplantation biopsies were evaluated in relation to DGF and estimated glomerular filtration rate (eGFR) to identify preoperative gene transcript changes associated with short-term function. Patients were stratified into those who required dialysis during the first week (DGF group) versus those without (noDGF group) and subclassified according to 1-month eGFR of >45 mL/min (eGFR(hi)) versus eGFR of ≤45 mL/min (eGFR(lo)). The groups and subgroups were compared in relation to clinical donor and recipient variables and transcriptome-associated biological pathways. A validation set was used to confirm target genes. Donor and recipient characteristics were similar between the DGF versus noDGF groups. A total of 206 probe sets were significant between groups (P < 0.01), but the gene functional analyses failed to identify any significantly affected pathways. However, the subclassification of the DGF and noDGF groups identified 283 probe sets to be significant among groups and associated with biological pathways. Kidneys that developed postoperative DGF and sustained an impaired 1-month function (DGF(lo) group) showed a transcriptome profile of significant immune activation already preimplant. In addition, these kidneys maintained a poorer transplant function throughout the first-year posttransplant. In conclusion, DGF is a poor marker for organ quality and transplant outcome. In contrast, preimplant gene expression profiles identify "poor quality" grafts and may eventually improve organ allocation.

  6. Urinary uromodulin, kidney function and cardiovascular disease in elderly adults

    PubMed Central

    Garimella, Pranav S.; Biggs, Mary L.; Katz, Ronit; Ix, Joachim H.; Bennett, Michael R.; Devarajan, Prasad; Kestenbaum, Bryan R.; Siscovick, David S.; Jensen, Majken K.; Shlipak, Michael G.; Chaves, Paulo H. M.; Sarnak, Mark J.

    2015-01-01

    Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end stage renal disease (ESRD), and in a random sub-cohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/mL. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each standard deviation higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77, (95% CI 0.62, 0.96)) and a 10% lower risk of mortality (hazard ratio 0.90, (95% CI 0.83, 0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function. PMID:26154925

  7. Kidney Disease

    MedlinePlus

    ... version of this page please turn Javascript on. Kidney Disease What is Kidney Disease? What the Kidneys Do Click for more information You have two ... damaged, wastes can build up in the body. Kidney Function and Aging Kidney function may be reduced ...

  8. MAGI-2 scaffold protein is critical for kidney barrier function.

    PubMed

    Balbas, Minna D; Burgess, Michael R; Murali, Rajmohan; Wongvipat, John; Skaggs, Brian J; Mundel, Peter; Weins, Astrid; Sawyers, Charles L

    2014-10-14

    MAGUK Inverted 2 (MAGI-2) is a PTEN-interacting scaffold protein implicated in cancer on the basis of rare, recurrent genomic translocations and deletions in various tumors. In the renal glomerulus, MAGI-2 is exclusively expressed in podocytes, specialized cells forming part of the glomerular filter, where it interacts with the slit diaphragm protein nephrin. To further explore MAGI-2 function, we generated Magi-2-KO mice through homologous recombination by targeting an exon common to all three alternative splice variants. Magi-2 null mice presented with progressive proteinuria as early as 2 wk postnatally, which coincided with loss of nephrin expression in the glomeruli. Magi-2-null kidneys revealed diffuse podocyte foot process effacement and focal podocyte hypertrophy by 3 wk of age, as well as progressive podocyte loss. By 5.5 wk, coinciding with a near-complete loss of podocytes, Magi-2-null mice developed diffuse glomerular extracapillary epithelial cell proliferations, and died of renal failure by 3 mo of age. As confirmed by immunohistochemical analysis, the proliferative cell populations in glomerular lesions were exclusively composed of activated parietal epithelial cells (PECs). Our results reveal that MAGI-2 is required for the integrity of the kidney filter and podocyte survival. Moreover, we demonstrate that PECs can be activated to form glomerular lesions resembling a noninflammatory glomerulopathy with extensive extracapillary proliferation, sometimes resembling crescents, following rapid and severe podocyte loss.

  9. Influence of the kidney histology at the time of donation on long term kidney function in living kidney donors.

    PubMed

    Goecke, H; Ortiz, A M; Troncoso, P; Martinez, L; Jara, A; Valdes, G; Rosenberg, H

    2005-10-01

    Living donation is the best choice for kidney transplantation, obtaining long-lasting good results for the recipient. Some concern still remains regarding the donor's long-term health. Kidney biopsy was routinely performed in our donor population at the time of donation many years ago. We found the existence of morphological kidney disease in those samples, in spite of normal clinical evaluations before donation. We attempted to correlate those abnormalities with long-term clinical outcomes. Donors were at least 10 years after surgery. A medical interview, including the SF-36 Health Survey, laboratory evaluation, and ambulatory blood pressure monitoring was performed on 27 donors meeting the inclusion criteria. Two donors had died after donation from unrelated causes with no known nephropathy. Histological analysis showed abnormalities in 16 of 29 donors. We found an increased prevalence of hypertension compared to the general population. Interestingly, there was no proteinuria in the donor population, and none developed clinical nephropathy. All subjects felt emotionally rewarded with donation, stating that their lives had no limitations. Our results suggest that kidney biopsy is neither necessary nor useful prior to donation because, although many donors had morphological kidney disease, none developed clinical nephropathy in the long term.

  10. The Association Between Periodontal Disease and Kidney Function Decline in African Americans: The Jackson Heart Study

    PubMed Central

    Grubbs, Vanessa; Vittinghoff, Eric; Beck, James D.; Kshirsagar, Abhijit V.; Wang, Wei; Griswold, Michael E.; Powe, Neil R.; Correa, Adolfo; Young, Bessie

    2015-01-01

    Background Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects African Americans, despite intense efforts targeting traditional risk factors. Periodontal disease, a chronic bacterial infection of the oral cavity, is both common and modifiable and has been implicated as a novel potential CKD risk factor. We sought to examine to what extent periodontal disease is associated with kidney function decline. Methods Retrospective cohort study of 699 African American participants with preserved kidney function defined by an estimated glomerular filtration rate (eGFR) >60ml/min/1.73m2 at baseline who underwent complete dental examinations as part of the Dental-Atherosclerosis Risk in Communities study (1996–1998) and subsequently enrolled in the Jackson Heart Study (2000–2004). Using multivariable Poisson regression we examined the association of periodontal disease (severe vs. non-severe) with incident CKD defined as incident eGFR<60ml/min/1.73m2 and rapid (5% annualized) eGFR decline at follow-up among those with preserved eGFR at baseline. Results Mean age at baseline was 65.4 years (SD 5.2) and 16.3% (n=114) had severe periodontal disease. There were 21 cases (3.0%) of incident CKD after a mean follow-up of 4.8 (SD 0.6) years. Compared to participants with non-severe periodontal disease, those with severe periodontal disease had a 4-fold greater rate of incident CKD [adjusted incidence rate ratio 4.18, 95% CI (1.68 – 10.39), p=0.002]. Conclusion Severe periodontal disease is prevalent among a population at high-risk for CKD and is associated with clinically significant kidney function decline. Further research is needed to determine if periodontal disease treatment alters the trajectory of renal deterioration. PMID:26110451

  11. [Considerations when using creatinine as a measure of kidney function].

    PubMed

    Drion, I Iefke; Fokkert, M J Marion; Bilo, H J G Henk

    2013-01-01

    Reported serum creatinine concentrations can sometimes vary considerably, even when the renal function does less so or even not. This variation is partly due to true changes in actual serum concentration, and partly due to interferences in the measurement technique, thus not reflecting a true change in concentration. Increased or decreased endogenous creatinine production, ingested creatinine sources through meat eating or certain creatine formulations, and interference by either browning of chromogenic substances in Jaffe measurement techniques or promotors and inhibitors of enzymatic reaction methods do play a role. Reliable serum creatinine measurements are needed for renal function estimating equations. In screening circumstances and daily practice, chronic kidney disease staging is based on these estimated glomerular filtration rate values. Given the possible influences on reported serum creatinine concentrations, it is important for health care workers to remain critical when interpreting outcomes of renal function estimating equations and to not see every reported result based on an equation as a true reflection of renal function. PMID:24330793

  12. Emerging role of autophagy in kidney function, diseases and aging.

    PubMed

    Huber, Tobias B; Edelstein, Charles L; Hartleben, Björn; Inoki, Ken; Jiang, Man; Koya, Daisuke; Kume, Shinji; Lieberthal, Wilfred; Pallet, Nicolas; Quiroga, Alejandro; Ravichandran, Kameswaran; Susztak, Katalin; Yoshida, Sei; Dong, Zheng

    2012-07-01

    Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy. PMID:22692002

  13. Primary Squamous Cell Carcinoma of Kidney Associated With Large Calculus in Non-functioning Kidney: A Case Report.

    PubMed

    Kumar, Sanjay; Tomar, Vinay; Yadav, Sher S; Udawat, Hema; Priyadarshi, Shivam; Vyas, Nachiket; Agarwal, Neeraj

    2016-09-01

    Primary squamous cell carcinoma (SCC) of renal pelvis is a rare neoplasm. A 75-year old male presented with history of chronic dull aching pain in left flank region for last 10-years with history of left pyelolithotomy about 30-years back. After proper workup, large calculus with heterogeneous density mass detected in nonfunctioning left kidney. After radical nephrectomy, histopathological examination revealed squamous cell carcinoma of renal pelvis. SCC should be suspected in a patient with long history of renal calculous and associated mass in non functioning kidney. PMID:27313983

  14. Renal artery stent in solitary functioning kidneys: 77% of benefit

    PubMed Central

    Ma, Zhenjiang; Liu, Liangshuai; Zhang, Bing; Chen, Wei; Yang, Jianyong; Li, Heping

    2016-01-01

    Abstract Background: Solitary functioning kidney (SFK) is tough issue to address in clinical, mostly developed from renal artery stenosis (RAS) in adults. Although renal artery stent is widely used to help SFK patients, the efficacy of the stent is still disputable. This study is aimed at reviewing a series of SFK cases to draw a conclusion about the efficacy of renal artery stent. Methods: All related papers published in PubMed, Web of Science, EMBASE, and Cochrane Library were searched. Studies or subsets were included only if they satisfied certain criteria. The benefit rate which equaled the rate of improvement subjoining the rate of stabilization was calculated. All analyses were conducted with Stata version 12.0 (Stata Corporation, College Station, TX). Results: According to 7 papers on the efficacy of renal artery stent, 253 SFK patients were included. The result revealed that the renal artery stent could help SFK patients to improve or stabilize their renal function (RF). The benefit rate was 0.77, with 95% confidence interval between 0.72 and 0.83. Conclusions: With proper patient selection, renal artery stent could benefit SFK patients with a percentage odd of 0.77 to improve or stabilize the RF. PMID:27603380

  15. Measuring dynamic kidney function in an undergraduate physiology laboratory.

    PubMed

    Medler, Scott; Harrington, Frederick

    2013-12-01

    Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on a "dipstick" approach of urinalysis. Although this technique can provide some basic insights into the functioning of the kidneys, it overlooks the dynamic processes of filtration, reabsorption, and secretion. In the present article, we provide a straightforward approach of using renal clearance measurements to estimate glomerular filtration rate, fractional water reabsorption, glucose clearance, and other physiologically relevant parameters. The estimated values from our measurements in laboratory are in close agreement with those anticipated based on textbook parameters. For example, we found glomerular filtration rate to average 124 ± 45 ml/min, serum creatinine to be 1.23 ± 0.4 mg/dl, and fractional water reabsorption to be ∼96.8%. Furthermore, analyses for the class data revealed significant correlations between parameters like fractional water reabsorption and urine concentration, providing opportunities to discuss urine concentrating mechanisms and other physiological processes. The procedures outlined here are general enough that most undergraduate physiology laboratory courses should be able to implement them without difficulty. PMID:24292917

  16. Paricalcitol and endothelial function in chronic kidney disease trial.

    PubMed

    Zoccali, Carmine; Curatola, Giuseppe; Panuccio, Vincenzo; Tripepi, Rocco; Pizzini, Patrizia; Versace, Marica; Bolignano, Davide; Cutrupi, Sebastiano; Politi, Raffaele; Tripepi, Giovanni; Ghiadoni, Lorenzo; Thadhani, Ravi; Mallamaci, Francesca

    2014-11-01

    Altered vitamin D metabolism and low levels of the active form of this vitamin, 1,25-dihydroxy-vitamin D, is a hallmark of chronic kidney disease (CKD), but there is still no randomized controlled trial testing the effect of active forms of vitamin D on vascular function in patients with CKD. Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY) is a double-blinded randomized controlled trial (ClinicalTrials.gov, NCT01680198) testing the effect of an active form of vitamin D, paricalcitol (2 μg/d×12 weeks) on endothelium-dependent and endothelium-independent vasodilatation in 88 patients with stage 3 to 4 CKD and parathormone >65 pg/mL (paricalcitol, n=44; placebo, n=44). Paricalcitol treatment reduced parathormone (-75 pg/mL; 95% confidence interval, -90 to -60), whereas parathormone showed a small rise during placebo (21 pg/mL; 95% confidence interval, 5-36). Blood pressure did not change in both study arms. Baseline flow-mediated dilation was identical in patients on paricalcitol (3.6±2.9%) and placebo (3.6±2.9%) groups. After 12 weeks of treatment, flow-mediated dilation rose in the paricalcitol but not in the placebo group, and the between-group difference in flow-mediated dilation changes (the primary end point, 1.8%; 95% confidence interval, 0.3-3.1%) was significant (P=0.016), and the mean proportional change in flow-mediated dilation was 61% higher in paricalcitol-treated patients than in placebo-treated patients. Such an effect was abolished 2 weeks after stopping the treatment. No effect of paricalcitol on endothelium-independent vasodilatation was registered. Paricalcitol improves endothelium-dependent vasodilatation in patients with stage 3 to 4 CKD. Findings in this study support the hypothesis that vitamin D may exert favorable effects on the cardiovascular system in patients with CKD.

  17. The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

    PubMed Central

    Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner

    2014-01-01

    The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies. PMID:25340655

  18. The tacrolimus metabolism rate influences renal function after kidney transplantation.

    PubMed

    Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner; Reuter, Stefan; Suwelack, Barbara

    2014-01-01

    The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient's risk management strategies. PMID:25340655

  19. Cross-sectional survey of kidney function in refinery employees

    SciTech Connect

    Viau, C.; Bernard, A.; Lauwerys, R.; Buchet, J.P.; Quaeghebeur, L.; Cornu, M.E.; Phillips, S.C.; Mutti, A.; Lucertini, S.; Franchini, I.

    1987-01-01

    We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

  20. The regulation and function of microRNAs in kidney diseases

    PubMed Central

    Wei, Qingqing; Mi, Qing-Sheng; Dong, Zheng

    2013-01-01

    MicroRNAs (miRNA) are endogenous short non-coding RNAs which regulate virtually all major cellular processes by inhibiting target gene expression. In kidneys, miRNAs have been implicated in renal development, homeostasis and physiological functions. In addition, miRNAs play important roles in the pathogenesis of various renal diseases, including renal carcinoma, diabetic nephropathy, acute kidney injury, hypertensive nephropathy, polycystic kidney disease and others. Furthermore, miRNAs may have great values as biomarkers in different kidney diseases. PMID:23794512

  1. The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli.

    PubMed

    Glassock, Richard J; Rule, Andrew D

    2012-08-01

    Aging is both a natural and inevitable biological process. With advancing age, the kidneys undergo anatomical and physiological changes that are not only the consequences of normal organ senescence but also of specific diseases (such as atherosclerosis or diabetes) that occur with greater frequency in older individuals. Disentangling these two processes, one pathologic and the other physiologic, is difficult. In this review we concentrate on the glomerular structural and functional alterations that accompany natural aging. We also analyze how these changes affect the identification of individuals of advancing age as having chronic kidney disease (CKD) and how these changes can influence prognosis for adverse outcomes, including all-cause mortality, end-stage renal disease, cardiovascular events and mortality, and acute kidney injury. This review describes important shortcomings and deficiencies with our current approach and understanding of CKD in the older and elderly adult.

  2. The associations of physical activity and television watching with change in kidney function in older adults

    PubMed Central

    Hawkins, Marquis; Newman, Anne B.; Madero, Magdalena; Patel, Kushang V.; Shlipak, Michael G.; Cooper, Jennifer; Johansen, Kirsten L.; Navaneethan, Sankar D.; Fried, Linda F

    2015-01-01

    BACKGROUND Physical activity (PA) may play a role in preserving kidney health. The purpose of this study was to determine if PA and sedentary behavior are associated with incident chronic kidney disease (CKD) and change in kidney function in older adults. METHODS The Health, Aging and Body Composition study is a prospective cohort of 3,075 well-functioning older adults. PA and television watching was measured by self-report and serum cystatin C was used to estimate glomerular filtration rate (eGFR). CKD was defined as an eGFR <60 ml/min/1.73m2. Rapid kidney function decline was defined as an annual loss in eGFR of >3ml/min/1.73m2. Discrete survival analysis was used to determine if baseline PA and television watching were related to 10-year cumulative incidence of CKD and rapid decline in kidney function. RESULTS Individuals who reported watching television >3 hours/day had a higher risk of incident CKD (HR 1.34; 95% CI: 1.09, 1.65) and experiencing a rapid decline in kidney function (HR 1.26; 95% CI 1.05, 1.52) compared to individuals who watched television < 2 hours/day. PA was not related to either outcome. CONCLUSIONS High levels of television watching are associated with declining kidney function; the mechanisms that underlie this association need further study. PMID:24762526

  3. Awareness level of kidney functions and diseases among adults in a Nigerian population.

    PubMed

    Okwuonu, C G; Chukwuonye, I I; Ogah, S O; Abali, C; Adejumo, O A; Oviasu, E

    2015-01-01

    The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher - administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18-78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria.

  4. Evaluation of factors associated with cadmium exposure and kidney function in the general population.

    PubMed

    Huang, Mingai; Choi, Seong-Jin; Kim, Dong-Won; Kim, Na-Young; Bae, Hye-Sun; Yu, Seung-Do; Kim, Dae-Seon; Kim, Heon; Choi, Byung-Sun; Yu, Il-Je; Park, Jung-Duck

    2013-10-01

    Cadmium (Cd) is a nonessential toxic metal which is widely distributed in the environment. The general population is exposed to low levels of Cd and the kidney is the organ most sensitive to Cd toxicity. This study was performed to simultaneously evaluate Cd exposure, kidney function, and oxidative stress biomarkers in the general population. A total of 643 adults were interviewed to document demographic characteristics, lifestyles, past-medical history, and diet during the last 24 h. We estimated daily Cd intake based on the diet of study subjects who had not been exposed to Cd occupationally. Whole blood and urine samples were collected and analyzed to determine Cd concentrations and kidney function indices (β₂ -microglobulin [β₂-MG], N-acetyl-β-D-glucosaminidase [NAG], metallothionein [MT]). The oxidative stress index (malondialdehyde [MDA]) was determined from the urine. The daily Cd intake from diet was established as 7.07 μg/day. The mean concentration of Cd measured in the blood was 1.22 μg/L and urine was 0.95 μg/g creatinine. The concentrations of Cd in blood and urine were higher in females than in males. The blood levels of Cd were affected by sex, age, and smoking, and urine Cd was influenced by sex, age, and blood Cd. The urine Cd was positively correlated with MT, NAG activity, and MDA in females, but with NAG only in males. The blood Cd was associated with MT in males. Increased NAG activity was observed when Cd in urine reached 1.0 μg Cd/g creatinine and was also affected by age, hypertension, and diabetes mellitus. Urinary MT only responded to Cd in urine or blood. In summary, exposure to Cd in the general population was influenced by various factors including sex, age, and smoking habits. Such exposure might eventually cause tubular damage in the kidneys through the oxidative stress mechanism, and females might be more susceptible than males to Cd exposure under the environment.

  5. Effect of radiation processing on nutritional, functional, sensory and antioxidant properties of red kidney beans

    NASA Astrophysics Data System (ADS)

    Marathe, S. A.; Deshpande, R.; Khamesra, Arohi; Ibrahim, Geeta; Jamdar, Sahayog N.

    2016-08-01

    In the present study dry red kidney beans (Phaseolus vulgaris), irradiated in the dose range of 0.25-10.0 kGy were evaluated for proximate composition, functional, sensory and antioxidant properties. Radiation processing up to 10 kGy did not affect proximate composition, hydration capacity and free fatty acid value. All the sensory attributes were unaffected at 1.0 kGy dose. The dose of 10 kGy, showed lower values for odor and taste, however, they were in acceptable range. Significant improvement in textural quality and reduction in cooking time was observed at dose of 10 kGy. Antioxidant activity of radiation processed samples was also assessed after normal processing such as soaking and pressure cooking. Both phenolic content and antioxidant activity evaluated in terms of DPPH free radical scavenging assay and inhibition in lipid peroxidation using rabbit erythrocyte ghost system, were marginally improved (5-10%) at the dose of 10 kGy in dry and cooked samples. During storage of samples for six months, no significant change was observed in sensory, cooking and antioxidant properties. Thus, radiation treatment of 1 kGy can be applied to get extended shelf life of kidney beans with improved functional properties without impairing bioactivity; nutritional quality and sensory property.

  6. Duration of chronic kidney disease reduces attention and executive function in pediatric patients

    PubMed Central

    Mendley, Susan R.; Matheson, Matthew; Shinnar, Shlomo; Lande, Marc; Gerson, Arlene C.; Butler, Robert; Warady, Bradley A.; Furth, Susan L.; Hooper, Stephen R.

    2014-01-01

    Chronic kidney disease (CKD) in childhood is associated with neurocognitive deficits. Affected children show worse performance on tests of intelligence than their unaffected siblings and skew toward the lower end of the normal range. Here we further assessed this association in 340 pediatric patients (ages 6 to 21) with mild-moderate CKD in The Chronic Kidney Disease in Childhood cohort from 48 pediatric centers in North America. Participants underwent a battery of age-appropriate tests including Conner’s Continuous Performance Test-II (CPT-II), Delis- Kaplan Executive Function System Tower task, and the Digit Span Backwards task from the age-appropriate Wechsler Intelligence Scale. Test performance was compared across the range of estimated GFR and duration of CKD with relevant covariates including maternal education, household income, IQ, blood pressure and preterm birth. Among the 340 patients, 35% had poor performance (below the mean by1.5 or more standard deviations) on at least one test of executive function. By univariate nonparametric comparison and multiple logistic regression, longer duration of CKD was associated with increased odds ratio for poor performance on the CPT-II Errors of Commission, a test of attention regulation and inhibitory control. Thus, in a population with mild to moderate CKD, the duration of disease rather than estimated GFR was associated with impaired attention regulation and inhibitory control. PMID:25252026

  7. A Teaching Aid for Physiologists--Simulation of Kidney Function

    ERIC Educational Resources Information Center

    Packer, J. S.; Packer, J. E.

    1977-01-01

    Presented is the development of a simulation model of the facultative water transfer mechanism of the mammalian kidney. Discussion topics include simulation philosophy, simulation facilities, the model, and programming the model as a teaching aid. Graphs illustrate typical program displays. A listing of references concludes the article. (MA)

  8. Failure to visualize acutely injured kidneys with technetium-99m DMSA does not preclude recoverable function

    SciTech Connect

    Taylor, A. Jr.; Akiya, F.; Gregory, M.C.

    1986-03-01

    A 35-yr-old patient developed severe acute tubular necrosis requiring hemodialysis. A (99mTc)dimercaptosuccinic acid scan of the kidneys showed no renal uptake at 4 or 24 hr, but the patient subsequently recovered normal renal function as judged by a normal serum creatinine. Based on this case report and a review of the literature, one cannot assume irreversible loss of function in patients with acute renal failure, based on the absence of radiopharmaceutical uptake by the kidneys.

  9. Diving into the abyss of undiscovered kidney function-related factors.

    PubMed

    Limou, Sophie; Parsa, Afshin

    2016-10-01

    Meta-analyses and reintroduction of biological knowledge are 2 classic strategies to increase genomewide association study statistical power and overcome the burden of multiple testing. These strategies have empowered the nephrology community to discover new signals associated with kidney function and nephropathies. Here we discuss the current genomewide association study limitations and strategies to dive further into the abyss of yet-to-be discovered kidney function-related factors. PMID:27633863

  10. Molecular anatomy of the kidney: what have we learned from gene expression and functional genomics?

    PubMed Central

    Rumballe, Bree; Georgas, Kylie; Wilkinson, Lorine

    2011-01-01

    The discipline of paediatric nephrology encompasses the congenital nephritic syndromes, renal dysplasias, neonatal renal tumours, early onset cystic disease, tubulopathies and vesicoureteric reflux, all of which arise due to defects in normal kidney development. Indeed, congenital anomalies of the kidney and urinary tract (CAKUT) represent 20–30% of prenatal anomalies, occurring in 1 in 500 births. Developmental biologists have studied the anatomical and morphogenetic processes involved in kidney development for the last five decades. However, with the advent of transgenic mice, the sequencing of the genome, improvements in mutation detection and the advent of functional genomics, our understanding of the molecular basis of kidney development has grown significantly. Here we discuss how the advent of new genetic and genomics approaches has added to our understanding of kidney development and paediatric renal disease, as well as identifying areas in which we are still lacking knowledge. PMID:20049614

  11. Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective.

    PubMed

    Al Otaibi, Torki; Ahmadpoor, Pedram; Allawi, Ali Abdulmajid Dyab; Habhab, Wael Taher; Khatami, Mohammad Reza; Nafar, Mohsen; Glotz, Denis

    2016-02-01

    With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question.

  12. Renal ultrasonographic and computed tomographic appearance, volume, and function of cats with autosomal dominant polycystic kidney disease.

    PubMed

    Reichle, Jean K; DiBartola, Stephen P; Léveillé, Renée

    2002-01-01

    The purpose of this study was to describe the ultrasonographic (US) and computed tomographic (CT) appearance of autosomal dominant polycystic kidney disease (ADPKD) in cats; to compare renal volume in cats with ADPKD (n = 5; mean age 59 +/- 10 months)) and normal cats (n = 5; mean age 66 +/- 10 months) using 2 imaging modalities, US and CT; and to calculate cyst volume using CT. Glomerular filtration rate (GFR) was determined by 2 methods: 99mTc-diethylene-triaminepentaacetic acid (99mTc-DPTA) scintigraphic uptake and 99-Tc-DTPA plasma clearance. Sonographically, ADPKD affected kidneys were characterized by multiple anechoic to hypoechoic, round to irregularly shaped structures with variation in size. Affected kidneys had indistinct corticomedullary junctions and foci of mineralization. Intravenous (IV) contrast medium administration allowed more definitive identification of cysts with CT, and identification of distortion of renal pelves by cysts. A significant difference (Welch ANOVA, P = 0.05) was detected between the US-estimated renal volumes of normal and affected cats. No statistically significant differences were detected in CT volume (between the normal and affected cats, or between US and CT volume measurements) or the 2 GFR methods. In this group of clinically normal, middle-aged ADPKD cats, renal function was within normal limits and not significantly different than normal. PMID:12175002

  13. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    PubMed

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  14. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy

    PubMed Central

    Kelly, K. J.; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Dominguez, Jesus H.

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA. PMID:26136112

  15. Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

    SciTech Connect

    Skröder, Helena; Hawkesworth, Sophie; Kippler, Maria; El Arifeen, Shams; Wagatsuma, Yukiko; Moore, Sophie E.; Vahter, Marie

    2015-07-15

    Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4–5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water was assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m{sup 2}, corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=−2.8; 95% CI: −5.5, −0.20; p=0.035), compared to those with higher selenium (B=−0.79; 95% CI: −3.0, 1.4; p=0.49). Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young children

  16. Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate.

    PubMed

    Smith, D F; Schou, M

    1979-03-01

    A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg-1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients. PMID:34690

  17. Associations of Perfusate Biomarkers and Pump Parameters With Delayed Graft Function and Deceased Donor Kidney Allograft Function.

    PubMed

    Parikh, C R; Hall, I E; Bhangoo, R S; Ficek, J; Abt, P L; Thiessen-Philbrook, H; Lin, H; Bimali, M; Murray, P T; Rao, V; Schröppel, B; Doshi, M D; Weng, F L; Reese, P P

    2016-05-01

    Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule 1, IL-18 and liver-type fatty acid-binding protein [L-FABP]) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6-mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1-h flow was inversely associated with DGF. Higher NGAL or L-FABP concentrations and increased resistance were inversely associated with 6-mo eGFR, whereas higher flow was associated with higher adjusted 6-mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated "undesirable" biomarker levels or HMP parameters experienced acceptable 6-mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality. PMID:26695524

  18. Monitoring the Intracellular Tacrolimus Concentration in Kidney Transplant Recipients with Stable Graft Function.

    PubMed

    Han, Seung Seok; Yang, Seung Hee; Kim, Min Chang; Cho, Joo-Youn; Min, Sang-Il; Lee, Jung Pyo; Kim, Dong Ki; Ha, Jongwon; Kim, Yon Su

    2016-01-01

    Although monitoring the intracellular concentration of immunosuppressive agents may be a promising approach to individualizing the therapy after organ transplantation, additional studies on this issue are needed prior to its clinical approval. We investigated the relationship between intracellular and whole blood concentrations of tacrolimus (IC-TAC and WB-TAC, respectively), the factors affecting this relationship, and the risk of rejection based upon IC-TAC in stable kidney recipients. Both IC-TAC and WB-TAC were measured simultaneously in 213 kidney recipients with stable graft function using LC-MS/MS. The tacrolimus ratio was defined as IC-TAC per WB-TAC. The genetic polymorphism of ABCB1 gene and flow cytometric analyses were conducted to probe the correlation between tacrolimus concentrations and the immunoreactivity status as a potential risk of rejection, respectively. The correlation between IC-TAC and WB-TAC was relatively linear (r = 0.67; P<0.001). The factors affecting the tacrolimus ratio were sex, hematocrit, and the transplant duration, as follows: a high tacrolimus ratio was noted in female patients, patients with a low hematocrit, and patients with a short transplant period. However, the tacrolimus ratio did not reflect the prior clinical outcomes (e.g., rejection) or the genetic polymorphism of ABCB1. After stimulation with phorbol-12-myristate 13-acetate and ionomycin, the proportion of T cells producing interferon-gamma or interleukin-2 was higher in the low-IC-TAC group than in the high-IC-TAC group. Further studies are required to evaluate the value of the intracellular tacrolimus concentrations in several clinical settings, such as rejection, infection, and drug toxicity.

  19. Essential function of Wnt-4 for tubulogenesis in the Xenopus pronephric kidney.

    PubMed

    Saulnier, Didier M E; Ghanbari, Hedyeh; Brändli, André W

    2002-08-01

    In the vertebrate embryo, development of the excretory system is characterized by the successive formation of three distinct kidneys: the pronephros, mesonephros, and metanephros. While tubulogenesis in the metanephric kidney is critically dependent on the signaling molecule Wnt-4, it is unknown whether Wnt signaling is equally required for the formation of renal epithelia in the other embryonic kidney forms. We therefore investigated the expression of Wnt genes during the pronephric kidney development in Xenopus. Wnt4 was found to be associated with developing pronephric tubules, but was absent from the pronephric duct. Onset of pronephric Wnt-4 expression coincided with mesenchyme-to-epithelium transformation. To investigate Wnt-4 gene function, we performed gain- and loss-of-function experiments. Misexpression of Wnt4 in the intermediate and lateral mesoderm caused abnormal morphogenesis of the pronephric tubules, but was not sufficient to initiate ectopic tubule formation. We used a morpholino antisense oligonucleotide-based gene knockdown strategy to disrupt Wnt-4 gene function. Xenopus embryos injected with antisense Wnt-4 morpholinos developed normally, but marker gene and morphological analysis revealed a complete absence of pronephric tubules. Pronephric duct development was largely unaffected, indicating that ductogenesis may occur normally in the absence of pronephric tubules. Our results show that, as in the metanephric kidney, Wnt-4 is critically required for tubulogenesis in the pronephric kidney, indicating that a common, evolutionary conserved gene regulatory network may control tubulogenesis in different vertebrate excretory organs. PMID:12142017

  20. Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats.

    PubMed

    Amin, Kamal A; Al-muzafar, Hessa M; Abd Elsttar, Adel H

    2016-01-01

    Food additives while attract consumers, improve quality, control weight and replace sugar, may affect seriously children and adults health. Here, we investigated the adverse effects of saccharin and methylsalicyltaes as sweetener and flavoring agent on lipid profile, blood glucose, renal, hepatic function and oxidative stress/antioxidants (lipid peroxidation, catalase and reduced glutathione in liver tissues). Saccharin and methylsalicylate were administered orally in young male albino rats at low and high dose for 30 days. Rats were divided into 5 groups, 1st control group, 2nd and 3rd (low and high saccharin-treated groups) and 4th and 5th (low and high methylsalicylate-treated group). Serum total cholesterol, triglyceride, glucose levels and body weight gain were found decreased in saccharin high dose group compared to control. Rats consumed high dose of saccharin showed a significant decrease in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Further, saccharin at high dose induced significant decrease in liver GSH levels, catalase and SOD activity and increase in hepatic MDA level. Overall saccharin harmfully altered biochemical markers in liver and kidney at higher as well as lower doses. Whereas, methyl salicylates did not pose a risk for renal function and hepatic oxidative markers. PMID:26891553

  1. Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function

    PubMed Central

    Kamińska, Dorota; Kościelska-Kasprzak, Katarzyna; Chudoba, Paweł; Mazanowska, Oktawia; Banasik, Mirosław; Żabinska, Marcelina; Boratyńska, Maria; Lepiesza, Agnieszka; Gomółkiewicz, Agnieszka; Dzięgiel, Piotr; Klinger, Marian

    2016-01-01

    Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan). Results. Immediate posttransplant graft function (14-day GFR) was influenced negatively by TGFB1 (P = 0.039) and positively by IL-2 gene expression (P = 0.040). Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18) and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P = 0.027, FAS: P = 0.021, and IFNG: P = 0.029) and long-term graft function (24-month GFR CASP3: P = 0.003, FAS: P = 0.033, IL-18: P = 0.044, and IFNG: P = 0.04). Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes' expression in the recipients' peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function. PMID:27382192

  2. Incidence of renal carcinoma in non-functioning kidney due to renal pelvic stone disease

    PubMed Central

    ZENGIN, KURSAD; TANIK, SERHAT; SENER, NEVZAT CAN; ALBAYRAK, SEBAHATTIN; EKICI, MUSA; BOZKURT, IBRAHIM HALIL; BAKIRTAS, HASAN; GURDAL, MESUT; IMAMOGLU, MUHAMMED ABDURRAHIM

    2015-01-01

    The objective of This study was to report our pathological findings in nephrectomy specimens from patients treated for non-functioning hydronephrotic kidney due to renal pelvic stone disease. A total of 97 patients who underwent nephrectomy for non-functioning hydronephrotic kidneys between January, 2011 and June, 2014 were retrospectively reviewed. A non-functioning kidney was defined as one having paper-thin parenchyma on urinary ultrasound or computed tomography, exhibiting no contrast visualization in the collecting duct system on intravenous urography and having a split renal function of <10% on nuclear renal function studies. Following pathological evaluation, 9 patients were diagnosed with xanthogranulomatous pyelonephritis, 9 with malignant tumors and 79 with chronic pyelonephritis. Of the patients with chronic pyelonephritis, 2 also had renal adenomas. The malignant tumors included 3 transitional cell carcinomas (TCC), 2 squamous cell carcinomas (SCC), 3 renal cell carcinomas (RCC) (1 sarcomatoid, 1 papillary and 1 clear cell RCC), whereas 1 patient had concurrent RCC and TCC. In conclusion, non-functioning kidneys, particularly those with kidney stones, should be managed as possible malignancies, due to the higher incidence of malignant tumors in such patients compared with the normal population. PMID:26171211

  3. [Validity of diagnostic methods for kidney function tests in the cat].

    PubMed

    Meyer-Lindenberg, A; Westhoff, A; Wohlsein, P; Nolte, I

    1996-08-01

    The diagnosis of kidney disease is difficult in the stage of compensation and impossible based solely on the routinely performed laboratory tests on blood and urine. For this reason, more sensitive methods are required. In the present study, three special techniques are compared with regard to their validity in the early diagnosis of kidney disease in the cat: 1. the molecular-weight related separation of urine proteins with the sodium-dodecyl-sulfate-polyacrylamide-gradient gel electrophoresis (SDS-page) in the PhastSystem, 2. measurement of the glomerular filtration rate (GFR) with the renalyzer PRX90 using an iodine containing contrast medium and 3. kidney scintigraphy. The results of this comparison demonstrate that these procedures are important adjuncts to common laboratory investigations in the testing of renal function. The SDS-page allows an early qualitative assessment on alterations of specific functional compartments of the kidney. However, it is not possible with this method alone to evaluate the degree of renal disturbance and it does not give information concerning the severity of renal functional impairment. Measurement of the GFR is also a valuable procedure which gives a quantitative result on the global renal function within a few hours. It is of special importance when subclinically disturbed kidney function is present. In the cat however it is until now not possible to give a correct prognosis in high grade nephropathies. Only scintigraphy allows unilateral assessment of renal function, which is most important in cats with morphologically altered kidneys, such as kidney cysts, hydronephrosis or tumours. PMID:9012026

  4. Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

    PubMed Central

    Fuchsberger, Christian; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Chouraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank B.; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Kolcic, Ivana; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Endlich, Karlhans; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Giulianini, Franco; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Metzger, Marie; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L. R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline C. M.; Hayward, Caroline; Ridker, Paul; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Chasman, Daniel I.; Kao, W. H. Linda; Fox, Caroline S.

    2012-01-01

    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD. PMID:22479191

  5. Polycystic Kidney Disease

    MedlinePlus

    ... a kidney transplant or blood-filtering treatments called dialysis. The two main types of PKD are autosomal ... so people with kidney failure must receive either dialysis or a kidney transplant to replace kidney function. ...

  6. DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC Study

    PubMed Central

    Wing, Maria R.; Devaney, Joseph M.; Joffe, Marshall M.; Xie, Dawei; Feldman, Harold I.; Dominic, Elizabeth A.; Guzman, Nicolas J.; Ramezani, Ali; Susztak, Katalin; Herman, James G.; Cope, Leslie; Harmon, Brennan; Kwabi-Addo, Bernard; Gordish-Dressman, Heather; Go, Alan S.; He, Jiang; Lash, James P.; Kusek, John W.; Raj, Dominic S.

    2014-01-01

    Background Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD). Methods We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate. Results The mean eGFR slope was 2.2 (1.4) and −5.1 (1.2) mL/min/1.73 m2 in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E−05 to 9.5E−05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E−03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD. Conclusions Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD. PMID:24516231

  7. Association Between Age-Related Decline of Kidney Function and Plasma Malondialdehyde

    PubMed Central

    Chen, Yaqin; Hu, Hui; Liu, Li; Hu, Xiaofei; Wang, Jun; Shi, Wang; Yin, Dazhong

    2012-01-01

    Abstract Oxidative stress is a key factor linked renal function decline with age. However, there is still no large cohort study exploring the potential role of oxidative stress in mild insufficiency of kidney function (MIKF) and chronic kidney disease (CKD) after adjusting for confounding factors. This study tested the hypothesis that oxidative stress, indicated by plasma malondialdehyde (MDA), is associated with the prevalence of MIKF and CKD after controlling the effects of confounding factors. Plasma levels of MDA and serum levels of fasting glucose, cholesterol, triglycerides, creatinine, alanine aminotransferase, and aspartate aminotransferase were analyzed from 2,169 Chinese Han adults. A questionnaire and physical examination were performed to identify and suspect risk factors of renal function decline with age. Kidney function, as indicated by estimated glomerular filtration rate, showed a significant decline with age in both male and female. Although the association between age and plasma MDA levels was nonlinear, MDA was negatively related to kidney function. The multivariate-adjusted odds ratios showed that plasma MDA had a significantly graded relation to the prevalence of MIKF and CKD with or without adjustment for covariates. By comparison with the lowest quartile, individuals with the highest quartile of MDA level had a 99% and 223% increased risk of developing MIKF and CKD, respectively. Further results from multiinteraction analysis demonstrated that plasma MDA may be the mediator linking different covariates with renal function decline. The most striking finding of this study was that oxidative stress, as indicated by plasma MDA levels, is associated with the prevalence of MIKF and/or CKD. Although imposing an increasing burden on the kidney and/or promoting a cyclical process of oxidative stress in the body, high levels of MDA in plasma may link the decline of kidney function with age. PMID:22530729

  8. Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study

    PubMed Central

    Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Vuistiner, Philippe; Guessous, Idris; Ehret, Georg; Alwan, Heba; Youhanna, Sonia; Paccaud, Fred; Mohaupt, Markus; Péchère-Bertschi, Antoinette; Vogt, Bruno; Burnier, Michel; Martin, Pierre-Yves; Devuyst, Olivier

    2015-01-01

    Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=−2.1; 95% confidence interval [95% CI], −3.3 to −0.8; P=0.002) and kidney length (β=−1.2; 95% CI, −1.9 to −0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts. PMID:25270071

  9. Fetal urinoma and prenatal hydronephrosis: how is renal function affected?

    PubMed Central

    Oktar, Tayfun; Salabaş, Emre; Kalelioğlu, İbrahim; Atar, Arda; Ander, Haluk; Ziylan, Orhan; Has, Recep; Yüksel, Atıl

    2013-01-01

    Objective: In our study, the functional prognosis of kidneys with prenatal urinomas were investigated. Material and methods: Between 2006 and 2010, fetal urinomas were detected in 19 fetuses using prenatal ultrasonography (US), and the medical records were reviewed retrospectively. Of the 19 cases, the follow-up data were available for 10 fetuses. The gestational age at diagnosis, prognosis of urinomas, clinical course and renal functions were recorded. Postnatal renal functions were assessed with renal scintigraphy. Results: Unilateral urinomas and increased parenchyma echogenicity in the ipsilateral kidney were detected in all of the fetuses. Of the 10 fetuses with follow-up data, the option of termination was offered in 6 cases of anhydramnios, including 3 cases with signs of infravesical obstruction (a possible posterior urethral valve (PUV) and poor prognostic factors and 3 cases with unilateral hydronephrosis and increased echogenicity in the contralateral kidney. Only one family agreed the termination. The other 5 fetuses died during the early postnatal period. The average postnatal follow-up period in the 4 surviving fetuses was 22.5 months (8–38 months). One patient with a PUV underwent ablation surgery during the early postnatal period. In the postnatal period, none of the 4 kidneys that were ipsilateral to the urinoma were functional on scintigraphic evaluation. The urinomas disappeared in 3 cases. Nephrectomy was performed in one case due to recurrent urinary tract infections. Conclusion: In our study, no function was detected in the ipsilateral kidney of surviving patients with urinomas. Upper urinary tract dilatation accompanied by a urinoma is a poor prognostic factor for renal function. PMID:26328088

  10. Analysis of nephron composition and function in the adult zebrafish kidney.

    PubMed

    McCampbell, Kristen K; Springer, Kristin N; Wingert, Rebecca A

    2014-08-09

    The zebrafish model has emerged as a relevant system to study kidney development, regeneration and disease. Both the embryonic and adult zebrafish kidneys are composed of functional units known as nephrons, which are highly conserved with other vertebrates, including mammals. Research in zebrafish has recently demonstrated that two distinctive phenomena transpire after adult nephrons incur damage: first, there is robust regeneration within existing nephrons that replaces the destroyed tubule epithelial cells; second, entirely new nephrons are produced from renal progenitors in a process known as neonephrogenesis. In contrast, humans and other mammals seem to have only a limited ability for nephron epithelial regeneration. To date, the mechanisms responsible for these kidney regeneration phenomena remain poorly understood. Since adult zebrafish kidneys undergo both nephron epithelial regeneration and neonephrogenesis, they provide an outstanding experimental paradigm to study these events. Further, there is a wide range of genetic and pharmacological tools available in the zebrafish model that can be used to delineate the cellular and molecular mechanisms that regulate renal regeneration. One essential aspect of such research is the evaluation of nephron structure and function. This protocol describes a set of labeling techniques that can be used to gauge renal composition and test nephron functionality in the adult zebrafish kidney. Thus, these methods are widely applicable to the future phenotypic characterization of adult zebrafish kidney injury paradigms, which include but are not limited to, nephrotoxicant exposure regimes or genetic methods of targeted cell death such as the nitroreductase mediated cell ablation technique. Further, these methods could be used to study genetic perturbations in adult kidney formation and could also be applied to assess renal status during chronic disease modeling.

  11. Atrazine affects kidney and adrenal hormones (AHs) related genes expressions of rare minnow (Gobiocypris rarus).

    PubMed

    Yang, Lihua; Zha, Jinmiao; Li, Wei; Li, Zhaoli; Wang, Zijian

    2010-05-01

    Atrazine, one of the most widely used herbicides, has been proved to interfere with sexual hormones. However few studies have considered the effects of atrazine on adrenal hormones (AH). In this study, rare minnow (Gobiocypris rarus) was exposed to 0, 3, 10, 33, 100 and 333microg/l atrazine for 28 days. The histopathology of kidney and gill was examined and the expressions of AHs-related genes including Na(+),K(+)-ATPase, glucocorticoid receptor (gr), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) in kidney and gill were quantitatively determined. Histopathological observation revealed obvious lesions in gill including hyperplasia, necrosis in epithelium region, aneurysm and lamellar fusion at concentrations as low as 10microg/l. The observed lesions in kidney included extensive expansion in the lumen, degenerative and necrotic changes of the tubular epithelia, shrinkage of the glomerulus as well as increase of the Bowman's space at concentrations as low as 10microg/l. The expressions of Na(+),K(+)-ATPase, gr, hsp70 and hsp90 in the kidney of females were significantly decreased at all concentrations. For males, the expressions of hsp90 in the kidney of all treated groups were significantly down-regulated, while gr at all concentrations and hsp70 at 10, 33, 100microg/l were significantly up-regulated. However in the gill, the expressions of these genes were not significantly different from the control. These results indicated that exposure to atrazine caused impairments of kidney and gill of fish at environmental related concentrations. Histopathological lesions could partly attribute to the changes of the expressions of AHs-related genes in kidney. We concluded also that atrazine is a potential AHs-disruptor and AHs-related genes in kidney of fish could be used as sensitive molecular biomarkers.

  12. Increased bone morphogenetic protein 7 signalling in the kidneys of dogs affected with a congenital portosystemic shunt.

    PubMed

    van Dongen, Astrid M; Heuving, Susanne M; Tryfonidou, Marianna A; van Steenbeek, Frank G; Rothuizen, Jan; Penning, Louis C

    2015-05-01

    Dogs with a congenital portosystemic shunt (CPSS) often have enlarged and hyper-filtrating kidneys. Although expression of different growth factors has been well-described in the livers of dogs affected with a CPSS, their expression in the kidneys has yet to be determined. Bone morphogenetic protein 7 (BMP-7), hepatocyte growth factor (HGF) and transforming growth factor (TGF)-β have been implicated in renal development (BMP-7, HGF) or the onset of renal fibrosis (TGF-β). Moreover, BMP-7 and HGF have protective properties in renal fibrosis. In this study, the expression and activity of BMP-7 were investigated in renal biopsies obtained from 13 dogs affected with a CPSS and compared to similar samples from age-matched healthy control dogs. Both quantitative reverse-transcriptase PCR and Western blotting showed up-regulated BMP-7 signalling in kidneys of CPPS-affected dogs. These research findings may help to explain the renal pathology/dysfunction in dogs affected with a CPSS.

  13. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

    PubMed Central

    Ali, Quaisar

    2016-01-01

    We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions. PMID:27528887

  14. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats.

    PubMed

    Pokkunuri, Indira; Ali, Quaisar; Asghar, Mohammad

    2016-01-01

    We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp (91phox) -NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions. PMID:27528887

  15. Does Swimming Exercise Affect Experimental Chronic Kidney Disease in Rats Treated with Gum Acacia?

    PubMed Central

    Ali, Badreldin H.; Al-Salam, Suhail; Al Za'abi, Mohammed; Al Balushi, Khalid A.; Ramkumar, Aishwarya; Waly, Mostafa I.; Yasin, Javid; Adham, Sirin A.; Nemmar, Abderrahim

    2014-01-01

    Different modes of exercise are reported to be beneficial in subjects with chronic kidney disease (CKD). Similar benefits have also been ascribed to the dietary supplement gum acacia (GA). Using several physiological, biochemical, immunological, and histopathological measurements, we assessed the effect of swimming exercise (SE) on adenine –induced CKD, and tested whether SE would influence the salutary action of GA in rats with CKD. Eight groups of rats were used, the first four of which were fed normal chow for 5 weeks, feed mixed with adenine (0.25% w/w) to induce CKD, GA in the drinking water (15% w/v), or were given adenine plus GA, as above. Another four groups were similarly treated, but were subjected to SE during the experimental period, while the first four groups remained sedentary. The pre-SE program lasted for four days (before the start of the experimental treatments), during which the rats were made to swim for 5 to 10 min, and then gradually extended to 20 min per day. Thereafter, the rats in the 5th, 6th, 7th, and 8th groups started to receive their respective treatments, and were subjected to SE three days a week for 45 min each. Adenine induced the typical signs of CKD as confirmed by histopathology, and the other measurements, and GA significantly ameliorated all these signs. SE did not affect the salutary action of GA on renal histology, but it partially improved some of the above biochemical and physiological analytes, suggesting that addition of this mode of exercise to GA supplementation may improve further the benefits of GA supplementation. PMID:25048380

  16. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure

    PubMed Central

    Boon, Ai-Ching; Lam, Alfred K.; Gopalan, Vinod; Benzie, Iris F.; Briskey, David; Coombes, Jeff S.; Fassett, Robert G.; Bulmer, Andrew C.

    2015-01-01

    Mildly elevated bilirubin is associated with a reduction in the presence and progression of chronic kidney disease and related mortality, which may be attributed to bilirubin’s antioxidant properties. This study investigated whether endogenously elevated bilirubin would protect against adenine-induced kidney damage in male hyperbilirubinaemic Gunn rats and littermate controls. Animals were orally administered adenine or methylcellulose solvent (vehicle) daily for 10 days and were then monitored for 28 days. Serum and urine were assessed throughout the protocol for parameters of kidney function and antioxidant/oxidative stress status and kidneys were harvested for histological examination upon completion of the study. Adenine-treated animals experienced weight-loss, polyuria and polydipsia; however, these effects were significantly attenuated in adenine-treated Gunn rats. No difference in the presence of dihydroadenine crystals, lymphocytic infiltration and fibrosis were noted in Gunn rat kidneys versus controls. However, plasma protein carbonyl and F2-isoprostane concentrations were significantly decreased in Gunn rats versus controls, with no change in urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine or kidney tissue F2-isoprostane concentrations. These data indicated that endogenously elevated bilirubin specifically protects from systemic oxidative stress in the vascular compartment. These data may help to clarify the protective relationship between bilirubin, kidney function and cardiovascular mortality in clinical investigations. PMID:26498893

  17. Kidney function of the American eel Anguilla rostrata.

    PubMed

    Schmidt-Nielsen, B; Renfro, J L

    1975-02-01

    Urine formation in the eel, acclimated to freshwater (FW) and seawater (SW) was studied. SW eels maintained higher plasma and urine osmotic and ionic concentrations than FW eels. Polyethylene-1,2-glycol-14C (PEG-14C) clearance was 29% greater than methoxy-inulin-3H clearance. PEG-14C clearance was considered to be the glomerular filtration rate (GFR). The GFR of SW and FW eels did not differ. Urine flow rate in SW eels was one-third of that in FW eels. The primary urinary solutes in both groups were Na and Cl. Apparently, tubular fluid secretion occurred in FW and, to a lesser degree, in SW eels. With the assumption that water reabsorption was secondary to Na reabsorption in the kidney, the clearance data were used to evaluate all possible explanations for what appeared to be fluid secretion. The data were inconsistent with the possibility that GFR had been underestimated due to glomerular sieving of PEG or active or passive reabsorption of the marker, but consistent with tubular fluid secretion. Furosemide caused diuresis in both groups of eels apparently by inhibition of Na reabsorption in the distal tubule, but it had no effect on the apparent tubular fluid secretion. Tubular ion secretion could not be conclusively implicated as a driving force for fluid secretion. However, the possibility of K, Ca, or Mg secretion in a proximal segment followed by reabsorption in a more distal part of the nephron was not ruled out.

  18. [Dynamic renal scintigraphy in assessing kidney function in patients with nonspecific colitis].

    PubMed

    Topchiĭ, T V; Moskalenko, N I; Man'kovskaia, O L; Morozova, N L

    1990-11-01

    Research into the morphofunctional status of the kidneys was conducted in patients with nonspecific colitis-NC (nonspecific ulcerative colitis-NUC and Crohn's disease). Urodynamics and partial function of the kidneys were assessed in 74 NC patients (51 NUC patients and 23 patients with Crohn's disease) on the basis of the findings of two-nuclide dynamic renal scintigraphy with 131I-hippuran and 99mTc-pentatech. Despite the absence of clinical symptomatology of urinary tract lesions, marked dysfunction of the kidneys of various degree (depending on severity of disease, tactics of its treatment and a type of surgical intervention) was noted in NC patients. In most cases changes of renal function were without visible clinical manifestations and were frequently undetectable by routine laboratory tests. Therefore dynamic renal scintigraphy was found necessary for investigation on NC patients. PMID:2259285

  19. The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients

    PubMed Central

    Zeraati, Abbas Ali; Nazemian, Fatemeh; Takalloo, Ladan; Sahebkar, Amirhossein; Heidari, Elahe; Yaghoubi, Mohammad Ali

    2016-01-01

    Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation. PMID:27366144

  20. The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients.

    PubMed

    Zeraati, Abbas Ali; Nazemian, Fatemeh; Takalloo, Ladan; Sahebkar, Amirhossein; Heidari, Elahe; Yaghoubi, Mohammad Ali

    2016-01-01

    Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation. PMID:27366144

  1. Common variants in Mendelian kidney disease genes and their association with renal function.

    PubMed

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

  2. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

    PubMed

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-06-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

  3. Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients

    PubMed Central

    do Nascimento, Wenna Gleyce Araújo; Cilião, Daiani Alves; Genre, Julieta; Gondim, Dikson Dibe; Alves, Renata Gomes; Hassan, Neife Deghaide; Lima, Francisco Pignataro; Pereira, Maurício Galvão; Donadi, Eduardo Antônio; de Oliveira Crispim, Janaina Cristiana

    2014-01-01

    Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45–4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients. PMID:25071398

  4. Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function

    PubMed Central

    Fuchsberger, Christian; Köttgen, Anna; O’Seaghdha, Conall M.; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I.; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J.; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V.; O’Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H.-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M.; Borecki, Ingrid; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M.; Bochud, Murielle; Heid, Iris M.; Siscovick, David S.; Fox, Caroline S.; Kao, W. Linda; Böger, Carsten A.

    2013-01-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. PMID:24029420

  5. Combined effects of fluoride and cadmium on liver and kidney function in male rats.

    PubMed

    Zhang, Junmin; Song, Jingjuan; Zhang, Jun; Chen, Xiao; Zhou, Meixia; Cheng, Guang; Xie, Xinyou

    2013-12-01

    It has been shown that cadmium and fluoride may both have adverse effects on liver and kidney functions, but most studies focus on a single agent. In this study, we observed the effects of cadmium and fluoride on liver and kidney functions using a rat model. Total of 24 Sprague-Dawley male rats were divided into four groups, one control group and three exposure groups that were given cadmium (50 mg/L) and fluoride (100 mg/L) alone or in combination via drinking water. At the 12th week, urine, blood, and kidney tissues were collected. Aspartate transaminase, alanine transaminase (ALT), urinary β2-microglobulin, and albumin were determined. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver and kidney homogenates were measured to evaluate oxidative stress. There was a significant increase in serum ALT and urinary β2-microglobulin of rats in exposure groups compared with control. Serum ALT and urinary β2-microglobulin of rats exposed to cadmium and fluoride in combination was significantly higher than those treated with cadmium alone and fluoride alone. SOD declined significantly and MDA increased in combination group compared with control and those treated with cadmium and fluoride alone. Cadmium and fluoride co-exposure increase the liver and kidney damage compared with that exposed to cadmium or fluoride alone.

  6. Bisphenol A affects androgen receptor function via multiple mechanisms.

    PubMed

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.

  7. Bisphenol A affects androgen receptor function via multiple mechanisms

    PubMed Central

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B. Alex; Jetten, Anton M.; Austin, Christopher, P.; Tice, Raymond R.

    2013-01-01

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. PMID:23562765

  8. Functional Genetic Targeting of Embryonic Kidney Progenitor Cells Ex Vivo

    PubMed Central

    Junttila, Sanna; Saarela, Ulla; Halt, Kimmo; Manninen, Aki; Pärssinen, Heikki; Lecca, M. Rita; Brändli, André W.; Sims-Lucas, Sunder; Skovorodkin, Ilya

    2015-01-01

    The embryonic mammalian metanephric mesenchyme (MM) is a unique tissue because it is competent to generate the nephrons in response to Wnt signaling. An ex vivo culture in which the MM is separated from the ureteric bud (UB), the natural inducer, can be used as a classic tubule induction model for studying nephrogenesis. However, technological restrictions currently prevent using this model to study the molecular genetic details before or during tubule induction. Using nephron segment-specific markers, we now show that tubule induction in the MM ex vivo also leads to the assembly of highly segmented nephrons. This induction capacity was reconstituted when MM tissue was dissociated into a cell suspension and then reaggregated (drMM) in the presence of human recombinant bone morphogenetic protein 7/human recombinant fibroblast growth factor 2 for 24 hours before induction. Growth factor–treated drMM also recovered the capacity for organogenesis when recombined with the UB. Cell tracking and time-lapse imaging of chimeric drMM cultures indicated that the nephron is not derived from a single progenitor cell. Furthermore, viral vector-mediated transduction of green fluorescent protein was much more efficient in dissociated MM cells than in intact mesenchyme, and the nephrogenic competence of transduced drMM progenitor cells was preserved. Moreover, drMM cells transduced with viral vectors mediating Lhx1 knockdown were excluded from the nephric tubules, whereas cells transduced with control vectors were incorporated. In summary, these techniques allow reproducible cellular and molecular examinations of the mechanisms behind nephrogenesis and kidney organogenesis in an ex vivo organ culture/organoid setting. PMID:25201883

  9. α-Melanocyte Stimulating Hormone Treatment in Pigs Does Not Improve Early Graft Function in Kidney Transplants from Brain Dead Donors

    PubMed Central

    van Rijt, Willem G.; Secher, Niels; Keller, Anna K.; Møldrup, Ulla; Chynau, Yahor; Ploeg, Rutger J.; van Goor, Harry; Nørregaard, Rikke; Birn, Henrik; Frøkiaer, Jørgen; Nielsen, Søren; Leuvenink, Henri G. D.; Jespersen, Bente

    2014-01-01

    Delayed graft function and primary non-function are serious complications following transplantation of kidneys derived from deceased brain dead (DBD) donors. α-melanocyte stimulating hormone (α-MSH) is a pleiotropic neuropeptide and its renoprotective effects have been demonstrated in models of acute kidney injury. We hypothesized that α-MSH treatment of the recipient improves early graft function and reduces inflammation following DBD kidney transplantation. Eight Danish landrace pigs served as DBD donors. After four hours of brain death both kidneys were removed and stored for 18 hours at 4°C in Custodiol preservation solution. Sixteen recipients were randomized in a paired design into two treatment groups, transplanted simultaneously. α-MSH or a vehicle was administered at start of surgery, during reperfusion and two hours post-reperfusion. The recipients were observed for ten hours following reperfusion. Blood, urine and kidney tissue samples were collected during and at the end of follow-up. α-MSH treatment reduced urine flow and impaired recovery of glomerular filtration rate (GFR) compared to controls. After each dose of α-MSH, a trend towards reduced mean arterial blood pressure and increased heart rate was observed. α-MSH did not affect expression of inflammatory markers. Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation possibly due to hemodynamic changes. Thus, in a porcine experimental model α-MSH did not reduce renal inflammation and did not improve short-term graft function following DBD kidney transplantation. PMID:24728087

  10. The kidney disease quality of life cognitive function subscale and cognitive performance maintenance hemodialysis patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Cognitive impairment is common but often undiagnosed in patients with end-stage renal disease, in part reflecting limited validated and easily administered tools to assess cognitive function in dialysis patients. Accordingly, we assessed the utility of the Kidney Disease Quality of Life ...

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  12. Radionuclide determination of individual kidney function in the treatment of chronic renal obstruction

    SciTech Connect

    Belis, J.A.; Belis, T.E.; Lai, J.C.; Goodwin, C.A.; Gabriele, O.F.

    1982-04-01

    Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The /sup 99m/Tc diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The /sup 131/I orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential /sup 99m/Tc diethylenetriaminepentaacetic acid and /sup 131/I orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on /supb 99m/Tc diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the /sup 131/I orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively.

  13. Shock wave lithotripsy (SWL) induces significant structural and functional changes in the kidney

    NASA Astrophysics Data System (ADS)

    Evan, Andrew P.; Willis, Lynn R.; Lingeman, James E.

    2003-10-01

    The foundation for understanding SWL-injury has been well-controlled renal structural and functional studies in pigs, a model that closely mimics the human kidney. A clinical dose (2000 shocks at 24 kV) of SWL administered by the Dornier HM3 induces a predictable, unique vascular injury at F2 that is associated with transient renal vasoconstriction, seen as a reduction in renal plasma flow, in both treated and untreated kidneys. Unilateral renal denervation studies links the fall in blood flow in untreated kidneys to autonomic nerve activity in the treated kidney. SWL-induced trauma is associated with an acute inflammatory process, termed Lithotripsy Nephritis and tubular damage at the site of damage that leads to a focal region of scar. Lesion size increases with shock number and kV level. In addition, risk factors like kidney size and pre-existing renal disease (e.g., pyelonephritis), can exaggerate the predicted level of renal impairment. Our new protection data show that lesion size can be greatly reduced by a pretreatment session with low kV and shock number. The mechanisms of soft tissue injury probably involves shear stress followed by acoustic cavitation. Because of the perceived enhanced level of bioeffects from 3rd generation lithotripters, these observations are more relevant than ever.

  14. Serum Paraoxonase Levels are Correlated with Impaired Aortic Functions in Patients with Chronic Kidney Disease

    PubMed Central

    Efe, Tolga H; Ertem, Ahmet G; Altunoglu, Alpaslan; Koseoglu, Cemal; Erayman, Ali; Bilgin, Murat; Kurmuş, Özge; Aslan, Turgay; Bilge, Mehmet

    2016-01-01

    Background The correlation between aortic functions and paraoxonase levels has been previously demonstrated by several earlier studies. In this study, we aimed to investigate the correlation between serum paraoxonase levels and aortic functions among patients with chronic kidney disease. Methods Our study enrolled 46 chronic kidney disease patients and 45 healthy controls. From these patients, serum cholesterol, creatinine, hemoglobin, and paraoxonase-1 levels were analyzed. Results Paraoxonase-1 levels were significantly lower in patients with chronic kidney disease compared to the controls (p < 0.001). Additionally, the extent of aortic stiffness index (%) was significantly higher in chronic kidney disease patients, but aortic strain and aortic distensibility were significantly higher in healthy controls (p < 0.001, p < 0.001, and p < 0.001, respectively). We further found that paraoxonase-1 levels were correlated with aortic stiffness index, aortic strain, and aortic distensibility (p < 0.001, p < 0.001, and p < 0.001, respectively). Conclusions Our study demonstrated that serum paraoxonase-1 levels were significantly correlated with impaired aortic functions. The results of this study highlight the impact of serum paraoxonase-1 activity on atherosclerosis and cardiovascular adverse events. PMID:27122934

  15. Renal Damage Frequency in Patients with Solitary Kidney and Factors That Affect Progression

    PubMed Central

    Basturk, T.; Koc, Y.; Ucar, Z.; Sakaci, T.; Ahbap, E.; Kara, E.; Bayraktar, F.; Sevinc, M.; Sahutoglu, T.; Kayalar, A.; Sinangil, A.; Akgol, C.; Unsal, A.

    2015-01-01

    Background. The aim of this study is to assess renal damage incidence in patients with solitary kidney and to detect factors associated with progression. Methods. Medical records of 75 patients with solitary kidney were investigated retrospectively and divided into two groups: unilateral nephrectomy (group 1) and unilateral renal agenesis/dysplasia (group 2). According to the presence of kidney damage, each group was divided into two subgroups: group 1a/b and group 2a/b. Results. Patients in group 1 were older than those in group 2 (p = 0.001). 34 patients who comprise group 1a had smaller kidney size (p = 0.002) and higher uric acid levels (p = 0.028) than those in group 1b at presentation. Uric acid levels at first and last visit were associated with renal damage progression (p = 0.004, 0.019). 18 patients who comprise group 2a were compared with those in group 2b in terms of presence of DM (p = 0.038), HT (p = 0.003), baseline proteinuria (p = 0.014), and uric acid (p = 0.032) levels and group 2a showed higher rates for each. Progression was more common in patients with DM (p = 0.039), HT (p = 0.003), higher initial and final visit proteinuria (p = 0.014, for both), and higher baseline uric acid levels (p = 0.047). Conclusions. The majority of patients with solitary kidney showed renal damage at presentation. Increased uric acid level is a risk factor for renal damage and progression. For early diagnosis of renal damage and reducing the risk of progression, patients should be referred to a nephrologist as early as possible. PMID:26783458

  16. Diabetes and Kidney Disease

    MedlinePlus

    ... Disease, and Other Dental Problems Diabetic Eye Disease Diabetes and Kidney Disease What are my kidneys and ... urine until releasing it through urination. How can diabetes affect my kidneys? Too much glucose , also called ...

  17. Measuring Dynamic Kidney Function in an Undergraduate Physiology Laboratory

    ERIC Educational Resources Information Center

    Medler, Scott; Harrington, Frederick

    2013-01-01

    Most undergraduate physiology laboratories are very limited in how they treat renal physiology. It is common to find teaching laboratories equipped with the capability for high-resolution digital recordings of physiological functions (muscle twitches, ECG, action potentials, respiratory responses, etc.), but most urinary laboratories still rely on…

  18. Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia.

    PubMed

    Bolar, Nikhita Ajit; Golzio, Christelle; Živná, Martina; Hayot, Gaëlle; Van Hemelrijk, Christine; Schepers, Dorien; Vandeweyer, Geert; Hoischen, Alexander; Huyghe, Jeroen R; Raes, Ann; Matthys, Erve; Sys, Emiel; Azou, Myriam; Gubler, Marie-Claire; Praet, Marleen; Van Camp, Guy; McFadden, Kelsey; Pediaditakis, Igor; Přistoupilová, Anna; Hodaňová, Kateřina; Vyleťal, Petr; Hartmannová, Hana; Stránecký, Viktor; Hůlková, Helena; Barešová, Veronika; Jedličková, Ivana; Sovová, Jana; Hnízda, Aleš; Kidd, Kendrah; Bleyer, Anthony J; Spong, Richard S; Vande Walle, Johan; Mortier, Geert; Brunner, Han; Van Laer, Lut; Kmoch, Stanislav; Katsanis, Nicholas; Loeys, Bart L

    2016-07-01

    Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1-c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)-both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild-type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD. PMID:27392076

  19. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

    PubMed

    Okada, Yukinori; Sim, Xueling; Go, Min Jin; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L; Aung, Tin; Seielstad, Mark; Teo, Yik-Ying; Kim, Young Jin; Lee, Jong-Young; Han, Bok-Ghee; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S-J Cathy; Mei, Hao; Rao, Dabeeru C; Hixson, James E; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Ogihara, Toshio; Chambers, John C; Zhang, Weihua; Kooner, Jaspal S; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Cho, Yoon Shin; Tai, E-Shyong; Tanaka, Toshihiro

    2012-08-01

    Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function. PMID:22797727

  20. Differential Expression of Functional Fc-Receptors and Additional Immune Complex Receptors on Mouse Kidney Cells

    PubMed Central

    Suwanichkul, Adisak; Wenderfer, Scott E.

    2013-01-01

    The precise mechanisms by which circulating immune complexes accumulate in the kidney to form deposits in glomerulonephritis are not well understood. In particular, the role of resident cells within glomeruli of the kidney has been widely debated. Immune complexes have been shown to bind one glomerular cell type (mesangial cells) leading to functional responses such as pro-inflammatory cytokine production. To further assess the presence of functional immunoreceptors on resident glomerular cells, cultured mouse renal epithelial, endothelial, and mesangial cells were treated with heat-aggregated mouse IgG or preformed murine immune complexes. Mesangial and renal endothelial cells were found to bind IgG complexes, whereas glomerular epithelial cell binding was minimal. A blocking antibody for Fc-gamma receptors reduced binding to mesangial cells but not renal endothelial cells, suggesting differential immunoreceptor utilization. RT-PCR and immunostaining based screening of cultured renal endothelial cells showed limited low-level expression of known Fc-receptors and Igbinding proteins. The interaction between mesangial cells and renal endothelial cells and immune complexes resulted in distinct, cell-specific patterns of chemokine and cytokine production. This novel pathway involving renal endothelial cells likely contributes to the predilection of circulating immune complex accumulation within the kidney and to the inflammatory responses that drive kidney injury. PMID:23911392

  1. Function and Change with Aging of α-Klotho in the Kidney.

    PubMed

    Akasaka-Manya, K; Manya, H; Endo, T

    2016-01-01

    The α-Klotho mouse is an animal model that prematurely shows phenotypes resembling human aging, such as osteoporosis, arteriosclerosis, pulmonary emphysema, and kidney damage. Interestingly, these abnormalities are triggered by a deficiency of a single protein, α-Klotho. The kidney is an organ that highly expresses α-Klotho, suggesting that α-Klotho is important for kidney function. Recent studies suggest that α-Klotho is associated with phosphate, vitamin D, and calcium homeostasis. The calcium imbalance in α-Klotho mice may induce calpain overactivation, leading to cell death and tissue destruction. α-Klotho is predicted to have glycosidase activity, capable of modifying the N-glycans of channels and transporters and regulating transmembrane movement of several ions, including calcium. Interestingly, N-glycan changes are observed in the kidney of α-Klotho mice and normal aged mice in association with decreased α-Klotho levels. These results imply that glycobiology and α-Klotho function are interesting targets for future studies. PMID:27125745

  2. Unconventional Functions of Mitotic Kinases in Kidney Tumorigenesis

    PubMed Central

    Hascoet, Pauline; Chesnel, Franck; Le Goff, Cathy; Le Goff, Xavier; Arlot-Bonnemains, Yannick

    2015-01-01

    Human tumors exhibit a variety of genetic alterations, including point mutations, translocations, gene amplifications and deletions, as well as aneuploid chromosome numbers. For carcinomas, aneuploidy is associated with poor patient outcome for a large variety of tumor types, including breast, colon, and renal cell carcinoma. The Renal cell carcinoma (RCC) is a heterogeneous carcinoma consisting of different histologic types. The clear renal cell carcinoma (ccRCC) is the most common subtype and represents 85% of the RCC. Central to the biology of the ccRCC is the loss of function of the Von Hippel–Lindau gene, but is also associated with genetic instability that could be caused by abrogation of the cell cycle mitotic spindle checkpoint and may involve the Aurora kinases, which regulate centrosome maturation. Aneuploidy can also result from the loss of cell–cell adhesion and apical–basal cell polarity that also may be regulated by the mitotic kinases (polo-like kinase 1, casein kinase 2, doublecortin-like kinase 1, and Aurora kinases). In this review, we describe the “non-mitotic” unconventional functions of these kinases in renal tumorigenesis. PMID:26579493

  3. Fluid and Electrolyte Balance and Kidney Function Research in Space

    NASA Astrophysics Data System (ADS)

    Norsk, P.; Juel, N.; Kramer, H. J.; de Santo, N. G.; Regnard, J.; Heer, M.

    2005-06-01

    Fluid and electrolyte regulation in humans is modulated by gravitational stress through a complex interaction of cardiovascular reflexes, neuroendocrine variables, physical factors and renal function.Weightlessness is a unique tool to obtain more information on integrated fluid volume control. Results from space, however, have been unexpected and unpredictable from the results of ground- based simulations.The concept of how weightlesness and gravity modulate the regulation of body fluids and associated blood components must therefore be revised and a new simulation model developed. There are several main questions to be asked. Does weightlessness induce diuresis and natriuresis during the initial hours of spaceflight, leading to an extracellular and intravascular fluid volume deficit? Why are fluid- and sodium-retaining systems activated by spaceflight, and why are the renal responses to saline and water stimuli attenuated? Can excess sodium be stored in an hitherto unknown way, in particular during spaceflight? How can the effects of weightlessness on fluid and electrolyte regulation be correctly simulated on the ground? The information obtained from space might help us to understand how gravity degrades the fluid and electrolyte balance in sodium-retaining and oedema- forming states, such as in heart failure.

  4. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis

    PubMed Central

    Davisson, Muriel T.; Cook, Susan A.; Akeson, Ellen C.; Liu, Don; Heffner, Caleb; Gudis, Polyxeni; Fairfield, Heather

    2015-01-01

    Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis. PMID:25834070

  5. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis.

    PubMed

    Davisson, Muriel T; Cook, Susan A; Akeson, Ellen C; Liu, Don; Heffner, Caleb; Gudis, Polyxeni; Fairfield, Heather; Murray, Stephen A

    2015-06-15

    Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis.

  6. Renal Nitric Oxide Deficiency and Chronic Kidney Disease in Young Sheep Born with a Solitary Functioning Kidney

    PubMed Central

    Singh, Reetu R.; Easton, Lawrence K.; Booth, Lindsea C.; Schlaich, Markus P.; Head, Geoffrey A.; Moritz, Karen M.; Denton, Kate M.

    2016-01-01

    Previously, we demonstrated that renal hemodynamic responses to nitric oxide (NO) inhibition were attenuated in aged, hypertensive sheep born with a solitary functioning kidney (SFK). NO is an important regulator of renal function, particularly, in the postnatal period. We hypothesized that the onset of renal dysfunction and hypertension in individuals with a SFK is associated with NO deficiency early in life. In this study, renal and cardiovascular responses to L-NAME infusion (Nw-nitro-L-arginine methyl ester) were examined in 6-month old lambs born with a SFK, induced by fetal unilateral nephrectomy (uni-x). Renal responses to L-NAME were attenuated in uni-x sheep with the fall in glomerular filtration rate (GFR) and urinary sodium excretion (UNaV) being less in the uni-x compared to sham lambs (%ΔGFR; −41 ± 3 vs −54 ± 4: P = 0.03, %ΔUNaV; −48 ± 5 vs −76 ± 3, P = 0.0008). 24 hour-basal urinary nitrate and nitrite (NOx) excretion was less in the uni-x animals compared to the sham (NOx excretion μM/min/kg; sham: 57 ± 7; uni-x: 38 ± 4, P = 0.02). L-NAME treatment reduced urinary NOx to undetectable levels in both groups. A reduction in NO bioavailability in early life may contribute to the initiation of glomerular and tubular dysfunction that promotes development and progression of hypertension in offspring with a congenital nephron deficit, including those with a SFK. PMID:27226113

  7. Does cerebral angiography of cadaveric kidney donors interfere with graft function?

    PubMed

    Weibull, H; Cederholm, C; Almén, T; Bergqvist, D; Takolander, R; Husberg, B

    1987-01-01

    Cerebral angiography is used to diagnose brain death of cadaver kidney donors. Clinical and animal data suggest that angiographic contrast media may potentiate the noxious effect of renal ischemia. In order to find out if cerebral angiography of cadaveric kidney donors prior to nephrectomy interferes with function or survival of the renal grafts, two groups of cadaveric donors were compared. One group had been exposed to contrast medium from cerebral angiography in median 18 hours before nephrectomy and the other had not. There was no difference in graft survival and function between the two groups. In a previous investigation angiography was performed two hours before explantation and in that investigation there was a shorter graft survival in the angiography group than in a control group. A delay of 12 hours is suggested between cerebral angiography and explanation, to decrease the combined harmful effects of contrast media and ischemia on renal grafts.

  8. Genome-wide association study of kidney function decline in individuals of European descent

    PubMed Central

    Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M.; Chu, Audrey Y.; Tayo, Bamidele O.; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I.; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tammara B.; Launer, Lenore J.; Smith, Albert V.; Mitchell, Braxton D.; O'Connell, Jeffrey R.; Shuldiner, Alan R.; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G.; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H.; Li, Guo; Siscovick, David S.; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A.; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J.; Kardia, Sharon L.R.; Turner, Stephen T.; Stafford, Jeanette M.; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A; Ridker, Paul M; Grallert, Harald; Meisinger, Christa; Müller-Nurasyid, Martina; Krämer, Bernhard K.; Kramer, Holly; Rosas, Sylvia E.; Nolte, Ilja M.; Penninx, Brenda W.; Snieder, Harold; Del Greco, Fabiola; Franke, Andre; Nöthlings, Ute; Lieb, Wolfgang; Bakker, Stephan J.L.; Gansevoort, Ron T.; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H.; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, André G.; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Völker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Goessling, Wolfram; Köttgen, Anna; Kao, H. Linda; Fox, Caroline S.; Böger, Carsten A.

    2014-01-01

    Genome wide association studies (GWAS) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, SNPs at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1 and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFRdecline of 3ml/min/1.73m2 or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11 and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 hours after gentamicin treatment compared to controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline. PMID:25493955

  9. Genome-wide association study of kidney function decline in individuals of European descent.

    PubMed

    Gorski, Mathias; Tin, Adrienne; Garnaas, Maija; McMahon, Gearoid M; Chu, Audrey Y; Tayo, Bamidele O; Pattaro, Cristian; Teumer, Alexander; Chasman, Daniel I; Chalmers, John; Hamet, Pavel; Tremblay, Johanne; Woodward, Marc; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur; Harris, Tamara B; Launer, Lenore J; Smith, Albert V; Mitchell, Braxton D; O'Connell, Jeffrey R; Shuldiner, Alan R; Coresh, Josef; Li, Man; Freudenberger, Paul; Hofer, Edith; Schmidt, Helena; Schmidt, Reinhold; Holliday, Elizabeth G; Mitchell, Paul; Wang, Jie Jin; de Boer, Ian H; Li, Guo; Siscovick, David S; Kutalik, Zoltan; Corre, Tanguy; Vollenweider, Peter; Waeber, Gérard; Gupta, Jayanta; Kanetsky, Peter A; Hwang, Shih-Jen; Olden, Matthias; Yang, Qiong; de Andrade, Mariza; Atkinson, Elizabeth J; Kardia, Sharon L R; Turner, Stephen T; Stafford, Jeanette M; Ding, Jingzhong; Liu, Yongmei; Barlassina, Cristina; Cusi, Daniele; Salvi, Erika; Staessen, Jan A; Ridker, Paul M; Grallert, Harald; Meisinger, Christa; Müller-Nurasyid, Martina; Krämer, Bernhard K; Kramer, Holly; Rosas, Sylvia E; Nolte, Ilja M; Penninx, Brenda W; Snieder, Harold; Fabiola Del Greco, M; Franke, Andre; Nöthlings, Ute; Lieb, Wolfgang; Bakker, Stephan J L; Gansevoort, Ron T; van der Harst, Pim; Dehghan, Abbas; Franco, Oscar H; Hofman, Albert; Rivadeneira, Fernando; Sedaghat, Sanaz; Uitterlinden, André G; Coassin, Stefan; Haun, Margot; Kollerits, Barbara; Kronenberg, Florian; Paulweber, Bernhard; Aumann, Nicole; Endlich, Karlhans; Pietzner, Mike; Völker, Uwe; Rettig, Rainer; Chouraki, Vincent; Helmer, Catherine; Lambert, Jean-Charles; Metzger, Marie; Stengel, Benedicte; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Raitakari, Olli; Johnson, Andrew; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Goessling, Wolfram; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S; Böger, Carsten A

    2015-05-01

    Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.

  10. Is impaired kidney function an independent predictor of the risk of myocardial infarction in HIV-infected individuals?

    PubMed

    Lang, Sylvie; Mary-Krause, Murielle; Partisani, Marialuisa; Gilquin, Jacques; Simon, Anne; Cotte, Laurent; Boccara, Franck; Costagliola, Dominique

    2014-08-24

    We examined whether impaired kidney function is an independent risk factor for myocardial infarction in HIV-infected individuals without pre-existing coronary artery disease. The odds ratio for impaired kidney function fell from 1.22 (95% confidence interval 0.90-1.66) to 0.99 (95% confidence interval 0.69-1.41) after adjustment for cardiovascular risk factors and HIV-related parameters, with hypertension, high-density lipoprotein cholesterol, smoking and the CD4 T-cell nadir as most influential confounders. In this setting, no association was found between impaired kidney function and the risk of myocardial infarction.

  11. Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function

    NASA Astrophysics Data System (ADS)

    Wu, Haiyun; Liao, Qilin; Chillrud, Steven N.; Yang, Qiang; Huang, Lei; Bi, Jun; Yan, Beizhan

    2016-07-01

    Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects.

  12. Ernest Henry Starling (1866-1927) on the glomerular and tubular functions of the kidney.

    PubMed

    Fine, Leon G

    2014-01-01

    Around the turn of the 20th century, Ernest Henry Starling (1866-1927) made many fundamental contributions to the understanding of human physiology. With a deep interest in how fluid balance is regulated, he naturally turned to explore the intricacies of kidney function. Early in his career he focused upon the process of glomerular filtration and was able to substantiate the view of Carl Ludwig that this process can be explained entirely upon the basis of hydrostatic and oncotic pressure gradients across the glomerular capillary wall and that the process can be regulated by alterations in the tone of the afferent and efferent arterioles. To explore renal tubular function he employed a heart-lung-kidney model in the dog and was able to infer that certain substances are reabsorbed by the tubules (e.g. sodium chloride) and certain by tubular secretion (e.g. uric acid, indigo carmine dye). By temporarily blocking tubular function using hydrocyanic acid he was able to conclude that secreted substances must be taken up on the peritubular side of the cell and concentrated within the cell to drive the secretory process. Finally, he was able to appreciate that the kidney is an organ which is regulated according to the needs of the organism and that the processes of glomerular filtration, tubular secretion and reabsorption are all subject to regulatory influences, which have evolved to conserve the normal chemical composition of the cells and fluids of the body. PMID:24970544

  13. Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function.

    PubMed

    Wu, Haiyun; Liao, Qilin; Chillrud, Steven N; Yang, Qiang; Huang, Lei; Bi, Jun; Yan, Beizhan

    2016-01-01

    Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468; 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects. PMID:27411493

  14. Environmental Exposure to Cadmium: Health Risk Assessment and its Associations with Hypertension and Impaired Kidney Function

    PubMed Central

    Wu, Haiyun; Liao, Qilin; Chillrud, Steven N.; Yang, Qiang; Huang, Lei; Bi, Jun; Yan, Beizhan

    2016-01-01

    Cadmium (Cd) is a toxic metal. This study was aimed to estimate the potential health risks in a Cd-polluted district in China, and examine the relationship between urinary cadmium(UCd) and hypertension and impaired kidney function at low exposure levels (UCd: GM 1.3 μg/g creatinine). Blood pressure measurement, questionnaires, and collection of urinary samples were conducted from 217 residents. Environmental samples, food, and cigarette samples were collected and detected to estimate the risks posed by Cd and the contribution of inhalation, ingestion, and dermal contact pathways to these risks. A logistic regression model was used in examining associations between exposure and hypertension and impaired kidney function. Results show that this population is at high risk. For non-smokers, incremental lifetime cancer risk (ILCR) and hazard quotient (HQ) are 1.74E-04 and 2.96, and for smokers, they are 1.07E-03 and 52.5, respectively. Among all exposure pathways, smoking and foods cause the major increases in ILCR and HQ. UCd is significantly associated with hypertension (odds ratio (OR) = 1.468; 95% confidence interval (CI): 1.104, 1.953; P = 0.008) and impaired kidney function (OR = 1.902, 95% CI: 1.054, 3.432; P = 0.033). The results demonstrate that Cd can potentially lead to adverse health effects. PMID:27411493

  15. Stone orientation affects the mechanism of failure in artificial kidney stones subject to shock waves

    NASA Astrophysics Data System (ADS)

    van Cauwelaert, Javier; Cleveland, Robin O.

    2003-10-01

    Micro computed tomography (CT) imaging was used to follow the progressive development of cracks in artificial kidney stones. The artificial stones were made from U30 cement with a cylindrical shape (6.5 mm diameter and 8.5 mm long). The stones were held within a polypropylene vial in one of three orientations: vertical, horizontal, and angled at 45 deg. The stones were treated with an electromagnetic lithotripter and the initiation and growth of cracks was observed using microCT. The images show that the orientation of the stones with respect to the shock changes the dominant mechanism for fragmentation. Vertical stones developed a spall-like crack near the distal surface, which propagated from the surface to the interior of the stone. Initiation of a secondary spall-like crack was observed proximal to the first crack. Little surface damage was observed. Horizontal stones presented pitting in the proximal surface and erosion in lateral faces, indicating the action of cavitation. Angled stones presented both spall-like fracture in either the leading or the distal corners and surface damage (pitting) in the proximal surface. Experiments are being performed to follow the development of cracks in human kidney stones. [Work supported by the Whitaker Foundation.

  16. Kidney (Renal) Failure

    MedlinePlus

    ... renal function using ureteral stenting, nephrostomy, surgery or dialysis. What is kidney (renal) failure? How is kidney ... as a urinary stent or kidney stone removal. Dialysis , including hemodialysis and peritoneal dialysis: These procedures remove ...

  17. Serum neutrophil gelatinase-associated lipocalin and recovery of kidney graft function after transplantation

    PubMed Central

    2014-01-01

    Background Neutrophil gelatinase-associated lipocalin (NGAL) is a marker for acute kidney injury. We studied whether serum NGAL predicts delayed graft function (DGF) and recovery of kidney function after transplantation. Methods Serum NGAL was analyzed using commercial ELISA and point-of-care (POC) (Triage®, Biosite) methods. Serum samples were collected from 176 consecutive, deceased-donor kidney recipients just before transplant surgery and on day 1 and 14 after transplantation. The first 132 samples were analyzed with both methods and the remaining samples with the POC method. Results The correlation between the ELISA and POC methods was 0.89, p < 0.0001 and hence the POC method was used for the remaining analyses. DGF was seen in 66/176 patients. Day 1 sNGAL was significantly higher in DGF (588 ng/ml, SD 189.6) compared to early graft function (355 ng/ml, SD 166.2, p < 0.0001) and this difference persisted on day 14. Day 1 sNGAL predicted DGF with an area under the curve (AUC) of 0.853 (CI 0.792-0.914, p < 0.0001). At the optimal cutoff level of 423 ng/ml the sensitivity was 87% and the specificity 77%. In a multivariate analysis, day 1 sNGAL emerged as an independent predictor of DGF. The sNGAL also predicted DGF lasting longer than 14 days with an AUC of 0.825 (CI 0.751-0.899, p < 0.0001). At the optimal cutoff level of 486 ng/ml, the sensitivity was 80% and specificity 75%. Conclusion Serum NGAL predicts clinically significant DGF and is useful in the care of kidney transplant recipients. PMID:25066815

  18. Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi-blinded prospective randomized trial.

    PubMed

    Woodside, Kenneth J; Goldfarb, David A; Rabets, John C; Sanchez, Edmund Q; Lebovitz, Daniel J; Schulak, James A; Fung, John J; Eghtesad, Bijan

    2015-12-01

    Kidneys from donors after cardiac death (DCD) are at risk for inferior outcomes, possibly due to microthrombi and additional warm ischemia. We describe an organ procurement organization-wide trial utilizing thrombolytic tissue plasminogen activator (tPA) during machine pulsatile perfusion (MPP). A kidney from each recovered kidney pair was prospectively randomized to receive tPA (50 mg Alteplase) or no tPA (control) in the MPP perfusate. From 2011 to 2013, 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors. There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups, nor rates of achieving discrete flow and resistance targets. While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3, 6, 9, and 12 months, these differences were not significant. Delayed graft function (DGF) rates were 41.7% in the tPA group vs. 58.4% in the control group (OR 0.51, 95%CI 0.10-2.59, p = 0.68). Death-censored graft survival was similar between the groups. In this pilot study, encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP, compared with standard MPP.

  19. [Experimental studies on effects of excessive iodine intake on morphology and function of kidney in mice].

    PubMed

    Zhou, X; Yin, G

    1996-11-01

    To understand that if excessive iodine can cause damage to tissues other than thyroid gland, mice were fed with iodine-excess water and iodine-excess goiter was caused in them. Hisitomorphology and function of the kidney, in addition to the thyroid gland, in goiter mice were observed. Results showed that two hundred days after being fed with 3,000 micrograms iodine per liter water, in addition to causing iodine-excess goiter characterized with proliferation of large amount of colloid in thyroid follicles, morphology and function of the kidneys in mice were significantly damaged, with prominent pathomorphological changes of crescent formation and metabolic inhibition in microsome membrane Na(+)-K(+)-ATPase activities in their kidneys. Na(+)-K(+)-ATPase activities were 21.95 +/- 7.50 mumolPi/mg Pr.hr in low iodine group, and 17.64 +/- 8.63 mumolPi/mg Pr.hr in excessive iodine group, with significant difference. It suggests that excessive iodine can cause damage not only to thyroid, but to the whole body.

  20. Can selective arterial clamping with fluorescence imaging preserve kidney function during robotic partial nephrectomy?

    PubMed Central

    McClintock, Tyler R.; Bjurlin, Marc A.; Wysock, James S.; Borofsky, Michael S.; Marien, Tracy P.; Okoro, Chinonyerem; Stifelman, Michael D.

    2015-01-01

    Objectives To compare renal functional outcomes in robotic partial nephrectomy (RPN) with selective arterial clamping guided by near infrared fluorescence (NIRF) imaging to a matched cohort of patients who underwent RPN without selective arterial clamping and NIRF imaging. Methods From April 2011 to December 2012, NIRF imaging-enhanced RPN with selective clamping was utilized in 42 cases. Functional outcomes of successful cases were compared with a cohort of patients, matched by tumor size, preoperative eGFR, functional kidney status, age, sex, body mass index, and American Society of Anesthesiologists score, who underwent RPN without selective clamping and NIRF imaging. Results In matched-pair analysis, selective clamping with NIRF was associated with superior kidney function at discharge, as demonstrated by postoperative eGFR (78.2 vs 68.5 ml/min per 1.73m2; P=0.04), absolute reduction of eGFR (−2.5 vs −14.0 ml/min per 1.73m2; P<0.01) and percent change in eGFR (−1.9% vs −16.8%, P<0.01). Similar trends were noted at three month follow up but these differences became non-significant (P[eGFR]=0.07], P[absolute reduction of eGFR]=0.10, and P[percent change in eGFR]=0.07). In the selective clamping group, a total of four perioperative complications occurred in three patients, all of which were Clavien I-III. Conclusion Utilization of NIRF imaging was associated with improved short-term renal functional outcomes when compared to RPN without selective arterial clamping and NIRF imaging. With this effect attenuated at later follow-up, randomized prospective studies and long-term assessment of kidney-specific functional outcomes are needed to further assess the benefits of this technology. PMID:24909960

  1. Water-borne diclofenac affects kidney and gill integrity and selected immune parameters in brown trout (Salmo trutta f. fario).

    PubMed

    Hoeger, Birgit; Köllner, Bernd; Dietrich, Daniel R; Hitzfeld, Bettina

    2005-10-01

    The detection of residues of various pharmaceuticals in surface waters during the last two decades has prompted concerns about possible adverse effects of this kind of pollution on aquatic organisms. The objective of the present study was to investigate effects of the non-steroidal anti-inflammatory drug diclofenac, one of the pharmaceuticals most prevalent in surface waters, on brown trout (Salmo trutta f. fario), a salmonid species native to German rivers. Brown trout were exposed to 0.5, 5 and 50 microg/L diclofenac for 7, 14 and 21 days, whereby the lowest exposure concentration is comparable with concentrations commonly found in the aquatic environment. Fish exposed to diclofenac displayed significantly reduced haematocrit levels after 7 and 14 days of exposure. After 21 days, trout were examined for histopathological alterations, whereby diclofenac exposure resulted in increased monocyte infiltration in the liver, telangiectasis in gills, and the occurrence of interstitial hyaline droplets, interstitial proteinaceous fluid and mild tubular necrosis in trunk kidney. Concurrent immunohistological analysis revealed an increase of granulocyte numbers in primary gill filaments, as well as granulocyte accumulation and increased major histocompatibility complex (MHC) II expression in kidney, suggestive of an inflammatory process in these organs. Moreover, the ability of diclofenac to hinder the stimulation of prostaglandin E2 synthesis was shown in head kidney macrophages of brown trout in vitro. These findings support the hypothesis that environmental exposure of fish to diclofenac provokes the same mechanism of action in these non-target organisms as previously described for mammalian species and can thus lead to similar (possibly adverse) effects. In general, the present study suggests that exposure of brown trout to diclofenac in concentration ranges commonly found in the environment can result in adverse effects in various organs and possibly compromise the

  2. l-Carnitine improves cognitive and renal functions in a rat model of chronic kidney disease.

    PubMed

    Abu Ahmad, Nur; Armaly, Zaher; Berman, Sylvia; Jabour, Adel; Aga-Mizrachi, Shlomit; Mosenego-Ornan, Efrat; Avital, Avi

    2016-10-01

    Over the past decade, the prevalence of chronic kidney disease (CKD) has reached epidemic proportions. The search for novel pharmacological treatment for CKD has become an area of intensive clinical research. l-Carnitine, considered as the "gatekeeper" responsible for admitting long chain fatty acids into cell mitochondria. l-Carnitine synthesis and turnover are regulated mainly by the kidney and its levels inversely correlate with serum creatinine of normal subjects and CKD patients. Previous studies showed that l-carnitine administration to elderly people is improving and preserving cognitive function. As yet, there are no clinical intervention studies that investigated the effect of l-carnitine administration on cognitive impairment evidenced in CKD patients. Thus, we aimed to investigate the effects of l-carnitine treatment on renal function and on the cognitive performance in a rat model of progressive CKD. To assess the role of l-carnitine on CKD condition, we estimated the renal function and cognitive abilities in a CKD rat model. We found that all CKD animals exhibited renal function deterioration, as indicated by elevated serum creatinine, BUN, and ample histopathological abnormalities. l-Carnitine treatment of CKD rats significantly reduced serum creatinine and BUN, attenuated renal hypertrophy and decreased renal tissue damage. In addition, in the two way shuttle avoidance learning, CKD animals showed cognitive impairment which recovered by the administration of l-carnitine. We conclude that in a rat model of CKD, l-carnitine administration significantly improved cognitive and renal functions.

  3. Safety of Eplerenone for Kidney-Transplant Recipients with Impaired Renal Function and Receiving Cyclosporine A

    PubMed Central

    Barbe, Coralie; Lavaud, Sylvie; Toupance, Olivier; Nazeyrollas, Pierre; Jaisser, Frederic; Rieu, Philippe

    2016-01-01

    Background Animal studies have highlighted the role of vascular mineralocorticoid receptor during Cyclosporine A-induced nephrotoxicity. Mineralocorticoid receptor antagonists could improve kidney survival but are not commonly used during renal impairment and in association with several immunosuppressive drugs due to a supposed higher risk of adverse events. We tested the tolerance of eplerenone according to its expected adverse events: hyperkalemia, metabolic acidosis, hypotension, acute kidney failure, or any other adverse event. Methods We conducted a single-center, prospective, open-label study in 31 kidney-transplant recipients with impaired renal function (30 and 50 mL/min/1.73m2) and receiving cyclosporine A. All patients received eplerenone 25 mg/d for 8 weeks. Serum potassium, renal function and expected adverse events were closely monitored. Results Eight patients experienced mild hyperkalemia (>5 mmol/L), one moderate hyperkalemia (>5.5 mmol/L) and had to receive potassium-exchange resin. No severe hyperkalemia (>6 mmol/L) occurred. One acute kidney failure was observed, secondary to diarrhea. Basal serum potassium and bicarbonate were independently associated with a higher risk of developing mild hyperkalemia (>5 mmol/L) under treatment (OR 6.5, p = 0.003 and 0.7, p = 0.007, respectively). A cut-off value of 4.35 mmol/L for basal serum potassium was the best factor to predict the risk of developing mild hyperkalemia (>5 mmol/L). Conclusions Until eGFR falls to 30 mL/min/1.73m2, eplerenone could be safely given to kidney-transplant recipients receiving cyclosporine A, if kalemia is closely monitored. When renal function is impaired and if basal kalemia is >4.35 mmol/L, then clinicians should properly balance risk and benefit of eplerenone use and offer dietary advice. An adequately powered prospective randomized study is now needed to test its efficiency (and safety) in this population. Trial Registration ClinicalTrials.gov NCT01834768 PMID:27088859

  4. Kidney function decline after a non-dialysis-requiring acute kidney injury is associated with higher long-term mortality in critically ill survivors

    PubMed Central

    2012-01-01

    Introduction The adverse consequences of a non-dialysis-requiring acute kidney injury (AKI) are unclear. This study aimed to assess the long-term prognoses for critically ill patients experiencing a non-dialysis-requiring AKI. Methods This retrospective observational cohort study investigated non-dialysis-requiring AKI survivors in surgical intensive care units between January 2002 and June 2010. All longitudinal post-discharge serum creatinine measurements and information regarding end-stage renal disease (ESRD) and death were collected. We assessed the long-term outcomes of chronic kidney disease (CKD), ESRD and all-cause mortality beyond discharge. Results Of the 922 identified critically ill patients with a non-dialysis-requiring AKI, 634 (68.8%) patients who survived to discharge were enrolled. A total of 207 patients died after a median follow-up of 700.5 days. The median intervals between the onset of the AKI and the composite endpoints "stage 3 CKD or death", "stage 4 CKD or death", "stage 5 CKD or death", and "ESRD or death" were 685, 1319, 1743, and 2048 days, respectively. This finding shows a steady long-term decline in kidney function after discharge. Using the multivariate Cox proportional hazard model, we found that every 1 mL/min/1.73 m2 decrease from baseline estimated glomerular filtration rate (eGFR) of individuals who progressed to stage 3, 4, and 5 CKD increased the risks of long-term mortality by 0.7%, 2.3%, and 4.1%, respectively (all p < 0.05). This result indicates that the mortality risk increased significantly in a graded manner as kidney function declined from the baseline eGFR to advanced stages of CKD during the follow-up period. Conclusions In critically ill patients who survive a non-dialysis-requiring AKI, there is a need for continuous monitoring and kidney function protection beyond discharge. PMID:22789111

  5. A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects

    PubMed Central

    Shafer, Maxwell E. R.; Aoudjit, Lamine; Hu, Di; Sharma, Richa; Tremblay, Mathieu; Ishii, Hidetaka; Marcotte, Michael; Stanga, Daniela; Tang, You Chi; Boualia, Sami Kamel; Nguyen, Alana H. T.; Takano, Tomoko; Lamarche-Vane, Nathalie; Vidal, Silvia; Bouchard, Maxime

    2016-01-01

    Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs), including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK) or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease. PMID:26859289

  6. Positive and negative affective processing exhibit dissociable functional hubs during the viewing of affective pictures.

    PubMed

    Zhang, Wenhai; Li, Hong; Pan, Xiaohong

    2015-02-01

    Recent resting-state functional magnetic resonance imaging (fMRI) studies using graph theory metrics have revealed that the functional network of the human brain possesses small-world characteristics and comprises several functional hub regions. However, it is unclear how the affective functional network is organized in the brain during the processing of affective information. In this study, the fMRI data were collected from 25 healthy college students as they viewed a total of 81 positive, neutral, and negative pictures. The results indicated that affective functional networks exhibit weaker small-worldness properties with higher local efficiency, implying that local connections increase during viewing affective pictures. Moreover, positive and negative emotional processing exhibit dissociable functional hubs, emerging mainly in task-positive regions. These functional hubs, which are the centers of information processing, have nodal betweenness centrality values that are at least 1.5 times larger than the average betweenness centrality of the network. Positive affect scores correlated with the betweenness values of the right orbital frontal cortex (OFC) and the right putamen in the positive emotional network; negative affect scores correlated with the betweenness values of the left OFC and the left amygdala in the negative emotional network. The local efficiencies in the left superior and inferior parietal lobe correlated with subsequent arousal ratings of positive and negative pictures, respectively. These observations provide important evidence for the organizational principles of the human brain functional connectome during the processing of affective information.

  7. Mechanisms and biological functions of autophagy in diseased and ageing kidneys.

    PubMed

    Fougeray, Sophie; Pallet, Nicolas

    2015-01-01

    Autophagy degrades pathogens, altered organelles and protein aggregates, and is characterized by the sequestration of cytoplasmic cargos within double-membrane-limited vesicles called autophagosomes. The process is regulated by inputs from the cellular microenvironment, and is activated in response to nutrient scarcity and immune triggers, which signal through a complex molecular network. Activation of autophagy leads to the formation of an isolation membrane, recognition of cytoplasmic cargos, expansion of the autophagosomal membrane, fusion with lysosomes and degradation of the autophagosome and its contents. Autophagy maintains cellular homeostasis during stressful conditions, dampens inflammation and shapes adaptive immunity. A growing body of evidence has implicated autophagy in kidney health, ageing and disease; it modulates tissue responses during acute kidney injuries, regulates podocyte homeostasis and protects against age-related renal disorders. The renoprotective functions of autophagy in epithelial renal cells and podocytes are mostly mediated by the clearance of altered mitochondria, which can activate inflammasomes and apoptosis, and the removal of protein aggregates, which might trigger inflammation and cell death. In translational terms, autophagy is undoubtedly an attractive target for developing new renoprotective treatments and identifying markers of kidney injury. PMID:25385287

  8. Impact of failed allograft nephrectomy on initial function and graft survival after kidney retransplantation.

    PubMed

    Schleicher, Christina; Wolters, Heiner; Kebschull, Linus; Anthoni, Christoph; Suwelack, Barbara; Senninger, Norbert; Palmes, Daniel; Mersfeld, Bernadette

    2011-03-01

    The management of an asymptomatic failed renal graft remains controversial. The aim of our study was to explore the effect of failed allograft nephrectomy on kidney retransplantation by comparing the outcome of recipients who underwent graft nephrectomy prior to retransplantation with those who did not. Retrospective comparison of patients undergoing kidney retransplantation with (group A, n = 121) and without (group B, n = 45) preliminary nephrectomy was performed, including subgroup analysis with reference to patients with multiple (≥2) retransplantations and patients of the European Senior Program (ESP). Nephrectomy leads to increased panel reactive antibody (PRA) levels prior to retransplantation and is associated with significantly increased rates of primary nonfunction (PNF; P = 0.05) and acute rejection (P = 0.04). Overall graft survival after retransplantation was significantly worse in group A compared with group B (P = 0.03). Among the subgroups especially ESP patients showed a shorter graft survival after previous allograft nephrectomy. On the multivariate analysis, pretransplant graft nephrectomy and PRA >70% were independent and significant risk factors associated with graft loss after kidney retransplantation. Nephrectomy of the failed allograft was not beneficial for retransplant outcome in our series. Patients with failed graft nephrectomy tended to have a higher risk of PNF and acute rejection after retransplantation. The possibility that the graft nephrectomy has a negative impact on graft function and survival after retransplantation is worth studying further.

  9. Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function.

    PubMed

    Jing, Jiaojiao; Pattaro, Cristian; Hoppmann, Anselm; Okada, Yukinori; Fox, Caroline S; Köttgen, Anna

    2016-10-01

    Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR-associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to-creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis.

  10. Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function.

    PubMed

    Jing, Jiaojiao; Pattaro, Cristian; Hoppmann, Anselm; Okada, Yukinori; Fox, Caroline S; Köttgen, Anna

    2016-10-01

    Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR-associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to-creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis. PMID:27263491

  11. The Power of Renal Function Estimation Equations for Predicting Long-Term Kidney Graft Survival

    PubMed Central

    Choi, Hoon Young; Joo, Dong Jin; Song, Mi Kyung; Kim, Myoung Soo; Park, Hyeong Cheon; Kim, Yu Seun; Kim, Beom Seok

    2016-01-01

    Abstract Evaluation of renal function using an accurate estimation equation is important for predicting long-term graft survival. We designed this retrospective cohort study to evaluate the predictive power of renal function estimation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) study equations for graft survival. We reviewed data of 3290 adult kidney transplant recipients who underwent transplantation at a single center between April 1979 and September 2012. The reliability and agreement of chronic kidney disease (CKD) stages based on the estimated glomerular filtration rate (eGFR) as calculated by the CKD-EPI and MDRD equations were evaluated using Bland–Altman plots and Cohen weighted kappa analyses. The predictive power of CKD stages as classified by each equation for graft survival was investigated using Cox regression models. Additionally, Pearson and Spearman correlation coefficients were used to reveal the relationship between graft survival and eGFR equations. Of 3290 kidney transplant recipients, 3040 were included in the analysis. The mean follow-up duration was 128.08 ± 83.54 months, and 29.8% of participants were reclassified to higher eGFR categories by the CKD-EPI equation compared to the category classification by the MDRD equation. eGFR calculated using the MDRD equation was underestimated compared to that calculated using the CKD-EPI equation, based on the Bland–Altman plot. In Cohen weighted kappa analysis, agreement across CKD stages classified using the 2 equations was reliable, but all CKD stages classified using the MDRD equation appeared to be in lower eGFR categories than those classified using the CKD-EPI equation. Pearson and Spearman correlation analyses indicated that the CKD stage as classified by the CKD-EPI equation, but not the MDRD equation, was significantly correlated with the risk of graft failure. In multivariable Cox regression analysis for

  12. Associations of Sugar and Artificially Sweetened Soda with Albuminuria and Kidney Function Decline in Women

    PubMed Central

    Curhan, Gary C.

    2011-01-01

    Summary Background and objectives Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. Design, setting, participants, & measurements This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥3 ml/min per 1.73 m2 per year was also examined. Results Consumption of ≥2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥3 ml/min per 1.73 m2 per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Conclusions Consumption of ≥2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women. PMID:20884773

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

    PubMed Central

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

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

  14. SDF-1/CXCR4 signaling preserves microvascular integrity and renal function in chronic kidney disease.

    PubMed

    Chen, Li-Hao; Advani, Suzanne L; Thai, Kerri; Kabir, M Golam; Sood, Manish M; Gibson, Ian W; Yuen, Darren A; Connelly, Kim A; Marsden, Philip A; Kelly, Darren J; Gilbert, Richard E; Advani, Andrew

    2014-01-01

    The progressive decline of renal function in chronic kidney disease (CKD) is characterized by both disruption of the microvascular architecture and the accumulation of fibrotic matrix. One angiogenic pathway recently identified as playing an essential role in renal vascular development is the stromal cell-derived factor-1α (SDF-1)/CXCR4 pathway. Because similar developmental processes may be recapitulated in the disease setting, we hypothesized that the SDF-1/CXCR4 system would regulate microvascular health in CKD. Expression of CXCR4 was observed to be increased in the kidneys of subtotally nephrectomized (SNx) rats and in biopsies from patients with secondary focal segmental glomerulosclerosis (FSGS), a rodent model and human correlate both characterized by aberration of the renal microvessels. A reno-protective role for local SDF-1/CXCR4 signaling was indicated by i) CXCR4-dependent glomerular eNOS activation following acute SDF-1 administration; and ii) acceleration of renal function decline, capillary loss and fibrosis in SNx rats treated with chronic CXCR4 blockade. In contrast to the upregulation of CXCR4, SDF-1 transcript levels were decreased in SNx rat kidneys as well as in renal fibroblasts exposed to the pro-fibrotic cytokine transforming growth factor β (TGF-β), the latter effect being attenuated by histone deacetylase inhibition. Increased renal SDF-1 expression was, however, observed following the treatment of SNx rats with the ACE inhibitor, perindopril. Collectively, these observations indicate that local SDF-1/CXCR4 signaling functions to preserve microvascular integrity and prevent renal fibrosis. Augmentation of this pathway, either purposefully or serendipitously with either novel or existing therapies, may attenuate renal decline in CKD. PMID:24637920

  15. Balanced Hydroxyethylstarch (HES 130/0.4) Impairs Kidney Function In-Vivo without Inflammation

    PubMed Central

    Schick, Martin Alexander; Baar, Wolfgang; Bruno, Raphael Romano; Wollborn, Jakob; Held, Christopher; Schneider, Reinhard; Flemming, Sven; Schlegel, Nicolas; Roewer, Norbert; Neuhaus, Winfried; Wunder, Christian

    2015-01-01

    Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1–4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion. PMID:26340751

  16. A correlation study of telomere length in peripheral blood leukocytes and kidney function with age.

    PubMed

    Zhang, Wei-Guang; Wang, Yong; Hou, Kai; Jia, Lin-Pei; Ma, Jie; Zhao, De-Long; Zhu, Shu-Ying; Bai, Xiao-Juan; Cai, Guang-Yan; Wang, Yan-Ping; Sun, Xue-Feng; Chen, Xiang-Mei

    2015-06-01

    The current study aimed to investigate the association between telomere length in peripheral blood leukocytes and kidney function in various age groups of a healthy population. A total of 139 healthy individuals were divided into five groups according to their age: 35‑44, 45‑54, 55‑64, 65‑74 and >75 years old. Peripheral blood leukocytes were obtained and the telomere restriction fragment (TRF) length was assayed using a digoxigenin‑labeled hybridization probe in Southern blot assays. Laboratory assays of kidney function were also performed. A correlation was observed between TRF length and age (r=‑0.314, P<0.001), with the telomere length of the individuals >75 years group being significantly shorter than the telomere length of the 35‑44, 45‑54 and 55‑64 years age groups (P<0.05). By contrast, the TRF length for males versus females did not differ for any of the age groups, while a correlation was observed between TRF length and serum levels of cystatin C (r=‑0.195, P<0.05). There was also a correlation between TRF length and glomerular filtration rate (r=‑0.184, P<0.05). The current study demonstrated that in this cohort, leukocyte telomere length reduced with age and was correlated with serum levels of cystatin C and glomerular filtration rate. Therefore, TRF length is associated with kidney function and may serve as a marker of aging.

  17. Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury.

    PubMed

    Skrypnyk, Nataliya I; Voziyan, Paul; Yang, Haichun; de Caestecker, Christian R; Theberge, Marie-Claude; Drouin, Mathieu; Hudson, Billy; Harris, Raymond C; de Caestecker, Mark P

    2016-08-01

    Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI. PMID:27194713

  18. [Do shock waves damage the kidney? Morphologic and functional changes of the kidney following exposure to shock waves].

    PubMed

    Jaeger, P; Redha, S; Alund, G; Uhlschmid, G

    1989-07-01

    The introduction of extracorporeal shockwave lithotripsy (ESWL) as a routine procedure has brought about a dramatic change in the therapy of urolithiasis. More than 500,000 patients have been treated successfully. Although a tissue damaging effect of the shock wave on the kidney was regarded as non-existent, phenomena such as hematuria during ESWL treatment and subsequent subcapsular hematomas suggest the possibility of damage in the region of the renal parenchyma by the shockwave itself. To investigate this possibility canine kidneys were examined histologically at different intervals after shockwave exposure. Extensive histological changes such as hemorrhage and sometimes direct tubular damage were found, with scar formation after three months. These changes are limited to the areas exposed to ESWL treatment.

  19. Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

    PubMed Central

    Faulhaber-Walter, Robert; Scholz, Sebastian; Haller, Herrmann; Kielstein, Jan T; Hafer, Carsten

    2016-01-01

    Background Critically ill patients with acute kidney injury (AKI) in need of renal replacement therapy (RRT) may have a protracted and often incomplete rehabilitation. Their long-term outcome has rarely been investigated. Study design Survivors of the HANnover Dialysis OUTcome (HANDOUT) study were evaluated after 5 years for survival, health status, renal function, and quality of life (QoL). The HANDOUT study had examinded mortality and renal recovery of patients with AKI receiving either standard extendend or intensified dialysis after multi organ failure. Results One hundred fifty-six former HANDOUT participants were analyzed. In-hospital mortality was 56.4%. Five-year survival after AKI/RRT was 40.1% (86.5% if discharged from hospital). Main causes of death were cardiovascular complications and sepsis. A total of 19 survivors presented to the outpatient department of our clinic and had good renal recovery (mean estimated glomerular filtration rate 72.5±30 mL/min/1.73 m2; mean proteinuria 89±84 mg/d). One person required maintenance dialysis. Seventy-nine percent of the patients had a pathological kidney sonomorphology. The Charlson comorbidity score was 2.2±1.4 and adjusted for age 3.3±2.1 years. Numbers of comorbid conditions averaged 2.38±1.72 per patient (heart failure [52%] > chronic kidney disease/myocardial infarction [each 29%]). Median 36-item short form health survey (SF-36™) index was 0.657 (0.69 physical health/0.66 mental health). Quality-adjusted life-years after 5 years were 3.365. Conclusion Mortality after severe AKI is higher than short-term prospective studies show, and morbidity is significant. Kidney recovery as well as general health remains incomplete. Reduction of QoL is minor, and social rehabilitation is very good. Affectivity is heterogeneous, but most patients experience emotional well-being. In summary, AKI in critically ill patients leads to incomplete rehabilitation but acceptable QoL after 5 years. PMID:27284261

  20. [NAG (N-acetyl-beta-D-glucosaminidase)--a sensitive marker for disorders of kidney function].

    PubMed

    Skrezek, C; Bertermann, H; Schulz, F P; König, B

    1990-01-01

    In a clinical study we tested the use of the lysosomal enzyme NAG as a parameter of kidney function. Following prospective randomization, we examined NAG excretion during cisplatin treatment with/without nephroprotection, after intravenous urography with ionic/non-ionic contrast media, during lower/upper urinary tract infections and before/after extracorporeal shockwave lithotripsy for intrarenal calculi (first-generation equipment used). Measurements were performed in 3-h urine specimens and in urine collected over 24 h, using a simple method of analysis. A correlation between NAG leakage and functional disorder of the renal tubular cells seemed likely on the basis of additional clinical and experimental data. Increases, in some cases dramatic, in NAG excretion were observed after the administration of cisplatin and ionic contrast media, in acute pyelonephritis, and after extracorporeal shockwave lithotripsy. However, the increase in NAG excretion was less impressive during cisplatin therapy when nephroprotective amino acids were infused, and in the urography group when non-ionic contrast media were used. Infections of the lower urinary tract did not increase NAG excretion. The results indicate that NAG is a sensitive marker of occult renal dysfunction, which can be checked by non-invasive techniques and can be used in a clinic setting to detect functional disorders of the kidney.

  1. Effects of 10 to 30 years of lithium treatment on kidney function.

    PubMed

    Aiff, Harald; Attman, Per-Ola; Aurell, Mattias; Bendz, Hans; Ramsauer, Bernd; Schön, Staffan; Svedlund, Jan

    2015-05-01

    Long-term lithium treatment is associated with end-stage renal disease, but there is little evidence of a clinically significant reduction in renal function in most patients. We previously found that 1.5% of people who took lithium from the 1960s and 1970s developed end-stage renal disease; however, none of the patients who started after 1980 had end-stage renal disease. Here we aimed to study the prevalence and extent of kidney damage during the course of long-term lithium treatment since 1980. We retrieved serum lithium and creatinine levels from 4879 patients examined between 1 January 1981 and 31 December 2010. Only patients who started their lithium treatment during the study period and had at least 10 years of cumulative treatment were included. The study group comprised 630 adult patients (402 women and 228 men) with normal creatinine levels at the start of lithium treatment. There was a yearly increase in median serum creatinine levels already from the first year of treatment. About one-third of the patients who had taken lithium for 10-29 years had evidence of chronic renal failure but only 5% were in the severe or very severe category. The results indicate that a substantial proportion of adult patients who are treated with lithium for more than a decade develop signs of renal functional impairment, also when treated according to modern therapeutic principles. Our results emphasise that lithium treatment requires continuous monitoring of kidney function.

  2. Association of Kidney Function with Changes in the Endothelial Surface Layer

    PubMed Central

    Dane, Martijn J.C.; Khairoun, Meriem; Lee, Dae Hyun; van den Berg, Bernard M.; Eskens, Bart J.M.; Boels, Margien G.S.; van Teeffelen, Jurgen W.G.E.; Rops, Angelique L.W.M.M.; van der Vlag, Johan; van Zonneveld, Anton Jan; Reinders, Marlies E.J.; Vink, Hans; Rabelink, Ton J.

    2014-01-01

    Background and objectives ESRD is accompanied by endothelial dysfunction. Because the endothelial glycocalyx (endothelial surface layer) governs interactions between flowing blood and the vessel wall, perturbation could influence disease progression. This study used a novel noninvasive sidestream–darkfield imaging method, which measures the accessibility of red blood cells to the endothelial surface layer in the microcirculation (perfused boundary region), to investigate whether renal function is associated with endothelial surface layer dimensions. Design, setting, participants, & measurements Perfused boundary region was measured in control participants (n=10), patients with ESRD (n=23), participants with normal kidney function after successful living donor kidney transplantation (n=12), and patients who developed interstitial fibrosis/tubular atrophy after kidney transplantation (n=10). In addition, the endothelial activation marker angiopoietin-2 and shed endothelial surface layer components syndecan-1 and soluble thrombomodulin were measured using ELISA. Results Compared with healthy controls (1.82±0.16 µm), ESRD patients had a larger perfused boundary region (+0.23; 95% confidence interval, 0.46 to <0.01; P<0.05), which signifies loss of endothelial surface layer dimensions. This large perfused boundary region was accompanied by higher circulating levels of syndecan-1 (+57.71; 95% confidence interval, 17.38 to 98.04; P<0.01) and soluble thrombomodulin (+12.88; 95% confidence interval, 0.29 to 25.46; P<0.001). After successful transplantation, the perfused boundary region was indistinguishable from healthy controls (without elevated levels of soluble thrombomodulin or syndecan-1). In contrast, however, patients who developed interstitial fibrosis and tubular atrophy showed a large perfused boundary region (+0.36; 95% confidence interval, 0.09 to 0.63; P<0.01) and higher levels of endothelial activation markers. In addition, a significant correlation

  3. Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly

    PubMed Central

    Kaboré, Jean; Metzger, Marie; Helmer, Catherine; Berr, Claudine; Tzourio, Christophe; Massy, Ziad A.; Stengel, Bénédicte

    2016-01-01

    Background Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown. Methods The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations. Results Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73m² drop, were 1.23 [95% confidence interval 0.91–1.64] compared to controlled hypertension and 1.10 [0.83–1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73m² per year were 1.89 [1.09–3.29] and 1.99 [1.19–3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73m² per year. Conclusion The speed of

  4. Kidney Function, Endothelial Activation and Atherosclerosis in Black and White Africans with Rheumatoid Arthritis

    PubMed Central

    Dessein, Patrick H.; Hsu, Hon-Chun; Tsang, Linda; Millen, Aletta M. E.; Woodiwiss, Angela J.; Norton, Gavin R.; Solomon, Ahmed; Gonzalez-Gay, Miguel A.

    2015-01-01

    Objective To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA). Methods We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (EGFR) equations in 233 (112 black) RA patients. Results The CKD-EPI eGFR was <90 ml/min/1.73m2 in 49.1% and 30.6% of black and white patients, respectively (odds ratio (95% confidence interval) = 2.19 (1.28–3.75), p = 0.004). EGFRs were overall consistently associated with monocyte chemoattractant protein-1 and angiopoietin 2 concentrations in white patients, and with carotid intima-media thickness and plaque in black participants. Amongst black patients, plaque prevalence was 36.7% and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was not associated with plaque presence for the MDRD equation (p = 0.3), whereas the respective relationship was significant or borderline significant (p = 0.003 to 0.08) and of similar extent (p>0.1 for comparisons of AUC (SE)) for the other 8 equations. Based on optimal eGFR cutoff values with sensitivities and specificities ranging from 42 to 60% and 70 to 91% respectively, as determined in ROC curve analysis, a low eGFR increased the odds ratio for plaque 2.2 to 4.0 fold. Conclusion Reduced kidney function is independently associated with atherosclerosis and endothelial activation in black and white Africans with RA, respectively. CKD is highly prevalent in black Africans with RA. Apart from the MDRD, eGFR equations are useful in predicting carotid plaque presence, a coronary heart disease equivalent, amongst black African RA patients. PMID:25806966

  5. Isoforms of Spectrin and Ankyrin Reflect the Functional Topography of the Mouse Kidney

    PubMed Central

    Stankewich, Michael C.; Moeckel, Gilbert W.; Ji, Lan; Ardito, Thomas; Morrow, Jon S.

    2016-01-01

    The kidney displays specialized regions devoted to filtration, selective reabsorption, and electrolyte and metabolite trafficking. The polarized membrane pumps, channels, and transporters responsible for these functions have been exhaustively studied. Less examined are the contributions of spectrin and its adapter ankyrin to this exquisite functional topography, despite their established contributions in other tissues to cellular organization. We have examined in the rodent kidney the expression and distribution of all spectrins and ankyrins by qPCR, Western blotting, immunofluorescent and immuno electron microscopy. Four of the seven spectrins (αΙΙ, βΙ, βΙΙ, and βΙΙΙ) are expressed in the kidney, as are two of the three ankyrins (G and B). The levels and distribution of these proteins vary widely over the nephron. αΙΙ/βΙΙ is the most abundant spectrin, found in glomerular endothelial cells; on the basolateral membrane and cytoplasmic vesicles in proximal tubule cells and in the thick ascending loop of Henle; and less so in the distal nephron. βΙΙΙ spectrin largely replaces βΙΙ spectrin in podocytes, Bowman’s capsule, and throughout the distal tubule and collecting ducts. βΙ spectrin is only marginally expressed; its low abundance hinders a reliable determination of its distribution. Ankyrin G is the most abundant ankyrin, found in capillary endothelial cells and all tubular segments. Ankyrin B populates Bowman’s capsule, podocytes, the ascending thick loop of Henle, and the distal convoluted tubule. Comparison to the distribution of renal protein 4.1 isoforms and various membrane proteins indicates a complex relationship between the spectrin scaffold, its adapters, and various membrane proteins. While some proteins (e.g. ankyrin B, βΙΙΙ spectrin, and aquaporin 2) tend to share a similar distribution, there is no simple mapping of different spectrins or ankyrins to most membrane proteins. The implications of this data are

  6. The effect of cold ischemia time on delayed graft function and acute rejection in kidney transplantation.

    PubMed

    Sert, Ismail; Colak, Hulya; Tugmen, Cem; Dogan, Sait Murat; Karaca, Cezmi

    2014-09-01

    The objective of this study is to evaluate the impact of cold ischemia time (CIT) on delayed graft function (DGF) and acute rejection (AR) among deceased donor kidney transplant recipients. The medical records of 111 patients who underwent kidney transplantation from deceased donors between November 1994 and July 2009 were retrospectively analyzed. DGF was observed in 54% of the patients and the prevalence of AR in the first year after transplantation was 9.9%. The incidence of DGF was higher among patients with longer CIT. There was no correlation between CIT and AR episodes. Higher body weight of recipients and donors, history of prior blood transfusion and advanced donor age were related with DGF. Patients with DGF had higher serum creatinine levels at the first, third and fifth years. There was a negative correlation between recipient body weight and creatinine clearance at the first year. CIT has an important role in the development of DGF as a modifiable risk factor. Moreover, donors with advanced age and higher body weight as well as recipients with higher body weight and history of blood transfusions are at risk for the development of DGF. Prevention of DGF may help to improve graft function at the first, third and fifth years and shorten the hospital stay.

  7. Dietary Energy Density, Renal Function, and Progression of Chronic Kidney Disease

    PubMed Central

    Rouhani, Mohammad Hossein; Najafabadi, Mojgan Mortazavi; Esmaillzadeh, Ahmad; Feizi, Awat

    2016-01-01

    Background. There is evidence of the association between dietary energy density and chronic diseases. However, no report exists regarding the relation between DED and chronic kidney disease (CKD). Objective. To examine the association between dietary energy density (DED), renal function, and progression of chronic kidney disease (CKD). Design. Cross-sectional. Setting. Three nephrology clinics. Subjects. Two hundred twenty-one subjects with diagnosed CKD. Main Outcome Measure. Dietary intake of patients was assessed by a validated food frequency questionnaire. DED (in kcal/g) was calculated with the use of energy content and weight of solid foods and energy yielding beverages. Renal function was measured by blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR). Results. Patients in the first tertile of DED consumed more amounts of carbohydrate, dietary fiber, potassium, phosphorus, zinc, magnesium, calcium, folate, vitamin C, and vitamin B2. After adjusting for confounders, we could not find any significant trend for BUN and Cr across tertiles of DED. In multivariate model, an increased risk of being in the higher stage of CKD was found among those in the last tertile of DED (OR: 3.15; 95% CI: 1.30, 7.63; P = 0.01). Conclusion. We observed that lower DED was associated with better nutrient intake and lower risk of CKD progression.

  8. Affect integration and reflective function: clarification of central conceptual issues.

    PubMed

    Solbakken, Ole André; Hansen, Roger Sandvik; Monsen, Jon Trygve

    2011-07-01

    The importance of affect regulation, modulation or integration for higher-order reflection and adequate functioning is increasingly emphasized across different therapeutic approaches and theories of change. These processes are probably central to any psychotherapeutic endeavor, whether explicitly conceptualized or not, and in recent years a number of therapeutic approaches have been developed that explicitly target them as a primary area of change. However, there still is important lack of clarity in the field regarding the understanding and operationalization of affect integration, particularly when it comes to specifying underlying mechanisms, the significance of different affect states, and the establishment of operational criteria for measurement. The conceptual relationship between affect integration and reflective function thus remains ambiguous. The present article addresses these topics, indicating ways in which a more complex and exhaustive understanding of integration of affect, cognition and behavior can be attained.

  9. How Does Maternal Employment Affect Children's Socioemotional Functioning?

    ERIC Educational Resources Information Center

    Lam, Gigi

    2015-01-01

    The maternal employment becomes an irreversible trend across the globe. The effect of maternal employment on children's socioemotional functioning is so pervasive that it warrants special attention to investigate into the issue. A trajectory of analytical framework of how maternal employment affects children's socioemotional functioning originates…

  10. Exome Sequencing and Prediction of Long-Term Kidney Allograft Function

    PubMed Central

    Mesnard, Laurent; Muthukumar, Thangamani; Burbach, Maren; Li, Carol; Shang, Huimin; Dadhania, Darshana; Lee, John R.; Xiang, Jenny; Suberbielle, Caroline; Carmagnat, Maryvonnick; Ouali, Nacera; Rondeau, Eric; Abecassis, Michael M.; Suthanthiran, Manikkam

    2016-01-01

    Current strategies to improve graft outcome following kidney transplantation consider information at the human leukocyte antigen (HLA) loci. Cell surface antigens, in addition to HLA, may serve as the stimuli as well as the targets for the anti-allograft immune response and influence long-term graft outcomes. We therefore performed exome sequencing of DNA from kidney graft recipients and their living donors and estimated all possible cell surface antigens mismatches for a given donor/recipient pair by computing the number of amino acid mismatches in trans-membrane proteins. We designated this tally as the allogenomics mismatch score (AMS). We examined the association between the AMS and post-transplant estimated glomerular filtration rate (eGFR) using mixed models, considering transplants from three independent cohorts (a total of 53 donor-recipient pairs, 106 exomes, and 239 eGFR measurements). We found that the AMS has a significant effect on eGFR (mixed model, effect size across the entire range of the score: -19.4 [-37.7, -1.1], P = 0.0042, χ2 = 8.1919, d.f. = 1) that is independent of the HLA-A, B, DR matching, donor age, and time post-transplantation. The AMS effect is consistent across the three independent cohorts studied and similar to the strong effect size of donor age. Taken together, these results show that the AMS, a novel tool to quantify amino acid mismatches in trans-membrane proteins in individual donor/recipient pair, is a strong, robust predictor of long-term graft function in kidney transplant recipients. PMID:27684477

  11. Aerobic training during hemodialysis improves body composition, muscle function, physical performance, and quality of life in chronic kidney disease patients

    PubMed Central

    Bae, Young-Hyeon; Lee, Suk Min; Jo, Jong Il

    2015-01-01

    [Purpose] We assessed the influences of individualized aerobic training on body composition, knee joint muscle function, physical performance, and quality of life in chronic kidney disease patients. [Subjects] Ten chronic kidney disease patients undergoing dialysis. [Methods] Overall physical function and quality of life before and after 12 weeks of aerobic training were evaluated by body composition, the six-minute walk test, cardiopulmonary exercise tests, and Short Form 36-item questionnaire. [Results] The six-minute walk test distance increased significantly after 12 weeks aerobic training. Resting metabolic rate, lactate threshold, maximum oxygen uptake, and quality of life tended to increase after training. Post-training weight, muscle mass, body fat mass, fat percentage, body mass index, and peak torque of right and left knee extension and flexion did not change significantly. [Conclusion] Intra-dialytic training can a safe approach to maintain or improve physical performance and quality of life of chronic kidney disease patients undergoing hemodialysis without adverse events or negative cardiovascular responses. Aerobic training may prevent a decline in body composition and knee joint muscle function due to inactivity in chronic kidney disease patients. Clinically, aerobic training may initially be adapted to maintain overall physical function or improve quality of life in chronic kidney disease patients undergoing hemodialysis. PMID:26157237

  12. Technetium-99m dimercaptosuccinic acid uptake in long-term catheterized kidney. Comparison with renal function

    SciTech Connect

    Higashihara, E.; Tokuda, H.; Kishi, H.; Niijima, T.; Okada, Y.; Nishikawa, J.; Iio, M.

    1988-04-01

    We studied 23 long-term catheterized kidneys in 14 patients. The uptake of /sup 99m/Tc acid (/sup 99m/Tc-DMSA) was measured at one- and two-hour intervals after injection, and the uptake was corrected for variations in renal depth. These values were compared with inulin, creatinine, and para-amino hippurate (PAH) clearances which were measured in each kidney by collecting urine through long-term catheterization. Correlation coefficient was obtained between PAH clearance corrected for the body surface area and the two-hour uptake of /sup 99m/Tc-DMSA. The correlation coefficients between the two-hour uptake of /sup 99m/Tc-DMSA and the clearance values are not significantly different from those between the one-hour uptake and the clearance values. Corrections of the uptake for variations in renal depth did not improve the correlation coefficients. The results show that /sup 99m/Tc-DMSA is an excellent method to estimate the renal plasma flow and the one-hour uptake without correction for renal depth is clinically sufficient to evaluate the split renal function.

  13. Optical spectroscopy approach for the predictive assessment of kidney functional recovery following ischemic injury

    NASA Astrophysics Data System (ADS)

    Raman, Rajesh N.; Pivetti, Christopher D.; Rubenchik, Alexander M.; Matthews, Dennis L.; Troppmann, Christoph; Demos, Stavros G.

    2010-02-01

    Tissue that has undergone significant yet unknown amount of ischemic injury is frequently encountered in organ transplantation and trauma clinics. With no reliable real-time method of assessing the degree of injury incurred in tissue, surgeons generally rely on visual observation which is subjective. In this work, we investigate the use of optical spectroscopy methods as a potentially more reliable approach. Previous work by various groups was strongly suggestive that tissue autofluorescence from NADH obtained under UV excitation is sensitive to metabolic response changes. To test and expand upon this concept, we monitored autofluorescence and light scattering intensities of injured vs. uninjured rat kidneys via multimodal imaging under 355 nm, 325 nm, and 266 nm excitation as well as scattering under 500 nm illumination. 355 nm excitation was used to probe mainly NADH, a metabolite, while 266 nm excitation was used to probe mainly tryptophan to correct for non-metabolic signal artifacts. The ratio of autofluorescence intensities derived under these two excitation wavelengths was calculated and its temporal profile was fit to a relaxation model. Time constants were extracted, and longer time constants were associated with kidney dysfunction. Analysis of both the autofluorescence and light scattering images suggests that changes in microstructure tissue morphology, blood absorption spectral characteristics, and pH contribute to the behavior of the observed signal which may be used to obtain tissue functional information and offer predictive capability.

  14. Antigravity suit inflation: kidney function and cardiovascular and hormonal responses in men.

    PubMed

    Geelen, G; Kravik, S E; Hadj-Aissa, A; Leftheriotis, G; Vincent, M; Bizollon, C A; Sem-Jacobsen, C W; Greenleaf, J E; Gharib, C

    1989-02-01

    To investigate the effects of lower body positive pressure (LBPP) on kidney function while controlling certain cardiovascular and endocrine responses, seven men [35 +/- 2 (SE) yr] underwent 30 min of sitting and then 4.5 h of 70 degrees head-up tilt. An antigravity suit was applied (60 Torr legs, 30 Torr abdomen) during the last 3 h of tilt. A similar noninflation experiment was conducted where the suited subjects were tilted for 3.5 h. To provide adequate urine flow, the subjects were hydrated during the course of both experiments. Immediately after inflation, mean arterial pressure increased by 8 +/- 3 Torr and pulse rate decreased by 16 +/- 3 beats/min. Plasma renin activity and aldosterone were maximally suppressed (P less than 0.05) after 2.5 h of inflation. Plasma vasopressin decreased by 40-50% (P less than 0.05) and plasma sodium and potassium remained unchanged during both experiments. Glomerular filtration rate was not increased significantly by inflation, whereas inflation induced marked increases (P less than 0.05) in effective renal plasma flow (ERPF), urine flow, osmolar and free water clearances, and total and fractional sodium excretion. No such changes occurred during control. Thus, LBPP induces 1) a significant increase in ERPF and 2) significant changes in kidney excretory patterns similar to those observed during water immersion or the early phase of bed rest, situations that also result in central vascular volume expansion.

  15. Optical Spectroscopy Approach for the Predictive Assessment of Kidney Functional Recovery Following Ischemic Injury

    SciTech Connect

    Raman, R N; Pivetti, C D; Rubenchik, A M; Matthews, D L; Troppmann, C; Demos, S G

    2010-02-11

    Tissue that has undergone significant yet unknown amount of ischemic injury is frequently encountered in organ transplantation and trauma clinics. With no reliable real-time method of assessing the degree of injury incurred in tissue, surgeons generally rely on visual observation which is subjective. In this work, we investigate the use of optical spectroscopy methods as a potentially more reliable approach. Previous work by various groups was strongly suggestive that tissue autofluorescence from NADH obtained under UV excitation is sensitive to metabolic response changes. To test and expand upon this concept, we monitored autofluorescence and light scattering intensities of injured vs. uninjured rat kidneys via multimodal imaging under 355 nm, 325 nm, and 266 nm excitation as well as scattering under 500 nm illumination. 355 nm excitation was used to probe mainly NADH, a metabolite, while 266 nm excitation was used to probe mainly tryptophan to correct for non-metabolic signal artifacts. The ratio of autofluorescence intensities derived under these two excitation wavelengths was calculated and its temporal profile was fit to a relaxation model. Time constants were extracted, and longer time constants were associated with kidney dysfunction. Analysis of both the autofluorescence and light scattering images suggests that changes in microstructure tissue morphology, blood absorption spectral characteristics, and pH contribute to the behavior of the observed signal which may be used to obtain tissue functional information and offer predictive capability.

  16. Effect of saline adaptation and renal portal sodium infusion on glomerular size distributions and kidney function in domestic fowl.

    PubMed

    Wideman, R F; Satnick, J L; Mitsos, W J; Bennett, K R; Smith, S R

    1987-02-01

    Experiments were designed to evaluate acute and chronic effects of sodium on glomerular size distributions and kidney function of Single Comb White Leghorns. Chicks were raised on either tap water (control) or .6% NaCl (saline) drinking water. Kidney function studies were conducted when the birds reached 14 to 16 weeks of age. Saline-adapted birds had significantly lower glomerular filtration rates and significantly higher sodium and potassium excretion rates when compared with birds raised on tap water. Acute effects of sodium on kidney function were assessed by infusing 25 mM tetrasodium pyrophosphate unilaterally into the renal portal system. For birds raised on tap water, unilateral sodium infusion caused a significant unilateral reduction in the glomerular filtration rate. However, neither the acute nor the chronic reductions in glomerular filtration rates in response to sodium were associated with a reduction in the number of filtering nephrons. Saline-adapted birds had significantly hypertrophied glomeruli.

  17. Nitric oxide synthesis in the kidney: isoforms, biosynthesis, and functions in health.

    PubMed

    Kone, Bruce C

    2004-07-01

    Nitric oxide (NO) is a gaseous free radical that serves cell signaling, cellular energetics, host defense, and inflammatory functions in virtually all cells. In the kidney and vasculature, NO plays fundamental roles in the control of systemic and intrarenal hemodynamics, the tubuloglomerular feedback response, pressure natriuresis, release of sympathetic neurotransmitters and renin, and tubular solute and water transport. NO is synthesized from L-arginine by NO synthases (NOS). Because of its high chemical reactivity and high diffusibility, NO production by each of the 3 major NOS isoforms is regulated tightly at multiple levels from gene transcription to spatial proximity near intended targets to covalent modification and allosteric regulation of the enzyme itself. Many of these regulatory mechanisms have yet to be tested in renal cells. The NOS isoforms are distributed differentially and regulated in the kidney, and there remains some controversy over the specific expression of functional protein for the NOS isoforms in specific renal cell populations. Mice with targeted deletion of each of the NOS isoforms have been generated, and these each have unique phenotypes. Studies of the renal and vascular phenotypes of these mice have yielded important insights into certain vascular diseases, ischemic acute renal failure, the tubuloglomerular feedback response, and some mechanisms of tubular fluid and electrolyte transport, but thus far have been underexploited. This review explores the collective knowledge regarding the structure, regulation, and function of the NOS isoforms gleaned from various tissues, and highlights the progress and gaps in understanding in applying this information to renal and vascular physiology. PMID:15252770

  18. Studies of lipid profile, liver function and kidney function parameters of rat plasma after chronic administration of "Sulavajrini Vatika".

    PubMed

    Kundu, N Krishna; Ullah, M Obayed; Hamid, Kaiser; Urmi, Kaniz Fatima; Bulbul, Israt Jahan; Khan, Muhammad Atikul Islam; Akter, Momita; Choudhuri, M S K

    2012-07-15

    The successful use of Ayurvedic medicines is for many years but there is no guideline for studying the toxicity of these preparations through preclinical or clinical investigations. The present study was conducted to evaluate the effect of conventionally prepared Sulavajrini Vatika (SBB), an Ayurvedic formulation on various biochemical parameters of experimental animals after chronic administration. The animal used was albino rats (Rattus norvegicus: Sprague-Dawley strain) and SBB was administered orally at a single dose of 100 mg kg(-1) b.wt. day(-1), up to 62 days. During the study, forty rats, equally of both sexes, were randomly grouped into four where one male and one female group were used as control and other groups were used as test. Among the lipid components, Triglyceride (TG) was decreased very high significantly in both sexes of animal. The decrease of Total Cholesterol (TC), Very Low Density Lipoprotein (VLDL) and high-density lipoprotein (HDL) were also highly significant. Low Density Lipoprotein (LDL) decreased in all SBB treated group. In the liver function parameters, the total protein and albumin content were increased very high significantly in both sexes of rat. But the bilirubin was decreased insignificantly in male and female rats. Serum Glutamic Pyruvic Transaminase (GPT), Glutamic Oxaloacetic Transaminase (GOT) and Alkaline Phosphatase (ALP) were decreased in all treated animals and it was very high significant. In case of kidney function parameters, creatinine was increased very high significantly but the urea was decreased very high significantly in both sexes of rat. The decrease in uric acid was not significant in none of the sexes of rat. The present study confirms that SBB can be contributory for the complications in diabetics with hyperlipidemia and nephropathy as it lowers most of the lipids components and improves liver function and kidney function parameters.

  19. Effects of acute and chronic hypohydration on kidney health and function.

    PubMed

    Feehally, John; Khosravi, Maryam

    2015-09-01

    The kidneys play a critical role in the homeostasis of body fluid tonicity and effective circulating volume. Renal homeostatic mechanisms are frequently challenged in acutely ill people. Fluid depletion causing hypovolemia may result in renal hypoperfusion that, if left untreated, may lead to acute kidney failure. Some populations, notably older people and neonates, are less tolerant of extremes in fluid loading and deprivation, similar to those with established chronic kidney disease. Risk of kidney injury during fluid depletion is increased by medications including diuretics, nonsteroidal antiinflammatory drugs, and renin-angiotensin system blockers. There is no consistent evidence indicating that lower-than-average fluid intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Increasing consumption of sugar-containing beverages is, however, a major concern for kidney health as a precursor of obesity and diabetes. There is no evidence that high dietary protein intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Idiosyncratic, adverse renal responses have been described with creatine supplements. There are only a few clinical conditions for which high fluid intake should be considered. These include recurrent kidney stones or urinary tract infections and, possibly, polycystic kidney disease. PMID:26290296

  20. Effects of acute and chronic hypohydration on kidney health and function.

    PubMed

    Feehally, John; Khosravi, Maryam

    2015-09-01

    The kidneys play a critical role in the homeostasis of body fluid tonicity and effective circulating volume. Renal homeostatic mechanisms are frequently challenged in acutely ill people. Fluid depletion causing hypovolemia may result in renal hypoperfusion that, if left untreated, may lead to acute kidney failure. Some populations, notably older people and neonates, are less tolerant of extremes in fluid loading and deprivation, similar to those with established chronic kidney disease. Risk of kidney injury during fluid depletion is increased by medications including diuretics, nonsteroidal antiinflammatory drugs, and renin-angiotensin system blockers. There is no consistent evidence indicating that lower-than-average fluid intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Increasing consumption of sugar-containing beverages is, however, a major concern for kidney health as a precursor of obesity and diabetes. There is no evidence that high dietary protein intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Idiosyncratic, adverse renal responses have been described with creatine supplements. There are only a few clinical conditions for which high fluid intake should be considered. These include recurrent kidney stones or urinary tract infections and, possibly, polycystic kidney disease.

  1. High-resolution genetic localization of a modifying locus affecting disease severity in the juvenile cystic kidneys (jck) mouse model of polycystic kidney disease

    PubMed Central

    Beier, David R.

    2016-01-01

    We have previously demonstrated that a locus on proximal Chr 4 modifies disease severity in the juvenile cystic kidney (jck) mouse, a model of polycystic kidney disease (PKD) that carries a mutation of the Nek8 serine-threonine kinase. In this study we used QTL analysis of independently constructed B6.D2 congenic lines to confirm this and showed that this locus has a highly significant effect. We constructed sub-congenic lines to more specifically localize the modifier and have determined it resides in a 3.2 Mb interval containing 28 genes. These include Invs and Anks6, which are both excellent candidates for the modifier as mutations in these genes result in PKD and both genes are known to genetically and physically interact with Nek8. However, examination of strain-specific DNA sequence and kidney expression did not reveal clear differences that might implicate either gene as a modifier of PKD severity. The fact that our high-resolution analysis did not yield an unambiguous result highlights the challenge of establishing the causality of strain-specific variants as genetic modifiers, and suggests that alternative strategies be considered. PMID:27114383

  2. Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease

    PubMed Central

    Harari-Steinberg, Orit; Metsuyanim, Sally; Omer, Dorit; Gnatek, Yehudit; Gershon, Rotem; Pri-Chen, Sara; Ozdemir, Derya D; Lerenthal, Yaniv; Noiman, Tzahi; Ben-Hur, Herzel; Vaknin, Zvi; Schneider, David F; Aronow, Bruce J; Goldstein, Ronald S; Hohenstein, Peter; Dekel, Benjamin

    2013-01-01

    Identification of tissue-specific renal stem/progenitor cells with nephrogenic potential is a critical step in developing cell-based therapies for renal disease. In the human kidney, stem/progenitor cells are induced into the nephrogenic pathway to form nephrons until the 34 week of gestation, and no equivalent cell types can be traced in the adult kidney. Human nephron progenitor cells (hNPCs) have yet to be isolated. Here we show that growth of human foetal kidneys in serum-free defined conditions and prospective isolation of NCAM1+ cells selects for nephron lineage that includes the SIX2-positive cap mesenchyme cells identifying a mitotically active population with in vitro clonogenic and stem/progenitor properties. After transplantation in the chick embryo, these cells—but not differentiated counterparts—efficiently formed various nephron tubule types. hNPCs engrafted and integrated in diseased murine kidneys and treatment of renal failure in the 5/6 nephrectomy kidney injury model had beneficial effects on renal function halting disease progression. These findings constitute the first definition of an intrinsic nephron precursor population, with major potential for cell-based therapeutic strategies and modelling of kidney disease. PMID:23996934

  3. Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function.

    PubMed

    Hall, I E; Bhangoo, R S; Reese, P P; Doshi, M D; Weng, F L; Hong, K; Lin, H; Han, G; Hasz, R D; Goldstein, M J; Schröppel, B; Parikh, C R

    2014-04-01

    Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

  4. New insights into potential functions for the protein 4.1superfamily of proteins in kidney epithelium

    SciTech Connect

    Calinisan, Venice; Gravem, Dana; Chen, Ray Ping-Hsu; Brittin,Sachi; Mohandas, Narla; Lecomte, Marie-Christine; Gascard, Philippe

    2005-06-17

    Members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. We have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1B, 4.1R and 4.1N, in mouse kidney. We describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidney yeast two-hybrid system cDNA library. The identification of putative protein 4.1-based complexes enables us to envision potential functions for 4.1 proteins in kidney: organization of signaling complexes, response to osmotic stress, protein trafficking, and control of cell proliferation. We discuss the relevance of these protein 4.1-based interactions in kidney physio-pathology in the context of their previously identified functions in other cells and tissues. Specifically, we will focus on renal 4.1 protein interactions with beta amyloid precursor protein (beta-APP), 14-3-3 proteins, and the cell swelling-activated chloride channel pICln. We also discuss the functional relevance of another member of the protein 4.1 superfamily, ezrin, in kidney physiopathology.

  5. Par3A is dispensable for the function of the glomerular filtration barrier of the kidney.

    PubMed

    Koehler, Sybille; Tellkamp, Frederik; Niessen, Carien M; Bloch, Wilhelm; Kerjaschki, Dontscho; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T

    2016-07-01

    Polarity signaling through the atypical PKC (aPKC)-Par polarity complex is essential for the development and maintenance of the podocyte architecture and the function of the glomerular filtration barrier of the kidney. To study the contribution of Par3A in this complex, we generated a novel Pard3 podocyte-specific knockout mouse model by targeting exon 6 of the Pard3 gene. Genetic deletion of Pard3a did not impair renal function, neither at birth nor later in life. Even challenging the animals did not result in glomerular disease. Despite its well-established role in aPKC-mediated signaling, Par3A appears to be dispensable for the function of the glomerular filtration barrier. Moreover, its homolog Pard3b, and not Pard3a, is the dominant Par3 gene expressed in podocytes and found at the basis of the slit diaphragm, where it partially colocalizes with podocin. In conclusion, Par3A function is either dispensable for slit diaphragm integrity, or compensatory mechanisms and a high redundancy of the different polarity proteins, including Par3B, Lgl, or PALS1, maintain the function of the glomerular filtration barrier, even in the absence of Par3A.

  6. Acute deterioration of renal function induced by star fruit ingestion in a patient with chronic kidney disease.

    PubMed

    Niticharoenpong, Kannika; Chalermsanyakorn, Panas; Panvichian, Ravat; Kitiyakara, Chagriya

    2006-01-01

    Star fruit (carambola) is a popular tropical fruit, usually consumed as fresh fruit or as fruit juice. In patients on dialysis, consumption of star fruits can lead to alterations of consciousness. In this case report, we describe a patient with underlying chronic kidney disease, who developed a rapid increase in serum creatinine and oxalate nephropathy after chronic ingestion of star fruit juice without overt neurotoxicity. The decline in renal function was not fully reversible after stoppage. This case demonstrates that star fruit consumption should be considered as a cause of rapid deterioration in renal function in patients with underlying chronic kidney disease that may result in permanent renal injury.

  7. Structure and Activity Changes of Phytohemagglutinin from Red Kidney Bean (Phaseolus vulgaris) Affected by Ultrahigh-Pressure Treatments.

    PubMed

    Lu, Yunjun; Liu, Cencen; Zhao, Mouming; Cui, Chun; Ren, Jiaoyan

    2015-11-01

    Phytohemagglutin (PHA), purified from red kidney beans (Phaseolus vulgaris) by Affi-Gel blue affinity chromatography, was subjected to ultrahigh-pressure (UHP) treatment (150, 250, 350, and 450 MPa). The purified PHA lost its hemagglutination activity after 450 MPa treatment and showed less pressure tolerance than crude PHA. However, the saccharide specificity and α-glucosidase inhibition activity of the purified PHA did not change much after UHP treatment. Electrophoresis staining by periodic acid-Schiff (PAS) manifested that the glycone structure of purified PHA remained stable even after 450 MPa pressure treatment. However, electrophoresis staining by Coomassie Blue as well as circular dichroism (CD) and differential scanning calorimetry (DSC) assay proved that the protein unit structure of purified PHA unfolded when treated at 0-250 MPa but reaggregates at 250-450 MPa. Therefore, the hemagglutination activity tends to be affected by the protein unit structure, while the stability of the glycone structure contributed to the remaining α-glucosidase inhibition activity.

  8. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease.

    PubMed

    Hill, Kathleen M; Martin, Berdine R; Wastney, Meryl E; McCabe, George P; Moe, Sharon M; Weaver, Connie M; Peacock, Munro

    2013-05-01

    Patients with chronic kidney disease (CKD) are given calcium carbonate to bind dietary phosphorus, reduce phosphorus retention, and prevent negative calcium balance; however, data are limited on calcium and phosphorus balance during CKD to support this. Here, we studied eight patients with stage 3 or 4 CKD (mean estimated glomerular filtration rate 36 ml/min) who received a controlled diet with or without a calcium carbonate supplement (1500 mg/day calcium) during two 3-week balance periods in a randomized placebo-controlled cross-over design. All feces and urine were collected during weeks 2 and 3 of each balance period and fasting blood, and urine was collected at baseline and at the end of each week. Calcium kinetics were determined using oral and intravenous (45)calcium. Patients were found to be in neutral calcium and phosphorus balance while on the placebo. Calcium carbonate supplementation produced positive calcium balance, did not affect phosphorus balance, and produced only a modest reduction in urine phosphorus excretion compared with placebo. Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance, suggesting soft-tissue deposition. Fasting blood and urine biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. Thus, the positive calcium balance produced by calcium carbonate treatment within 3 weeks cautions against its use as a phosphate binder in patients with stage 3 or 4 CKD, if these findings can be extrapolated to long-term therapy.

  9. Structure and Activity Changes of Phytohemagglutinin from Red Kidney Bean (Phaseolus vulgaris) Affected by Ultrahigh-Pressure Treatments.

    PubMed

    Lu, Yunjun; Liu, Cencen; Zhao, Mouming; Cui, Chun; Ren, Jiaoyan

    2015-11-01

    Phytohemagglutin (PHA), purified from red kidney beans (Phaseolus vulgaris) by Affi-Gel blue affinity chromatography, was subjected to ultrahigh-pressure (UHP) treatment (150, 250, 350, and 450 MPa). The purified PHA lost its hemagglutination activity after 450 MPa treatment and showed less pressure tolerance than crude PHA. However, the saccharide specificity and α-glucosidase inhibition activity of the purified PHA did not change much after UHP treatment. Electrophoresis staining by periodic acid-Schiff (PAS) manifested that the glycone structure of purified PHA remained stable even after 450 MPa pressure treatment. However, electrophoresis staining by Coomassie Blue as well as circular dichroism (CD) and differential scanning calorimetry (DSC) assay proved that the protein unit structure of purified PHA unfolded when treated at 0-250 MPa but reaggregates at 250-450 MPa. Therefore, the hemagglutination activity tends to be affected by the protein unit structure, while the stability of the glycone structure contributed to the remaining α-glucosidase inhibition activity. PMID:26416299

  10. In vitro interactions between Neoparamoeba spp. and salmonid leucocytes; The effect of parasite sonicate on anterior kidney leucocyte function

    USGS Publications Warehouse

    Gross, K.; Alcorn, S.; Murray, A.; Morrison, R.; Nowak, B.

    2006-01-01

    Sonicated Neoparamoeba spp. (Nspp) did not affect the in vitro respiratory burst response of leucocytes isolated from Atlantic salmon Salmo salar, rainbow trout Oncorhynchus mykiss and chinook salmon Oncorhynchus tshawytscha anterior kidneys (P > 0.05). Atlantic salmon and chinook salmon leucocytes pre-incubated with the parasites, however, responded to phorbol myristate acetate (PMA) stimulation with a greater response compared to cells incubated with PMA on its own (P < 0.05). Sonicated Nspp was not chemo-attractive for anterior kidney leucocytes isolated from all three fish species. ?? 2006 The Fisheries Society of the British Isles.

  11. The effects of the recommended dose of creatine monohydrate on kidney function.

    PubMed

    Taner, Basturk; Aysim, Ozagari; Abdulkadir, Unsal

    2011-02-01

    We report a case of a heretofore healthy 18-year-old man who presented with a 2-day history of nausea, vomiting and stomach ache while taking creatine monohydrate for bodybuilding purposes. The patient had acute renal failure, and a renal biopsy was performed to determine the cause of increased creatinine and proteinuria. The biopsy showed acute tubular necrosis. In the literature, creatine monohydrate supplementation and acute tubular necrosis coexistence had not been reported previously. Twenty-five days after stopping the creatine supplements, the patient recovered fully. Even recommended doses of creatine monohydrate supplementation may cause kidney damage; therefore, anybody using this supplement should be warned about this possible side effect, and their renal functions should be monitored regularly.

  12. Dynamic nuclear renography kinetic analysis: Four-compartment model for assessing kidney function

    SciTech Connect

    Raswan, T. R. Haryanto, F.

    2014-09-30

    Dynamic nuclear renography method produces TACs of kidneys and bladder. Multiple TACs data can be further analyzed to obtain the overview of urinary system's condition. Tracer kinetic analysis was performed using four-compartment models. The system's model consist of four irreversible compartment with four transport constants (k1, k2, k3 and k4). The mathematical expressions of tracer's distributions is fitted to experimental data (TACs) resulting in model constants. This transport constants represent the urinary system behavior, and later can be used for analyzing system's condition. Different intervals of kinetics parameter are clearly shown by abnormal system with respect to the normal one. Furthermore, the system with delayed uptake has 82% lower uptake parameters (k1 and k2) than normal one. Meanwhile, the system with prolonged clearance time has its kinetics parameters k3 or k4 lower than the others. This model is promising for quantitatively describe urinary system's function especially if supplied with more data.

  13. Estimating kidney function and use of oral antidiabetic drugs in elderly.

    PubMed

    Douros, Antonios; Ebert, Natalie; Jakob, Olga; Martus, Peter; Kreutz, Reinhold; Schaeffner, Elke

    2015-06-01

    The prevalence of diabetes mellitus (DM) and renal impairment rises with age making regular estimation of glomerular filtration rate (eGFR) in older diabetics necessary. This study investigated the differences among available estimating equations in assessing eGFR in older diabetics and examined the use of oral antidiabetic drugs (OADs) in relation to renal function. Patients with DM were participants of the Berlin Initiative Study (BIS), a population-based cohort study initiated in 2009 in Berlin, Germany, to evaluate kidney function in people ≥70 years. GFR was estimated with the creatinine-based CKD-EPICREA (Chronic Kidney Disease Epidemiology Collaboration), the MDRD (Modification of Diet in Renal Diseases) and the BIS1 equation and was directly measured (mGFR) with iohexol clearance as a gold standard in a subgroup (n = 137). Creatinine clearance was estimated with the Cockcroft-Gault equation (CrCl). DM prevalence was 26% (539 of 2070 overall participants). The antidiabetic drugs most commonly used among OAD patients were metformin (67%), glimepiride (27%) and glibenclamide (14%). Three of ten metformin patients had a CrCl <60 mL/min. Compared to mGFR, the mean differences of filtration rates calculated by MDRD, CKD-EPICREA and BIS1 were +8.9, +6.7 and -1.8 mL/min/1.73 m(2) , respectively. Summing up, many patients with a CrCl <60 mL/min received metformin, although this represents a contraindication in Germany. Glibenclamide was commonly used despite its classification as potentially inappropriate medication in older adults. Finally, BIS1 performed better in estimating GFR in older diabetics than MDRD or CKD-EPICREA . PMID:25817734

  14. Renal progenitors derived from human iPSCs engraft and restore function in a mouse model of acute kidney injury

    PubMed Central

    Imberti, Barbara; Tomasoni, Susanna; Ciampi, Osele; Pezzotta, Anna; Derosas, Manuela; Xinaris, Christodoulos; Rizzo, Paola; Papadimou, Evangelia; Novelli, Rubina; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    Acute kidney injury (AKI) is one of the most relevant health issues, leading to millions of deaths. The magnitude of the phenomenon remarks the urgent need for innovative and effective therapeutic approaches. Cell-based therapy with renal progenitor cells (RPCs) has been proposed as a possible strategy. Studies have shown the feasibility of directing embryonic stem cells or induced Pluripotent Stem Cells (iPSCs) towards nephrogenic intermediate mesoderm and metanephric mesenchyme (MM). However, the functional activity of iPSC-derived RPCs has not been tested in animal models of kidney disease. Here, through an efficient inductive protocol, we directed human iPSCs towards RPCs that robustly engrafted into damaged tubuli and restored renal function and structure in cisplatin-mice with AKI. These results demonstrate that iPSCs are a valuable source of engraftable cells with regenerative activity for kidney disease and create the basis for future applications in stem cell-based therapy. PMID:25744951

  15. Krüppel-like factor 6 regulates mitochondrial function in the kidney

    PubMed Central

    Mallipattu, Sandeep K.; Horne, Sylvia J.; D’Agati, Vivette; Narla, Goutham; Liu, Ruijie; Frohman, Michael A.; Dickman, Kathleen; Chen, Edward Y.; Ma’ayan, Avi; Bialkowska, Agnieszka B.; Ghaleb, Amr M.; Nandan, Mandayam O.; Jain, Mukesh K.; Daehn, Ilse; Chuang, Peter Y.; Yang, Vincent W.; He, John C.

    2015-01-01

    Maintenance of mitochondrial structure and function is critical for preventing podocyte apoptosis and eventual glomerulosclerosis in the kidney; however, the transcription factors that regulate mitochondrial function in podocyte injury remain to be identified. Here, we identified Krüppel-like factor 6 (KLF6), a zinc finger domain transcription factor, as an essential regulator of mitochondrial function in podocyte apoptosis. We observed that podocyte-specific deletion of Klf6 increased the susceptibility of a resistant mouse strain to adriamycin-induced (ADR-induced) focal segmental glomerulosclerosis (FSGS). KLF6 expression was induced early in response to ADR in mice and cultured human podocytes, and prevented mitochondrial dysfunction and activation of intrinsic apoptotic pathways in these podocytes. Promoter analysis and chromatin immunoprecipitation studies revealed that putative KLF6 transcriptional binding sites are present in the promoter of the mitochondrial cytochrome c oxidase assembly gene (SCO2), which is critical for preventing cytochrome c release and activation of the intrinsic apoptotic pathway. Additionally, KLF6 expression was reduced in podocytes from HIV-1 transgenic mice as well as in renal biopsies from patients with HIV-associated nephropathy (HIVAN) and FSGS. Together, these findings indicate that KLF6-dependent regulation of the cytochrome c oxidase assembly gene is critical for maintaining mitochondrial function and preventing podocyte apoptosis. PMID:25689250

  16. Cyclosporine increases calcium in kidney medulla

    SciTech Connect

    Borowitz, J.L.

    1988-01-01

    Treatment of rats with 20, 50, or 100 mg/kg of cyclosporine p.o. markedly increased /sup 45/Ca accumulation in kidney slices especially in medulla. The effect was related to dose and duration of treatment, and was also observed in slices of kidney medulla from cyclosporine-treated mice. Total calcium was elevated in kidney medulla of cyclosporine-treated rats so that the effect is not merely an increased exchange but a build-up of calcium in the tissue. No histopathologic evidence of cyclosporine-related cell necrosis was present in mouse kidney, showing that calcium accumulation is not dystrophic in character. Accumulation of /sup 45/Ca in slices of rat heart, liver, or brain was not affected by cyclosporine pretreatment of the animals. It is suggested that cyclosporine-induced changes in calcium metabolism in kidney medulla may influence kidney function.

  17. Kidney, thyroid and other organ functions after 40 years or more of lithium therapy: a case series of five patients.

    PubMed

    Permoda-Osip, Agnieszka; Abramowicz, Maria; Kraszewska, Agnieszka; Suwalska, Aleksandra; Chlopocka-Wozniak, Maria; Rybakowski, Janusz K

    2016-08-01

    We present the cases of five patients (two men aged 64 years and 79 years) and three women (aged 64 years, 65 years and 75 years) who have received lithium treatment for 40-45 years, with particular regard to kidney and thyroid functions, hypercalcaemia and cognition, in the context of disease course and overall functioning. Lithium was initiated in the early phase of the illness (in three patients within the first 2 years). In four patients, lithium concentration was between 0.60 and 0.65 mmol/l and in one patient, between 0.7 and 0.8 mmol/l. Four were very good lithium responders. One man had stage 3 chronic kidney disease, and the other stage 2/3 chronic kidney disease. All three women had asymptomatic stage 2 chronic kidney disease. One woman had severe thyroid dysfunction (Hashimoto's disease) with extremely high levels of antithyroid peroxidase antibodies and antithyroglobulin antibodies and was receiving thyroxine. Serum calcium levels were normal or borderline in all five patients, and most cognitive functions were comparable to healthy persons of similar gender, age and years of education. All the patients were professionally active until 55-65 years and their family and social functioning were satisfactory. It was concluded that, in good lithium responders, ultra-long-term treatment with lithium enables good professional and psychosocial functioning, and the possible somatic side effects are manageable. PMID:27536347

  18. [Complex investigation and functional evaluation of patients with a solitary kidney and urolithic disease].

    PubMed

    Boĭko, A I; Hurzhenko, A Iu; Hanzhyĭ, V V; Hubar', A O

    2013-11-01

    Complex examination of patients, having solitary kidney and urolithic disease, was conducted. While comparing the calcium accumulation in glomerular and reabsorbed ultrafiltrate and radio-pharmpreparation in a solitary nonaffected kidney, their step by step increase was noted during follow-up to 1 yr after nephrectomy conduction. The static scintigraphy gives possibility to reveal the calcium content rising in glomerular and reabsorbed ultrafiltrate in each kidney separately.

  19. Functional rescue of a kidney anion exchanger 1 trafficking mutant in renal epithelial cells.

    PubMed

    Chu, Carmen Y S; King, Jennifer C; Berrini, Mattia; Alexander, R Todd; Cordat, Emmanuelle

    2013-01-01

    Mutations in the SLC4A1 gene encoding the anion exchanger 1 (AE1) can cause distal renal tubular acidosis (dRTA), a disease often due to mis-trafficking of the mutant protein. In this study, we investigated whether trafficking of a Golgi-retained dRTA mutant, G701D kAE1, or two dRTA mutants retained in the endoplasmic reticulum, C479W and R589H kAE1, could be functionally rescued to the plasma membrane of Madin-Darby Canine Kidney (MDCK) cells. Treatments with DMSO, glycerol, the corrector VX-809, or low temperature incubations restored the basolateral trafficking of G701D kAE1 mutant. These treatments had no significant rescuing effect on trafficking of the mis-folded C479W or R589H kAE1 mutants. DMSO was the only treatment that partially restored G701D kAE1 function in the plasma membrane of MDCK cells. Our experiments show that trafficking of intracellularly retained dRTA kAE1 mutants can be partially restored, and that one chemical treatment rescued both trafficking and function of a dRTA mutant. These studies provide an opportunity to develop alternative therapeutic solutions for dRTA patients. PMID:23460825

  20. Multiparametric Functional MRI: Non-Invasive Imaging of Inflammation and Edema Formation after Kidney Transplantation in Mice

    PubMed Central

    Gutberlet, Marcel; Bräsen, Jan Hinrich; Jang, Mi-Sun; Thorenz, Anja; Chen, Rongjun; Hertel, Barbara; Barrmeyer, Amelie; Schmidbauer, Martina; Meier, Martin; von Vietinghoff, Sibylle; Khalifa, Abedalrazag; Hartung, Dagmar; Haller, Hermann; Wacker, Frank

    2016-01-01

    Background Kidney transplantation (ktx) in mice is used to learn about rejection and to develop new treatment strategies. Past studies have mainly been based on histological or molecular biological methods. Imaging techniques to monitor allograft pathology have rarely been used. Methods Here we investigated mice after isogenic and allogenic ktx over time with functional MRI with diffusion-weighted imaging (DWI) and mapping of T2-relaxation time (T2-mapping) to assess graft inflammation and edema formation. To characterize graft pathology, we used PAS-staining, counted CD3-positive T-lymphocytes, analyzed leukocytes by means flow cytometry. Results DWI revealed progressive restriction of diffusion of water molecules in allogenic kidney grafts. This was paralleled by enhanced infiltration of the kidney by inflammatory cells. Changes in tissue diffusion were not seen following isogenic ktx. T2-times in renal cortex were increased after both isogenic and allogenic transplantation, consistent with tissue edema due to ischemic injury following prolonged cold ischemia time of 60 minutes. Lack of T2 increase in the inner stripe of the inner medulla in allogenic kidney grafts matched loss of tubular autofluorescence and may result from rejection-driven reductions in tubular water content due to tubular dysfunction and renal functional impairment. Conclusions Functional MRI is a valuable non-invasive technique for monitoring inflammation, tissue edema and tubular function. It permits on to differentiate between acute rejection and ischemic renal injury in a mouse model of ktx. PMID:27632553

  1. Potential role of PFOB enhanced sonography of the kidney. I. Detection of renal function and acute tubular necrosis.

    PubMed

    Munzing, D; Mattrey, R F; Reznik, V M; Mitten, R M; Peterson, T

    1991-04-01

    Perfluorooctylbromide (PFOB) enhances the echogenicity of perfused tissues on sonography. Since PFOB is not filtered and is limited to the intravascular space, the particles are concentrated in the vasa rectae as they travel across the osmotic gradient. Because sonography has been unable to detect renal function, we aimed to determine whether sonography when aided by PFOB could detect and distinguish the normal from the abnormal osmotic gradient. The sonographer, unaware of rabbit assignment, imaged both kidneys in 17 rabbits before and 24 hours after the temporary occlusion of one of the renal arteries and then again after the infusion of up to 5 ml/kg of PFOB (N = 10) or saline (N = 7). Two normal rabbits were imaged before and after PFOB infusion and then again after i.v. furosemide. Without PFOB, the normal and impaired kidneys were indistinguishable. The echogenicity of the medulla which was darker than cortex in normal kidneys became brighter than cortex after PFOB (increased by 117% +/- 10%; P less than 0.01). PFOB, which was visible in the renal medulla on real-time sonography, produced an echogenic gradient that increased in brightness towards the papillary tip. Because the medulla of kidneys with ATN mildly increased in brightness after PFOB (increased by 40% +/- 7.8%; P less than 0.01), and because the echogenic gradient produced by PFOB was reversed (decreased in brightness towards the papillary tip), ATN kidneys were distinguished from normal kidneys in all 10 rabbits after 2.5 ml/kg PFOB. Medullary echogenicity produced by PFOB in normal kidneys was lost after furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Natural progression of renal function in the elderly: analysis of poor prognosis factors associated with chronic kidney disease.

    PubMed

    Heras, Manuel; García-Cosmes, Pedro; Fernández-Reyes, María J; Sánchez, Rosa

    2013-01-01

    In the last few years a debate has emerged on the range of normal renal function and the rate at which renal disease progresses in the elderly. In this review we analysed, on the basis of the results of the study Ancianos con enfermedad renal crónica del Hospital General de Segovia (Elderly people with chronic kidney disease of the Hospital General de Segovia), the poor prognosis factors associated with this disease: proteinuria, episodes of acute renal failure and heart failure, and the role of uric acid. Elderly people with chronic kidney disease who present these poor prognosis factors may benefit from follow-up by Nephrology. PMID:23897177

  3. Kidney Failure

    MedlinePlus

    ... if You Have Kidney Disease Kidney Failure Expand Dialysis Kidney Transplant Preparing for Kidney Failure Treatment Choosing Not to Treat with Dialysis or Transplant Paying for Kidney Failure Treatment Contact ...

  4. Kidney Function and Cognitive Impairment in US Adults: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study

    PubMed Central

    Kurella-Tamura, Manjula; Wadley, Virginia; Yaffe, Kristine; McClure, Leslie A.; Howard, George; Go, Rodney; Allman, Richard M.; Warnock, David G.; McClellan, William

    2008-01-01

    Background The association between kidney function and cognitive impairment has not been assessed in a national sample with a wide spectrum of kidney disease severity. Study Design Cross-sectional. Setting & Participants 23,405 participants [EF1](mean age 64.9 ± 9.6 years) with baseline measurements of creatinine and cognitive function participating in the REGARDS (REasons for Geographic And Racial Differences in Stroke) Study, a study of stroke risk factors in a large national sample. Predictor Estimated glomerular filtration rate (eGFR). Outcome Cognitive impairment. Measurements Chronic kidney disease (CKD) was defined as an eGFR <60 ml/min/1.73m2 Kidney function was analyzed in 10 ml/min/1.73 m2 increments among those with CKD, and in exploratory analyses, across the range of kidney function. Cognitive function was assessed using the Six-item Screener and participants with a score ≤4 were considered to have cognitive impairment. Results CKD was associated with an increased prevalence of cognitive impairment, independent of confounding factors (odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.06, 1.43). Among those with CKD, each 10 ml/min/1.73m2 decrease in eGFR below 60 ml/min/1.73m2 was associated with an 11% increased prevalence of impairment (OR 1.11, 95% CI 1.04, 1.19). Exploratory analyses revealed a non-linear association between eGFR and the prevalence of cognitive impairment, with a significant, increased prevalence of impairment among those with eGFR <50 and ≥100 ml/min/1.73m2. Limitations Longitudinal measures of cognitive function were not available. Conclusions Among US adults, lower levels of kidney function are associated with an increased prevalence of cognitive impairment. The prevalence of impairment appears to increase early in the course of kidney disease; therefore screening for impairment should be considered among all adults with CKD. PMID:18585836

  5. Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea

    PubMed Central

    Lee, Jung Pyo; Bae, Eunjin; Kang, Eunjeong; Kim, Hack-Lyoung; Kim, Yong-Jin; Oh, Yun Kyu; Kim, Yon Su; Kim, Young Hoon; Lim, Chun Soo

    2016-01-01

    Background Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. PMID:27501048

  6. Association of apolipoprotein A1 and B with kidney function and chronic kidney disease in two multiethnic population samples

    PubMed Central

    Goek, Oemer-Necmi; Köttgen, Anna; Hoogeveen, Ron C.; Ballantyne, Christie M.; Coresh, Josef; Astor, Brad C.

    2012-01-01

    Background Circulating lipoproteins and their protein constituents, apolipoproteins, are risk factors for chronic kidney disease (CKD). The associations between apolipoprotein A1, apolipoprotein B and their ratio with glomerular filtration rate estimated from the new CKD Epidemiology Collaboration (CKD-EPI) equation (eGFR) are not well studied in the general population. Methods Associations between apolipoprotein A1, B and their ratio with the outcomes of eGFR, CKD (eGFR <60 mL/min/1.73m2) and albuminuria were examined in the Atherosclerosis Risk in Communities study (ARIC, n = 10 292, 1996–98) and the Third National Health and Nutrition Examination Survey (NHANES III, n = 7023, 1988–91). Cross-sectional multivariable-adjusted analyses were performed using linear and logistic regression. Prospective analyses related baseline apolipoprotein levels to subsequent CKD incidence over 10 years using the ARIC Carotid MRI follow-up cohort (n = 1659). Results Higher apolipoprotein A1 quartiles were associated with a lower prevalence of CKD [Q4 versus Q1: odds ratio (OR) 0.73, P-trend = 0.02 in ARIC; Q4 versus Q1: OR 0.53, P-trend <0.01 in NHANES III] as well as with higher eGFR (P-trend <0.01 in ARIC and NHANES III). No consistent significant associations were found for apolipoprotein B in either study. The apolipoprotein B/A1 ratio was significantly associated with eGFR across quartiles in both studies (P-trend <0.01) and with CKD in ARIC (Q4 versus Q1: OR 1.23, P-trend = 0.01). Prospectively, there were trends for the association of apolipoproteins with incident CKD [Q4 versus Q1: incidence rate ratio (IRR) = 0.68 for apolipoprotein A1, P-trend = 0.1; Q4 versus Q1: IRR = 1.35 for apolipoprotein B, P-trend = 0.2]. Associations were not systematically stronger when comparing traditional lipids (total cholesterol, low-density lipoprotein or high-density lipoprotein) to apolipoproteins. Conclusions Higher serum apolipoprotein A1 was associated with lower prevalence of CKD

  7. Performance of Chronic Kidney Disease Epidemiology Collaboration Creatinine-Cystatin C Equation for Estimating Kidney Function in Cirrhosis

    PubMed Central

    Mindikoglu, Ayse L.; Dowling, Thomas C.; Weir, Matthew R.; Seliger, Stephen L.; Christenson, Robert H.; Magder, Laurence S.

    2013-01-01

    Conventional creatinine-based glomerular filtration rate (GFR) equations are insufficiently accurate for estimating GFR in cirrhosis. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels. Performance of the new CKD-EPI creatinine-cystatin C equation (2012) was superior to previous creatinine- or cystatin C-based GFR equations. To evaluate the performance of the CKD-EPI creatinine-cystatin C equation in subjects with cirrhosis, we compared it to GFR measured by non-radiolabeled iothalamate plasma clearance (mGFR) in 72 subjects with cirrhosis. We compared the “bias”, “precision” and “accuracy” of the new CKD-EPI creatinine-cystatin C equation to that of 24-hour urinary creatinine clearance (CrCl), Cockcroft-Gault (CG) and previously reported creatinine- and/or cystatin C-based GFR-estimating equations. Accuracy of CKD-EPI creatinine-cystatin C equation as quantified by root mean squared error of difference scores [differences between mGFR and estimated GFR (eGFR) or between mGFR and CrCl, or between mGFR and CG equation for each subject] (RMSE=23.56) was significantly better than that of CrCl (37.69, P=0.001), CG (RMSE=36.12, P=0.002) and GFR-estimating equations based on cystatin C only. Its accuracy as quantified by percentage of eGFRs that differed by greater than 30% with respect to mGFR was significantly better compared to CrCl (P=0.024), CG (P=0.0001), 4-variable MDRD (P=0.027) and CKD-EPI creatinine 2009 (P=0.012) equations. However, for 23.61% of the subjects, GFR estimated by CKD-EPI creatinine-cystatin C equation differed from the mGFR by more than 30%. CONCLUSIONS The diagnostic performance of CKD-EPI creatinine-cystatin C equation (2012) in patients with cirrhosis was superior to conventional equations in clinical practice for estimating GFR. However, its diagnostic performance was substantially worse than

  8. STRUCTURAL AND FUNCTIONAL TRANSFORMATIONS IN THE TUBULAR EPITHELIUM OF THE DOG'S KIDNEY IN CHRONIC BRIGHT'S DISEASE AND THEIR RELATION TO MECHANISMS OF RENAL COMPENSATION AND FAILURE

    PubMed Central

    Oliver, Jean; Bloom, Frank; MacDowell, Muriel

    1941-01-01

    1. The wall of the proximal convolution in chronic canine nephritis is composed of various types of epithelial cells which can be recognized as definite structural types from their cytological characteristics. 2. The function of these cell types, as tested by their reaction to the administration of trypan blue, varies with their structural constitution. 3. As a result of the varied cellular content of its wall the abnormal proximal convolution handles trypan blue by mechanisms which differ both quantitatively and qualitatively from those of the normal convolution. 4. A distinguishing characteristic of the decompensated kidney in chronic canine nephritis is the inability of its epithelium to concentrate trypan blue within its cells and to prevent diffusion of the dye from the lumen into the tubule wall. 5. It follows: (a) (from conclusion 3), that it cannot be assumed that the renal mechanisms concerned with other substances are not unaltered and that comparisons of blood and urine concentrations (clearances) have similar significance in the normal and nephritic kidney; (b) (from conclusion 4), that tubular dysfunction may play a part in the ultimate failure of the compensating kidney in all forms of chronic Bright's disease where the tubule walls are similarly affected. PMID:19871063

  9. THE CALCIUM CONTENT OF THE KIDNEY AS RELATED TO PARATHYROID FUNCTION

    PubMed Central

    Donohue, William; Spingarn, Clifford; Pappenheimer, Alwin M.

    1937-01-01

    Partial nephrectomy in rats leads to an increase in the calcium content of the residual renal tissue. This increase is correlated with enlargement of the parathyroid glands, the degree depending upon the severity of the kidney lesions. Early removal of the parathyroid glands almost completely prevents this increase in kidney calcium. PMID:19870692

  10. Morpho-functional patterns of kidney injury in the experimental leptospirosis of the guinea-pig (L. icterohaemorrhagiae).

    PubMed

    Dávila de Arriaga, A J; Rocha, A S; Yasuda, P H; De Brito, T

    1982-10-01

    Thirty-seven guinea-pigs experimentally infected with a virulent strain of L. icterohaemorrhagiae, were submitted to a renal function study as evaluated through the maximal urinary concentration (MUC) test, blood urea nitrogen (BUN) and afterwards had their kidneys examined by light and electron microscopy. Vascular changes were also studied after the administration of colloidal carbon as a marker. Through the MUC test and BUN determination, two groups of tubulo-interstitial lesions can be visualised, one in animals without renal sufficiency, manifested chiefly by cell edema with RE dilation and another, in animals with renal insufficiency, characterised not only by marked cell edema and mitochondrial changes, but also by proximal tubule regenerative aspects without overt tubular necrosis. Interstitial edema and focal nephritis was prominent in both groups, a finding which minimises their role in the pathogenesis of renal failure in experimental leptospirosis. Vascular injury, affecting the vessels of the renal microcirculation chiefly at the cortico-medular junction, was observed in both groups. Its severity and extension ran parallel to the intensity of the tubular injury. This suggests a simultaneous action of a noxious agent liberated by the leptospires over both structures, tubular damage being accentuated by the local circulatory changes. PMID:7131130

  11. [Radioisotopic quantification of kidney function using Tc-99m-DMSA. Comparison with creatinine clearance in children with a single kidney].

    PubMed

    Baillet, G; Gagnadoux, M F; Mathonnat, F; de Vernejoul, P; Broyer, M

    1986-01-01

    To assess the accuracy of renal function quantification with Tc 99m-DMSA in children, we compared DMSA renal uptake and creatinine clearance in 16 cases of children with single kidney. The age of the patients ranged from two month to fourteen years. DMSA renal uptake was measured 7 hours after injection and was normalized in percent of the injected activity. A significant correlation was found between creatinine clearance and DMSA uptake (Pearson's r = 0.866, p less than 0.01). Normal creatinine clearance in children (80 to 120 ml/min-1 X 1.73 m-2) allowed determination of normal renal uptake (36 to 60%). This study indicates that in cases of asymmetrical renal impairment renal uptake reflects split renal creatinine clearance. Since the former is much easier to measure, DMSA should play an important role in the evaluation of differential renal function.

  12. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model

    PubMed Central

    Keller, Anna K.; Hansen, Rie Schultz; Nørregaard, Rikke; Krag, Søren Palmelund; Møldrup, Ulla; Pedersen, Michael; Jespersen, Bente; Birn, Henrik

    2016-01-01

    Introduction Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up. Methods Unilateral renal I/R-I was induced in pigs by clamping the left renal artery over a two hour period. The model allowed examination of renal blood flow by magnetic resonance imaging (MRI) and the measurement of single kidney GFR two weeks after injury. Eleven animals were randomized to Danegaptide-infusion while nine animals received placebo. Kidney histology and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion were included as markers of AKI. Results Unilateral kidney I/R-I resulted in an immediate ~50% GFR reduction, associated with a four-fold increase in urinary NGAL-excretion. Fourteen days after I/R-I, the total GFR was ~75% of baseline with a significantly lower GFR in the injured left kidney compared to the right kidney. No differences in GFR were observed between the treated and non-treated animals immediately after I/R-I or at Day 14. Furthermore, no differences were observed in the urinary excretion of NGAL, renal blood flow or other markers of renal function. Conclusions As expected this porcine renal I/R-I model was associated with reduced GFR two weeks after injury. Danegaptide did not improve renal function after I/R-I. PMID:27760220

  13. Hypertension and nephrotoxicity in the rate of decline in kidney function in diabetic nephropathy.

    PubMed

    Aubia, J; Hojman, L; Chine, M; Lloveras, J; Masramon, J; Llorach, I; Cuevas, X; Puig, J M

    1987-01-01

    Serum creatinine levels were determined prospectively every 2 to 3 months in 40 patients with diabetic nephropathy for a global observation period of 864 months. The monthly creatinine increasing rate was significantly lower in normotensive periods, mean arterial pressure (MAP) less than 115 mmHg, when compared with hypertensive periods, MAP greater than 125 mmHg. No significant difference was shown in periods with borderline hypertension (MAP between 115-124 mmHg). The mean creatinine increases were of 0.036 mg/dl/month, 0.3 mg/dl/month and 0.046 mg/dl/month respectively. Normotension was associated with a slowing down of the rate of decline in renal function in this group of moderate kidney failure with an initial mean serum creatinine of 2.26 mg/dl. The exposure of patients to nephrotoxics (aminoglycosides, and possibly anesthesia) significantly accelerated the decline in renal function: 0.39 mg/dl/month and 0.17 mg/dl/month respectively according to the concomitance or not of toxics and hypertension. The reported protective effect of diabetes against aminoglycosides nephrotoxicity in experimental conditions was not reflected in our clinical results. On the contrary, we suggest a possible enhanced sensibility of the diabetic patient with diabetic nephropathy to aminoglycosides leading to an acceleration of the progression of renal failure.

  14. Cognitive function in the affective disorders: a prospective study.

    PubMed

    Bulbena, A; Berrios, G E

    1993-01-01

    A prospective, controlled study of 50 subjects confirmed claims that major depression or mania may cause temporary disorders of attention, memory, visuo-spatial function, and choice reaction time, and cause-independently of medication-the appearance of glabellar tap, positive hand-face test, nuchocephalic reflex, and graphesthesia. On follow-up, all these phenomena either disappeared or markedly improved. Age and age of onset, but not pre-morbid intelligence or history of ECT, seemed to modulate the severity of the cognitive impairment. Presence of delusions predicted poor (but reversible) visuo-spatial function. Cognitive impairment accompanied by reversible soft neurological signs was more marked but patients thus affected surprisingly showed lower depressive scores; this was interpreted as representing a secondary, 'organic' form of affective disorder (i.e. a behavioural phenocopy of depression) characterised by a reduced capacity to experience depressive symptoms and by little improvement at follow-up.

  15. [Lithiasis and ectopic pelvic kidney. Therapeutic aspects].

    PubMed

    Aboutaieb, R; Rabii, R; el Moussaoui, A; Joual, A; Sarf, I; el Mrini, M; Benjelloun, S

    1996-01-01

    Kidney in ectopic position is dysplasic, and associated to other malformations. The advent of a lithiasis in these conditions rises questions about therapeutic options. We report on five observations of pelvic ectopic kidney with urinary lithiasis. Patients were aged from 16 to 42 years. Kidney was non functional in two cases, or with normal appearance sized 10 to 12 cm. We performed total nephrectomy in two cases, pyelolithotomy in the other cases. Surgical approach was subperitoneal via iliac route. A dismembered pyeloplasty was associated in one case. All patients did well. Radiologic control at 6 and 12 months showed no recurrence in a well functioning kidney. Surgical lithotomy is advocated as a treatment in urinary lithiasis affecting ectopic kidney. It is an easy procedure which permits correction of other associated malformations.

  16. Plasma Levels of Middle Molecules to Estimate Residual Kidney Function in Haemodialysis without Urine Collection

    PubMed Central

    Vilar, Enric; Boltiador, Capella; Wong, Jonathan; Viljoen, Adie; Machado, Ashwini; Uthayakumar, Arani; Farrington, Ken

    2015-01-01

    Background Residual Kidney Function (RKF) is associated with survival benefits in haemodialysis (HD) but is difficult to measure without urine collection. Middle molecules such as Cystatin C and β2-microglobulin accumulate in renal disease and plasma levels have been used to estimate kidney function early in this condition. We investigated their use to estimate RKF in patients on HD. Design Cystatin C, β2-microglobulin, urea and creatinine levels were studied in patients on incremental high-flux HD or hemodiafiltration(HDF). Over sequential HD sessions, blood was sampled pre- and post-session 1 and pre-session 2, for estimation of these parameters. Urine was collected during the whole interdialytic interval, for estimation of residual GFR (GFRResidual = mean of urea and creatinine clearance). The relationships of plasma Cystatin C and β2-microglobulin levels to GFRResidual and urea clearance were determined. Results Of the 341 patients studied, 64% had urine output>100ml/day, 32.6% were on high-flux HD and 67.4% on HDF. Parameters most closely correlated with GFRResidual were 1/β2-micoglobulin (r2 0.67) and 1/Cystatin C (r2 0.50). Both these relationships were weaker at low GFRResidual. The best regression model for GFRResidual, explaining 67% of the variation, was: GFRResidual=160.3⋅(1β2m)−4.2 Where β2m is the pre-dialysis β2 microglobulin concentration (mg/L). This model was validated in a separate cohort of 50 patients using Bland-Altman analysis. Areas under the curve in Receiver Operating Characteristic analysis aimed at identifying subjects with urea clearance≥2ml/min/1.73m2 was 0.91 for β2-microglobulin and 0.86 for Cystatin C. A plasma β2-microglobulin cut-off of ≤19.2mg/L allowed identification of patients with urea clearance ≥2ml/min/1.73m2 with 90% specificity and 65% sensitivity. Conclusion Plasma pre-dialysis β2-microglobulin levels can provide estimates of RKF which may have clinical utility and appear superior to cystatin C. Use

  17. Effect of White Kidney Beans (Phaseolus vulgaris L. var. Beldia) on Small Intestine Morphology and Function in Wistar Rats.

    PubMed

    Nciri, Nader; Cho, Namjun; Bergaoui, Nacef; El Mhamdi, Faiçal; Ben Ammar, Aouatef; Trabelsi, Najoua; Zekri, Sami; Guémira, Fathi; Ben Mansour, Abderraouf; Sassi, Fayçal Haj; Ben Aissa-Fennira, Fatma

    2015-12-01

    The chronic ingestion of raw or undercooked kidney beans (Phaseolus vulgaris L.) causes functional and morphological derangement in various tissues. The major objectives of this study were to investigate the gavage effects of a raw Beldia bean variety that is widely consumed in Tunisia, on the small intestine morphology and jejunal absorption of water, electrolytes, and glucose in Wistar rats. Twenty young male rats were randomly divided into two groups of 10 rats. The first group served as the control and was gavaged with 300 mg of a rodent pellet flour suspension (RPFS), whereas the second experimental group was challenged with 300 mg of a Beldia bean flour suspension (BBFS) for 10 days. Histological studies were performed using light and electron microcopy. The intestinal transport of water, sodium, potassium, and glucose was studied by perfusing the jejunal loops of the small bowels in vivo. The feeding experiments indicated that BBFS did not affect weight gain. Histomorphometric analyses showed that the villus heights, crypt depths, and crypt/villus ratios in the jejunum and ileum were greater in the BBFS-fed rats than controls. Electron microscopy studies demonstrated that the rats exposed to RPFS exhibited intact intestinal tracts; however, the BBFS-treated rats demonstrated intestinal alterations characterized by abnormal microvillus architectures, with short and dense or long and slender features, in addition to the sparse presence of vesicles near the brush border membrane. BBFS administration did not significantly affect glucose absorption. However, significant decreases were observed in water and electrolyte absorption compared with the uptake of the controls. In conclusion, raw Beldia beans distorted jejunum morphology and disturbed hydroelectrolytic flux.

  18. Effect of White Kidney Beans (Phaseolus vulgaris L. var. Beldia) on Small Intestine Morphology and Function in Wistar Rats.

    PubMed

    Nciri, Nader; Cho, Namjun; Bergaoui, Nacef; El Mhamdi, Faiçal; Ben Ammar, Aouatef; Trabelsi, Najoua; Zekri, Sami; Guémira, Fathi; Ben Mansour, Abderraouf; Sassi, Fayçal Haj; Ben Aissa-Fennira, Fatma

    2015-12-01

    The chronic ingestion of raw or undercooked kidney beans (Phaseolus vulgaris L.) causes functional and morphological derangement in various tissues. The major objectives of this study were to investigate the gavage effects of a raw Beldia bean variety that is widely consumed in Tunisia, on the small intestine morphology and jejunal absorption of water, electrolytes, and glucose in Wistar rats. Twenty young male rats were randomly divided into two groups of 10 rats. The first group served as the control and was gavaged with 300 mg of a rodent pellet flour suspension (RPFS), whereas the second experimental group was challenged with 300 mg of a Beldia bean flour suspension (BBFS) for 10 days. Histological studies were performed using light and electron microcopy. The intestinal transport of water, sodium, potassium, and glucose was studied by perfusing the jejunal loops of the small bowels in vivo. The feeding experiments indicated that BBFS did not affect weight gain. Histomorphometric analyses showed that the villus heights, crypt depths, and crypt/villus ratios in the jejunum and ileum were greater in the BBFS-fed rats than controls. Electron microscopy studies demonstrated that the rats exposed to RPFS exhibited intact intestinal tracts; however, the BBFS-treated rats demonstrated intestinal alterations characterized by abnormal microvillus architectures, with short and dense or long and slender features, in addition to the sparse presence of vesicles near the brush border membrane. BBFS administration did not significantly affect glucose absorption. However, significant decreases were observed in water and electrolyte absorption compared with the uptake of the controls. In conclusion, raw Beldia beans distorted jejunum morphology and disturbed hydroelectrolytic flux. PMID:26488416

  19. Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease

    PubMed Central

    Missailidis, Catharina; Hällqvist, Jenny; Qureshi, Abdel Rashid; Barany, Peter; Heimbürger, Olof; Lindholm, Bengt

    2016-01-01

    Background The microbial metabolite Trimethylamine-N-oxide (TMAO) has been linked to adverse cardiovascular outcome and mortality in the general population. Objective To assess the contribution of TMAO to inflammation and mortality in chronic kidney disease (CKD) patients ranging from mild-moderate to end-stage disease and 1) associations with glomerular filtration rate (GFR) 2) effect of dialysis and renal transplantation (Rtx) 3) association with inflammatory biomarkers and 4) its predictive value for all-cause mortality. Methods Levels of metabolites were quantified by a novel liquid chromatography/tandem mass spectrometry-based method in fasting plasma samples from 80 controls and 179 CKD 3–5 patients. Comorbidities, nutritional status, biomarkers of inflammation and GFR were assessed. Results GFR was the dominant variable affecting TMAO (β = -0.41; p<0.001), choline (β = -0.38; p<0.001), and betaine (β = 0.45; p<0.001) levels. A longitudinal study of 74 CKD 5 patients starting renal replacement therapy demonstrated that whereas dialysis treatment did not affect TMAO, Rtx reduced levels of TMAO to that of controls (p<0.001). Following Rtx choline and betaine levels continued to increase. In CKD 3–5, TMAO levels were associated with IL-6 (Rho = 0.42; p<0.0001), fibrinogen (Rho = 0.43; p<0.0001) and hsCRP (Rho = 0.17; p = 0.022). Higher TMAO levels were associated with an increased risk for all-cause mortality that remained significant after multivariate adjustment (HR 4.32, 95% CI 1.32–14.2; p = 0.016). Conclusion Elevated TMAO levels are strongly associated with degree of renal function in CKD and normalize after renal transplantation. TMAO levels correlates with increased systemic inflammation and is an independent predictor of mortality in CKD 3–5 patients. PMID:26751065

  20. Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

    PubMed Central

    Graceli, J.B.; Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R.

    2013-01-01

    The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1, sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl-, respectively) and renal and plasma catecholamine release concentrations. FENa+, FECl-, water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+, FECl-, water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function. PMID:23828583

  1. Effect of Bicarbonate Supplementation on Renal Function and Nutritional Indices in Predialysis Advanced Chronic Kidney Disease

    PubMed Central

    Jeong, Jiwon; Kwon, Soon Kil

    2014-01-01

    Current practice guidelines recommend alkali therapy in patients with chronic kidney disease (CKD) and metabolic acidosis to prevent complications. This study aims to investigate the effect of oral sodium bicarbonate supplementation on the progression of renal function and nutritional indices in patients with predialysis advanced CKD. Forty patients with predialysis stage 5 CKD(estimated glomerular filtration rate, eGFR <15mL/min per 1.73m2) and 40 patients with stage 4 CKD (eGFR 15 to 30mL/min per 1.73m2) who had a total CO2 less than 22mEq/L were assigned into the bicarbonate treatment group or control group for 12 months. In stage 4 CKD, there were significant differences in the changes of eGFR during the study between the treatment group and the control group (-2.30±4.49 versus -6.58±6.32mL/min/1.73m2, p<0.05). However, in stage 5 CKD, there were no significant differences in the change of eGFR during the study between the two groups (-2.10±2.06 versus -3.23±1.95mL/min/1.73 m2).There were no significant differences in the changes of nutritional indices such as albumin, prealbumin, transferrin, total lymphocyte count (TLC), and Ondodera's prognostic nutritional index (OPNI) during the study between the two groups. In stage 5 CKD, there were significant differences in the changes of TLC and OPNI between the two groups. In conclusion, our results demonstrate that bicarbonate supplementation slows the rate of decline of renal function in stage 4 CKD and improves nutritional indices in stage 5 CKD. Alkali therapy in advanced CKD may have beneficial effect on renal function and malnutrition. PMID:25606047

  2. Effects of Recombinant Human Erythropoietin on Resistance Artery Endothelial Function in Stage 4 Chronic Kidney Disease

    PubMed Central

    Briet, Marie; Barhoumi, Tlili; Mian, Muhammad Oneeb Rehman; Sierra, Cristina; Boutouyrie, Pierre; Davidman, Michael; Bercovitch, David; Nessim, Sharon J.; Frisch, Gershon; Paradis, Pierre; Lipman, Mark L.; Schiffrin, Ernesto L.

    2013-01-01

    Background Recent studies have raised concern about the safety of erythropoiesis‐stimulating agents because of evidence of increased risk of hypertension and cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. In the present study, we investigated the effects of recombinant human erythropoietin (EPO) on endothelial function of gluteal subcutaneous resistance arteries isolated from 17 stage 4 patients (estimated glomerular filtration rate 21.9±7.4 mL/min per 1.73 m2) aged 63±13 years. Methods and Results Arteries were mounted on a pressurized myograph. EPO impaired endothelium‐dependent relaxation in a concentration‐dependent manner. The maximal response to acetylcholine with EPO at 1, 10, and 20 IU/mL was reduced by 12%, 34%, and 43%, respectively, compared with the absence of EPO (P<0.001). EPO‐induced endothelial dysfunction was significantly associated with carotid stiffness and history of cardiovascular events. EPO had no effect on norepinephrine‐induced vasoconstriction or sodium nitroprusside–induced relaxation. ABT‐627, an endothelin type A receptor antagonist, and tempol, a superoxide dismutase mimetic, partially reversed the altered endothelial function in the presence of EPO (P<0.01). Increased expression of endothelin‐1 was found in the vessel wall after incubation with EPO. Conclusions EPO alters endothelial function of resistance arteries in CKD patients via a mechanism involving in part oxidative stress and signaling through an endothelin type A receptor. EPO‐induced endothelial dysfunction could contribute to deleterious effects of EPO described in large interventional trials. PMID:23584809

  3. Kidney Facts

    MedlinePlus

    ... Home / Before The Transplant / Organ Facts / Kidney Organ Facts Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver ... Receiving "the call" About the Operation Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Kidney Facts The kidneys are a pair of reddish-brown ...

  4. The risk of allograft failure and the survival benefit of kidney transplantation are complicated by delayed graft function.

    PubMed

    Gill, Jagbir; Dong, Jianghu; Rose, Caren; Gill, John S

    2016-06-01

    Concern about the long-term impact of delayed graft function (DGF) may limit the use of high-risk organs for kidney transplantation. To understand this better, we analyzed 29,598 mate kidney transplants from the same deceased donor where only 1 transplant developed DGF. The DGF associated risk of graft failure was greatest in the first posttransplant year, and in patients with concomitant acute rejection (hazard ratio: 8.22, 95% confidence interval: 4.76-14.21). In contrast, the DGF-associated risk of graft failure after the first posttransplant year in patients without acute rejection was far lower (hazard ratio: 1.15, 95% confidence interval: 1.02-1.29). In subsequent analysis, recipients of transplants complicated by DGF still derived a survival benefit when compared with patients who received treatment with dialysis irrespective of donor quality as measured by the Kidney Donor Profile Index (KDPI). The difference in the time required to derive a survival benefit was longer in transplants with DGF than in transplants without DGF, and this difference was greatest in recipients of lower quality kidneys (difference: 250-279 days for KDPI 20%-60% vs. 809 days for the KDPI over 80%). Thus, the association of DGF with graft failure is primarily limited to the first posttransplant year. Transplants complicated by DGF provide a survival benefit compared to treatment with dialysis, but the survival benefit is lower in kidney transplants with lower KDPI. This information may increase acceptance of kidneys at high risk for DGF and inform strategies to minimize the risk of death in the setting of DGF.

  5. Functional and histologic alterations in growing solitary rat kidney as result of extracorporeal shockwaves.

    PubMed

    Ferreira, U; Claro, J de A; Rodrigues Netto, N; Denardi, F; Figueiredo, J F; Riccetto, C L

    1995-02-01

    The long-term effects of extracorporeal shockwave lithotripsy (SWL) on children treated for renal calculi are unclear. To study the effects on the immature animal, we evaluated 31 Wistar white rats that underwent right nephrectomy at 30 days of age. At 40 days of age they were divided into three groups: a control group of 10 rats that received no shockwaves; Group I (9 rats) that received 1000 shockwaves at 16.0 kV, and Group II (12 animals) that received 1000 shock waves at 17.2 kV. Six months later at maturity (7 months and 10 days of age), the following parameters were measured: (1) body and renal weight; (2) blood lithium, sodium, potassium, and creatinine; (3) fractional lithium, sodium, and potassium excretion; and (4) clearances of lithium and creatinine. The kidneys were studied grossly and histologically. We found no significant changes in overall animal and renal growth between the post-SWL and control groups. However, there were significant changes in renal function. The animals in Groups I and II presented significant increases in blood potassium compared with the control group. Furthermore, the 1000 x 17.2 kV group showed permanent histologic renal changes, including red cells in Bowman's capsule and glomerular congestion. The disorders caused by SWL are compatible with hyporeninemic hypoaldosteronism, inappropriately low plasma renin activity, and aldosterone deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Acute effects of grayanotoxin in rhododendron honey on kidney functions in rats.

    PubMed

    Silici, S; Doğan, Z; Sahin, H; Atayoğlu, T; Yakan, B

    2016-02-01

    The aim of the study is to evaluate the acute biochemical and histological changes in rat kidneys after treatment with grayanotoxin (GTX) of rhododendron honey (RH). A total of 60 Sprague-Dawley female rats were divided into five groups of 12 rats each, one being a control group (group 1) and group 2 was treated with 0.015 mg/kg/bw of GTX standard preparation via intraperitoneal injection. Groups 3, 4, and 5 were given RH at doses of 0.1, 0.5, and 2.5 g/kg/bw, respectively, via oral gavage. Compared to the control group, significant increases were observed in glucose, blood urea nitrogen (BUN), and creatinine levels of the GTX-injected groups after 1 h. However, in low dose RH group, such an increase was not observed and had a normal appearance histologically. Therefore, low dose (1 g/kg/bw) of RH produces no acute adverse effects on renal functions of rats.

  7. The Effects of Simvastatin on Proteinuria and Renal Function in Patients with Chronic Kidney Disease

    PubMed Central

    Satirapoj, Bancha; Promrattanakun, Anan; Supasyndh, Ouppatham; Choovichian, Panbuppa

    2015-01-01

    Current data suggests that statins might have beneficial effects on renal outcomes. Beneficial effects of statin treatment on renal progression in advanced chronic kidney disease (CKD) are obviously controversial. In a retrospective, controlled study, the authors have evaluated the effects of 53-week treatment with simvastatin, versus no treatment on proteinuria and renal function among 51 patients with CKD stages III-IV. By the end of the 53-week treatment, urine protein excretion decreased from 0.96 (IQR 0.54, 2.9) to 0.48 (IQR 0.18, 0.79) g/g creatinine (P < 0.001) in patients treated with simvastatin in addition to ACEI and ARBs, while no change was observed among the untreated patients. Moreover, a significantly greater decrease in urine protein excretion was observed in the simvastatin group as compared with the untreated group. The mean changes of serum creatinine and eGFR did not significantly differ in both groups. A significantly greater decrease in total cholesterol and LDL-cholesterol was found in the simvastatin group than in the untreated group. In summary, apart from lipid lowering among CKD patients, ingesting simvastatin was associated with a decrease in proteinuria. These statin effects may become important for supportive therapy in renal damage in the future. PMID:26543646

  8. Kidney function and risk triage in adults: threshold values and hierarchical importance

    PubMed Central

    Foley, Robert N.; Wang, Changchun; Snyder, Jon J.; Rule, Andrew D.; Collins, Allan J.

    2012-01-01

    In this study, we attempted to identify threshold values for kidney function measures that maximally discriminate short-term mortality, to identify major population segments in which these thresholds apply, and to classify the hierarchical rank of the thresholds when other classic risk factors are also considered. To do this we retrospectively identified estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio (ACR) thresholds to maximize sensitivity and specificity predictions for death in non-institutionalized NHANES III participants, representative of the United States population from 1988 to 1994 and followed through 2000. In a classification tree excluding dichotomizing variables, age 57 years was initially selected; ACR appeared in the second round and eGFR in the third. The prognostic discrimination of optimum eGFR and ACR thresholds exceeded those of commonly advocated public health screening measures, such as LDL cholesterol and fasting blood glucose, with body mass index appearing in the third round, and smoking and LDL cholesterol in the fourth. In a tree permitting dichotomizing variables, the ACR, systolic blood pressure, and glucose first appeared in the third round, with eGFR, smoking, and LDL in the fourth. Thus, the albumin–creatinine ratio and eGFR may be at least as efficient for survival-based clinical triage as most other classic risk factors. PMID:20720528

  9. Polarized endocytosis by Madin-Darby canine kidney cells transfected with functional chicken liver glycoprotein receptor

    PubMed Central

    1989-01-01

    We have studied the expression of the chicken hepatic glycoprotein receptor (chicken hepatic lectin [CHL]) in Madin-Darby canine kidney (MDCK) cells, by transfection of its cDNA under the control of a retroviral promotor. Transfected cell lines stably express 87,000 surface receptors/cell with a kd = 13 nM. In confluent monolayers, approximately 40% of CHL is localized at the plasma membrane. 98% of the surface CHL is expressed at the basolateral surface where it performs polarized endocytosis and degradation of glycoproteins carrying terminal N-acetylglucosamine at a rate of 50,000 ligand molecules/h. Studies of the half-life of metabolically labeled receptor and of the stability of biotinylated cell surface receptor after internalization indicate that transfected CHL performs several rounds of uptake and recycling before it gets degraded. The successful expression of a functional basolateral receptor in MDCK cells opens the way for the characterization of the mechanisms that control targeting and recycling of proteins to the basolateral membrane of epithelial cells. PMID:2687287

  10. /sup 99m/Tc-aprotinin: A new tracer for kidney morphology and function

    SciTech Connect

    Bianchi, C.; Donadio, C.; Tramonti, G.; Lorusso, P.; Bellitto, L.; Lunghi, F.

    1984-01-01

    Aprotinin (Ap), a low molecular weight polyeptide (6500 dalton), is a protease inhibitor which is electively and stably accumulated in the kidney. In 112 adult patients, with either uni- or bilateral renal disease with different degrees of renal impairment (from normal GFR to advanced renal failure), renal scans were performed by means of Ap labelled with /sup 99m/Tc. Highly satisfactory renal scans were obtained in all patients. In 20 patients with renal failure (serum creatinine 1.8 - 8.5 mg/dl, mean 4.7) a comparison was made of the renal scans obtained with /sup 99m/Tc-Ap and with /sup 99m/Tc-DMSA. /sup 99m/Tc-Ap was slightly better than /sup 99m/Tc-DMSA, especially in patients with far advanced renal failure. Some aspects of the pharmacokinetics of /sup 99m/Tc-Ap were studied in 72 cases. In 22 of these patients plasma clearance of /sup 99m/Tc-Ap was determined by the single injection method using a two-compartment model. In patients with GFR>90 ml/min plasma cl of /sup 99m/Tc-Ap was 67.6 +- 8.4 SD ml/min. A good correlation was observed between plasma clearance of /sup 99m/Tc-Ap and GFR (r = 0.74). After i.v. injection /sup 99m/Tc-Ap was stably fixed by the kidney. Renal radioactivity remained stable between the 2nd and the 8th hour after the injection. Urinary excretion of radioactivity measured in 35 patients in the first and in the second 2-hour interval after i.v. injection of /sup 99m/Tc-Ap was negligible in all patients (2.7 +- 1.5 SD percent of the dose in the fist 2 hours; 2.8 +- 1.4 SD between the 2nd and the 4th hour). Conclusions. /sup 99m/Tc-Ap is an excellent agent for renal imaging. It also seems promising for renal function studies.

  11. Human kidney amiloride-binding protein: cDNA structure and functional expression

    SciTech Connect

    Barbry, P.; Chassande, O.; Champigny, G.; Lingueglia, E.; Frelin, C.; Lazdunski, M. ); Champe, M.; Munemitsu, S.; Ullrich, A. ); Maes, P.; Tartar, A. Institut Pasteur de Lille )

    1990-10-01

    Phenamil, an analog of amiloride, is a potent blocker of the epithelial Na{sup plus} channel. It has been used to purify the porcine kidney amiloride-binding protein. Synthetic oligonucleotides derived from partial sequences have been used to screen a human kidney cDNA library and to isolate the cDNA encoding the human amiloride-binding protein. The primary structure was deduced from the DNA sequence analysis. The protein is 713 residues long, with a 19-amino acid signal peptide. The mRNA was expressed in 293-S and NIH 3T3 cells, yielding a glycoprotein (i) that binds amiloride and amiloride analogs with affinities similar to the amiloride receptor associated with the apical Na{sup plus} channel in pig kidney membranes and (ii) that is immunoprecipitated with monoclonal antibodies raised against pig kidney amiloride-binding protein.

  12. Human kidney amiloride-binding protein: cDNA structure and functional expression.

    PubMed Central

    Barbry, P; Champe, M; Chassande, O; Munemitsu, S; Champigny, G; Lingueglia, E; Maes, P; Frelin, C; Tartar, A; Ullrich, A

    1990-01-01

    Phenamil, an analog of amiloride, is a potent blocker of the epithelial Na+ channel. It has been used to purify the porcine kidney amiloride-binding protein. Synthetic oligonucleotides derived from partial sequences have been used to screen a human kidney cDNA library and to isolate the cDNA encoding the human amiloride-binding protein. The primary structure was deduced from the DNA sequence analysis. The protein is 713 residues long, with a 19-amino acid signal peptide. The mRNA was expressed in 293-S and NIH 3T3 cells, yielding a glycoprotein (i) that binds amiloride and amiloride analogs with affinities similar to the amiloride receptor associated with the apical Na+ channel in pig kidney membranes and (ii) that is immunoprecipitated with monoclonal antibodies raised against pig kidney amiloride-binding protein. Images PMID:2217167

  13. Factors affecting sexual function in menopause: A review article.

    PubMed

    Nazarpour, Soheila; Simbar, Masoumeh; Tehrani, Fahimeh Ramezani

    2016-08-01

    This study aimed to systematically review the articles on factors affecting sexual function during menopause. Searching articles indexed in Pubmed, Science Direct, Iranmedex, EMBASE, Scopus, and Scientific Information Database databases, a total number of 42 studies published between 2003 and 2013 were selected. Age, estrogen deficiency, type of menopause, chronic medical problems, partner's sex problems, severity of menopause symptoms, dystocia history, and health status were the physical factors influencing sexual function of menopausal women. There were conflicting results regarding the amount of androgens, hormonal therapy, exercise/physical activity, and obstetric history. In the mental-emotional area, all studies confirmed the impact of depression and anxiety. Social factors, including smoking, alcohol consumption, the quality of relationship with husband, partner's loyalty, sexual knowledge, access to health care, a history of divorce or the death of a husband, living apart from a spouse, and a negative understanding of women's health were found to affect sexual function; however, there were conflicting results regarding the effects of education, occupation, socioeconomic status, marital duration, and frequency of sexual intercourse. PMID:27590367

  14. Microbial composition affects the functioning of estuarine sediments

    PubMed Central

    Reed, Heather E; Martiny, Jennifer BH

    2013-01-01

    Although microorganisms largely drive many ecosystem processes, the relationship between microbial composition and their functioning remains unclear. To tease apart the effects of composition and the environment directly, microbial composition must be manipulated and maintained, ideally in a natural ecosystem. In this study, we aimed to test whether variability in microbial composition affects functional processes in a field setting, by reciprocally transplanting riverbed sediments between low- and high-salinity locations along the Nonesuch River (Maine, USA). We placed the sediments into microbial ‘cages' to prevent the migration of microorganisms, while allowing the sediments to experience the abiotic conditions of the surroundings. We performed two experiments, short- (1 week) and long-term (7 weeks) reciprocal transplants, after which we assayed a variety of functional processes in the cages. In both experiments, we examined the composition of bacteria generally (targeting the 16S rDNA gene) and sulfate-reducing bacteria (SRB) specifically (targeting the dsrAB gene) using terminal restriction fragment length polymorphism (T-RFLP). In the short-term experiment, sediment processes (CO2 production, CH4 flux, nitrification and enzyme activities) depended on both the sediment's origin (reflecting differences in microbial composition between salt and freshwater sediments) and the surrounding environment. In the long-term experiment, general bacterial composition (but not SRB composition) shifted in response to their new environment, and this composition was significantly correlated with sediment functioning. Further, sediment origin had a diminished effect, relative to the short-term experiment, on sediment processes. Overall, this study provides direct evidence that microbial composition directly affects functional processes in these sediments. PMID:23235294

  15. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

    PubMed

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  16. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

    PubMed Central

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar; Ganesh, Santhi K.; Garcia, Melissa; Gaunt, Tom R.; Glazer, Nicole L.; Go, Min Jin; Goel, Anuj; Grässler, Jürgen; Grobbee, Diederick E.; Groop, Leif; Guarrera, Simonetta; Guo, Xiuqing; Hadley, David; Hamsten, Anders; Han, Bok-Ghee; Hardy, Rebecca; Hartikainen, Anna-Liisa; Heath, Simon; Heckbert, Susan R.; Hedblad, Bo; Hercberg, Serge; Hernandez, Dena; Hicks, Andrew A.; Hilton, Gina; Hingorani, Aroon D.; Bolton, Judith A Hoffman; Hopewell, Jemma C.; Howard, Philip; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Ikram, M. Arfan; Islam, Muhammad; Iwai, Naoharu; Jarvelin, Marjo-Riitta; Jackson, Anne U.; Jafar, Tazeen H.; Janipalli, Charles S.; Johnson, Toby; Kathiresan, Sekar; Khaw, Kay-Tee; Kim, Hyung-Lae; Kinra, Sanjay; Kita, Yoshikuni; Kivimaki, Mika; Kooner, Jaspal S.; Kumar, M. J. Kranthi; Kuh, Diana; Kulkarni, Smita R.; Kumari, Meena; Kuusisto, Johanna; Kuznetsova, Tatiana; Laakso, Markku; Laan, Maris; Laitinen, Jaana; Lakatta, Edward G.; Langefeld, Carl D.; Larson, Martin G.; Lathrop, Mark; Lawlor, Debbie A.; Lawrence, Robert W.; Lee, Jong-Young; Lee, Nanette R.; Levy, Daniel; Li, Yali; Longstreth, Will T.; Luan, Jian'an; Lucas, Gavin; Ludwig, Barbara; Mangino, Massimo; Mani, K. Radha; Marmot, Michael G.; Mattace-Raso, Francesco U. S.; Matullo, Giuseppe; McArdle, Wendy L.; McKenzie, Colin A.; Meitinger, Thomas; Melander, Olle; Meneton, Pierre; Meschia, James F.; Miki, Tetsuro; Milaneschi, Yuri; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Morris, Richard W.; Mosley, Thomas H.; Najjar, Samer; Narisu, Narisu; Newton-Cheh, Christopher; Nguyen, Khanh-Dung Hoang; Nilsson, Peter; Nyberg, Fredrik; O'Donnell, Christopher J.; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ong, RickTwee-Hee; Ongen, Halit; Onland-Moret, N. Charlotte; O'Reilly, Paul F.; Org, Elin; Orru, Marco; Palmas, Walter; Palmen, Jutta; Palmer, Lyle J.; Palmer, Nicholette D.; Parker, Alex N.; Peden, John F.; Peltonen, Leena; Perola, Markus; Pihur, Vasyl; Platou, Carl G. P.; Plump, Andrew; Prabhakaran, Dorairajan; Psaty, Bruce M.; Raffel, Leslie J.; Rao, Dabeeru C.; Rasheed, Asif; Ricceri, Fulvio; Rice, Kenneth M.; Rosengren, Annika; Rotter, Jerome I.; Rudock, Megan E.; Sõber, Siim; Salako, Tunde; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J.; Schwartz, Steven M.; Schwarz, Peter E. H.; Scott, Laura J.; Scott, James; Scuteri, Angelo; Sehmi, Joban S.; Seielstad, Mark; Seshadri, Sudha; Sharma, Pankaj; Shaw-Hawkins, Sue; Shi, Gang; Shrine, Nick R. G.; Sijbrands, Eric J. G.; Sim, Xueling; Singleton, Andrew; Sjögren, Marketa; Smith, Nicholas L.; Artigas, Maria Soler; Spector, Tim D.; Staessen, Jan A.; Stancakova, Alena; Steinle, Nanette I.; Strachan, David P.; Stringham, Heather M.; Sun, Yan V.; Swift, Amy J.; Tabara, Yasuharu; Tai, E-Shyong; Talmud, Philippa J.; Taylor, Andrew; Terzic, Janos; Thelle, Dag S.; Tobin, Martin D.; Tomaszewski, Maciej; Tripathy, Vikal; Tuomilehto, Jaakko; Tzoulaki, Ioanna; Uda, Manuela; Ueshima, Hirotsugu; Uiterwaal, Cuno S. P. M.; Umemura, Satoshi; van der Harst, Pim; van der Schouw, Yvonne T.; van Gilst, Wiek H.; Vartiainen, Erkki; Vasan, Ramachandran S.; Veldre, Gudrun; Verwoert, Germaine C.; Viigimaa, Margus; Vinay, D. G.; Vineis, Paolo; Voight, Benjamin F.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wain, Louise V.; Wang, Xiaoling; Wang, Thomas J.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Whincup, Peter H.; Wiggins, Kerri L.; Witteman, Jacqueline C. M.; Wong, Andrew; Wu, Ying; Yajnik, Chittaranjan S.; Yao, Jie; Young, J. H.; Zelenika, Diana; Zhai, Guangju; Zhang, Weihua; Zhang, Feng; Zhao, Jing Hua; Zhu, Haidong; Zhu, Xiaofeng; Zitting, Paavo; Zukowska-Szczechowska, Ewa; Okada, Yukinori; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L.; Aung, Tin; Teo, Yik-Ying; Kim, Young Jin; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S. -J. Cathy; Mei, Hao; Hixson, James E.; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Tanaka, Toshihiro; Reilly, Muredach P; Schunkert, Heribert; Assimes, Themistocles L.; Hall, Alistair; Hengstenberg, Christian; König, Inke R.; Laaksonen, Reijo; McPherson, Ruth; Thompson, John R.; Thorsteinsdottir, Unnur; Ziegler, Andreas; Absher, Devin; Chen, Li; Cupples13, L. Adrienne; Halperin, Eran; Li, Mingyao; Musunuru, Kiran; Preuss, Michael; Schillert, Arne; Thorleifsson, Gudmar; Wells, George A.; Holm, Hilma; Roberts, Robert; Stewart, Alexandre F. R.; Fortmann, Stephen; Go, Alan; Hlatky, Mark; Iribarren, Carlos; Knowles, Joshua; Myers, Richard; Quertermous, Thomas; Sidney, Steven; Risch, Neil; Tang, Hua; Blankenberg, Stefan; Schnabel, Renate; Sinning, Christoph; Lackner, Karl J.; Tiret, Laurence; Nicaud, Viviane; Cambien, Francois; Bickel, Christoph; Rupprecht, Hans J.; Perret, Claire; Proust, Carole; Münzel, Thomas F.; Barbalic, Maja; Chen, Ida Yii-Der; Demissie-Banjaw, Serkalem; Folsom, Aaron; Lumley, Thomas; Marciante, Kristin; Taylor, Kent D.; Volcik, Kelly; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Stefansson, Kari; Thorgeirsson, Gudmundur; Andersen, Karl; Fischer, Marcus; Grosshennig, Anika; Linsel-Nitschke, Patrick; Stark, Klaus; Schreiber, Stefan; Aherrahrou, Zouhair; Bruse, Petra; Doering, Angela; Klopp, Norman; Diemert, Patrick; Loley, Christina; Medack, Anja; Nahrstedt, Janja; Peters, Annette; Wagner, Arnika K.; Willenborg, Christina; Böhm, Bernhard O.; Dobnig, Harald; Grammer, Tanja B.; Hoffmann, Michael M.; Meinitzer, Andreas; Winkelmann, Bernhard R.; Pilz, Stefan; Renner, Wilfried; Scharnagl, Hubert; Stojakovic, Tatjana; Tomaschitz, Andreas; Winkler, Karl; Guiducci, Candace; Burtt, Noel; Gabriel, Stacey B.; Dandona, Sonny; Jarinova, Olga; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Epstein, Stephen E.; Rader, Daniel J.; Nelson, Christopher P.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Loehr, Laura R.; Rosamond, Wayne D.; Benjamin, Emelia; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A.; Stricker, Bruno H.; Chang, Patricia P.; Willerson, James T.; Felix, Stephan B.; Watzinger, Norbert; Aragam, Jayashri; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J.; Greiser, Karin Halina; Deckers, Jaap W.; Stritzke, Jan; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; Reffelmann, Thorsten; Redfield, Margaret M.; Werdan, Karl; Mitchell, Gary F.; Arnett, Donna K.; Gottdiener, John S.; Blettner, Maria; Friedrich, Nele; Kovacs, Peter; Wild, Philipp S.; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P. S.; Carroll, Robert J.; Penninx, Brenda W.; Scott, Rodney J.; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H.; Kardia, Sharon L. R.; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J.; Turner, Stephen T.; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J. F.; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P.; Parsa, Afshin; O'Connell, Jeffrey R.; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H.; Böger, Carsten A.; Goessling, Wolfram; Chasman, Daniel I.; Köttgen, Anna; Kao, W. H. Linda; Fox, Caroline S.

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  17. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

    PubMed

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

    2016-01-21

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

  18. Endothelial Markers May Link Kidney Function to Cardiovascular Events in Type 2 Diabetes

    PubMed Central

    Maier, Christina; Clodi, Martin; Neuhold, Stephanie; Resl, Michael; Elhenicky, Marie; Prager, Rudolf; Moertl, Deddo; Strunk, Guido; Luger, Anton; Struck, Joachim; Pacher, Richard; Hülsmann, Martin

    2009-01-01

    OBJECTIVE The increased cardiovascular risk in diabetes has been linked to endothelial and renal dysfunction. The aim of this study was to investigate the role of stable fragments of the precursors of adrenomedullin, endothelin-1, vasopressin, and atrial natriuretic peptide in progression of cardiovascular disease in patients with diabetes. RESEARCH DESIGN AND METHODS This was a prospective, observational study design with a composite end point (death or unexpected admission to hospital due to a cardiovascular event) on 781 patients with type 2 diabetes (54 events, median duration of observation 15 months). The four stable precursor peptides midregional adrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), COOH-terminal proendothelin-1 (CT-proET-1), and COOH-terminal provasopressin or copeptin (CT-proAVP) were determined at baseline, and their association to renal function and cardiovascular events was studied using stepwise linear and Cox logistic regression analysis and receiver operating characteristic analysis, respectively. RESULTS MR-proADM, CT-proET-1, CT-proAVP, and MR-proANP were all elevated in patients with future cardiovascular events and independently correlated to serum creatinine. MR-proADM and MR-proANP were significant predictors of a future cardiovascular event, with MR-proANP being the stronger (area under the curve 0.802 ± 0.034, sensitivity 0.833, specificity 0.576, positive predictive value 0.132, and negative predictive value 0.978 with a cutoff value of 75 pmol/l). CONCLUSIONS The four serum markers of vasoactive and natriuretic peptides are related to both kidney function and cardiovascular events, thus linking two major complications of diabetes, diabetic nephropathy and cardiovascular disease. PMID:19564455

  19. From potential donor to actual donation: does socioeconomic position affect living kidney donation? A systematic review of the evidence.

    PubMed

    Bailey, Phillippa; Tomson, Charles; Risdale, Saira; Ben-Shlomo, Yoav

    2014-11-15

    Evidence from Europe, Australia and the United States demonstrates that socioeconomically deprived individuals with advanced chronic kidney disease are less likely to receive a living kidney transplant compared with less deprived individuals. This systematic review focuses on how socioeconomic position (SEP) may influence hypothetical and actual living kidney donors and where appropriate, summarizes the quantitative evidence.In the general population, a higher SEP appears to be associated with an increased 'hypothetical' willingness to be a living kidney donor but with marked heterogeneity in the absolute differences (I = 95.9%, P < 0.001). In a commercial setting, lower SEP motivates people to donate. Outside of this setting, there is no evidence of discordance in the SEP of donors and recipients that would suggest undisclosed financial exchange. There is evidence for a complex interaction between SEP and other variables, such as ethnicity, sex, and the national economic climate. Some evidence suggests that measures to remove financial disincentives to donation are associated with an increase in living donation rates. Future research needs to study how SEP impacts the potential donor population from willingness to donate, progression through donor assessment to actual donor nephrectomy.

  20. High intensity interval training favourably affects antioxidant and inflammation mRNA expression in early-stage chronic kidney disease.

    PubMed

    Tucker, Patrick S; Briskey, David R; Scanlan, Aaron T; Coombes, Jeff S; Dalbo, Vincent J

    2015-12-01

    Increased levels of oxidative stress and inflammation have been linked to the progression of chronic kidney disease. To reduce oxidative stress and inflammation related to chronic kidney disease, chronic aerobic exercise is often recommended. Data suggests high intensity interval training may be more beneficial than traditional aerobic exercise. However, appraisals of differing modes of exercise, along with explanations of mechanisms responsible for observed effects, are lacking. This study assessed effects of eight weeks of high intensity interval training (85% VO2max), versus low intensity exercise (45-50% VO2max) and sedentary behaviour, in an animal model of early-stage chronic kidney disease. We examined kidney-specific mRNA expression of genes related to endogenous antioxidant enzyme activity (glutathione peroxidase 1; Gpx1, superoxide dismutase 1; Sod1, and catalase; Cat) and inflammation (kidney injury molecule 1; Kim1 and tumour necrosis factor receptor super family 1b; Tnfrsf1b), as well as plasma F2-isoprostanes, a marker of lipid peroxidation. Compared to sedentary behaviour, high intensity interval training resulted in increased mRNA expression of Sod1 (p=0.01) and Cat (p<0.001). Compared to low intensity exercise, high intensity interval training resulted in increased mRNA expression of Cat (p<0.001) and Tnfrsf1b (p=0.047). In this study, high intensity interval training was superior to sedentary behaviour and low intensity exercise as high intensity interval training beneficially influenced expression of genes related to endogenous antioxidant enzyme activity and inflammation.

  1. Kidney Cysts

    MedlinePlus

    ... fluid-filled sac. There are two types of kidney cysts. Polycystic kidney disease (PKD) runs in families. In PKD, the ... place of the normal tissue. They enlarge the kidneys and make them work poorly, leading to kidney ...

  2. Your Kidneys

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Your Kidneys KidsHealth > For Kids > Your Kidneys Print A A ... and it will be lighter. What Else Do Kidneys Do? Kidneys are always busy. Besides filtering the ...

  3. Kidney Disease

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Kidney Disease KidsHealth > For Teens > Kidney Disease Print A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...

  4. Kidney Dysplasia

    MedlinePlus

    ... following early in life: blood-filtering treatments called dialysis a kidney transplant Children with dysplasia in only ... mild dysplasia of both kidneys may not need dialysis or a kidney transplant for several years. Kidney ...

  5. Diurnal blood pressure changes one year after kidney transplantation: relationship to allograft function, histology, and resistive index.

    PubMed

    Wadei, Hani M; Amer, Hatem; Taler, Sandra J; Cosio, Fernando G; Griffin, Matthew D; Grande, Joseph P; Larson, Timothy S; Schwab, Thomas R; Stegall, Mark D; Textor, Stephen C

    2007-05-01

    Loss of circadian BP change has been linked to target organ damage and accelerated kidney function loss in hypertensive patients with and without chronic kidney disease. Ambulatory BP-derived data from 119 consecutive kidney transplant recipients who presented for the first annual evaluation were examined in relation to allograft function, histology, and ultrasound findings. A total of 101 (85%) patients were receiving antihypertensive medications (median 2), and 85 (71%) achieved target awake average systolic BP (SBP) of <135 mmHg. A day-night change in SBP by 10% or more (dippers) was detected in 29 (24%). Dipping status was associated with younger recipient age, lack of diabetes, low chronic vascular score, and low resistive index. Nondippers and reverse dippers had lower GFR compared with dippers (P = 0.04). For every 10% nocturnal drop in SBP, GFR increased by 4.6 ml/min per 1.73 m(2) (R = 0.3, P = 0.003). Nondippers and reverse dippers were equally common in recipients with normal histology and in those with pathologic findings on surveillance biopsy. On multivariate analysis, percentage of nocturnal fall in SBP and elevated resistive index independently correlated with GFR. This study indicates that lack of nocturnal fall in SBP is related to poor allograft function, high chronic vascular score, and high resistive index irrespective of allograft fibrosis. Further studies are needed to determine whether restoration of normal BP pattern will confer better allograft outcome.

  6. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    PubMed

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI. PMID:27034930

  7. Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women

    PubMed Central

    Singh, Namisha; Gandhi, Sonja; McArthur, Eric; Moist, Louise; Jain, Arsh K.; Liu, Aiden R.; Sood, Manish M.; Garg, Amit X.

    2015-01-01

    Background: The antibiotic nitrofurantoin is commonly used to treat uncomplicated urinary tract infections. However, when this drug is used by patients with reduced kidney function, its urine concentration may be subtherapeutic. Methods: We conducted a population-based study of older women (mean age 79 years) in Ontario, Canada, whose estimated glomerular filtration rate was relatively low (median 38 mL/min per 1.73 m2) and for whom 1 of 4 antibiotics had been prescribed for urinary tract infection: nitrofurantoin, ciprofloxacin, norfloxacin or trimethoprim–sulfamethoxazole. We assessed 2 measures of treatment failure in the subsequent 14 days: receipt of a second antibiotic indicated for urinary tract infection and hospital encounter (emergency department visit or hospital admission) with a urinary tract infection. We repeated the analysis for older women with relatively high estimated glomerular filtration rate (median 69 mL/min per 1.73 m2). Results: The baseline characteristics of the 4 antibiotic groups were similar. Relative to nitrofurantoin, the other antibiotics (including ciprofloxacin) were associated with a lower rate of treatment failure among women with relatively low estimated glomerular filtration rate (for ciprofloxacin v. nitrofurantoin: second antibiotic prescription, 130/1989 [6.5%] v. 516/3739 [13.8%], odds ratio [OR] 0.44, 95% confidence interval [CI] 0.36–0.53; hospital encounter, 21/1989 [1.1%] v. 95/3739 [2.5%], OR 0.41, 95% CI 0.25–0.66). However, a similar risk of treatment failure with nitrofurantoin was also observed among women with relatively high estimated glomerular filtration rate. The results were consistent in multiple additional analyses. Interpretation: In this study, the presence of mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of nitrofurantoin. PMID:25918178

  8. Chronic Renal Insufficiency Cohort (CRIC) Study: Baseline Characteristics and Associations with Kidney Function

    PubMed Central

    Go, Alan S.; Appel, Lawrence J.; He, Jiang; Ojo, Akinlolu; Rahman, Mahboob; Townsend, Raymond R.; Xie, Dawei; Cifelli, Denise; Cohan, Janet; Fink, Jeffrey C.; Fischer, Michael J.; Gadegbeku, Crystal; Hamm, L. Lee; Kusek, John W.; Landis, J. Richard; Narva, Andrew; Robinson, Nancy; Teal, Valerie; Feldman, Harold I.

    2009-01-01

    Background and objectives: The Chronic Renal Insufficiency Cohort (CRIC) Study was established to examine risk factors for the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with CKD. We examined baseline demographic and clinical characteristics. Design, setting, participants, & measurements: Seven clinical centers recruited adults who were aged 21 to 74 yr and had CKD using age-based estimated GFR (eGFR) inclusion criteria. At baseline, blood and urine specimens were collected and information regarding health behaviors, diet, quality of life, and functional status was obtained. GFR was measured using radiolabeled iothalamate in one third of participants. Results: A total of 3612 participants were enrolled with mean age ± SD of 58.2 ± 11.0 yr; 46% were women, and 47% had diabetes. Overall, 45% were non-Hispanic white, 46% were non-Hispanic black, and 5% were Hispanic. Eighty-six percent reported hypertension, 22% coronary disease, and 10% heart failure. Mean body mass index was 32.1 ± 7.9 kg/m2, and 47% had a BP >130/80 mmHg. Mean eGFR was 43.4 ± 13.5 ml/min per 1.73 m2, and median (interquartile range) protein excretion was 0.17 g/24 h (0.07 to 0.81 g/24 h). Lower eGFR was associated with older age, lower socioeconomic and educational level, cigarette smoking, self-reported CVD, peripheral arterial disease, and elevated BP. Conclusions: Lower level of eGFR was associated with a greater burden of CVD as well as lower socioeconomic and educational status. Long-term follow-up of participants will provide critical insights into the epidemiology of CKD and its relationship to adverse outcomes. PMID:19541818

  9. Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption.

    PubMed

    Hyodo, Susumu; Kakumura, Keigo; Takagi, Wataru; Hasegawa, Kumi; Yamaguchi, Yoko

    2014-12-15

    For adaptation to high-salinity marine environments, cartilaginous fishes (sharks, skates, rays, and chimaeras) adopt a unique urea-based osmoregulation strategy. Their kidneys reabsorb nearly all filtered urea from the primary urine, and this is an essential component of urea retention in their body fluid. Anatomical investigations have revealed the extraordinarily elaborate nephron system in the kidney of cartilaginous fishes, e.g., the four-loop configuration of each nephron, the occurrence of distinct sinus and bundle zones, and the sac-like peritubular sheath in the bundle zone, in which the nephron segments are arranged in a countercurrent fashion. These anatomical and morphological characteristics have been considered to be important for urea reabsorption; however, a mechanism for urea reabsorption is still largely unknown. This review focuses on recent progress in the identification and mapping of various pumps, channels, and transporters on the nephron segments in the kidney of cartilaginous fishes. The molecules include urea transporters, Na(+)/K(+)-ATPase, Na(+)-K(+)-Cl(-) cotransporters, and aquaporins, which most probably all contribute to the urea reabsorption process. Although research is still in progress, a possible model for urea reabsorption in the kidney of cartilaginous fishes is discussed based on the anatomical features of nephron segments and vascular systems and on the results of molecular mapping. The molecular anatomical approach thus provides a powerful tool for understanding the physiological processes that take place in the highly elaborate kidney of cartilaginous fishes.

  10. Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals

    PubMed Central

    de Sandes-Freitas, Tainá Veras; Felipe, Cláudia Rosso; Aguiar, Wilson Ferreira; Cristelli, Marina Pontello; Tedesco-Silva, Hélio; Medina-Pestana, José Osmar

    2015-01-01

    It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1–5, 6–10, 11–15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064–4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117–2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1–5), DGF(6–10), and DGF(11–15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270–6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055–8.193, p<0.001), and death (OR 3.065, CI95% 1.536–6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year. PMID:26679933

  11. Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter.

    PubMed Central

    Boll, M; Herget, M; Wagener, M; Weber, W M; Markovich, D; Biber, J; Clauss, W; Murer, H; Daniel, H

    1996-01-01

    The presence of a proton-coupled electrogenic high-affinity peptide transporter in the apical membrane of tubular cells has been demonstrated by microperfusion studies and by use of brush border membrane vesicles. The transporter mediates tubular uptake of filtered di- and tripeptides and aminocephalosporin antibiotics. We have used expression cloning in Xenopus laevis oocytes for identification and characterization of the renal high-affinity peptide transporter. Injection of poly(A)+ RNA isolated from rabbit kidney cortex into oocytes resulted in expression of a pH-dependent transport activity for the aminocephalosporin antibiotic cefadroxil. After size fractionation of poly(A)+ RNA the transport activity was identified in the 3.0- to 5.0-kb fractions, which were used for construction of a cDNA library. The library was screened for expression of cefadroxil transport after injection of complementary RNA synthesized in vitro from different pools of clones. A single clone (rPepT2) was isolated that stimulated cefadroxil uptake into oocytes approximately 70-fold at a pH of 6.0. Kinetic analysis of cefadroxil uptake expressed by the transporter's complementary RNA showed a single saturable high-affinity transport system shared by dipeptides, tripeptides, and selected amino-beta-lactam antibiotics. Electrophysiological studies established that the transport activity is electrogenic and affected by membrane potential. Sequencing of the cDNA predicts a protein of 729 amino acids with 12 membrane-spanning domains. Although there is a significant amino acid sequence identity (47%) to the recently cloned peptide transporters from rabbit and human small intestine, the renal transporter shows distinct structural and functional differences. Images Fig. 7 PMID:8552623

  12. Common chronic conditions do not affect performance of cell cycle arrest biomarkers for risk stratification of acute kidney injury

    PubMed Central

    Heung, Michael; Ortega, Luis M.; Chawla, Lakhmir S.; Wunderink, Richard G.; Self, Wesley H.; Koyner, Jay L.; Shi, Jing; Kellum, John A.

    2016-01-01

    Background Identification of acute kidney injury (AKI) can be challenging in patients with underlying chronic disease, and biomarkers often perform poorly in this population. In this study we examined the performance characteristics of the novel biomarker panel of urinary tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 ([IGFBP7]) in patients with a variety of comorbid conditions. Methods We analyzed data from two multicenter studies of critically ill patients in which [TIMP2]•[IGFBP7] was validated for prediction of Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2 or 3 AKI within 12 h. We constructed receiver operating characteristic (ROC) curves for AKI prediction both overall and by comorbid conditions common among patients with AKI, including diabetes mellitus, congestive heart failure (CHF) and chronic kidney disease (CKD). Results In the overall cohort of 1131 patients, 139 (12.3%) developed KDIGO Stage 2 or 3 AKI. [TIMP2]•[IGFBP7] was significantly higher in AKI versus non-AKI patients, both overall and within each comorbidity subgroup. The AUC for [TIMP2]•[IGFBP7] in predicting AKI was 0.81 overall. Higher AUC was noted in patients with versus without CHF (0.89 versus 0.79; P = 0.026) and CKD (0.91 versus 0.80; P = 0.024). Conclusions We observed no significant impairment in the performance of cell cycle arrest biomarkers due to the presence of chronic comorbid conditions. PMID:27342582

  13. Renal handling of cadmium in perfused rat kidney and effects on renal function and tissue composition.

    PubMed

    Diamond, G L; Cohen, J J; Weinstein, S L

    1986-11-01

    Isolated rat kidneys perfused with a Krebs-Ringer bicarbonate (KRB) solution containing 1 microM CdCl2 plus 6% substrate-free albumin (SFA) and a mixture of substrates accumulated substantially less cadmium in tissue than kidneys perfused with 1 microM CdCl2 in a protein-free KRB solution containing the same substrates: 11 vs. 205 nmol Cd/g dry wt. Decreasing the glomerular filtration rate (GFR) by occluding the ureters of kidneys perfused in the absence of albumin did not change the rate of net tissue uptake of cadmium (Cd), suggesting that the kidney can extract Cd from the peritubular capillary fluid and that net uptake of Cd is not dependent on the reabsorption of filtered Cd. The tissue accumulation of large quantities of Cd (1.8 mumol Cd/g dry wt), which established levels of non-metallothionein-bound Cd exceeding 1 mumol Cd/g dry wt, caused no changes in either GFR, perfusion flow rate, fractional reabsorption of Na+, fractional reabsorption of K+, fractional reabsorption of glucose, or free-water clearance. However, discrete changes in renal tissue K+ content were observed. Exposure to 1 microM CdCl2 resulted in a net loss of renal tissue K+ in rat kidneys perfused with substrate-enriched KRB containing 6% albumin. Exposure to 0.8 microM or 7 microM CdCl2 completely prevented K+ loss from kidneys perfused with a substrate-enriched, protein-free KRB solution. PMID:3777178

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  15. Can lifestyle modification affect men’s erectile function?

    PubMed Central

    Hehemann, Marah C.

    2016-01-01

    Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. The pathophysiology and epidemiologic links between ED and risk factors for cardiovascular disease (CVD) are well-established. Lifestyle modifications such as smoking cessation, weight reduction, dietary modification, physical activity, and psychological stress reduction have been increasingly recognized as foundational to the prevention and treatment of ED. The aim of this review is to outline behavioral choices which may increase ones risk of developing ED, to present relevant studies addressing lifestyle factors correlated with ED, and to highlight proposed mechanisms for intervention aimed at improving erectile function in men with ED. These recommendations can provide a framework for counseling patients with ED about lifestyle modification. PMID:27141445

  16. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  17. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing. PMID:20336685

  18. Functional roles affect diversity-succession relationships for boreal beetles.

    PubMed

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  19. Effects of acute sodium fluoride exposure on kidney function, water homeostasis, and renal handling of calcium and inorganic phosphate.

    PubMed

    Santoyo-Sanchez, Mitzi Paola; del Carmen Silva-Lucero, Maria; Arreola-Mendoza, Laura; Barbier, Olivier Christophe

    2013-06-01

    Fluoride compounds are abundant and widely distributed in the environment at a variety of concentrations. Further, fluoride induces toxic effects in target organs such as the liver and kidney. In this study, we performed an early analysis of renal function using a clearance technique in Wistar rats acutely exposed to fluoride at a plasma concentration of 0.625 μg/ml. Our results revealed that fluoride, at a concentration close to the concentration present in the serum after environmental exposure, induced a significant tubular dysfunction, resulting in diluted urine, impaired protein reabsorption, and increased calcium and phosphate urinary excretion. Our work demonstrates that even acute exposures to low concentrations of NaF may induce renal damage and confirms that, after exposure, the kidney participates directly in the calcium and phosphate deficiencies observed in fluoride-exposed populations.

  20. Functional characterisation of human SGLT-5 as a novel kidney-specific sodium-dependent sugar transporter.

    PubMed

    Grempler, Rolf; Augustin, Robert; Froehner, Stefanie; Hildebrandt, Tobias; Simon, Eric; Mark, Michael; Eickelmann, Peter

    2012-02-01

    Sodium glucose cotransporters (SGLT) actively catalyse carbohydrate transport across cellular membranes. Six of the 12 known SGLT family members have the capacity to bind and/or transport monosaccharides (SGLT-1 to 6); of these, all but SGLT-5 have been characterised. Here we demonstrate that human SGLT-5 is exclusively expressed in the kidney. Four splice variants were detected and the most abundant SGLT-5-mRNA was functionally characterised. SGLT-5 mediates sodium-dependent [(14)C]-α-methyl-D-glucose (AMG) transport that can be inhibited by mannose, fructose, glucose, and galactose. Uptake studies using demonstrated high capacity transport for mannose and fructose and, to a lesser extent, glucose, AMG, and galactose. SGLT-5 mediated mannose, fructose and AMG transport was weakly (μM potency) inhibited by SGLT-2 inhibitors. In summary, we have characterised SGLT-5 as a kidney mannose transporter. Further studies are warranted to explore the physiological role of SGLT-5.

  1. Preserved Renal Function in Kidney Transplantation over a Thrombosed Aortobifemoral Bypass Graft: The Role of Retrograde Flow and Early Thrombolysis.

    PubMed

    Pampa-Saico, Saúl; Jiménez-Alvaro, Sara; Caravaca-Fontán, Fernando; Fernández-Rodríguez, Ana; Rivera-Gorrín, Maite; Sánchez, Juan; Chinchilla, Antonio; Marcén, Roberto

    2016-01-01

    Aortobifemoral bypass (ABFB) thrombosis is not uncommon, and when the artery of a renal graft is implanted on a bypass the risk of graft loss is high. We report the case of a 48-year-old woman with a previous history of ABFB under antiplatelet therapy and a kidney allograft implanted on the vascular prosthesis, who presented with acute limb ischemia and severe renal impairment. Imaging techniques revealed a complete thrombosis of the proximal left arm of the ABFB. However, a faint retrograde flow over the graft was observed thanks to the recanalization of distal left bypass by collateral native arteries. This unusual situation not previously reported in a kidney transplant setting, together with an early diagnosis, allowed graft survival until an early local thrombolysis resolved the problem. Two years later, renal function remains normal. PMID:27579209

  2. Preserved Renal Function in Kidney Transplantation over a Thrombosed Aortobifemoral Bypass Graft: The Role of Retrograde Flow and Early Thrombolysis

    PubMed Central

    Jiménez-Alvaro, Sara; Fernández-Rodríguez, Ana; Rivera-Gorrín, Maite; Sánchez, Juan; Chinchilla, Antonio; Marcén, Roberto

    2016-01-01

    Aortobifemoral bypass (ABFB) thrombosis is not uncommon, and when the artery of a renal graft is implanted on a bypass the risk of graft loss is high. We report the case of a 48-year-old woman with a previous history of ABFB under antiplatelet therapy and a kidney allograft implanted on the vascular prosthesis, who presented with acute limb ischemia and severe renal impairment. Imaging techniques revealed a complete thrombosis of the proximal left arm of the ABFB. However, a faint retrograde flow over the graft was observed thanks to the recanalization of distal left bypass by collateral native arteries. This unusual situation not previously reported in a kidney transplant setting, together with an early diagnosis, allowed graft survival until an early local thrombolysis resolved the problem. Two years later, renal function remains normal. PMID:27579209

  3. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury.

    PubMed

    Santos, M S Biagioni; Seguro, A C; Andrade, L

    2010-03-01

    The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm(3), 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

  4. Urinary miR-16 transactivated by C/EBPβ reduces kidney function after ischemia/reperfusion–induced injury

    PubMed Central

    Chen, Hsi-Hsien; Lan, Yi-Fan; Li, Hsiao-Fen; Cheng, Ching-Feng; Lai, Pei-Fang; Li, Wei-Hua; Lin, Heng

    2016-01-01

    Ischemia-reperfusion (I/R) induced acute kidney injury (AKI) is regulated by transcriptional factors and microRNAs (miRs). However, modulation of miRs by transcriptional factors has not been characterized in AKI. Here, we found that urinary miR-16 was 100-fold higher in AKI patients. MiR-16 was detected earlier than creatinine in mouse after I/R. Using TargetScan, the 3′UTR of B-cell lymphoma 2 (BCL-2) was found complementary to miR-16 to decrease the fluorescent reporter activity. Overexpression of miR-16 in mice significantly attenuated renal function and increased TUNEL activity in epithelium tubule cells. The CCAAT enhancer binding protein beta (C/EBP-β) increased the expression of miR-16 after I/R injury. The ChIP and luciferase promoter assay indicated that about −1.0 kb to −0.5 kb upstream of miR-16 genome promoter region containing C/EBP-β binding motif transcriptionally regulated miR-16 expression. Meanwhile, the level of pri-miR-16 was higher in mice infected with lentivirus containing C/EBP-β compared with wild-type (WT) mice and overexpression of C/EBP-β in the kidney of WT mice reduced kidney function, increased kidney apoptosis, and elevated urinary miR-16 level. Our results indicated that miR-16 was transactivated by C/EBP-β resulting in aggravated I/R induced AKI and that urinary miR-16 may serve as a potential biomarker for AKI. PMID:27297958

  5. To what extent does urbanisation affect fragmented grassland functioning?

    PubMed

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  6. To what extent does urbanisation affect fragmented grassland functioning?

    PubMed

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  7. Biological monitoring of kidney function among workers occupationally exposed to trichloroethylene

    PubMed Central

    Green, T; Dow, J; Ong, C; Ng, V; Ong, H; Zhuang, Z; Yang, X; Bloemen, L

    2004-01-01

    Aims: To investigate the nephrotoxic potential of trichloroethylene in a currently exposed population using sensitive urinary markers of kidney toxicity. Methods: Renal dysfunction was monitored in a cross-sectional study of 70 workers currently exposed to trichloroethylene. An age and sex matched control population of 54 individuals was drawn from hospital and administrative staff. Results: The mean exposure to trichloroethylene, estimated from urinary trichloroacetic acid concentrations, was 32 ppm (range 0.5–252 ppm) with an average duration of exposure of 4.1 years (range 1–20 years). Significant differences between the exposed and control populations were found for nephrotoxicity markers N-acetylglucosaminidase (NAG) and albumin, and for the mode of action marker, formic acid. However, neither NAG nor albumin showed a significant correlation with either the magnitude or duration of exposure to trichloroethylene. There was a significant correlation between urinary formic acid and trichloroacetic acid concentrations. Within the exposed population there were dose dependent increases in urinary methylmalonic acid concentrations and urinary glutathione S-transferase α activity. Although still within the control range, these changes were clearly dose dependent and consistent with one of the proposed mechanisms of trichloroethylene induced kidney toxicity. Conclusion: Although there was no evidence of kidney toxicity within the population studied, the results suggest that kidney damage could occur at exposure concentrations higher (>250 ppm) than those encountered in this study. PMID:15031388

  8. Integrating Negative Affect Measures in a Measurement Model: Assessing the Function of Negative Affect as Interference to Self-Regulation

    ERIC Educational Resources Information Center

    Magno, Carlo

    2010-01-01

    The present study investigated the composition of negative affect and its function as inhibitory to thought processes such as self-regulation. Negative affect in the present study were composed of anxiety, worry, thought suppression, and fear of negative evaluation. These four factors were selected based on the criteria of negative affect by…

  9. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  10. Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition

    PubMed Central

    Li, Bing; Cui, Wenpeng; Tan, Yi; Luo, Ping; Chen, Qiang; Zhang, Chi; Qu, Wei; Miao, Lining; Cai, Lu

    2014-01-01

    Increasing evidence from human and laboratory studies showed the effect of zinc (Zn) on diabetic complications. Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays important role in the prevention of oxidative damage. This study was to define whether Zn statues (deficiency or supplement) affect the Nrf2 expression and function, and also affect the damage severity of human renal tubular (HK11) cells exposed to high glucose (HG) with palmitate (Pal) and kidney of diabetic mice induced by multiple low-dose streptozotocins. For Zn deficiency diabetic mice were treated with Zn chelator PTEN at 5 mg/kg bw daily for 4 months. Results showed that HG/Pal significantly increased the expression of pro-fibrotic mediators, connective tissue growth factor and PAI-1, in HK11 cells, which was exacerbated by TPEN that depleted intracellular free Zn and decreased Nrf2 expression and transcription. Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3β phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn. All these effects of Zn were abolished by Akt inhibitor. Therefore, Zn up-regulates Nrf2 function via activating Akt-mediated inhibition of Fyn function. Treatment of diabetic mice with TPEN decreased renal Zn level and Nrf2 expression and transcription, with an exacerbation of renal oxidative damage, inflammation and fibrosis. These results suggest the essentiality of Zn for Nrf2 expression and transcription function. PMID:24597671

  11. Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition.

    PubMed

    Li, Bing; Cui, Wenpeng; Tan, Yi; Luo, Ping; Chen, Qiang; Zhang, Chi; Qu, Wei; Miao, Lining; Cai, Lu

    2014-05-01

    Increasing evidence from human and laboratory studies showed the effect of zinc (Zn) on diabetic complications. Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays important role in the prevention of oxidative damage. This study was to define whether Zn statues (deficiency or supplement) affect the Nrf2 expression and function, and also affect the damage severity of human renal tubular (HK11) cells exposed to high glucose (HG) with palmitate (Pal) and kidney of diabetic mice induced by multiple low-dose streptozotocins. For Zn deficiency diabetic mice were treated with Zn chelator PTEN at 5 mg/kg bw daily for 4 months. Results showed that HG/Pal significantly increased the expression of pro-fibrotic mediators, connective tissue growth factor and PAI-1, in HK11 cells, which was exacerbated by TPEN that depleted intracellular free Zn and decreased Nrf2 expression and transcription. Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3β phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn. All these effects of Zn were abolished by Akt inhibitor. Therefore, Zn up-regulates Nrf2 function via activating Akt-mediated inhibition of Fyn function. Treatment of diabetic mice with TPEN decreased renal Zn level and Nrf2 expression and transcription, with an exacerbation of renal oxidative damage, inflammation and fibrosis. These results suggest the essentiality of Zn for Nrf2 expression and transcription function.

  12. Functional Roles Affect Diversity-Succession Relationships for Boreal Beetles

    PubMed Central

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of “functional” groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience. PMID:23977350

  13. High Mobility Group Box Protein-1 Correlates with Renal Function in Chronic Kidney Disease (CKD)

    PubMed Central

    Bruchfeld, Annette; Qureshi, Abdul Rashid; Lindholm, Bengt; Barany, Peter; Yang, LiHong; Stenvinkel, Peter; Tracey, Kevin J

    2008-01-01

    Chronic kidney disease (CKD) is associated with inflammation and malnutrition and carries a markedly increased risk of cardiovascular disease (CVD). High Mobility Group Box Protein-1 (HMGB-1) is a 30-kDa nuclear and cytosolic protein known as a transcription and growth factor, recently identified as a proinflammatory mediator of tissue injury. Recent data implicates HMGB-1 in endotoxin lethality, rheumatoid arthritis, and atherosclerosis. The aim of this post-hoc, cross-sectional study was to determine whether HMGB-1 serum levels are elevated in CKD patients. The study groups were categorized as follows: 110 patients starting dialysis defined as CKD 5; 67 patients with moderately to severely reduced renal function or CKD 3–4; and 48 healthy controls. High-sensitivity C-reactive-protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF), serum-albumin (S-albumin), hemoglobin A1c (HbA1c), hemoglobin, subjective global nutritional assessment (SGA), and glomerular filtration rate (GFR) were analyzed. Kruskal-Wallis test was used to compare groups and Spearman’s rank correlation test was used for continuous variables. HMGB-1, measured by Western blot, was significantly (P < 0.001) elevated in CKD 5 (146.7 ± 58.6 ng/mL) and CKD 3–4 (85.6 ± 31.8) compared with controls (10.9 ± 10.5). HMGB-1 levels were correlated positively with TNF (Rho = 0.52; P < 0.001), hs-CRP (Rho = 0.38; P < 0.001), IL-6 (Rho = 0.30; P < 0.001), HbA1c (Rho = 0.14; P = 0.02) and SGA (Rho = 0.21; P = 0.002) and negatively correlated with GFR (Rho = –0.69; P = 0.0001), Hb (Rho = –0.60; P < 0.001), S-albumin (Rho = –0.31; P < 0.001). The current study has revealed that HMGB-1 is elevated significantly in CKD patients and correlates with GFR as well as markers of inflammation and malnutrition. Future studies may delineate whether HMGB-1 is also a marker of disease activity and severity as well as a predictor of outcome in CKD. PMID:18317568

  14. Modifiable lifestyle and social factors affect chronic kidney disease in high-risk individuals with type 2 diabetes mellitus.

    PubMed

    Dunkler, Daniela; Kohl, Maria; Heinze, Georg; Teo, Koon K; Rosengren, Annika; Pogue, Janice; Gao, Peggy; Gerstein, Hertzel; Yusuf, Salim; Oberbauer, Rainer; Mann, Johannes F E

    2015-04-01

    This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes.

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

    PubMed

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

    2016-05-01

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

  16. Image-derived and arterial blood sampled input functions for quantitative PET imaging of the angiotensin II subtype 1 receptor in the kidney

    SciTech Connect

    Feng, Tao; Tsui, Benjamin M. W.; Li, Xin; Vranesic, Melin; Lodge, Martin A.; Gulaldi, Nedim C. M.; Szabo, Zsolt

    2015-11-15

    phase of the ID-IF. The combined use of FBP and OS-EM resulted in reduced bias and noise. After performing all the necessary corrections, the areas under the curves (AUCs) of the AD-IF were close to that of the AD-IF (average AUC ratio =1 ± 0.08) during the early phase. When applied in a two-tissue-compartmental kinetic model, the average difference between the estimated model parameters from ID-IF and AD-IF was 10% which was within the error of the estimation method. Conclusions: The bias of radioligand concentration in the aorta from the OS-EM image reconstruction is significantly affected by radioligand uptake in the adjacent kidney and cannot be neglected for quantitative evaluation. With careful calibrations and corrections, the ID-IF derived from quantitative dynamic PET images can be used as the input function of the compartmental model to quantify the renal kinetics of {sup 11}C-KR31173 in experimental animals and the authors intend to evaluate this method in future human studies.

  17. Assessments of factors that affect glomerular filtration rate and indirect markers of renal function in dogs and cats.

    PubMed

    Miyagawa, Yuichi; Takemura, Naoyuki; Hirose, Hisashi

    2010-09-01

    Chronic kidney disease is one of the most common disorders in dogs and cats. The plasma urea nitrogen (P-UN) and creatinine (P-Cre) concentrations are not sufficiently sensitive for early diagnosis of renal dysfunction. Although urine and plasma clearance methods allow earlier detection of reductions in the GFR, it is difficult to estimate a mildly reduced GFR from the values obtained by these methods, as they are also affected by physiological factors, such as body weight (BW) and age. The present study is a retrospective survey designed to assess the factors that affect markers of kidney function and to revaluate the clinical utility of the markers, including P-UN, P-Cre and GFR determined by plasma iohexol clearance (PCio) in dogs and cats. The P-UN, P-Cre and PCio values in dogs and the P-Cre and PCio values in cats were significantly correlated with BW (P<0.001). PCio in smaller dogs (≤ 15.0 kg) was significantly and inversely correlated with age. In smaller dogs, increase of P-UN alone might warrant a suspicion of a decreased GFR, but in contrast, P-Cre may be inefficient for detecting renal dysfunction or determining the severity of CKD compared with that in larger dogs (≥ 15.1 kg). P-Cre in larger dogs correlated better with PCio than in smaller dogs, suggesting that P-Cre in larger dogs was a more sensitive marker of reduced GFR. PMID:20410678

  18. Renal function, calcium regulation, and time to hospitalization of patients with chronic kidney disease

    PubMed Central

    2013-01-01

    Background Chronic kidney disease is associated with disruption of the endocrine system that distorts the balance between calcitriol, calcium, phosphate and parathyroid hormone in the calcium regulation system. This can lead to calcification of the arterial tree and increased risk of cardiovascular disease and death. In this study we develop a health metric, based on biomarkers involved in the calcium regulation system, for use in identifying patients at high risk for future high-cost complications. Methods This study is a retrospective observational study involving a secondary analysis of data from the kidney disease registry of a regional managed care organization. Chronic kidney disease patients in the registry from November 2007 through November 2011 with a complete set of observations of estimated glomerular filtration rate, calcitriol, albumin, free calcium, phosphate, and parathyroid hormone were included in the study (n = 284). Weibull regression model was used to identify the most significant lab tests in predicting “waiting time to hospitalization”. A multivariate linear path model was then constructed to investigate direct and indirect effects of the biomarkers on this outcome. Results The results showed negative significant direct effects of phosphate and parathyroid hormone on “waiting time to hospitalization”. Base on this result, the risk of hospitalization increases 16.8% for each 0.55 mg/dl increase in phosphate level and 13.5% for each 0.467 increase in the natural logarithm of parathyroid hormone. Positive indirect effects of calcitriol surrogate (calcidiol), free calcium, albumin and estimated glomerular filtration rate were observed but were relatively small in magnitude. Conclusion Variables involved in the calcium regulation system should be included in future efforts to develop a quality of care index for Chronic Kidney disease patients. PMID:23865435

  19. Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney

    PubMed Central

    Westland, Rik; Verbitsky, Miguel; Vukojevic, Katarina; Perry, Brittany J.; Fasel, David A.; Zwijnenburg, Petra J.G.; Bökenkamp, Arend; Gille, Johan J.P.; Saraga-Babic, Mirna; Ghiggeri, Gian Marco; D’Agati, Vivette D.; Schreuder, Michiel F.; Gharavi, Ali G.; van Wijk, Joanna A.E.; Sanna-Cherchi, Simone

    2016-01-01

    Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to be difficult. Here we studied the role of rare copy number variations in 80 patients from the KIMONO-study cohort for which pathogenic mutations in three genes commonly implicated in CAKUT were excluded. In total, 13 known or novel genomic imbalances in 11 of 80 patients were absent or extremely rare in 23,362 population controls. To identify the most likely genetic drivers for the CAKUT phenotype underlying these rare copy number variations, we used a systematic in silico approach based on frequency in a large dataset of controls, annotation with publicly available databases for developmental diseases, tolerance and haploinsufficiency scores, and gene expression profile in the developing kidney and urinary tract. Five novel candidate genes for CAKUT were identified that showed specific expression in the human and mouse developing urinary tract. Among these genes, DLG1 and KIF12 are likely novel susceptibility genes for CAKUT in humans. Thus, there is a significant role of genomic imbalance in the determination of kidney developmental phenotypes. Additionally, we defined a systematic strategy to identify genetic drivers underlying rare copy number variations. PMID:26352300

  20. Biochemical studies on the effect of different water resources in Hail region on liver and kidney functions of rats.

    PubMed

    Talkhan, Ola F A; Abd Elwahab, Safaa A E; Shalapy, Ebtessam M

    2016-08-01

    Low concentration of a heavy metal is toxic and can be classified as one of the pollution sources. Industrial and human waste can pollute water with heavy metals and soils breaking down under the effect of acidic rain, which release heavy metals into river, streams, lakes, and ground water. Bioaccumulation of heavy metals in vital organs of the human body damages these organs, including the liver and kidney, which are the main organs for metabolism, detoxification, and excretion. The present study aims to investigate into concentrations of such heavy metals (Fe, Cu, Zn, and Pb) in both ground and tap water samples collected from different areas in Hail region, KSA. Then, this study moves forward to examine the effects of such concentrations on the biochemistry of serum in rats. In this regard, the results demonstrate the presence of significant differences (p < 0.05) in the liver function parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total proteins, albumin, and globulin between all the studied groups that were exposed to heavy-metals-polluted water, when compared with the control group. In addition, there were significant differences (p < 0.05) in the kidney function parameters, uric acid, urea, and creatinine, when compared with the control group. Thence, and as this study indicates, heavy-metals-polluted water can cause disturbance in the liver and kidney function parameters, which highlights health risks of the water polluted with heavy metals. In this sense, the concerned authorities should regularly carry out survey and should monitor underground water, and people have to be aware of such risks. PMID:27461423

  1. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function.

    PubMed

    Chasman, Daniel I; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; O'Seaghdha, Conall M; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D; Gierman, Hinco J; Feitosa, Mary F; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; de Andrade, Mariza; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S; van Duijn, Cornelia M; Borecki, Ingrid B; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M; Kao, W H Linda; Fox, Caroline S; Köttgen, Anna

    2012-12-15

    In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10(-9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10(-4)-2.2 × 10(-7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

  2. Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function

    PubMed Central

    Chasman, Daniel I.; Fuchsberger, Christian; Pattaro, Cristian; Teumer, Alexander; Böger, Carsten A.; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Taliun, Daniel; Li, Man; Gao, Xiaoyi; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C.; O'Seaghdha, Conall M.; Glazer, Nicole; Isaacs, Aaron; Liu, Ching-Ti; Smith, Albert V.; O'Connell, Jeffrey R.; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Johnson, Andrew D.; Gierman, Hinco J.; Feitosa, Mary F.; Hwang, Shih-Jen; Atkinson, Elizabeth J.; Lohman, Kurt; Cornelis, Marilyn C.; Johansson, Åsa; Tönjes, Anke; Dehghan, Abbas; Lambert, Jean-Charles; Holliday, Elizabeth G.; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y.; Murgia, Federico; Trompet, Stella; Imboden, Medea; Coassin, Stefan; Pistis, Giorgio; Harris, Tamara B.; Launer, Lenore J.; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D.; Boerwinkle, Eric; Schmidt, Helena; Cavalieri, Margherita; Rao, Madhumathi; Hu, Frank; Demirkan, Ayse; Oostra, Ben A.; de Andrade, Mariza; Turner, Stephen T.; Ding, Jingzhong; Andrews, Jeanette S.; Freedman, Barry I.; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Meisinger, Christa; Gieger, Christian; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E.; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H.; Wright, Alan F.; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K.; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G.; Rivadeneira, Fernando; Aulchenko, Yurii S.; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Ketkar, Shamika; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K.; Portas, Laura; Ford, Ian; Buckley, Brendan M.; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Kim, Stuart K.; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J. Wouter; Probst-Hensch, Nicole M.; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R.; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; Siscovick, David S.; van Duijn, Cornelia M.; Borecki, Ingrid B.; Kardia, Sharon L.R.; Liu, Yongmei; Curhan, Gary C.; Rudan, Igor; Gyllensten, Ulf; Wilson, James F.; Franke, Andre; Pramstaller, Peter P.; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Parsa, Afshin; Bochud, Murielle; Heid, Iris M.; Kao, W.H. Linda; Fox, Caroline S.; Köttgen, Anna

    2012-01-01

    In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10−9) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10−4–2.2 × 10−7. Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general. PMID:22962313

  3. Biochemical studies on the effect of different water resources in Hail region on liver and kidney functions of rats.

    PubMed

    Talkhan, Ola F A; Abd Elwahab, Safaa A E; Shalapy, Ebtessam M

    2016-08-01

    Low concentration of a heavy metal is toxic and can be classified as one of the pollution sources. Industrial and human waste can pollute water with heavy metals and soils breaking down under the effect of acidic rain, which release heavy metals into river, streams, lakes, and ground water. Bioaccumulation of heavy metals in vital organs of the human body damages these organs, including the liver and kidney, which are the main organs for metabolism, detoxification, and excretion. The present study aims to investigate into concentrations of such heavy metals (Fe, Cu, Zn, and Pb) in both ground and tap water samples collected from different areas in Hail region, KSA. Then, this study moves forward to examine the effects of such concentrations on the biochemistry of serum in rats. In this regard, the results demonstrate the presence of significant differences (p < 0.05) in the liver function parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total proteins, albumin, and globulin between all the studied groups that were exposed to heavy-metals-polluted water, when compared with the control group. In addition, there were significant differences (p < 0.05) in the kidney function parameters, uric acid, urea, and creatinine, when compared with the control group. Thence, and as this study indicates, heavy-metals-polluted water can cause disturbance in the liver and kidney function parameters, which highlights health risks of the water polluted with heavy metals. In this sense, the concerned authorities should regularly carry out survey and should monitor underground water, and people have to be aware of such risks.

  4. Tissue engineering the kidney.

    PubMed

    Hammerman, Marc R

    2003-04-01

    The means by which kidney function can be replaced in humans include dialysis and renal allotransplantation. Dialytic therapies are lifesaving, but often poorly tolerated. Transplantation of human kidneys is limited by the availability of donor organs. During the past decades, a number of different approaches have been applied toward tissue engineering the kidney as a means to replace renal function. The goals of one or another of them included the recapitulation of renal filtration, reabsorptive and secretory functions, and replacement of endocrine/metabolic activities. This review will delineate the progress to date recorded for five approaches: (1) integration of new nephrons into the kidney; (2) growing new kidneys in situ; (3) use of stem cells; (4) generation of histocompatible tissues using nuclear transplantation; and (5) bioengineering of an artificial kidney. All five approaches utilize cellular therapy. The first four employ transplantation as well, and the fifth uses dialysis.

  5. Do Kidney Stone Formers Have A Kidney Disease?

    PubMed Central

    Zisman, Anna L.; Evan, Andrew P.; Coe, Fredric L.; Worcester, Elaine M.

    2015-01-01

    Nephrolithiasis is a highly prevalent disorder affecting approximately one in eleven people and is associated with multiple complications including hypertension, cardiovascular disease, and chronic kidney disease. Significant epidemiologic associations with chronic kidney disease and ESRD have been noted and are reviewed herein, but debate persists in the literature as to whether kidney stone formation is a pathogenic process contributing to kidney disease. Corroborating evidence supporting the presence of kidney disease in stone formers includes the variability of renal function by stone type, the positive association of stone size with renal dysfunction, the presence of markers of renal injury in the urine of even asymptomatic stone formers, and direct evidence of renal tissue injury on histopathology. Proposed pathogenic mechanisms include recurrent obstruction and comorbid conditions such as recurrent urinary tract infections and structural abnormalities. Recent work evaluating the renal histopathology of different groups of stone formers adds further granularity, suggesting variability in mechanisms of renal injury by stone type and confirming the pathogenic effects of crystal formation. Genetic abnormalities leading to stone formation including cystinuria and primary hyperoxaluria, among others, contribute to the burden of disease in the stone-forming population. PMID:26376133

  6. Sympathoactivation and rho-kinase-dependent baroreflex function in experimental renovascular hypertension with reduced kidney mass

    PubMed Central

    2014-01-01

    Background Dysregulation of the autonomic nervous system is frequent in subjects with cardiovascular disease. The contribution of different forms of renovascular hypertension and the mechanisms contributing to autonomic dysfunction in hypertension are incompletely understood. Here, murine models of renovascular hypertension with preserved (2-kidneys-1 clip, 2K1C) and reduced (1-kidney-1 clip, 1K1C) kidney mass were studied with regard to autonomic nervous system regulation (sympathetic tone: power-spectral analysis of systolic blood pressure; parasympathetic tone: power-spectral analysis of heart rate) and baroreflex sensitivity of heart rate by spontaneous, concomitant changes of systolic blood pressure and pulse interval. Involvement of the renin-angiotensin system and the rho-kinase pathway were determined by application of inhibitors. Results C57BL6N mice (6 to 11) with reduced kidney mass (1K1C) or with preserved kidney mass (2K1C) developed a similar degree of hypertension. In comparison to control mice, both models presented with a significantly increased sympathetic tone and lower baroreflex sensitivity of heart rate. However, only 2K1C animals had a lower parasympathetic tone, whereas urinary norepinephrine excretion was reduced in the 1K1C model. Rho kinase inhibition given to a subset of 1K1C and 2K1C animals improved baroreflex sensitivity of heart rate selectively in the 1K1C model. Rho kinase inhibition had no additional effects on autonomic nervous system in either model of renovascular hypertension and did not change the blood pressure. Blockade of AT1 receptors (in 2K1C animals) normalized the sympathetic tone, decreased resting heart rate, improved baroreflex sensitivity of heart rate and parasympathetic tone. Conclusions Regardless of residual renal mass, blood pressure and sympathetic tone are increased, whereas baroreflex sensitivity is depressed in murine models of renovascular hypertension. Reduced norepinephrine excretion and/or degradation

  7. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation.

    PubMed

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-03-01

    Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support the use of

  8. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation.

    PubMed

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-03-01

    Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support the use of

  9. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation

    PubMed Central

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support

  10. Kidney Diseases

    MedlinePlus

    ... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...

  11. Kidney Tests

    MedlinePlus

    ... taking out waste products and making urine. Kidney tests check to see how well your kidneys are working. They include blood, urine, and imaging tests. Early kidney disease usually does not have signs ...

  12. Kidney Problems

    MedlinePlus

    ... our e-newsletter! Aging & Health A to Z Kidney Problems Basic Facts & Information The kidneys are two ... the production of red blood cells. What are Kidney Diseases? For about one-third of older people, ...

  13. Kidney stones

    MedlinePlus Videos and Cool Tools

    ... urine exits the kidney and enters the ureter. As urine can become very concentrated as it passes through the kidneys. When the urine ... chemicals dissolved in the urine can crystallize, forming a kidney stone (renal calculus). Usually the calculus is ...

  14. Effects of PEG-PLA-nano artificial cells containing hemoglobin on kidney function and renal histology in rats.

    PubMed

    Liu, Zun Chang; Chang, Thomas M S

    2008-01-01

    This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology.

  15. Dose-effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children.

    PubMed

    Xiong, Xianzhi; Liu, Junling; He, Weihong; Xia, Tao; He, Ping; Chen, Xuemin; Yang, Kedi; Wang, Aiguo

    2007-01-01

    Although a dose-effect relationship between water fluoride levels and damage to liver and kidney functions in animals has been reported, it was not demonstrated in humans. To evaluate the effects of drinking water fluoride levels on the liver and kidney functions in children with and without dental fluorosis, we identified 210 children who were divided into seven groups with 30 each based on different drinking water fluoride levels in the same residential area. We found that the fluoride levels in serum and urine of these children increased as the levels of drinking water fluoride increased. There were no significant differences in the levels of total protein (TP), albumin (ALB), aspartate transamine (AST), and alanine transamine (ALT) in serum among these groups. However, the activities of serum lactic dehydrogenase (LDH), urine N-acetyl-beta-glucosaminidase (NAG), and urine gamma-glutamyl transpeptidase (gamma-GT) in children with dental fluorosis and having water fluoride of 2.15-2.96 mg/L and in children having water fluoride of 3.15-5.69 mg/L regardless of dental fluorosis were significantly higher than children exposed to water fluoride of 0.61-0.87 mg/L in a dose-response manner. In contrast to children with dental fluorosis and having water fluoride of 2.15-2.96 and 3.10-5.69 mg/L, serum LDH activity of children without dental fluorosis but exposed to the same levels of water fluoride as those with dental fluorosis were also markedly lower, but the activities of NAG and gamma-GT in their urine were not. Therefore, our results suggest that drinking water fluoride levels over 2.0mg/L can cause damage to liver and kidney functions in children and that the dental fluorosis was independent of damage to the liver but not the kidney. Further studies on the mechanisms and significance underlying damage to the liver without dental fluorosis in the exposed children are warranted.

  16. Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

    PubMed Central

    Nkuipou-Kenfack, Esther; Duranton, Flore; Gayrard, Nathalie; Argilés, Àngel; Lundin, Ulrika; Weinberger, Klaus M.; Dakna, Mohammed; Delles, Christian; Mullen, William; Husi, Holger; Klein, Julie; Koeck, Thomas; Zürbig, Petra; Mischak, Harald

    2014-01-01

    Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In

  17. [The effect of exenatide analogs on hydruretic function of rat kidney under water load].

    PubMed

    Bogolepova, A E; Shakhmatova, E I

    2012-01-01

    Injection (0.05 nmol/100 g b.w.) of exenatide or its amino-acid-substituted synthetic analogs I (substitution at positions 14 and 39) and II (substitution at positions 14, 35, and 39) led to an increase in diuresis and excretion of sodium, magnesium and potassium, but only exenatide caused the excretion of solute free water. In experiments with 1% water load, only exenatide analog I stimulated the solute free water excretion. These features of exenatide and its analogs show the possibility of searching for substances with various power of action upon ion and water excretion by the kidney, which may have a clinical significance.

  18. Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920)

    PubMed Central

    Velasquez-Vottelerd, P.; Anton, Y.; Salazar-Lugo, R.

    2015-01-01

    The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd) effect on the mitochondrial viability (MV) and acid soluble thiols levels (AST) in A. brevifilis tissues (liver, kidney, heart, and gill) was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate) were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l-1). We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman’s method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions. PMID:26623384

  19. Cadmium affects the mitochondrial viability and the acid soluble thiols concentration in liver, kidney, heart and gills of Ancistrus brevifilis (Eigenmann, 1920).

    PubMed

    Velasquez-Vottelerd, P; Anton, Y; Salazar-Lugo, R

    2015-01-01

    The freshwater fish Ancistrus brevifilis, which is found in Venezuelan rivers, is considered a potential sentinel fish in ecotoxicological studies. The cadmium (Cd) effect on the mitochondrial viability (MV) and acid soluble thiols levels (AST) in A. brevifilis tissues (liver, kidney, heart, and gill) was evaluated. Forty-two fish with similar sizes and weights were randomly selected, of which 7 fish (with their respective replicate) were exposed for 7 and 30 days to a Cd sublethal concentration (0.1 mg.l(-1)). We determined the MV through a Janus Green B colorimetric assay and we obtained the concentration of AST by Ellman's method. Mitochondrial viability decreased in fish exposed to Cd for 30 days with the liver being the most affected tissue. We also detected a significant decrease in AST levels was in fishes exposed to Cd for 7 days in liver and kidney tissues; these results suggests that AST levels are elevated in some tissues may act as cytoprotective and adaptive alternative mechanism related to the ROS detoxification, maintenance redox status and mitochondrial viability. Organ-specifics variations were observed in both assays. We conclude that the Cd exposure effect on AST levels and MV, vary across fish tissues and is related to the exposure duration, the molecule dynamics in different tissues, the organism and environmental conditions. PMID:26623384

  20. Structure-function relationships of purple acid phosphatase from red kidney beans based on heterologously expressed mutants.

    PubMed

    Truong, Ngoc Thanh; Naseri, Joseph Itor; Vogel, Andreas; Rompel, Annette; Krebs, B

    2005-08-01

    Purple acid phosphatases are binuclear metalloenzymes, which catalyze the conversion of orthophosphoric monoesters to alcohol and orthophosphate. The enzyme from red kidney beans is characterized with a Fe(III)-Zn(II) active center. So far, the reaction mechanisms postulated for PAPs assume the essentiality of two amino acids, residing near the bimetallic active site. Based on the amino acid sequence of kidney bean PAP (kbPAP), residues H296 and H202 are believed to be essential for catalytic function of the enzyme. In the present study, the role of residue H202 has been elucidated. Mutants H202A and H202R were prepared by site-directed mutagenesis and expressed in baculovirus-infected insect cells. Based on kinetic studies, residue H202 is assumed to play a role in stabilizing the transition state, particularly in charge compensation, steric positioning of the substrate, and facilitating the release of the product by protonating the substrate leaving groups. The study confirmed the essentiality and elucidates the functional role of H202 in the catalytic mechanism of kbPAP.

  1. Reversal of Dabigatran Using Idarucizumab in a Septic Patient with Impaired Kidney Function in Real-Life Practice.

    PubMed

    Sauter, Thomas C; Blum, Sina; Nagler, Michael; Schlittler, Fabian L; Ricklin, Meret E; Exadaktylos, Aristomenis K

    2016-01-01

    Background. Immediate reversal of anticoagulation is essential when facing severe bleeding or emergency surgery. Although idarucizumab is approved for the reversal of dabigatran in many countries, clinical experiences are lacking, particularly in special patient-populations such as sepsis and impaired renal function. Case Presentation. We present the case of a 67-year-old male septic patient with a multilocular facial abscess and chronic kidney disease (GFR 36.5 mL/min). Thrombin time (TT) and activated partial thromboplastin time (aPTT) 15 hours after the last intake of 150 mg dabigatran were both prolonged (>120 sec, resp., 61 sec), as well as unbound dabigatran concentration (119.05 ng/mL). Before immediate emergency surgery dabigatran was antagonised using idarucizumab 2 × 2.5 g. Dabigatran concentration was not detectable 10 min after idarucizumab administration (<30 ng/mL). TT and aPTT time were normalised (16.2 sec, resp., 30.2 sec). Sepsis was controlled after surgery and kidney function remained stable. In the absence of postoperative bleeding, dabigatran was restarted 36 hours after admission. Conclusion. Idarucizumab successfully reversed the effect of dabigatran in real-life practice in a patient with sepsis and renal impairment and allowed emergency surgery with normal haemostasis. Efficacy and safety in real-life practice will nevertheless require prospective registries monitoring.

  2. Reversal of Dabigatran Using Idarucizumab in a Septic Patient with Impaired Kidney Function in Real-Life Practice

    PubMed Central

    Blum, Sina; Nagler, Michael; Schlittler, Fabian L.; Exadaktylos, Aristomenis K.

    2016-01-01

    Background. Immediate reversal of anticoagulation is essential when facing severe bleeding or emergency surgery. Although idarucizumab is approved for the reversal of dabigatran in many countries, clinical experiences are lacking, particularly in special patient-populations such as sepsis and impaired renal function. Case Presentation. We present the case of a 67-year-old male septic patient with a multilocular facial abscess and chronic kidney disease (GFR 36.5 mL/min). Thrombin time (TT) and activated partial thromboplastin time (aPTT) 15 hours after the last intake of 150 mg dabigatran were both prolonged (>120 sec, resp., 61 sec), as well as unbound dabigatran concentration (119.05 ng/mL). Before immediate emergency surgery dabigatran was antagonised using idarucizumab 2 × 2.5 g. Dabigatran concentration was not detectable 10 min after idarucizumab administration (<30 ng/mL). TT and aPTT time were normalised (16.2 sec, resp., 30.2 sec). Sepsis was controlled after surgery and kidney function remained stable. In the absence of postoperative bleeding, dabigatran was restarted 36 hours after admission. Conclusion. Idarucizumab successfully reversed the effect of dabigatran in real-life practice in a patient with sepsis and renal impairment and allowed emergency surgery with normal haemostasis. Efficacy and safety in real-life practice will nevertheless require prospective registries monitoring. PMID:27547476

  3. Influence of T-calcium channel blocker treatment on deterioration of renal function in chronic kidney disease.

    PubMed

    Omae, Kiyotsugu; Ogawa, Tetsuya; Nitta, Kosaku

    2009-07-01

    Some calcium channel blockers (CCBs) have renoprotective effects. Our aim was to compare the effects of different subclasses of CCBs on the deterioration of renal function in chronic kidney disease (CKD). This is a prospective, observational cohort study in a single center. The subjects were 107 nondiabetic CKD patients. The rate of deterioration of estimated glomerular filtration rate (DeltaeGFR) was calculated by [last visit eGFR - baseline eGFR/follow-up duration]. Multivariate analysis was performed using the change in urinary protein (DeltaUP) and DeltaeGFR during follow-up as response variables. CCB subclasses were L-type in 76 patients, T- and L-type in 28 patients, and nondihydropyridines in 6 patients. Multiregression analysis indicated that higher baseline proteinuria (UP) and the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers were associated with the decrease of UP, while the use of L-type CCBs, prednisolone, and probucol was associated with the increase of UP. The use of T- and L-type CCBs, ACEIs and diuretics was associated with a good outcome in terms of DeltaeGFR, whereas chronic glomerulonephritis, polycystic kidney disease, and higher baseline eGFR and UP were associated with a poor outcome. It is suggested that the use of T- and L-type CCB among other subclasses may improve the outcome of patients with nondiabetic CKD in terms of renal function.

  4. Structure-function relationships of purple acid phosphatase from red kidney beans based on heterologously expressed mutants.

    PubMed

    Truong, Ngoc Thanh; Naseri, Joseph Itor; Vogel, Andreas; Rompel, Annette; Krebs, B

    2005-08-01

    Purple acid phosphatases are binuclear metalloenzymes, which catalyze the conversion of orthophosphoric monoesters to alcohol and orthophosphate. The enzyme from red kidney beans is characterized with a Fe(III)-Zn(II) active center. So far, the reaction mechanisms postulated for PAPs assume the essentiality of two amino acids, residing near the bimetallic active site. Based on the amino acid sequence of kidney bean PAP (kbPAP), residues H296 and H202 are believed to be essential for catalytic function of the enzyme. In the present study, the role of residue H202 has been elucidated. Mutants H202A and H202R were prepared by site-directed mutagenesis and expressed in baculovirus-infected insect cells. Based on kinetic studies, residue H202 is assumed to play a role in stabilizing the transition state, particularly in charge compensation, steric positioning of the substrate, and facilitating the release of the product by protonating the substrate leaving groups. The study confirmed the essentiality and elucidates the functional role of H202 in the catalytic mechanism of kbPAP. PMID:16009331

  5. Structural and functional analyses of liver cysts from the BALB/c-cpk mouse model of polycystic kidney disease.

    PubMed

    Muchatuta, Monalisa N; Gattone, Vincent H; Witzmann, Frank A; Blazer-Yost, Bonnie L

    2009-01-01

    Liver cysts arising from hepatic bile ducts are a common extra-renal pathology associated with both autosomal dominant and recessive polycystic kidney disease in humans. To elucidate the functional and structural changes inherent in cyst formation and growth, hepatic bile duct epithelia were isolated from the BALB/ c-cpk mouse model of polycystic kidney disease. Light and transmission electron microscopy revealed substantial fibrosis in the basal lamina surrounding hepatic bile duct cysts isolated from heterozygous (BALB/c-cpk/+) and homozygous (BALB/c-cpk/cpk) animals. Scanning electron microscopy and length analysis of normal, precystic and cystic bile ducts provided the unique observation that primary cilia in cholangiocytes isolated from bile ducts and cysts of animals expressing the mutated cpk gene had lengths outside the minimal and maximal ranges of those in cells lining bile ducts of wild-type animals. Based on the hypothesis that PKD is one of several diseases characterized as ciliopathies, this abnormal variability in the length of the primary cilia may have functional implications. Electrophysiological analyses of freshly isolated cysts indicate that the amiloride-sensitive epithelial Na(+) channel (ENaC) is inactive/absent and cAMP-mediated anion secretion is the electrogenic transport process contributing to cyst fluid accumulation. Anion secretion can be stimulated by the luminal stimulation of adenylyl cyclase. PMID:18997107

  6. Treatment with insulin analogs, especially Glargine and Lispro, associates with better renal function and higher hemoglobin levels in Type 1 diabetic patients with impaired kidney function

    PubMed Central

    Hasslacher, Christoph; Kulozik, Felix; Lorenzo Bermejo, Justo

    2016-01-01

    Objectives: The influence of type of insulin treatment - insulin analogs versus human insulin - on the development of diabetes related vascular complications has been sparsely investigated. We examine here possible differences regarding kidney function and hemoglobin levels. Methods: Multiple linear regression was used to investigate the relationship between the following characteristics measured in 509 type 1 diabetic patients who were recruited in an outpatient practice: current clinical status and treatment modalities, type of injected insulin and the routine laboratory parameters hemoglobin, HbA1c, serum creatinine, eGFR, hs CRP and urinary albumin/creatinine ratio. Results: Compared with human insulin, multiple regression analysis taking into account possible confounders revealed that treatment with insulin analogs was associated with increased eGFR (+7.1 ml/min; P=0.0002), lower urinary albumin/creatinine ratio (ratio logarithm -0.4; P=0.003) and higher hemoglobin concentration (+0.31 g/dl; P=0.04). Stratification by type of insulin showed the best renal status for treatment with insulins Glargine and Lispro. Differences were consistent both for patients with normal (eGFR → 90 ml/min) and with an impaired (eGFR ← 90 ml/min) kidney function. Conclusions: Present results suggest that treatment of type 1 diabetic patients with normal and impaired renal function with insulin analogs, especially Glargine and Lispro, is associated with better kidney function, lower urinary albumin/creatinine ratio and lower hemoglobin concentration compared to therapy with human insulin. If confirmed by other studies, treatment with insulin analogs may be a further possibility in delaying progression of nephropathy and in preventing early hemoglobin decline. PMID:27540462

  7. Effect of low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats.

    PubMed

    Kostogrys, Renata B; Franczyk-Żarów, Magdalena; Maślak, Edyta; Topolska, Kinga

    2015-03-01

    The objective of this study was to compare effects of Western diet (WD) with low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats. Eighteen rats were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: Control (7% of soybean oil, 20% protein), WD (21% of butter, 20% protein), and LCHP (21% of butter and 52.4% protein) diet. The LCHP diet significantly decreased the body weight of the rats. Diet consumption was differentiated among groups, however significant changes were observed since third week of the experiment duration. Rats fed LCHP diet ate significantly less (25.2g/animal/day) than those from Control (30.2g/animal/day) and WD (27.8 g/animal/day) groups. Additionally, food efficiency ratio (FER) tended to decrease in LCHP fed rats. Serum homocysteine concentration significantly decreased in rats fed WD and LCHP diets. Liver weights were significantly higher in rats fed WD and LCHP diets. At the end of the experiment (2 months) the triacylglycerol (TAG) was significantly decreased in animals fed LCHP compared to WD. qRT-PCR showed that SCD-1 and FAS were decreased in LCHP fed rats, but WD diet increased expression of lipid metabolism genes. Rats receiving LCHP diet had two fold higher kidney weight and 54.5% higher creatinin level compared to Control and WD diets. In conclusion, LCHP diet decreased animal's body weight and decreased TAG in rat's serum. However, kidney damage in LCHP rats was observed. PMID:25766070

  8. Effect of low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats.

    PubMed

    Kostogrys, Renata B; Franczyk-Żarów, Magdalena; Maślak, Edyta; Topolska, Kinga

    2015-03-01

    The objective of this study was to compare effects of Western diet (WD) with low carbohydrate high protein (LCHP) diet on lipid metabolism, liver and kidney function in rats. Eighteen rats were randomly assigned to three experimental groups and fed for the next 2 months. The experimental diets were: Control (7% of soybean oil, 20% protein), WD (21% of butter, 20% protein), and LCHP (21% of butter and 52.4% protein) diet. The LCHP diet significantly decreased the body weight of the rats. Diet consumption was differentiated among groups, however significant changes were observed since third week of the experiment duration. Rats fed LCHP diet ate significantly less (25.2g/animal/day) than those from Control (30.2g/animal/day) and WD (27.8 g/animal/day) groups. Additionally, food efficiency ratio (FER) tended to decrease in LCHP fed rats. Serum homocysteine concentration significantly decreased in rats fed WD and LCHP diets. Liver weights were significantly higher in rats fed WD and LCHP diets. At the end of the experiment (2 months) the triacylglycerol (TAG) was significantly decreased in animals fed LCHP compared to WD. qRT-PCR showed that SCD-1 and FAS were decreased in LCHP fed rats, but WD diet increased expression of lipid metabolism genes. Rats receiving LCHP diet had two fold higher kidney weight and 54.5% higher creatinin level compared to Control and WD diets. In conclusion, LCHP diet decreased animal's body weight and decreased TAG in rat's serum. However, kidney damage in LCHP rats was observed.

  9. Optimising the management of polycystic kidney disease.

    PubMed

    Keenan, Declan; Maxwell, Alexander P

    2016-02-01

    Polycystic kidney disease (PKD) is the most common inherited renal disorder that results in chronic kidney disease. PKD has an autosomal dominant pattern of inheritance. The prevalence is between 1:500 and 1:1,000. Up to 10% of adults with end-stage renal disease (ESRD) have a genetic disorder such as PKD. A family history of PKD may be absent in up to 25% of affected individuals. The most common clinical features are visible haematuria, loin pain, UTI and hypertension. The typical clinical course is a progressive increase in the number and size of renal cysts associated with gradual loss of kidney function (falling eGFR). Risk factors for progression include: younger age at diagnosis; large kidney volume; rapid cyst growth; hypertension; male gender; and visible haematuria. Approximately 50% of individuals with PKD will require renal replacement therapy by the sixth decade of life. PKD is a multisystem disorder associated with multiple bilateral renal cysts, slowly increasing kidney size and progressive chronic kidney disease. Diagnosis of PKD is confirmed by ultrasound showing the presence of multiple kidney cysts. More than 80% will also have multiple liver cysts, which can lead to local pressure effects. Cerebral haemorrhage, secondary to rupture of a berry aneurysm, occurs in up to 8% of individuals. Mitral valve prolapse occurs in up to 25% of patients. PMID:27032221

  10. Solitary Kidney

    MedlinePlus

    ... Institute, Inc., Kidney School National Kidney Foundation MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Solitary Kidney Page Content On this page: What is a ...

  11. Systemic and renal lipids in kidney disease development and progression.

    PubMed

    Wahl, Patricia; Ducasa, Gloria Michelle; Fornoni, Alessia

    2016-03-15

    Altered lipid metabolism characterizes proteinuria and chronic kidney diseases. While it is thought that dyslipidemia is a consequence of kidney disease, a large body of clinical and experimental studies support that altered lipid metabolism may contribute to the pathogenesis and progression of kidney disease. In fact, accumulation of renal lipids has been observed in several conditions of genetic and nongenetic origins, linking local fat to the pathogenesis of kidney disease. Statins, which target cholesterol synthesis, have not been proven beneficial to slow the progression of chronic kidney disease. Therefore, other therapeutic strategies to reduce cholesterol accumulation in peripheral organs, such as the kidney, warrant further investigation. Recent advances in the understanding of the biology of high-density lipoprotein (HDL) have revealed that functional HDL, rather than total HDL per se, may protect from both cardiovascular and kidney diseases, strongly supporting a role for altered cholesterol efflux in the pathogenesis of kidney disease. Although the underlying pathophysiological mechanisms responsible for lipid-induced renal damage have yet to be uncovered, several studies suggest novel mechanisms by which cholesterol, free fatty acids, and sphingolipids may affect glomerular and tubular cell function. This review will focus on the clinical and experimental evidence supporting a causative role of lipids in the pathogenesis of proteinuria and kidney disease, with a primary focus on podocytes.

  12. Effects of transcutaneous electrical nerve stimulation on pain, walking function, respiratory muscle strength and vital capacity in kidney donors: a protocol of a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Pain is a negative factor in the recovery process of postoperative patients, causing pulmonary alterations and complications and affecting functional capacity. Thus, it is plausible to introduce transcutaneous electrical nerve stimulation (TENS) for pain relief to subsequently reduce complications caused by this pain in the postoperative period. The objective of this paper is to assess the effects of TENS on pain, walking function, respiratory muscle strength and vital capacity in kidney donors. Methods/design Seventy-four patients will be randomly allocated into 2 groups: active TENS or placebo TENS. All patients will be assessed for pain intensity, walk function (Iowa Gait Test), respiratory muscle strength (maximal inspiratory pressure and maximal expiratory pressure) and vital capacity before and after the TENS application. The data will be collected by an assessor who is blinded to the group allocation. Discussion This study is the first to examine the effects of TENS in this population. TENS during the postoperative period may result in pain relief and improvements in pulmonary tests and mobility, thus leading to an improved quality of life and further promoting organ donation. Trial registration Registro Brasileiro de Ensaios Clinicos (ReBEC), number RBR-8xtkjp. PMID:23311705

  13. Renal functional recovery of the hydronephrotic kidney predicted before relief of the obstruction

    SciTech Connect

    McDougal, W.S.; Flanigan, R.C.

    1981-05-01

    Employing technetium labeled dimercaptosuccinic acid, we predicted the inulin and p-aminohippuric acid (PAH) clearances after recovery of an obstructed kidney before relief of the obstruction. Sixteen rabbits had one renal unit obstructed for varying period of time. The animals were scanned immediately before relief of the obstruction. After 4 to 6 months recovery, inulin and PAH clearances were measured in all animals. The scans were mathematically analyzed, and accurately predicted the inulin and PAH clearances obtained after complete recovery (P less than 0.001 and P less than 0.001, respectively). Six rabbits were scanned at the time of the clearance measurements. By a different mathematical analysis, inulin and PAH clearance measured concurrently correlated with the scan (P less than 0.001 and P less than 0.01 respectively).

  14. Impact of obesity on kidney function and blood pressure in children

    PubMed Central

    Ding, Wei; Cheung, Wai W; Mak, Robert H

    2015-01-01

    In recent years, obesity has become an increasingly important epidemic health problem in children and adolescents. The prevalence of the overweight status in children grew from 5% to 11% from 1960s to 1990s. The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease (CKD) and hypertension. Results of several studies have demonstrated that obesity and metabolic syndrome were independent predictors of renal injury. The pathophysiology of obesity related hypertension is complex, including activation of sympathetic nervous system, renin angiotensin aldosterone system, hyperinsulinemia and inflammation. These same mechanisms likely contribute to the development of increased blood pressure in children. This review summarizes the recent epidemiologic data linking obesity with CKD and hypertension in children, as well as the potential mechanisms. PMID:25949935

  15. Role of Vitamin D in Cognitive Function in Chronic Kidney Disease

    PubMed Central

    Cheng, Zhen; Lin, Jing; Qian, Qi

    2016-01-01

    Both vitamin D deficiency and cognitive impairment are common in patients with chronic kidney disease (CKD). Vitamin D exerts neuroprotective and regulatory roles in the central nervous system. Hypovitaminosis D has been associated with muscle weakness and bone loss, cardiovascular diseases (hypertension, diabetes and hyperlipidemia), inflammation, oxidative stress, immune suppression and neurocognitive impairment. The combination of hypovitaminosis D and CKD can be even more debilitating, as cognitive impairment can develop and progress through vitamin D-associated and CKD-dependent/independent processes, leading to significant morbidity and mortality. Although an increasingly recognized comorbidity in CKD, cognitive impairment remains underdiagnosed and often undermanaged. Given the association of cognitive decline and hypovitaminosis D and their deleterious effects in CKD patients, determination of vitamin D status and when appropriate, supplementation, in conjunction with neuropsychological screening, should be considered integral to the clinical care of the CKD population. PMID:27187460

  16. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy.

    PubMed

    Karanovic, Danijela; Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  17. Effects of Single and Combined Losartan and Tempol Treatments on Oxidative Stress, Kidney Structure and Function in Spontaneously Hypertensive Rats with Early Course of Proteinuric Nephropathy

    PubMed Central

    Grujic-Milanovic, Jelica; Miloradovic, Zoran; Ivanov, Milan; Jovovic, Djurdjica; Vajic, Una-Jovana; Zivotic, Maja; Markovic-Lipkovski, Jasmina; Mihailovic-Stanojevic, Nevena

    2016-01-01

    Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression

  18. Kidney function during exercise in healthy and diseased humans. An update.

    PubMed

    Poortmans, J R; Vanderstraeten, J

    1994-12-01

    Exercise induces profound changes in renal haemodynamics and protein excretion. The rate of ultrafiltration across the glomerular capillary is determined by the imbalance between the transcapillary hydraulic and colloid osmotic pressure gradients. Despite a major reduction in the renal plasma flow, the filtration fraction can double with maximal exercise, preserving the transfer of metabolites or substances through the glomerulus. Tubular processes and excretion rates are modified by exercise. Despite large increases in plasma lactate during strenuous exercise, renal excretion plays a limited role in lactate metabolism. Apparently, the mechanism of transcellular transport of lactate is saturated during severe exercise. Urea reabsorption is enhanced during prolonged exercise, and this process may act to limit the dehydration of an individual. As uric acid transport is also carrier-mediated, it appears that there is no saturation of the carrier system during prolonged exercise. Postexercise proteinuria is directly related to the intensity of exercise rather than to its duration. This excretion of excess proteins is a transient state with a half-time decay of about 1 hour. The increased clearance of plasma proteins suggests an increased glomerular permeability and a partial inhibition of tubular reabsorption. Studies suggest that exercise decreases the glomerular electrostatic barrier and facilitates transfer of macromolecules. Postexercise proteinuria appears to be age-dependent. Nephropathy is a common observation in the diabetic patient. In young and adult diabetic patients, exhaustive physical exercise does not provoke an enhanced dysfunction of the kidney to what is already found in healthy individuals. Heart and kidney transplant patients have a lesser postexercise proteinuria as compared with healthy individuals. PMID:7886356

  19. Objective sleep, a novel risk factor for alterations in kidney function: the CARDIA Study

    PubMed Central

    Petrov, Megan E.; Kim, Yongin; Lauderdale, Diane S.; Lewis, Cora E.; Reis, Jared P.; Carnethon, Mercedes R.; Knutson, Kristen L.; Glasser, Stephen P.

    2014-01-01

    Objective To determine the association between objectively measured sleep and 10-year changes in estimated glomerular filtration rate (eGFR). Methods From 2003 to 2005, an ancillary sleep study was conducted at the Chicago site of the Coronary Artery Disease in Young Adults (CARDIA) study. Community-based black and white adults (aged 32–51 years) wore a wrist actigraph up to six nights to record sleep duration and fragmentation. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Participants without history of cardiovascular or chronic kidney diseases, proteinuria, or hypertension at the 2000–2001 CARDIA examination were followed over 10 years (n = 463). eGFR was estimated from serum creatinine (eGFRCr) at the 2000–2001, 2005–2006, and 2010–2011 CARDIA examinations, whereas cystatin-C-estimated eGFR (eGFRCys) was measured at the 2000–2001 and 2005–2006 examinations. Generalized estimating equation regression and linear models estimated the associations of each sleep parameter with changes in eGFRCr and eGFRCys, controlling for cardiovascular and renal risk. Results Sleep parameters were not related to 5-year change in eGFRCys. However, each 1 h decrease in sleep duration was significantly associated with a 1.5 mL/min/1.73 m2 higher eGFRCr [95% confidence interval (CI), 0.2–2.7], and each one-point increase in PSQI was significantly associated with a 0.5 mL/min/1.73 m2 higher eGFRCr (95% CI, 0.04–0.9) over 10 years. Conclusion In this community-based sample, shorter sleep and poorer sleep quality were related to higher kidney filtration rates over 10 years. PMID:25037841

  20. Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

    PubMed

    Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

    2016-05-01

    Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

  1. Saccharomyces cerivisiae as a model system for kidney disease: what can yeast tell us about renal function?

    PubMed

    Kolb, Alexander R; Buck, Teresa M; Brodsky, Jeffrey L

    2011-07-01

    Ion channels, solute transporters, aquaporins, and factors required for signal transduction are vital for kidney function. Because mutations in these proteins or in associated regulatory factors can lead to disease, an investigation into their biogenesis, activities, and interplay with other proteins is essential. To this end, the yeast, Saccharomyces cerevisiae, represents a powerful experimental system. Proteins expressed in yeast include the following: 1) ion channels, including the epithelial sodium channel, members of the inward rectifying potassium channel family, and cystic fibrosis transmembrane conductance regulator; 2) plasma membrane transporters, such as the Na(+)-K(+)-ATPase, the Na(+)-phosphate cotransporter, and the Na(+)-H(+) ATPase; 3) aquaporins 1-4; and 4) proteins such as serum/glucocorticoid-induced kinase 1, phosphoinositide-dependent kinase 1, Rh glycoprotein kidney, and trehalase. The variety of proteins expressed and studied emphasizes the versatility of yeast, and, because of the many available tools in this organism, results can be obtained rapidly and economically. In most cases, data gathered using yeast have been substantiated in higher cell types. These attributes validate yeast as a model system to explore renal physiology and suggest that research initiated using this system may lead to novel therapeutics.

  2. Association between fluid intake and kidney function, and survival outcomes analysis: a nationwide population-based study

    PubMed Central

    Wu, Li-Wei; Chen, Wei-Liang; Liaw, Fang-Yih; Sun, Yu-Shan; Yang, Hui-Fang; Wang, Chung-Ching; Lin, Chien-Ming; Tsao, Yu-Tzu

    2016-01-01

    Objectives Fluid intake, one of the most common daily activities, has not been well studied in chronic kidney disease (CKD) populations, and clinical outcomes are rarely addressed. The aim of this nationwide study is to explore the influence of daily fluid intake on cardiovascular and all-cause mortality and its association with renal function. Design Observational cohort study. Participants In all, 2182 participants aged more than 20 years participated in the Third National Health and Nutrition Examination Survey (1988–1994). Main outcome measures Survival outcomes in patients with or without CKD, using multiple variable adjusted Cox proportional hazard models. Results In a longitudinal survey with a median follow-up length of 15.4 years, 1080 participants died and 473 cardiovascular deaths were recorded. For all-cause mortality in the CKD group, individuals in the highest quartile of fluid intake (≧3.576 L/day) had better survival outcomes than those in the lowest quartile of fluid intake (≤2.147 L/day) (p=0.029) after adjustment of several pertinent variables. Conclusions Although the interpretation of this observational study was limited by the failure to identify the compositions of ingested fluids, adequate hydration may offer some advantages in patients with CKD. However, the underlying pathophysiological mechanisms of the responses of normal and injured kidneys to chronic changes in fluid consumption warrant further investigation. PMID:27173809

  3. Effect of CTLA-4 gene polymorphisms on long-term kidney allograft function in Han Chinese recipients

    PubMed Central

    Guo, Fang

    2016-01-01

    Single nucleotide polymorphisms (SNPs) of cytotoxic T lymphocyte associated antigen-4 gene (CTLA-4) have been associated with graft rejection and long-term clinical outcome after organ transplantation. Our aim was to examine the association between CTLA-4 SNPs (rs733618, rs4553808, rs5742909, rs231775, rs3087243) and long-term allograft function in Chinese renal transplant recipients. Genotyping of CTLA-4 SNPs was performed in 292 renal transplantation recipients. To assess long-term allograft function, the estimated glomerular filtration rate (eGFR) was determined 1, 3, 6, 12, 24, 36, 48 and 60 months after renal transplantation. CTLA-4 rs733618 and rs3087243 alleles and genotypes as well as the rs5742909 and rs231775 genotypes were significantly associated with long-term allograft function after transplantation (P<0.05). Patients with favorable genotypes had higher allograft function during the 60 months after transplantation. The TACGG, CACAG and CGTAA haplotypes were also associated with long-term kidney function after renal transplantation (P<0.05 or P<0.01). In sum, the favorable CTLA-4 rs5742909TT genotype, CTLA-4 rs733618C and rs3087243A alleles, and CACAG and CGTAA haplotypes, as well as the unfavorable rs733618TT, rs3087243GG and rs231775GG genotypes and TACGG haplotype could potentially serve as effective indicators of long-term allograft function in Chinese renal transplantation recipients. PMID:27081086

  4. Nephrology Update: Chronic Kidney Disease.

    PubMed

    Saha, Sharmeela; Rahman, Mahboob

    2016-05-01

    Chronic kidney disease (CKD) affects more than 1 in 10 individuals in the United States. The care of these patients must be managed by family physicians and nephrology subspecialists. The kidneys often are affected by systemic processes such as diabetes and hypertension, and optimal management of these conditions is critical to slow decline in renal function in CKD patients. These patients are at high risk of cardiovascular disease, and statin therapy is recommended for adults with CKD who are at least age 50 years and not receiving dialysis. Patients with CKD and anemia can be treated with iron therapy and often with an erythropoietin-stimulating agent. Electrolyte abnormalities are managed with dietary changes and drugs. Sodium restriction and modification of dietary protein intake also may be needed. Consultation with a renal dietitian may be helpful. Because many drugs are metabolized by the kidneys, physicians should ensure that drug dosages are appropriate for the level of renal function. Early consultation with or referral to a nephrology subspecialist for patients with reduced renal function, resistant hypertension or electrolyte levels, and other conditions have been associated with improved outcomes in CKD patients.

  5. Nephrology Update: Chronic Kidney Disease.

    PubMed

    Saha, Sharmeela; Rahman, Mahboob

    2016-05-01

    Chronic kidney disease (CKD) affects more than 1 in 10 individuals in the United States. The care of these patients must be managed by family physicians and nephrology subspecialists. The kidneys often are affected by systemic processes such as diabetes and hypertension, and optimal management of these conditions is critical to slow decline in renal function in CKD patients. These patients are at high risk of cardiovascular disease, and statin therapy is recommended for adults with CKD who are at least age 50 years and not receiving dialysis. Patients with CKD and anemia can be treated with iron therapy and often with an erythropoietin-stimulating agent. Electrolyte abnormalities are managed with dietary changes and drugs. Sodium restriction and modification of dietary protein intake also may be needed. Consultation with a renal dietitian may be helpful. Because many drugs are metabolized by the kidneys, physicians should ensure that drug dosages are appropriate for the level of renal function. Early consultation with or referral to a nephrology subspecialist for patients with reduced renal function, resistant hypertension or electrolyte levels, and other conditions have been associated with improved outcomes in CKD patients. PMID:27163761

  6. Concomitant gastroparesis negatively affects children with functional gallbladder disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of the present study was to determine whether concomitant gastroparesis and biliary dyskinesia (BD) occur in children, and if so, to determine whether concomitant gastroparesis affects clinical outcome in children with BD. We conducted a retrospective chart review of children with BD (ejecti...

  7. Noninvasive Central Systolic Blood Pressure Is More Strongly Related to Kidney Function Decline Than Peripheral Systolic Blood Pressure in a Chinese Community-Based Population.

    PubMed

    Fan, Fangfang; Qi, Litong; Jia, Jia; Xu, Xin; Liu, Yan; Yang, Yang; Qin, Xianhui; Li, Jianping; Li, Haixia; Zhang, Yan; Huo, Yong

    2016-06-01

    This study aimed to investigate the association of noninvasive central aortic blood pressure with kidney function decline in a Chinese community-based population with normal kidney function at baseline. A total of 3153 Chinese participants from an atherosclerosis cohort were included in our analysis. The primary outcome was renal function decline defined as a drop in estimated glomerular filtration rate (eGFR) category accompanied by a ≥25% drop in eGFR from baseline; or a sustained decline in eGFR of >5 mL/min per 1.73 m(2)/y. The secondary outcomes were rapid eGFR decline (a decline in eGFR of >3 mL/min per 1.73 m(2)/y) and new incidence of chronic kidney disease. Participants were 56.6±8.5 years old, 36.0% were males, and 48.8% had hypertension. Mean (SD) baseline eGFR was 101.2±10.6 mL/min per 1.73 m(2) After a mean 2.35-year follow-up, the incidence of renal function decline, rapid eGFR decline and chronic kidney disease were 7.3%, 19.7%, and 0.7%, respectively. In multivariate logistic-regression analyses, central and peripheral systolic blood pressure (SBP) were both independently associated with all outcomes after adjustment for various confounders. When peripheral SBP was forced into the model with central SBP simultaneously, its significant association with the 3 outcomes all disappeared; however, central SBP was still significantly related with all outcomes even after further adjusting peripheral SBP. In conclusion, central SBP is a stronger predictor compared with peripheral SBP for early kidney function decline in a Chinese community-based population with normal kidney function at baseline.

  8. SUMO1 Affects Synaptic Function, Spine Density and Memory.

    PubMed

    Matsuzaki, Shinsuke; Lee, Linda; Knock, Erin; Srikumar, Tharan; Sakurai, Mikako; Hazrati, Lili-Naz; Katayama, Taiichi; Staniszewski, Agnieszka; Raught, Brian; Arancio, Ottavio; Fraser, Paul E

    2015-01-01

    Small ubiquitin-like modifier-1 (SUMO1) plays a number of roles in cellular events and recent evidence has given momentum for its contributions to neuronal development and function. Here, we have generated a SUMO1 transgenic mouse model with exclusive overexpression in neurons in an effort to identify in vivo conjugation targets and the functional consequences of their SUMOylation. A high-expressing line was examined which displayed elevated levels of mono-SUMO1 and increased high molecular weight conjugates in all brain regions. Immunoprecipitation of SUMOylated proteins from total brain extract and proteomic analysis revealed ~95 candidate proteins from a variety of functional classes, including a number of synaptic and cytoskeletal proteins. SUMO1 modification of synaptotagmin-1 was found to be elevated as compared to non-transgenic mice. This observation was associated with an age-dependent reduction in basal synaptic transmission and impaired presynaptic function as shown by altered paired pulse facilitation, as well as a decrease in spine density. The changes in neuronal function and morphology were also associated with a specific impairment in learning and memory while other behavioral features remained unchanged. These findings point to a significant contribution of SUMO1 modification on neuronal function which may have implications for mechanisms involved in mental retardation and neurodegeneration. PMID:26022678

  9. Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

    PubMed

    Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

    2013-01-01

    The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of

  10. Telomerase deficiency affects normal brain functions in mice.

    PubMed

    Lee, Jaehoon; Jo, Yong Sang; Sung, Young Hoon; Hwang, In Koo; Kim, Hyuk; Kim, Song-Yi; Yi, Sun Shin; Choi, June-Seek; Sun, Woong; Seong, Je Kyung; Lee, Han-Woong

    2010-02-01

    Telomerase maintains telomere structures and chromosome stability, and it is essential for preserving the characteristics of stem and progenitor cells. In the brain, the hippocampus and the olfactory bulbs are continuously supplied with neural stem and progenitor cells that are required for adult neurogenesis throughout the life. Therefore, we examined whether telomerase plays important roles in maintaining normal brain functions in vivo. Telomerase reverse transcriptase (TERT) expression was observed in the hippocampus, the olfactory bulbs, and the cerebellum, but the telomerase RNA component (TERC) was not detected in hippocampus and olfactory bulbs. Interestingly, TERT-deficient mice exhibited significantly altered anxiety-like behaviors and abnormal olfaction measuring the functions of the hippocampus and the olfactory bulbs, respectively. However, the cerebellum-dependent behavior was not changed in these mutant mice. These results suggest that TERT is constitutively expressed in the hippocampus and the olfactory bulbs, and that it is important for regulating normal brain functions. PMID:19685288

  11. Amniotic Fluid-Derived Mesenchymal Stem Cells Prevent Fibrosis and Preserve Renal Function in a Preclinical Porcine Model of Kidney Transplantation

    PubMed Central

    Baulier, Edouard; Favreau, Frederic; Le Corf, Amélie; Jayle, Christophe; Schneider, Fabrice; Goujon, Jean-Michel; Feraud, Olivier; Bennaceur-Griscelli, Annelise; Turhan, Ali G.

    2014-01-01

    It is well known that ischemia/reperfusion injuries strongly affect the success of human organ transplantation. Development of interstitial fibrosis and tubular atrophy is the main deleterious phenomenon involved. Stem cells are a promising therapeutic tool already validated in various ischemic diseases. Amniotic fluid-derived mesenchymal stem cells (af-MSCs), a subpopulation of multipotent cells identified in amniotic fluid, are known to secrete growth factors and anti-inflammatory cytokines. In addition, these cells are easy to collect, present higher proliferation and self-renewal rates compared with other adult stem cells (ASCs), and are suitable for banking. Consequently, af-MSCs represent a promising source of stem cells for regenerative therapies in humans. To determine the efficiency and the safety of af-MSC infusion in a preclinical porcine model of renal autotransplantation, we injected autologous af-MSCs in the renal artery 6 days after transplantation. The af-MSC injection improved glomerular and tubular functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The strong proof of concept generated by this translational porcine model is a first step toward evaluation of af-MSC-based therapies in human kidney transplantation. PMID:24797827

  12. Chemical Modifications that Affect Nutritional and Functional Properties of Proteins.

    ERIC Educational Resources Information Center

    Richardson, T.; Kester, J. J.

    1984-01-01

    Discusses chemical alterations of selected amino acids resulting from environmental effects (photooxidations, pH extremes, thermally induced effects). Also dicusses use of intentional chemical derivatizations of various functional groups in amino acid residue side chains and how recombinant DNA techniques might be useful in structure/function…

  13. Can Particulate Pollution Affect Lung Function in Healthy Adults?

    EPA Science Inventory

    Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

  14. Drying process strongly affects probiotics viability and functionalities.

    PubMed

    Iaconelli, Cyril; Lemetais, Guillaume; Kechaou, Noura; Chain, Florian; Bermúdez-Humarán, Luis G; Langella, Philippe; Gervais, Patrick; Beney, Laurent

    2015-11-20

    Probiotic formulations are widely used and are proposed to have a variety of beneficial effects, depending on the probiotic strains present in the product. The impact of drying processes on the viability of probiotics is well documented. However, the impact of these processes on probiotics functionality remains unclear. In this work, we investigated variations in seven different bacterial markers after various desiccation processes. Markers were composed of four different viability evaluation (combining two growth abilities and two cytometric measurements) and in three in vitro functionalities: stimulation of IL-10 and IL-12 production by PBMCs (immunomodulation) and bacterial adhesion to hexadecane. We measured the impact of three drying processes (air-drying, freeze-drying and spray-drying), without the use of protective agents, on three types of probiotic bacteria: Bifidobacterium bifidum, Lactobacillus plantarum and Lactobacillus zeae. Our results show that the bacteria respond differently to the three different drying processes, in terms of viability and functionality. Drying methods produce important variations in bacterial immunomodulation and hydrophobicity, which are correlated. We also show that adherence can be stimulated (air-drying) or inhibited (spray-drying) by drying processes. Results of a multivariate analysis show no direct correlation between bacterial survival and functionality, but do show a correlation between probiotic responses to desiccation-rewetting and the process used to dry the bacteria.

  15. Glycosphingolipids and kidney disease.

    PubMed

    Mather, Andrew R; Siskind, Leah J

    2011-01-01

    Glycosphingolipids, derived from the addition of sugar-moieties to the sphingolipid ceramide, are highly abundant in the kidney. Glycosphingolipids are known to play an important role in organ function at least in part from inherited lipid storage diseases such as Anderson-Fabry disease (Fabry's disease; FD) that results from a mutation in alpha-galactosidase a (α-GLA or α-Gal A), the enzyme responsible for catalyzing the removal of terminal galactose residues from glycosphingolipids. The inactivation in α-GLA in FD results in the accumulation of glycosphingolipids, including globosides and lactosylceramides, which manifests as several common pathologies including end-stage kidney disease. More recently, glycosphingolipids and other sphingolipids have become increasingly recognized for their roles in a variety of other kidney diseases including polycystic kidney disease, acute kidney injury, glomerulonephritis, diabetic nephropathy and kidney cancer. This chapter reviews evidence supporting a mechanistic role for glycosphingolipids in kidney disease and discusses data implicating a role for these lipids in kidney disease resulting from metabolic syndrome. Importantly, inhibitors of glycosphingolipid synthesis are well tolerated in animal models as well as in humans. Thus, an increased understanding of the mechanisms by which altered renal glycosphingolipid metabolism leads to kidney disease has great therapeutic potential.

  16. Effects of obstruction on single-kidney function: clinical and experimental results with 131I-hippurate and 99mTc-DMSA.

    PubMed

    Moser, E; Jocham, D; Beer, M; Büll, U

    1980-12-01

    In 35 patients, renography with 131I-o-hippurate (OIH) and static renal imaging with 99mTc-dimercaptosuccinic acid (DMSA) were used to measure differential renal function (DRF). The results were compared. Depth correction was applied in both methods. In non-obstructed kidneys (19 patients), both methods revealed nearly identical kidney function (r = 0.98). For completely obstructed kidneys (16 patients), OIH gave a significantly better DRF (14 ml/min) than DMSA. This small difference was of no clinical value. Because DMSA is reported to give unreliable results in unilateral obstructed kidneys, the right ureter was ligated in 8 dogs for 10 days and DRF was measured before and after opening an ureteral fistula. The difference in DRF was about 1% and could be accounted for by the amount of urinary radioactivity collected from the pelvic system after the ligature had been opened. Although DMSA appears to give reliable values in determining DRF, even in obstructed kidneys, OIH is preferred since total clearance values and postrenal urinary dynamics can be determined simultaneously.

  17. SLE-associated risk factors affect DC function.

    PubMed

    Son, Myoungsun; Kim, Sun Jung; Diamond, Betty

    2016-01-01

    Numerous risk alleles for systemic lupus erythematosus (SLE) have now been identified. Analysis of the expression of genes with risk alleles in cells of hematopoietic origin demonstrates them to be most abundantly expressed in B cells and dendritic cells (DCs), suggesting that these cell types may be the drivers of the inflammatory changes seen in SLE. DCs are of particular interest as they act to connect the innate and the adaptive immune response. Thus, DCs can transform inflammation into autoimmunity, and autoantibodies are the hallmark of SLE. In this review, we focus on mechanisms of tolerance that maintain DCs in a non-activated, non-immunogenic state. We demonstrate, using examples from our own studies, how alterations in DC function stemming from either DC-intrinsic abnormalities or DC-extrinsic regulators of function can predispose to autoimmunity.

  18. SLE-associated risk factors affect DC function.

    PubMed

    Son, Myoungsun; Kim, Sun Jung; Diamond, Betty

    2016-01-01

    Numerous risk alleles for systemic lupus erythematosus (SLE) have now been identified. Analysis of the expression of genes with risk alleles in cells of hematopoietic origin demonstrates them to be most abundantly expressed in B cells and dendritic cells (DCs), suggesting that these cell types may be the drivers of the inflammatory changes seen in SLE. DCs are of particular interest as they act to connect the innate and the adaptive immune response. Thus, DCs can transform inflammation into autoimmunity, and autoantibodies are the hallmark of SLE. In this review, we focus on mechanisms of tolerance that maintain DCs in a non-activated, non-immunogenic state. We demonstrate, using examples from our own studies, how alterations in DC function stemming from either DC-intrinsic abnormalities or DC-extrinsic regulators of function can predispose to autoimmunity. PMID:26683148

  19. SLE-associated risk factors affect DC function

    PubMed Central

    Son, Myoungsun; Kim, Sun Jung; Diamond, Betty

    2016-01-01

    Numerous risk alleles for systemic lupus erythematosus (SLE) have now been identified. Analysis of the expression of genes with risk alleles in cells of hematopoietic origin demonstrates them to be most abundantly expressed in B cells and dendritic cells (DCs), suggesting that these cell types may be the drivers of the inflammatory changes seen in SLE. DCs are of particular interest as they act to connect the innate and the adaptive immune response. Thus, DCs can transform inflammation into autoimmunity, and autoantibodies are the hallmark of SLE. In this review, we focus on mechanisms of tolerance that maintain DCs in a non-activated, non-immunogenic state. We demonstrate, using examples from our own studies, how alterations in DC function stemming from either DC-intrinsic abnormalities or DC-extrinsic regulators of function can predispose to autoimmunity. PMID:26683148

  20. Prenatal drug exposure affects neonatal brain functional connectivity.

    PubMed

    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention.

  1. Prenatal drug exposure affects neonatal brain functional connectivity.

    PubMed

    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention. PMID:25855194

  2. Nuclear cyclophilins affect spliceosome assembly and function in vitro.

    PubMed

    Adams, B M; Coates, Miranda N; Jackson, S RaElle; Jurica, Melissa S; Davis, Tara L

    2015-07-15

    Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.

  3. Development of affective theory of mind across adolescence: disentangling the role of executive functions.

    PubMed

    Vetter, Nora C; Altgassen, Mareike; Phillips, Louise; Mahy, Caitlin E V; Kliegel, Matthias

    2013-01-01

    Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence. Affective theory of mind and three subcomponents of executive functions (inhibition, updating, and shifting) were measured. Affective theory of mind was positively related to age, and all three executive functions. Specifically, inhibition explained the largest amount of variance in age-related differences in affective theory of mind.

  4. Associations of low-level urine cadmium with kidney function in lead workers

    PubMed Central

    Weaver, Virginia M.; Kim, Nam-Soo; Jaar, Bernard G.; Schwartz, Brian S.; Parsons, Patrick J.; Steuerwald, Amy J.; Todd, Andrew C.; Simon, David; Lee, Byung-Kook

    2010-01-01

    Objectives Low-level cadmium exposure, e.g., urinary cadmium < 2.0 μg/g creatinine, is widespread; recent data suggest nephrotoxicity even at these lower levels. Few studies have examined the impact of low-level cadmium exposure in workers who are occupationally exposed to other nephrotoxicants such as lead. Methods We evaluated associations of urine cadmium, a measure of cumulative dose, with four glomerular filtration measures and N-acetyl-β-D-glucosaminidase (NAG) in lead workers. Recent and cumulative lead dose was assessed via blood and tibia lead, respectively. Results In 712 lead workers, mean (SD) blood and tibia lead, urine cadmium, and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation were 23.1 (14.1) μg/dl, 26.6 (28.9) μg Pb/g bone mineral, 1.15 (0.66) μg/g creatinine, and 97.4 (19.2) ml/min/1.73m2, respectively. After adjustment for age, sex, body mass index, urine creatinine, smoking, alcohol, education, annual income, diastolic blood pressure, current or former lead worker job status, new or returning study participant, and blood and tibia lead, higher ln-urine cadmium was associated with higher calculated creatinine clearance, eGFR (β = 8.7 ml/min/1.73 m2; 95% CI = 5.4, 12.1) and ln-NAG but lower serum creatinine. Conclusions Potential explanations for these results include a normal physiologic response in which urine cadmium levels reflect renal filtration; the impact of adjustment for urine dilution with creatinine in models of kidney outcomes; and cadmium-related hyperfiltration. PMID:20974743

  5. Na sup + -H sup + exchanger in proximal cells isolated from rabbit kidney. I. Functional characteristics

    SciTech Connect

    Bidet, M.; Tauc, M.; Merot, J.; Vandewalle, A.; Poujeol, P. )

    1987-11-01

    The purpose of this study was to investigate the characteristics of the Na{sup +}-H{sup +} exchange in isolated proximal cells from rabbit kidney cortex. The cells were prepared by mechanical dissociation and sequential passages through nylon meshes. The intracellular pH (pH{sub i}) was measured in a bicarbonate-free medium using the fluorescent dye 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). Resting pH{sub i} was 7.13 {+-} 0.04. Cells were acid loaded with nigericin in choline solution and H{sup +} efflux, induced by extracellular Na{sup +} (Na{sub e}), was calculated using a buffering power of 23.6 {+-} 0.6 mmol {center dot} l{sup {minus}1} {center dot} pH unit{sup {minus}1} estimated by NH{sub 4}Cl exposure. The intracellular H{sup +} concentration dependence did not follow simple Michaelis-Menten kinetics. Of the different cations tested on pH{sub i} recovery, such as Li{sup +}, choline{sup +}, K{sup +}, and tetramethylammonium, only Li{sup +} induced an alkalinization of acidified cells similar to that of Na{sup +}. {sup 22}Na influx measurements indicated that cellular depletion of Na{sup +} stimulated Na{sup +}-H{sup +} exchange. The results permit the conclusion that the isolation procedures did not impair the main features of the Na{sup +}-H{sup +} antiporter, at least as compared with those previously described in renal brush-border membrane vesicles or in other cellular systems. The integrity of the transporter in isolated proximal cells would permit the direct study of its hormonal and metabolic control.

  6. The effect of negative affect on cognition: Anxiety, not anger, impairs executive function.

    PubMed

    Shields, Grant S; Moons, Wesley G; Tewell, Carl A; Yonelinas, Andrew P

    2016-09-01

    It is often assumed that negative affect impairs the executive functions that underlie our ability to control and focus our thoughts. However, support for this claim has been mixed. Recent work has suggested that different negative affective states like anxiety and anger may reflect physiologically separable states with distinct effects on cognition. However, the effects of these 2 affective states on executive function have never been assessed. As such, we induced anxiety or anger in participants and examined the effects on executive function. We found that anger did not impair executive function relative to a neutral mood, whereas anxiety did. In addition, self-reports of induced anxiety, but not anger, predicted impairments in executive function. These results support functional models of affect and cognition, and highlight the need to consider differences between anxiety and anger when investigating the influence of negative affect on fundamental cognitive processes such as memory and executive function. (PsycINFO Database Record PMID:27100367

  7. Kidney Biopsy

    MedlinePlus

    ... right diagnosis. [ Top ] What should a person do days before a kidney biopsy? Days before the procedure, ... Top ] What can a person expect on the day of the kidney biopsy? A person should arrive ...

  8. Kidney Failure

    MedlinePlus

    Healthy kidneys clean your blood by removing excess fluid, minerals, and wastes. They also make hormones that keep your ... strong and your blood healthy. But if the kidneys are damaged, they don't work properly. Harmful ...

  9. Kidney transplant

    MedlinePlus

    Renal transplant; Transplant - kidney ... Barry JM, Conlin MJ. In: Renal transplantation. Wein AJ, ed. Campbell-Walsh Urology . 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 44. Kidney Disease: Improving Global Outcomes ( ...

  10. Kidney removal

    MedlinePlus

    ... the kidney. In: Wein AJ, ed. Campbell-Walsh Urology . 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap ... the kidney. In: Wein AJ, ed. Campbell-Walsh Urology . 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap ...

  11. Does prolonged cycling of moderate intensity affect immune cell function?

    PubMed Central

    Scharhag, J; Meyer, T; Gabriel, H; Schlick, B; Faude, O; Kindermann, W; Shephard, R

    2005-01-01

    Background: Prolonged exercise may induce temporary immunosuppression with a presumed increased susceptibility for infection. However, there are only few data on immune cell function after prolonged cycling at moderate intensities typical for road cycling training sessions. Methods: The present study examined the influence on immune cell function of 4 h of cycling at a constant intensity of 70% of the individual anaerobic threshold. Interleukin-6 (IL-6) and C-reactive protein (CRP), leukocyte and lymphocyte populations, activities of natural killer (NK), neutrophils, and monocytes were examined before and after exercise, and also on a control day without exercise. Results: Cycling for 4 h induced a moderate acute phase response with increases in IL-6 from 1.0 (SD 0.5) before to 9.6 (5.6) pg/ml 1 h after exercise and CRP from 0.5 (SD 0.4) before to 1.8 (1.3) mg/l 1 day after exercise. Although absolute numbers of circulating NK cells, monocytes, and neutrophils increased during exercise, on a per cell basis NK cell activity, neutrophil and monocyte phagocytosis, and monocyte oxidative burst did not significantly change after exercise. However, a minor effect over time for neutrophil oxidative burst was noted, tending to decrease after exercise. Conclusions: Prolonged cycling at moderate intensities does not seem to seriously alter the function of cells of the first line of defence. Therefore, the influence of a single typical road cycling training session on the immune system is only moderate and appears to be safe from an immunological point of view. PMID:15728699

  12. Yersinia enterocolitica Affects Intestinal Barrier Function in the Colon.

    PubMed

    Hering, Nina A; Fromm, Anja; Kikhney, Judith; Lee, In-Fah M; Moter, Annette; Schulzke, Jörg D; Bücker, Roland

    2016-04-01

    Infection with Yersinia enterocolitica causes acute diarrhea in early childhood. A mouse infection model presents new findings on pathological mechanisms in the colon. Symptoms involve diarrhea with watery feces and weight loss that have their functional correlates in decreased transepithelial electrical resistance and increased fluorescein permeability. Y. enterocolitica was present within the murine mucosa of both ileum and colon. Here, the bacterial insult was of focal nature and led to changes in tight junction protein expression and architecture. These findings are in concordance with observations from former cell culture studies and suggest a leak flux mechanism of diarrhea.

  13. Roles of Iroquois Transcription Factors in Kidney Development

    PubMed Central

    Marra, Amanda N.; Wingert, Rebecca A.

    2014-01-01

    Congenital anomalies of the kidney and urinary tract (CAKUT) affect 1/500 live births. CAKUT lead to end stage renal failure in children, and are associated with high morbidity rates. Understanding the mechanisms of kidney development, and that of other associated urogenital tissues, is crucial to the prevention and treatment of CAKUT. The kidney arises from self-renewing mesenchymal renal stem cells that produce nephrons, which are the principal functional units of the organ. To date, the genetic and cellular mechanisms that control nephrogenesis have remained poorly understood. In recent years, developmental studies using amphibians and zebrafish have revealed that their simple embryonic kidney, known as the pronephros, is a useful paradigm for comparative studies of nephron ontogeny. Here, we discuss the new found roles for Iroquois transcription factors in pronephric nephron patterning, and explore the relevance of these findings for kidney development in humans. PMID:24855634

  14. Repeated Traumatic Brain Injury Affects Composite Cognitive Function in Piglets

    PubMed Central

    Friess, Stuart H.; Ichord, Rebecca N.; Ralston, Jill; Ryall, Karen; Helfaer, Mark A.; Smith, Colin

    2009-01-01

    Abstract Cumulative effects of repetitive mild head injury in the pediatric population are unknown. We have developed a cognitive composite dysfunction score that correlates white matter injury severity in neonatal piglets with neurobehavioral assessments of executive function, memory, learning, and problem solving. Anesthetized 3- to 5-day-old piglets were subjected to single (n = 7), double one day apart (n = 7), and double one week apart (n = 7) moderate (190 rad/s) rapid non-impact axial rotations of the head and compared to instrumented shams (n = 7). Animals experiencing two head rotations one day apart had a significantly higher mortality rate (43%) compared to the other groups and had higher failures rates in visual-based problem solving compared to instrumented shams. White matter injury, assessed by β-APP staining, was significantly higher in the double one week apart group compared to that with single injury and sham. Worsening performance on cognitive composite score correlated well with increasing severity of white matter axonal injury. In our immature large animal model of TBI, two head rotations produced poorer outcome as assessed by neuropathology and neurobehavioral functional outcomes compared to that with single rotations. More importantly, we have observed an increase in injury severity and mortality when the head rotations occur 24 h apart compared to 7 days apart. These observations have important clinical translation to infants subjected to repeated inflicted head trauma. PMID:19275468

  15. The Effects of Tai Chi on the Renal and Cardiac Functions of Patients with Chronic Kidney and Cardiovascular Diseases

    PubMed Central

    Shi, Zhi-Min; Wen, Hai-Ping; Liu, Fu-Rong; Yao, Chun-Xia

    2014-01-01

    [Purpose] To assess the effects of Tai Chi on the renal and cardiac functions of patients with chronic kidney disease (CKD) and cardiovascular disease (CVD). [Subjects and Methods] Twenty-one patients with CKD and CVD were randomly divided into control and exercise groups. The exercise group performed Tai Chi training for 30 minutes three to five times a week for 12 weeks, while the control group did not. All patients’ renal and cardiac functions and blood lipid parameters were measured at baseline and after 12 weeks. [Results] The 12 weeks Tai Chi intervention improved the estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), and the high density lipoprotein (HDL) level, and decreased the serum creatintine (Scr) level, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the total cholesterol (CH), triglyceride (TG) and low density lipoprotein (LDL) levels. The change in eGFR correlated negatively with the changes in CH, TG and LDL, and positively with the change in HDL. In addition, the change in SBP correlated positively with the changes in CH, TG and LDL, and negatively with the change in HDL. [Conclusion] Tai Chi training might improve the renal and cardiac functions of CKD and CVD patients via improved regulation of lipid metabolism. PMID:25435688

  16. Donor-derived peripheral mononuclear cell DNA is associated with stable kidney allograft function: a randomized controlled trial.

    PubMed

    Solgi, Ghasem; Mytilineos, Joannis; Gadi, Vijayakrishna; Paul, Biswajit; Pourmand, Gholamreza; Mehrsai, Abdolrasoul; Nikbin, Behrouz; Amirzargar, Ali Akbar

    2011-01-01

    A large body of literature has documented an inconsistent relationship of peripheral donor cell chimerism with alloimmune tolerance following kidney transplantation. We revisit this association with assays capable of quantifying cellular microchimerism with 150-1500-fold greater sensitivity than previously utilized allo-antibody based flow cytometric approaches. Forty renal transplant patients, 20 with concurrent donor bone marrow infusion (DBMI) and 20 control participants without infusion were prospectively monitored for peripheral blood microchimerism using donor polymorphism-specific quantitative real-time PCR. Thirty-eight patients were evaluated for microchimerism, 19 in each group. The frequency of testing positive for (95% vs. 58%, p = 0.02) and mean concentrations of microchimerism (115 ± 66 vs. 13 ± 3 donor genomes/million recipient genomes, p = 0.007), respectively, were higher in infused patients compared with controls. Thirty-one patients maintained stable graft function; 17 in the DBMI group vs. 14 in controls. Patients with stable graft function in the DBMI group compared with control patients harbored microchimerism more frequently (94 vs. 50%, p = 0.01) and at higher concentrations (123 ± 67 vs. 11 ± 4, p = 0.007), respectively. Significant correlation between dose of infused cells and microchimerism levels was found post-transplant (p = 0.01). Using very sensitive assays, our findings demonstrate associations between the presence and quantity of microchimerism with stable graft function in infused patients.

  17. Functional and oncologic outcomes after nephron-sparing surgery in a solitary kidney: 10 years of experience

    PubMed Central

    Costabel, José Ignacio; Marchiñena, Patricio García; Tirapegui, Federico; Dantur, Augusto; Jurado, Alberto; Gueglio, Guillermo

    2016-01-01

    ABSTRACT Objectives: To evaluate functional and oncologic outcomes of partial nephrectomy (PN) in patients with a solitary kidney. Materials and Methods: A retrospective analysis of patients with a solitary kidney undergoing nephron-sparing surgery between March 2003 and March 2013 was performed. GFR was recorded before the procedure and 3 months after surgery, thus establishing a change (cGFR). Several variables that may influence cGFR were analyzed. Complications are herein described, namely bleeding, fistula, acute renal failure and end-stage renal disease (ESRD). Local recurrence and margin status are also described. Survival rates were calculated using the Kaplan Meier method (2 patients with metastasis at the time of surgery were excluded from the analysis). Results: Forty-five patients were available for analysis. Median follow-up was 27.56 months (r 3-96). Mean cGFR was-7.12mL/min (SD 2.1). Variables significantly related with lower GFR after surgery were loss of renal mass (p=0.01)) and male gender (p=0.03). Four patients (8.8%) experienced hemorrhage. Nine patients (20%) developed a urinary fistula. Only one patient with bleeding required open surgery. Two patients (4.4%) needed transient dialysis. Three patients (6.6%) developed ESRD. Four patients (8.8%) had positive surgical margins (PSMs) and four patients (88%) had local recurrence (2 of these had PSMs). Five patients (11.1%) died during follow-up. Four patients (8.8%) died because of renal cancer. Estimated 2-year overall survival, disease-free survival and cancer specific survival rates were 88.4% (CI 95% 70.5-96); 87.7% (CI 95% 68.1-96) and 92.4% (CI 95% 75-98), respectively. Conclusion: Loss of renal mass and male gender were associated with lower postoperative GFR. Our outcomes were comparable with those in the World literature. PMID:27256179

  18. Kidney Replacement Therapy

    MedlinePlus

    ... their function with either dialysis or a transplant. Dialysis Dialysis, the more common form of kidney-replacement ... the result of diabetes, not of hemodialysis. Peritoneal dialysis Another form of dialysis is called peritoneal dialysis. ...

  19. Na+-H+ exchanger in proximal cells isolated from rabbit kidney. I. Functional characteristics.

    PubMed

    Bidet, M; Tauc, M; Merot, J; Vandewalle, A; Poujeol, P

    1987-11-01

    The purpose of this study was to investigate the characteristics of the Na+-H+ exchange in isolated proximal cells from rabbit kidney cortex. The cells were prepared by mechanical dissociation and sequential passages through nylon meshes. The intracellular pH (pHi) was measured in a bicarbonate-free medium [extracellular pH (pHe) = 7.30], using the fluorescent dye 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). Resting pHi was 7.13 +/- 0.04 (n = 11) at 20-22 degrees C. Cells were acid loaded with nigericin in choline solution and H+ efflux, induced by extracellular Na+ (Nae), was calculated using a buffering power of 23.6 +/- 0.6 mmol.1-1.pH unit-1 (n = 19) estimated by NH4Cl exposure. In isolated proximal cells, the Na+-H+ antiporter had an apparent Km for Nae of 86.7 +/- 1.5 mM (n = 4) and was competitively inhibited by amiloride with a Ki of 33.3 +/- 6.4 X 10(-6) M (n = 3). Lowering pHe, inhibited the Na+-H+ exchanger. This inhibition was not purely competitive and the Ki was 40.4 +/- 12.7 nM (n = 3). The Na+-H+ exchange was greatly activated when the cytoplasm was acidified. The intracellular H+ concentration dependence did not follow simple Michaelis-Menten kinetics. Of the different cations tested on pHi recovery, such as Li+, choline+, K+, and tetramethylammonium, only Li+ induced an alkalinization of acidified cells similar to that of Na+. 22Na influx measurements indicated that cellular depletion of Na+ stimulated Na+-H+ exchange. The results permit the conclusion that the isolation procedures did not impair the main features of the Na+-H+ antiporter, at least as compared with those previously described in renal brush-border membrane vesicles or in other cellular systems. The integrity of the transporter in isolated proximal cells would permit the direct study of its hormonal and metabolic control. PMID:2825539

  20. Does vitamin C deficiency affect cognitive development and function?

    PubMed

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-09-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

  1. Does Vitamin C Deficiency Affect Cognitive Development and Function?

    PubMed Central

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(−/−) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies. PMID:25244370

  2. Endocannabinoids affect the reproductive functions in teleosts and amphibians.

    PubMed

    Cottone, E; Guastalla, A; Mackie, K; Franzoni, M F

    2008-04-16

    Following the discovery in the brain of the bonyfish Fugu rubripes of two genes encoding for type 1 cannabinoid receptors (CB1A and CB1B), investigations on the phylogeny of these receptors have indicated that the cannabinergic system is highly conserved. Among the multiple functions modulated by cannabinoids/endocannabinoids through the CB1 receptors one of the more investigated is the mammalian reproduction. Therefore, since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, the major aim of the present paper was to review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, namely bonyfish and amphibians. The expression and distribution of CB1 receptors were investigated in the CNS and gonads of two teleosts, Pelvicachromis pulcher and Carassius auratus as well as in the anuran amphibians Xenopus laevis and Rana esculenta. In general the large diffusion of neurons targeted by cannabinoids in both fish and amphibian forebrain indicate endocannabinoids as pivotal local messengers in several neural circuits involved in either sensory integrative activities, like the olfactory processes (in amphibians) and food response (in bonyfish), or neuroendocrine machinery (in both). By using immunohistochemistry for CB1 and GnRH-I, the codistribution of the two signalling molecules was found in the fish basal telencephalon and preoptic area, which are key centers for gonadotropic regulation in all vertebrates. A similar topographical codistribution was observed also in the septum of the telencephalon in Rana esculenta and Xenopus laevis. Interestingly, the double standard immunofluorescence on the same brain section, aided with a laser confocal microscope, showed that in anurans a subset of GnRH-I neurons exhibited also the CB1 immunostaining. The fact that CB1-LI-IR was found indeed in the FSH gonadotrophs of the Xenopus

  3. Consumption of bee pollen affects rat ovarian functions.

    PubMed

    Kolesarova, A; Bakova, Z; Capcarova, M; Galik, B; Juracek, M; Simko, M; Toman, R; Sirotkin, A V

    2013-12-01

    The aim of this study was to examine possible effects of bee pollen added to the feed mixture (FM) on rat ovarian functions (secretion activity and apoptosis). We evaluated the bee pollen effect on the release of insulin-like growth factor I (IGF-I) and steroid hormones (progesterone and estradiol), as well as on the expression of markers of apoptosis (Bcl-2, Bax and caspase-3) in rat ovarian fragments. Female rats (n = 15) were fed during 90 days by FM without or with rape seed bee pollen in dose either 3 kg/1000 kg FM or 5 kg/1000 kg FM. Fragments of ovaries isolated from rats of each group (totally 72 pieces) were incubated for 24 h. Hormonal secretion into the culture medium was detected by RIA. The markers of apoptosis were evaluated by Western blotting. It was observed that IGF-I release by rat ovarian fragments was significantly (p < 0.05) decreased; on the other hand, progesterone and estradiol secretion was increased after bee pollen treatment at dose 5 kg/1000 kg FM but not at 3 kg/1000 FM. Accumulation of Bcl-2 was increased by bee pollen added at 3 kg/1000 kg FM, but not at higher dose. Accumulation of Bax was increased in ovaries of rats fed by bee pollen at doses either 3 or 5 kg/1000 kg FM, whilst accumulation of caspase-3 increased after feeding with bee pollen at dose 5 kg/1000 kg FM, but not at 3 kg/1000 kg FM. Our results contribute to new insights regarding the effect of bee pollen on both secretion activity (release of growth factor IGF-I and steroid hormones progesterone and estradiol) and apoptosis (anti- and pro-apoptotic markers Bcl-2, Bax and caspase-3). Bee pollen is shown to be a potent regulator of rat ovarian functions. PMID:23137268

  4. Ectomycorrhizal symbiosis affects functional diversity of rhizosphere fluorescent pseudomonads.

    PubMed

    Frey-Klett, Pascale; Chavatte, Michaël; Clausse, Marie-Lise; Courrier, Sébastien; Le Roux, Christine; Raaijmakers, Jos; Martinotti, Maria Giovanna; Pierrat, Jean-Claude; Garbaye, Jean

    2005-01-01

    Here we characterized the effect of the ectomycorrhizal symbiosis on the genotypic and functional diversity of soil Pseudomonas fluorescens populations and analysed its possible consequences in terms of plant nutrition, development and health. Sixty strains of P. fluorescens were isolated from the bulk soil of a forest nursery, the ectomycorrhizosphere and the ectomycorrhizas of the Douglas fir (Pseudostuga menziesii) seedlings-Laccaria bicolor S238N. They were characterized in vitro with the following criteria: ARDRA, phosphate solubilization, siderophore, HCN and AIA production, genes of N2-fixation and antibiotic synthesis, in vitro confrontation with a range of phytopathogenic and ectomycorrhizal fungi, effect on the Douglas fir-L. bicolor symbiosis. For most of these criteria, we demonstrated that the ectomycorrhizosphere significantly structures the P. fluorescens populations and selects strains potentially beneficial to the symbiosis and to the plant. This prompts us to propose the ectomycorrhizal symbiosis as a true microbial complex where multitrophic interactions take place. Moreover it underlines the fact that this symbiosis has an indirect positive effect on plant growth, via its selective pressure on bacterial communities, in addition to its known direct positive effect. PMID:15720643

  5. Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions

    PubMed Central

    Pabla, Navjotsingh; Gibson, Alice A.; Buege, Mike; Ong, Su Sien; Li, Lie; Hu, Shuiying; Du, Guoqing; Sprowl, Jason A.; Vasilyeva, Aksana; Janke, Laura J.; Schlatter, Eberhard; Chen, Taosheng; Ciarimboli, Giuliano; Sparreboom, Alex

    2015-01-01

    Acute kidney injury (AKI) is a potentially fatal syndrome characterized by a rapid decline in kidney function caused by ischemic or toxic injury to renal tubular cells. The widely used chemotherapy drug cisplatin accumulates preferentially in the renal tubular cells and is a frequent cause of drug-induced AKI. During the development of AKI the quiescent tubular cells reenter the cell cycle. Strategies that block cell-cycle progression ameliorate kidney injury, possibly by averting cell division in the presence of extensive DNA damage. However, the early signaling events that lead to cell-cycle activation during AKI are not known. In the current study, using mouse models of cisplatin nephrotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6 (CDK4/6) pathway is activated in parallel with renal cell-cycle entry but before the development of AKI. Targeted inhibition of CDK4/6 pathway by small-molecule inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in inhibition of cell-cycle progression, amelioration of kidney injury, and improved overall survival. Of additional significance, these compounds were found to be potent inhibitors of organic cation transporter 2 (OCT2), which contributes to the cellular accumulation of cisplatin and subsequent kidney injury. The unique cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with their potential for clinical translation, support their further exploration as therapeutic candidates for prevention of AKI. PMID:25848011

  6. Factors affecting outcomes in patients reaching end-stage kidney disease worldwide: differences in access to renal replacement therapy, modality use, and haemodialysis practices.

    PubMed

    Robinson, Bruce M; Akizawa, Tadao; Jager, Kitty J; Kerr, Peter G; Saran, Rajiv; Pisoni, Ronald L

    2016-07-16

    More than 2 million people worldwide are being treated for end-stage kidney disease (ESKD). This Series paper provides an overview of incidence, modality use (in-centre haemodialysis, home dialysis, or transplantation), and mortality for patients with ESKD based on national registry data. We also present data from an international cohort study to highlight differences in haemodialysis practices that affect survival and the experience of patients who rely on this therapy, which is both life-sustaining and profoundly disruptive to their quality of life. Data illustrate disparities in access to renal replacement therapy of any kind and in the use of transplantation or home dialysis, both of which are widely considered preferable to in-centre haemodialysis for many patients with ESKD in settings where infrastructure permits. For most patients with ESKD worldwide who are treated with in-centre haemodialysis, overall survival is poor, but longer in some Asian countries than elsewhere in the world, and longer in Europe than in the USA, although this gap has reduced. Commendable haemodialysis practice includes exceptionally high use of surgical vascular access in Japan and in some European countries, and the use of longer or more frequent dialysis sessions in some countries, allowing for more effective volume management. Mortality is especially high soon after ESKD onset, and improved preparation for ESKD is needed including alignment of decision making with the wishes of patients and families.

  7. Aluminum fluoride affects the structure and functions of cell membranes.

    PubMed

    Suwalsky, M; Norris, B; Villena, F; Cuevas, F; Sotomayor, P; Zatta, P

    2004-06-01

    No useful biological function for aluminum has been found. To the contrary, it might play an important role in several pathologies, which could be related to its interactions with cell membranes. On the other hand, fluoride is a normal component of body fluids, soft tissues, bones and teeth. Its sodium salt is frequently added to drinking water to prevent dental caries. However, large doses cause severe pathological alterations. In view of the toxicity of Al(3+) and F(-) ions, it was thought of interest to explore the damaging effects that AlF(3) might induce in cell membranes. With this aim, it was incubated with human erythrocytes, which were examined by phase contrast and scanning electron microscopy, and molecular models of biomembranes. The latter consisted of large unilamellar vesicles (LUV) of dimyristoylphosphatidylcholine (DMPC) and bilayers of DMPC and dimyristoylphosphatidylethanolamine (DMPE) which were studied by fluorescence spectroscopy and X-ray diffraction, respectively. In order to understand the effects of AlF(3) on ion transport (principally sodium and chloride) we used the isolated toad skin to which electrophysiological measurements were applied. It was found that AlF(3) altered the shape of erythrocytes inducing the formation of echinocytes. This effect was explained by X-ray diffraction which revealed that AlF(3) perturbed the structure of DMPC, class of lipids located in the outer monolayer of the erythrocyte membrane. This result was confirmed by fluorescence spectroscopy on DMPC LUV. The biphasic (stimulatory followed by inhibitory) effects on the isolated skin suggested changes in apical Cl(-) secretion and moderate ATPase inactivation. PMID:15110101

  8. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    ERIC Educational Resources Information Center

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  9. Quantitation of renal function with 99Tcm-DMSA. A comparison with creatinine clearance in children with single kidney.

    PubMed

    Baillet, G; Gagnadoux, M F; De Vernejoul, P; Broyer, M

    1985-11-01

    To study the accuracy of renal function quantification with 99Tcm-DMSA we compared DMSA renal uptake and creatinine clearance in 16 cases of children with single kidney. The age of the patients ranged from two months to fourteen years. Creatinine clearance was normalized to 1.73 m2. DMSA uptake was measured 7 h after intravenous injection. Background subtraction was used and soft tissue attenuation was taken into account. The uptake was normalized in percentage of the injected activity. A significant correlation was found between creatinine clearance and DMSA uptake (rt = 0.866, p less than 0.01). Normal creatinine clearance range in children (80 to 120 ml min-1/1.73 m2) allowed determination of normal uptake range (36 to 60%). This study indicates that in case of asymmetrical renal impairment renal uptake will reflect split renal creatinine clearance. Since the former is much easier to measure, DMSA should play an important role in the evaluation of differential renal function.

  10. Phosphate Ions Affect the Water Structure at Functionalized Membrane Surfaces.

    PubMed

    Barrett, Aliyah; Imbrogno, Joseph; Belfort, Georges; Petersen, Poul B

    2016-09-01

    Antifouling surfaces improve function, efficiency, and safety in products such as water filtration membranes, marine vehicle coatings, and medical implants by resisting protein and biofilm adhesion. Understanding the role of water structure at these materials in preventing protein adhesion and biofilm formation is critical to designing more effective coatings. Such fouling experiments are typically performed under biological conditions using isotonic aqueous buffers. Previous studies have explored the structure of pure water at a few different antifouling surfaces, but the effect of electrolytes and ionic strength (I) on the water structure at antifouling surfaces is not well studied. Here sum frequency generation (SFG) spectroscopy is used to characterize the interfacial water structure at poly(ether sulfone) (PES) and two surface-modified PES films in contact with 0.01 M phosphate buffer with high and low salt (Ionic strength, I= 0.166 and 0.025 M, respectively). Unmodified PES, commonly used as a filtration membrane, and modified PES with a hydrophobic alkane (C18) and with a poly(ethylene glycol) (PEG) were used. In the low ionic strength phosphate buffer, water was strongly ordered near the surface of the PEG-modified PES film due to exclusion of phosphate ions and the creation of a surface potential resulting from charge separation between phosphate anions and sodium cations. However, in the high ionic strength phosphate buffer, the sodium and potassium chloride (138 and 3 mM, respectively) in the phosphate buffered saline screened this charge and substantially reduced water ordering. A much smaller water ordering and subsequent reduction upon salt addition was observed for the C18-modified PES, and little water structure change was seen for the unmodified PES. The large difference in water structuring with increasing ionic strength between widely used phosphate buffer and phosphate buffered saline at the PEG interface demonstrates the importance of studying

  11. Familial Clustering of Executive Functioning in Affected Sibling Pair Families with ADHD

    ERIC Educational Resources Information Center

    Slaats-Willemse, Dorine; Swaab-Barneveld, Hanna; De Sonneville, Leo; Buitelaar, Jan

    2005-01-01

    Objective: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. Method: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the…

  12. The cerebellum: its role in language and related cognitive and affective functions.

    PubMed

    De Smet, Hyo Jung; Paquier, Philippe; Verhoeven, Jo; Mariën, Peter

    2013-12-01

    The traditional view on the cerebellum as the sole coordinator of motor function has been substantially redefined during the past decades. Neuroanatomical, neuroimaging and clinical studies have extended the role of the cerebellum to the modulation of cognitive and affective processing. Neuroanatomical studies have demonstrated cerebellar connectivity with the supratentorial association areas involved in higher cognitive and affective functioning, while functional neuroimaging and clinical studies have provided evidence of cerebellar involvement in a variety of cognitive and affective tasks. This paper reviews the recently acknowledged role of the cerebellum in linguistic and related cognitive and behavioral-affective functions. In addition, typical cerebellar syndromes such as the cerebellar cognitive affective syndrome (CCAS) and the posterior fossa syndrome (PFS) will be briefly discussed and the current hypotheses dealing with the presumed neurobiological mechanisms underlying the linguistic, cognitive and affective modulatory role of the cerebellum will be reviewed.

  13. Evidence of a Structural and Functional Ammonium Transporter RhBG·Anion Exchanger 1·Ankyrin-G Complex in Kidney Epithelial Cells*

    PubMed Central

    Genetet, Sandrine; Ripoche, Pierre; Le Van Kim, Caroline; Colin, Yves; Lopez, Claude

    2015-01-01

    The renal ammonium transporter RhBG and anion exchanger 1 kAE1 colocalize in the basolateral domain of α-intercalated cells in the distal nephron. Although we have previously shown that RhBG is linked to the spectrin-based skeleton through ankyrin-G and that its NH3 transport activity is dependent on this association, there is no evidence for an interaction of kAE1 with this adaptor protein. We report here that the kAE1 cytoplasmic N terminus actually binds to ankyrin-G, both in yeast two-hybrid analysis and by coimmunoprecipitation in situ in HEK293 cells expressing recombinant kAE1. A site-directed mutagenesis study allowed the identification of three dispersed regions on kAE1 molecule linking the third and fourth repeat domains of ankyrin-G. One secondary docking site corresponds to a major interacting loop of the erythroid anion exchanger 1 (eAE1) with ankyrin-R, whereas the main binding region of kAE1 does not encompass any eAE1 determinant. Stopped flow spectrofluorometry analysis of recombinant HEK293 cells revealed that the Cl−/HCO3− exchange activity of a kAE1 protein mutated on the ankyrin-G binding site was abolished. This disruption impaired plasma membrane expression of kAE1 leading to total retention on cytoplasmic structures in polarized epithelial Madin-Darby canine kidney cell transfectants. kAE1 also directly interacts with RhBG without affecting its surface expression and NH3 transport function. This is the first description of a structural and functional RhBG·kAE1·ankyrin-G complex at the plasma membrane of kidney epithelial cells, comparable with the well known Rh·eAE1·ankyrin-R complex in the red blood cell membrane. This renal complex could participate in the regulation of acid-base homeostasis. PMID:25616663

  14. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    SciTech Connect

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

    2013-08-15

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

  15. Compliance Index, a Marker of Peripheral Arterial Stiffness, may Predict Renal Function Decline in Patients with Chronic Kidney Disease

    PubMed Central

    Kuo, Te-Hui; Yang, Deng-Chi; Lin, Wei-Hung; Tseng, Chin-Chung; Chen, Ju-Yi; Ho, Chin-Shan; Cheng, Meng-Fu; Tsai, Wei-Chuan; Wang, Ming-Cheng

    2015-01-01

    Background: Compliance index derived from digital volume pulse (CI-DVP), measuring the relationship between volume and pressure changes in fingertip, is a surrogate marker of peripheral arterial stiffness. This study investigated if CI-DVP can predict renal function deterioration, cardiovascular events and mortality in patients with chronic kidney disease (CKD). Methods: In this prospective observational study, 149 CKD patients were included for final analysis. CI-DVP and brachial-ankle pulse wave velocity (baPWV) were measured, decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope. Composite renal and cardiovascular outcomes were evaluated, including ≥50% eGFR decline, start of renal replacement therapy, and major adverse events. Results: Patients in CKD stages 3b to 5 had higher baPWV and lower CI-DVP values than those in patients with CKD stages 1 to 3a. Stepwise multivariate linear regression analysis showed that lower CI-DVP (p =0.0001) and greater proteinuria (p =0.0023) were independent determinants of higher eGFR decline rate. Multivariate Cox regression analysis revealed that CI-DVP (HR 0.68, 95% CI 0.46-1.00), baseline eGFR (HR 0.96, 95% CI 0.94-0.98) and serum albumin (HR 0.17, 95% CI 0.07-0.42) were independent predictors for composite renal and cardiovascular outcomes. Conclusions: Compliance index, CI-DVP, was significantly associated with renal function decline in patients with CKD. A higher CI-DVP may have independent prognostic value in slower renal function decline and better composite renal and cardiovascular outcomes in CKD patients. PMID:26180508

  16. Identification of two functional guanylin receptors in eel: multiple hormone-receptor system for osmoregulation in fish intestine and kidney.

    PubMed

    Yuge, Shinya; Yamagami, Sayaka; Inoue, Koji; Suzuki, Norio; Takei, Yoshio

    2006-10-01

    Guanylyl cyclase C (GC-C) is a single transmembrane receptor for a family of intestinal hormones, guanylins. In the eel, we previously identified three guanylins, whose gene expression was enhanced in the intestine after transfer from fresh water to seawater. However, only limited information is available about the structure and function of their receptor(s). In the present study, we cloned full-length cDNAs encoding two isoforms of GC-C, named GC-C1 and GC-C2, from eel intestine. The predicted GC-C proteins consisted of extracellular ligand-binding domain, membrane-spanning domain, kinase-like domain and cyclase catalytic domain, in which GC-C-specific sequences were largely conserved. Phylogenetic analyses showed that the cloned membrane GCs are grouped with the GC-C of other vertebrates but not with GC-A and GC-B. However, eel GC-Cs appear to have undergone unique structural evolution compared with other GC-Cs. The three eel guanylins (guanylin, uroguanylin and renoguanylin), but not eel atrial natriuretic peptide, stimulated cGMP production dose-dependently in COS cells expressing either of the cloned cDNAs, providing functional support for assignment as eel guanylin receptors. The potency order for cGMP production was uroguanylin > guanylin > or = renoguanylin for GC-C1; guanylin > or = renoguanylin > uroguanylin for GC-C2. The distinctive ligand selectivity was consistent with the low homology (53%) of the extracellular domain of the two GC-Cs compared with that observed for other domains (74-90%). Both GC-C genes were expressed in the alimentary tract (esophagus, stomach and intestine) and kidney, and their expression was higher in the intestine of seawater-adapted eels than that of freshwater eels just as observed with the guanylin genes. However, the expression of the receptor genes was unchanged for 24h after transfer of eels from fresh water to seawater or vice versa, showing slower response of the receptors to salinity changes than their ligands

  17. The Association between a Mediterranean-Style Diet and Kidney Function in the Northern Manhattan Study Cohort

    PubMed Central

    Moon, Yeseon P.; Scarmeas, Nikolaos; Gu, Yian; Gardener, Hannah; Cheung, Ken; Wright, Clinton B.; Sacco, Ralph L.; Nickolas, Thomas L.; Elkind, Mitchell S.V.

    2014-01-01

    Background and objectives Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function. Design, setting, participants, & measurements This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m2using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥2.5 ml/min per 1.73 m2 per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. Results Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m2. Incident eGFR<60 ml/min per 1.73 m2 developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m2 (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). Conclusions A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m2 and upper quartile of eGFR decline in a multiethnic cohort. PMID:25359387

  18. The impacts of thyroid function on the diagnostic accuracy of Cystatin C to detect acute kidney injury in ICU patients: a prospective, observational study

    PubMed Central

    2014-01-01

    Introduction Cystatin C (Cysc) could be affected by thyroid function both in vivo and in vitro and thereby may have limited ability to reflect renal function. We aimed to assess the association between Cysc and thyroid hormones as well as the effect of thyroid function on the diagnostic accuracy of Cysc to detect acute kidney injury (AKI). Methods A total of 446 consecutive intensive care unit (ICU) patients were screened for eligibility in this prospective AKI observational study. Serum Cysc, thyroid hormones and serum creatinine (Scr) were measured upon entry to the ICU. We also collected each patient's baseline characteristics including the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. The diagnostic performance of Cysc was assessed from the area under the receiver operator characteristic curve (AUC) in each quartile of thyroid hormone(s). Results A total of 114 (25.6%) patients had a clinical diagnosis of AKI upon entry to the ICU. The range of free thyroxine (FT4) value was 4.77 to 39.57 pmol/L. Multivariate linear regression showed that age (standardized beta = 0.128, P < 0.0001), baseline Scr level (standardized beta = 0.290, P < 0.0001), current Scr (standardized beta = 0.453, P < 0.0001), albumin (standardized beta = -0.086, P = 0.006), and FT4 (standardized beta = 0.062, P = 0.039) were related with Cysc. Patients were divided into four quartiles based on FT4 levels. The AUC for Cysc in detecting AKI in each quartile were as follows: 0.712 in quartile I, 0.754 in quartile II, 0.829 in quartile III and 0.797 in quartile IV. There was no significant difference in the AUC between any two groups (all P > 0.05). The optimal cut-off value of Cysc for diagnosing AKI increased across FT4 quartiles (1.15 mg/L in quartile I, 1.15 mg/L in quartile II, 1.35 mg/L in quartile III and 1.45 mg/L in quartile IV). Conclusions There was no significant impact of thyroid function on the diagnostic accuracy

  19. What Are the Risk Factors for Kidney Cancer?

    MedlinePlus

    ... kidney cancer? What are the risk factors for kidney cancer? A risk factor is anything that affects ... not cancer). Other risk factors Family history of kidney cancer People with a strong family history of ...

  20. Kidney function changes with aging in adults: comparison between cross-sectional and longitudinal data analyses in renal function assessment.

    PubMed

    Chung, Sang M; Lee, David J; Hand, Austin; Young, Philip; Vaidyanathan, Jayabharathi; Sahajwalla, Chandrahas

    2015-12-01

    The study evaluated whether the renal function decline rate per year with age in adults varies based on two primary statistical analyses: cross-section (CS), using one observation per subject, and longitudinal (LT), using multiple observations per subject over time. A total of 16628 records (3946 subjects; age range 30-92 years) of creatinine clearance and relevant demographic data were used. On average, four samples per subject were collected for up to 2364 days (mean: 793 days). A simple linear regression and random coefficient models were selected for CS and LT analyses, respectively. The renal function decline rates per year were 1.33 and 0.95 ml/min/year for CS and LT analyses, respectively, and were slower when the repeated individual measurements were considered. The study confirms that rates are different based on statistical analyses, and that a statistically robust longitudinal model with a proper sampling design provides reliable individual as well as population estimates of the renal function decline rates per year with age in adults. In conclusion, our findings indicated that one should be cautious in interpreting the renal function decline rate with aging information because its estimation was highly dependent on the statistical analyses. From our analyses, a population longitudinal analysis (e.g. random coefficient model) is recommended if individualization is critical, such as a dose adjustment based on renal function during a chronic therapy.

  1. HIV and Kidney Disease

    MedlinePlus

    ... FOR KIDNEY DISEASE? HIV MEDICATIONS AND THE KIDNEYS DIALYSIS AND KIDNEY TRANSPLANTATION THE BOTTOM LINE WHY SHOULD ... disease (ESRD) or kidney failure. This can require dialysis or a kidney transplant. The rate of kidney ...

  2. Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.

    PubMed

    Yousef, Mokhtar I; Omar, Sahar A M; El-Guendi, Marwa I; Abdelmegid, Laila A

    2010-11-01

    The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.

  3. Extraction and purification of a lectin from red kidney bean and preliminary immune function studies of the lectin and four Chinese herbal polysaccharides.

    PubMed

    Hou, Yufang; Hou, Yubao; Yanyan, Liu; Qin, Guang; Li, Jichang

    2010-01-01

    Reversed micelles were used to extract lectin from red kidney beans and factors affecting reverse micellar systems (pH value, ionic strength and extraction time) were studied. The optimal conditions were extraction at pH 4-6, back extraction at pH 9-11, ion strength at 0.15 M NaCl, extraction for 4-6 minutes and back extraction for 8 minutes. The reverse micellar system was compared with traditional extraction methods and demonstrated to be a time-saving method for the extraction of red kidney bean lectin. Mitogenic activity of the lectin was reasonably good compared with commercial phytohemagglutinin (extracted from Phaseolus vulgaris) Mitogenic properties of the lectin were enhanced when four Chinese herbal polysaccharides were applied concurrently, among which 50 μg/mL Astragalus mongholicus polysaccharides (APS) with 12.5 μg/mL red kidney bean lectin yielded the highest mitogenic activity and 100 mg/kg/bw APS with 12.5 mg/kg/bw red kidney bean lectin elevated mouse nonspecific immunity.

  4. Extraction and purification of a lectin from red kidney bean and preliminary immune function studies of the lectin and four Chinese herbal polysaccharides.

    PubMed

    Hou, Yufang; Hou, Yubao; Yanyan, Liu; Qin, Guang; Li, Jichang

    2010-01-01

    Reversed micelles were used to extract lectin from red kidney beans and factors affecting reverse micellar systems (pH value, ionic strength and extraction time) were studied. The optimal conditions were extraction at pH 4-6, back extraction at pH 9-11, ion strength at 0.15 M NaCl, extraction for 4-6 minutes and back extraction for 8 minutes. The reverse micellar system was compared with traditional extraction methods and demonstrated to be a time-saving method for the extraction of red kidney bean lectin. Mitogenic activity of the lectin was reasonably good compared with commercial phytohemagglutinin (extracted from Phaseolus vulgaris) Mitogenic properties of the lectin were enhanced when four Chinese herbal polysaccharides were applied concurrently, among which 50 μg/mL Astragalus mongholicus polysaccharides (APS) with 12.5 μg/mL red kidney bean lectin yielded the highest mitogenic activity and 100 mg/kg/bw APS with 12.5 mg/kg/bw red kidney bean lectin elevated mouse nonspecific immunity. PMID:20976304

  5. "Exercise as medicine" in chronic kidney disease.

    PubMed

    Wilkinson, T J; Shur, N F; Smith, A C

    2016-08-01

    Exercise and physical activity are increasingly becoming key tools in the treatment and prevention of several medical conditions including arthritis and diabetes; this notion has been termed "exercise as medicine". Exercise has favorable effects on reducing cardiovascular risk, inflammation, cachexia, and hypertension, in addition to increasing physical functioning, strength, and cardio-respiratory capacity. Chronic kidney disease, a condition that affects around 10% of the population, is often overlooked as a target for exercise-based therapy. Despite the vast range of severity in kidney disease (e.g., pre-dialysis, dialysis, transplant), exercise has a potential role in all patients suffering from the condition. In this review, we summarise the important role exercise may have in the clinical management of kidney disease and how this form of 'medicine' should be best administered and 'prescribed'. PMID:27334146

  6. Technology innovation for patients with kidney disease.

    PubMed

    Mitsides, Nicos; Keane, David F; Lindley, Elizabeth; Mitra, Sandip

    2014-01-01

    The loss of kidney function is a life-changing event leading to life-long dependence on healthcare. Around 5000 people are diagnosed with kidney failure every year. Historically, technology in renal medicine has been employed for replacement therapies. Recently, a lot of emphasis has been placed on technologies that aid early identification and prevent progression of kidney disease, while at the same time empowering affected individuals to gain control over their chronic illness. There is a shift in diversity of technology development, driven by collaborative innovation initiatives such the National Institute's for Health Research Healthcare Technology Co-operative for Devices for Dignity. This has seen the emergence of the patient as a key figure in designing technologies that are fit for purpose, while business involvement has ensured uptake and sustainability of these developments. An embodiment of this approach is the first successful Small Business Research Initiative in the field of renal medicine in the UK.

  7. Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

    PubMed Central

    Zhang, Ai-Di; Dai, Shao-Xing; Huang, Jing-Fei

    2013-01-01

    With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases. PMID:24222897

  8. Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

    PubMed Central

    Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

    2016-01-01

    Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

  9. Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population.

    PubMed

    Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

    2016-01-01

    Ferritin is considered to be a marker of the body's iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002-1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001-1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

  10. The Synthetic Tie2 Agonist Peptide Vasculotide Protects Renal Vascular Barrier Function In Experimental Acute Kidney Injury

    PubMed Central

    Rübig, Eva; Stypmann, Jörg; Van Slyke, Paul; Dumont, Daniel J; Spieker, Tilmann; Buscher, Konrad; Reuter, Stefan; Goerge, Tobias; Pavenstädt, Hermann; Kümpers, Philipp

    2016-01-01

    Microvascular barrier dysfunction plays a major role in the pathophysiology of acute kidney injury (AKI). Angiopoietin-1, the natural agonist ligand for the endothelial-specific Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor. Here we evaluate the efficacy of a polyethylene glycol-clustered Tie2 agonist peptide, vasculotide (VT), to protect against endothelial-cell activation with subsequent microvascular dysfunction in a murine model of ischemic AKI. Renal ischemia reperfusion injury (IRI) was induced by clamping of the renal arteries for 35 minutes. Mice were treated with VT or PEGylated cysteine before IRI. Sham-operated animals served as time-matched controls. Treatment with VT significantly reduced transcapillary albumin flux and renal tissue edema after IRI. The protective effects of VT were associated with activation of Tie2 and stabilization of its downstream effector, VE-cadherin in renal vasculature. VT abolished the decline in renal tissue blood flow, attenuated the increase of serum creatinine and blood urea nitrogen after IRI, improved recovery of renal function and markedly reduced mortality compared to PEG [HR 0.14 (95% CI 0.05–0.78) P < 0.05]. VT is inexpensive to produce, chemically stable and unrelated to any Tie2 ligands. Thus, VT may represent a novel therapy to prevent AKI in patients. PMID:26911791

  11. Isotonic saline in elderly men: an open-labelled controlled infusion study of electrolyte balance, urine flow and kidney function.

    PubMed

    Hahn, R G; Isacson, M Nyberg; Fagerström, T; Rosvall, J; Nyman, C R

    2016-02-01

    Isotonic saline is a widely-used infusion fluid, although the associated chloride load may cause metabolic acidosis and impair kidney function in young, healthy volunteers. We wished to examine whether these effects also occurred in the elderly, and conducted a crossover study in 13 men with a mean age of 73 years (range 66-84), who each received intravenous infusions of 1.5 l of Ringer's acetate and of isotonic saline. Isotonic saline induced mild changes in plasma sodium (mean +1.5 mmol.l(-1) ), plasma chloride (+3 mmol.l(-1) ) and standard bicarbonate (-2 mmol.l(-1) ). Three hours after starting the infusions, 68% of the Ringer's acetate and 30% of the infused saline had been excreted (p < 0.01). The glomerular filtration rate increased in response to both fluids, but more after the Ringer's acetate (p < 0.03). Pre-infusion fluid retention, as evidenced by high urinary osmolality (> 700 mOsmol.kg(-1) ) and/or creatinine (> 7 mmol.l(-1) ), was a strong factor governing the responses to both fluid loads.

  12. Improved lipids, diastolic pressure and kidney function are potential contributors to familial longevity: a study on 60 Chinese centenarian families

    PubMed Central

    He, Yong-Han; Pu, Shao-Yan; Xiao, Fu-Hui; Chen, Xiao-Qiong; Yan, Dong-Jing; Liu, Yao-Wen; Lin, Rong; Liao, Xiao-Ping; Yu, Qin; Yang, Li-Qin; Yang, Xing-Li; Ge, Ming-Xia; Li, Ying; Jiang, Jian-Jun; Cai, Wang-Wei; Kong, Qing-Peng

    2016-01-01

    Centenarians are a good healthy aging model. Interestingly, centenarians’ offspring are prone to achieve longevity. Here we recruited 60 longevity families and investigated the blood biochemical indexes of family members to seek candidate factors associated with familial longevity. First, associations of blood indexes with age were tested. Second, associations of blood parameters in centenarians (CEN) with their first generation of offspring (F1) and F1 spouses (F1SP) were analyzed. Third, genes involved in regulating target factors were investigated. We found that total cholesterol (TC) and triglyceride (TG) increased with age (20–80 years), but decreased in CEN. Similarly, blood urea nitrogen (BUN) and blood creatinine (BCr) increased with age (20–80 years), but were maintained on a plateau in CEN. Importantly, we first revealed dual changes in blood pressure, i.e., decreased diastolic blood pressure but increased systolic blood pressure in CEN, which associated with altered CST3 expression. Genetic analysis revealed a significant association of blood uric acid (BUA) and BCr in CEN with F1 but not with F1SP, suggesting they may be heritable traits. Taken together, our results suggest serum lipids, kidney function and especially diastolic pressure rather than systolic pressure were improved in CEN or their offspring, suggesting these factors may play an important role in familial longevity. PMID:26911903

  13. Effect of feeding Murraya koeingii and Brassica juncea diet on [correction] kidney functions and glucose levels in streptozotocin diabetic mice.

    PubMed

    Grover, J K; Yadav, S P; Vats, V

    2003-03-01

    Purpose of the study was to investigate the effects of daily oral feeding 15% of powdered leaves of Murraya koeingii (MK) (commonly called as Curry patta) and 10% powder of seeds of Brassica juncea (BJ) (commonly called as Rai) for 60 days on serum glucose concentrations and kidney functions in streptozotocin (STZ; 100mg/kg) diabetic rats. Serum glucose levels, body weight, urine volume, serum creatinine, and urinary albumin (UAE) levels were monitored on day 0, 10, 25, 40, and 70 of the experiment. After 60 days of STZ administration, urine volume per day and UAE levels were significantly higher (P<0.0005) in diabetic controls (DC) as compared to normal controls (NC). Although feeding of the MK/BJ showed a trend towards improvement in most of the parameters, results were not statistically different from the DC except in serum creatinine values in BJ-fed rats on day 70. Thus, these plants can be best utilized by promoting them as preferable food adjuvants for diabetic patients.

  14. Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy

    PubMed Central

    Scarfe, Lauren; Rak-Raszewska, Aleksandra; Geraci, Stefania; Darssan, Darsy; Sharkey, Jack; Huang, Jiaguo; Burton, Neal C.; Mason, David; Ranjzad, Parisa; Kenny, Simon; Gretz, Norbert; Lévy, Raphaël; Kevin Park, B.; García-Fiñana, Marta; Woolf, Adrian S.; Murray, Patricia; Wilm, Bettina

    2015-01-01

    Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers. PMID:26329825

  15. Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy.

    PubMed

    Scarfe, Lauren; Rak-Raszewska, Aleksandra; Geraci, Stefania; Darssan, Darsy; Sharkey, Jack; Huang, Jiaguo; Burton, Neal C; Mason, David; Ranjzad, Parisa; Kenny, Simon; Gretz, Norbert; Lévy, Raphaël; Kevin Park, B; García-Fiñana, Marta; Woolf, Adrian S; Murray, Patricia; Wilm, Bettina

    2015-09-02

    Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers.

  16. Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells.

    PubMed Central

    Pearce, S H; Bai, M; Quinn, S J; Kifor, O; Brown, E M; Thakker, R V

    1996-01-01

    The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that plays a key role in extracellular calcium ion homeostasis. We have engineered 11 CaR mutants that have been described in the disorders familial benign hypercalcemia (FBH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant hypocalcaemia (ADH), and studied their function by characterizing intracellular calcium [Ca2+]i transients in response to varying concentrations of extracellular calcium [Ca2+]o or gadolinium [Gd3+]o. The wild type receptor had an EC50 for calcium (EC50[Ca2+]o) (the value of [Ca2+]o producing half of the maximal increase in [Ca2+]i) of 4.0 mM (+/- 0.1 SEM). However, five missense mutations associated with FBH or NSHPT, (P55L, N178D, P221S, R227L, and V817I) had significantly higher EC50[Ca2+]os of between 5.5 and 9.3 mM (all P < 0.01). Another FBH mutation, Y218S, had an EC50[Ca2+]o of > 50 mM but had only a mildly attenuated response to gadolinium, while the FBH mutations, R680C and P747fs, were unresponsive to either calcium or gadolinium. In contrast, three mutations associated with ADH, (F128L, T151M, and E191K), showed significantly reduced EC50[Ca2+]os of between 2.2 and 2.8 mM (all P < 0.01). These findings provide insights into the functional domains of the CaR and demonstrate that mutations which enhance or reduce the responsiveness of the CaR to [Ca2+]o cause the disorders ADH, FBH, and NSHPT, respectively. PMID:8878438

  17. Iron Indices in Patients with Functional Anemia in Chronic Kidney Disease

    PubMed Central

    Reddy, G. Chinnapu; Rao, Pragna

    2013-01-01

    Background Despite high ferritin level, HDCKD patients may have functional iron deficiency even after intravenous iron (iv) therapy. The aim of this study was to test the hypothesis that lowered serum transferrin level may contribute to functional anemia and erythropoietin hypo responsiveness by the failure to transport accumulated tissue iron to the relevant target tissue. Materials and methods The study subjects were divided into four groups. Group-A: HDCKD Patients receiving iv iron (n=290). Group-B: Patients not initiated on to hemodialysis (NDCKD), and received oral iron (n=38). Group-C: HDCKD patients with erythropoietin hypo responsiveness (n=9). Group-D: Healthy controls (n=36). The group-A, patients were sub-divided into five groups (A-1 to A-5) based on their serum ferritin levels. Results Serum ferritin and tissue iron levels in group-A and C patients were significantly greater than the group-D(p<0.0001) and group-B patients(p<0.001). Transferrin level of group-A and C showed lowered values and consequently a higher %TSAT when compared to group-D. The percent of patients with iron overload was 2.6%, 31%, and 44% in group-B, group-A and group-C respectively. Serum transferrin level significantly correlated with TIBC in group-A and B patients (p<0.0001;p<0.05 respectively). Transferrin level significantly correlated with TIBC in all subgroups of HDCKD(p<0.05) with the exception in subgroup-A2 and with hemoglobin in subgroups A3 (p<0.05) and A5(p<0.01) respectively. Conclusions The lowered transferrin level prevents the proper transport of the iron to the hematopoietic sites, which may be a reason for the low hemoglobin synthesis and also for the development of erythropoietin hypo responsiveness in some of the dialysis patients.

  18. Changes in Kidney Functions during Middle-distance Triathlon in Male Athletes.

    PubMed

    Poortmans, J R; Jeannaud, F; Baudry, S; Carpentier, A

    2015-11-01

    Strenuous exercise induces proteinuria which is related to the intensity of exercise. However, renal responses to each type of exercise during a middle-distance triathlon have not been reported. The present study, carried out on 7 healthy athletes, investigated renal function at rest and after each exercise of a half-triathlon race. Blood and urine samples were collected at rest and after each specific event. Protein excretion and renal clearances were determined on each sample. Compared with resting values, albuminuria was increased by a factor of 30 (p<0.05) after swimming but did not differ from the resting value after cycling and running (p>0.05). Rates of β2-microglobulin and retinol-binding protein excretion did not change throughout the triathlon (p>0.05). Glomerular filtration rate (expressed as creatinine clearance) remained stable after each exercise event, whereas tubular reabsorption rate (expressed as urea clearance) was reduced by 50, 40 and 65% after swimming, cycling and running, respectively, compared to pre-exercise values (p<0.05). Glomerular membrane permeability (expressed as albumin clearance) was significantly increased by the swimming event (13 times, p<0.05). These results suggest that middle-distance triathlon has a noticeable impact on the glomerular membrane permeability (albumin clearance) and elimination of protein waste (urea clearance) depending on exercise type.

  19. Training of affect recognition (TAR) in schizophrenia--impact on functional outcome.

    PubMed

    Sachs, G; Winklbaur, B; Jagsch, R; Lasser, I; Kryspin-Exner, I; Frommann, N; Wölwer, W

    2012-07-01

    Deficits in facial affect recognition as one aspect of social cognitive deficits are treatment targets to improve functional outcome in schizophrenia. According to preliminary results antipsychotics alone show little effects on affect recognition. A few randomized intervention studies have evaluated special psychosocial treatment programs on social cognition. In this study, the effects of a computer-based training of affect recognition were investigated as well as its impact on facial affect recognition and functional outcome, particularly on patients' quality of life. Forty clinically stabilized schizophrenic patients were randomized to a six-week training on affect recognition (TAR) or treatment as usual including occupational therapy (TAU) and completed pre- and post-treatment assessments of emotion recognition, cognition, quality of life and clinical symptoms. Between pre- and post treatment, the TAR group achieved significant improvements in facial affect recognition, in particular in recognizing sad faces and, in addition, in the quality of life domain social relationship. These changes were not found in the TAU group. Furthermore, the TAR training contributes to enhancing some aspects of cognitive functioning and negative symptoms. These improvements in facial affect recognition and quality of life were independent of changes in clinical symptoms and general cognitive functions. The findings support the efficacy of an affect recognition training for patients with schizophrenia and the generalization to social relationship. Further development is needed in the impact of a psychosocial intervention in other aspects of social cognition and functional outcome.

  20. Functioning pancreas graft with thromboses of splenic and superior mesenteric arteries after simultaneous pancreas-kidney transplantation: a case report.

    PubMed

    Matsumoto, I; Shinzeki, M; Asari, S; Goto, T; Shirakawa, S; Ajiki, T; Fukumoto, T; Ku, Y

    2014-04-01

    Graft thrombosis is the most common cause of early graft loss after pancreas transplantation. The grafted pancreas is difficult to salvage after complete thrombosis, especially arterial thrombosis, and graft pancreatectomy is required. We describe a patient presenting with a functioning pancreas graft with thromboses of the splenic artery (SA) and superior mesenteric artery (SMA) after simultaneous pancreas-kidney transplantation (SPK). A 37-year-old woman with a 20-year history of type 1 diabetes mellitus underwent SPK. The pancreaticoduodenal graft was implanted in the right iliac fossa with enteric drainage. A Carrel patch was anastomosed to the recipient's right common iliac artery, and the graft gastroduodenal artery was anastomosed to the common hepatic artery using an arterial I-graft. The donor portal vein was anastomosed to the recipient's inferior vena cava. Four days after surgery, graft thromboses were detected by Doppler ultrasound without increases in the serum amylase and blood glucose levels. Contrast enhanced computed tomography revealed thromboses in the SA, splenic vein and SMA. Selective angiography showed that blood flow was interrupted in the SA and SMA. However, pancreatic graft perfusion was maintained by the I-graft in the head of the pancreas and the transverse pancreatic artery in the body and tail of the pancreas. We performed percutaneous direct thrombolysis and adjuvant thrombolytic therapy. However, we had to stop the thrombolytic therapy because of gastrointestinal hemorrhage. Thereafter, the postoperative course was uneventful and the pancreas graft was functioning with a fasting blood glucose level of 75 mg/dL, HbA1c of 5.1%, and serum C-peptide level of 1.9 ng/mL at 30 months post-transplantation.

  1. Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease

    PubMed Central

    Kuczmarski, James M.; Martens, Christopher R.; Kim, Jahyun; Lennon-Edwards, Shannon L.

    2014-01-01

    The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO. PMID:25059238

  2. Predicting the accuracy of facial affect recognition: the interaction of child maltreatment and intellectual functioning.

    PubMed

    Shenk, Chad E; Putnam, Frank W; Noll, Jennie G

    2013-02-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying levels of intellectual functioning. A sample of maltreated (n=50) and nonmaltreated (n=56) adolescent females, 14 to 19 years of age, was recruited to participate in this study. Participants completed demographic and study-related questionnaires and interviews to control for potential psychological and psychiatric confounds such as symptoms of posttraumatic stress disorder, negative affect, and difficulties in emotion regulation. Participants also completed an experimental paradigm that recorded responses to facial affect displays starting in a neutral expression and changing into a full expression of one of six emotions: happiness, sadness, anger, disgust, fear, or surprise. Hierarchical multiple regression assessed the incremental advantage of evaluating the interaction between child maltreatment and intellectual functioning. Results indicated that the interaction term accounted for a significant amount of additional variance in the accurate identification of facial affect after controlling for relevant covariates and main effects. Specifically, maltreated females with lower levels of intellectual functioning were least accurate in identifying facial affect displays, whereas those with higher levels of intellectual functioning performed as well as nonmaltreated females. These results suggest that maltreatment and intellectual functioning interact to predict the recognition of facial affect, with potential long-term consequences for the interpersonal functioning of maltreated females.

  3. Predicting the accuracy of facial affect recognition: the interaction of child maltreatment and intellectual functioning.

    PubMed

    Shenk, Chad E; Putnam, Frank W; Noll, Jennie G

    2013-02-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying levels of intellectual functioning. A sample of maltreated (n=50) and nonmaltreated (n=56) adolescent females, 14 to 19 years of age, was recruited to participate in this study. Participants completed demographic and study-related questionnaires and interviews to control for potential psychological and psychiatric confounds such as symptoms of posttraumatic stress disorder, negative affect, and difficulties in emotion regulation. Participants also completed an experimental paradigm that recorded responses to facial affect displays starting in a neutral expression and changing into a full expression of one of six emotions: happiness, sadness, anger, disgust, fear, or surprise. Hierarchical multiple regression assessed the incremental advantage of evaluating the interaction between child maltreatment and intellectual functioning. Results indicated that the interaction term accounted for a significant amount of additional variance in the accurate identification of facial affect after controlling for relevant covariates and main effects. Specifically, maltreated females with lower levels of intellectual functioning were least accurate in identifying facial affect displays, whereas those with higher levels of intellectual functioning performed as well as nonmaltreated females. These results suggest that maltreatment and intellectual functioning interact to predict the recognition of facial affect, with potential long-term consequences for the interpersonal functioning of maltreated females. PMID:23036371

  4. Remote ischaemic conditioning on recipients of deceased renal transplants, effect on immediate and extended kidney graft function: a multicentre, randomised controlled trial protocol (CONTEXT)

    PubMed Central

    Krogstrup, Nicoline V; Oltean, Mihai; Bibby, Bo M; Nieuwenhuijs-Moeke, Gertrude J; Dor, Frank J M F; Birn, Henrik; Jespersen, Bente

    2015-01-01

    Introduction Delayed graft function due to ischaemia-reperfusion injury is a frequent complication in deceased donor renal transplantation. Experimental evidence indicates that remote ischaemic conditioning (RIC) provides systemic protection against ischaemia-reperfusion injury in various tissues. Methods and analysis ‘Remote ischaemic conditioning in renal transplantation—effect on immediate and extended kidney graft function’ (the CONTEXT study) is an investigator initiated, multicentre, randomised controlled trial investigating whether RIC of the leg of the recipient improves short and long-term graft function following deceased donor kidney transplantation. The study will include 200 kidney transplant recipients of organ donation after brain death and 20 kidney transplant recipients of organ donation after circulatory death. Participants are randomised in a 1:1 design to RIC or sham-RIC (control). RIC consists of four cycles of 5 min occlusion of the thigh by a tourniquet inflated to 250 mm Hg, separated by 5 min of deflation. Primary end point is the time to a 50% reduction from the baseline plasma creatinine, estimated from the changes of plasma creatinine values 30 days post-transplant or 30 days after the last performed dialysis post-transplant. Secondary end points are: need of dialysis post-transplant, measured and estimated-glomerular filtration rate (GFR) at 3 and 12 months after transplantation, patient and renal graft survival, number of rejection episodes in the first year, and changes in biomarkers of acute kidney injury and inflammation in plasma, urine and graft tissue. Ethics and dissemination The study is approved by the local ethical committees and national data security agencies. Results are expected to be published in 2016. Trial registration number NCT01395719. PMID:26297360

  5. Relationship of left ventricular hypertrophy and diastolic function with cardiovascular and renal outcomes in African Americans with hypertensive chronic kidney disease.

    PubMed

    Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A

    2013-09-01

    African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.

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

    PubMed Central

    2012-01-01

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

  7. Distinct injury markers for the early detection and prognosis of incident acute kidney injury in critically ill adults with preserved kidney function

    PubMed Central

    Siew, Edward D.; Ware, Lorraine B.; Bian, Aihua; Shintani, Ayumi; Eden, Svetlana; Wickersham, Nancy; Cripps, Ben; Ikizler, T. Alp

    2013-01-01

    The use of novel biomarkers to detect incident acute kidney injury (AKI) in the critically ill is hindered by heterogeneity of injury and the potentially confounding effects of prevalent AKI. Here we examined the ability of urine NGAL (NGAL), L-type Fatty Acid Binding Protein (L-FABP), and Cystatin C to predict AKI development, death, and dialysis in a nested case-control study of 380 critically ill adults with an eGFR over 60 ml/min/1.73 m2. One-hundred thirty AKI cases were identified following biomarker measurement and were compared to 250 controls without AKI. Areas under the receiver-operator characteristic curves (AUC-ROCs) for discriminating incident AKI from non-AKI were 0.58(95%CI: 0.52-0.64), 0.59(0.52-0.65), and 0.50(0.48-0.57) for urine NGAL, L-FABP, and Cystatin C, respectively. The combined AUC-ROC for NGAL and L-FABP was 0.59(56-0.69). Both urine NGAL and L-FABP independently predicted AKI during multivariate regression; however, risk reclassification indices were mixed. Neither urine biomarker was independently associated with death or acute dialysis [NGAL hazard ratio 1.35(95%CI: 0.93-1.96), L-FABP 1.15(0.82-1.61)] though both independently predicted the need for acute dialysis [NGAL 3.44(1.73-6.83), L-FABP 2.36(1.30-4.25)]. Thus, urine NGAL and L-FABP independently associated with the development of incident AKI and receipt of dialysis but exhibited poor discrimination for incident AKI using conventional definitions. PMID:23698227

  8. Kidney Cancer

    MedlinePlus

    You have two kidneys. They are fist-sized organs on either side of your backbone above your waist. The tubes inside filter and ... blood, taking out waste products and making urine. Kidney cancer forms in the lining of tiny tubes ...

  9. Ectopic Kidney

    MedlinePlus

    ... Human Development March of Dimes National Office MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Ectopic Kidney Page Content On this page: What is an ...

  10. Lexical and Affective Prosody in Children with High-Functioning Autism

    ERIC Educational Resources Information Center

    Grossman, Ruth B.; Bemis, Rhyannon H.; Skwerer, Daniela Plesa; Tager-Flusberg, Helen

    2010-01-01

    Purpose: To investigate the perception and production of lexical stress and processing of affective prosody in adolescents with high-functioning autism (HFA). We hypothesized preserved processing of lexical and affective prosody but atypical lexical prosody production. Method: Sixteen children with HFA and 15 typically developing (TD) peers…

  11. Histopathological changes in the head kidney induced by cadmium in a neotropical fish Colossoma macropomum

    PubMed Central

    Salazar-Lugo, R.; Vargas, A.; Rojas, L.; Lemus, M.

    2013-01-01

    We evaluated the effect of cadmium (Cd) on the structure and function of the head kidney in the freshwater fish Colossoma macropomum (C. macropomum). Juveniles were exposed to 0.1 mg/L CdCl2 for 31 days. Blood samples were examined using hematological tests and head kidney histology was determined by light microscopy. The concentration of Cd in the head and trunk kidneys was measured using an atomic absorption spectrophotometer. Cd produced histopathological changes in the head kidney, the most evident of these being: the thickening of the vein wall, an increase in the number of basophils/mast cells close to blood vessels and a severe depletion of hematopoietic precursors especially the granulopoietic series. In the blood, a decrease in the total leucocytes and hemoglobin concentration was observed. Cd-exposed fish showed higher Cd concentrations in the trunk kidney than the head kidney. In conclusion, exposure to Cd affected precursor hematopoietic cells in C. macropomum. PMID:26623329

  12. Histopathological changes in the head kidney induced by cadmium in a neotropical fish Colossoma macropomum.

    PubMed

    Salazar-Lugo, R; Vargas, A; Rojas, L; Lemus, M

    2013-01-01

    We evaluated the effect of cadmium (Cd) on the structure and function of the head kidney in the freshwater fish Colossoma macropomum (C. macropomum). Juveniles were exposed to 0.1 mg/L CdCl2 for 31 days. Blood samples were examined using hematological tests and head kidney histology was determined by light microscopy. The concentration of Cd in the head and trunk kidneys was measured using an atomic absorption spectrophotometer. Cd produced histopathological changes in the head kidney, the most evident of these being: the thickening of the vein wall, an increase in the number of basophils/mast cells close to blood vessels and a severe depletion of hematopoietic precursors especially the granulopoietic series. In the blood, a decrease in the total leucocytes and hemoglobin concentration was observed. Cd-exposed fish showed higher Cd concentrations in the trunk kidney than the head kidney. In conclusion, exposure to Cd affected precursor hematopoietic cells in C. macropomum. PMID:26623329

  13. Histopathological changes in the head kidney induced by cadmium in a neotropical fish Colossoma macropomum.

    PubMed

    Salazar-Lugo, R; Vargas, A; Rojas, L; Lemus, M

    2013-01-01

    We evaluated the effect of cadmium (Cd) on the structure and function of the head kidney in the freshwater fish Colossoma macropomum (C. macropomum). Juveniles were exposed to 0.1 mg/L CdCl2 for 31 days. Blood samples were examined using hematological tests and head kidney histology was determined by light microscopy. The concentration of Cd in the head and trunk kidneys was measured using an atomic absorption spectrophotometer. Cd produced histopathological changes in the head kidney, the most evident of these being: the thickening of the vein wall, an increase in the number of basophils/mast cells close to blood vessels and a severe depletion of hematopoietic precursors especially the granulopoietic series. In the blood, a decrease in the total leucocytes and hemoglobin concentration was observed. Cd-exposed fish showed higher Cd concentrations in the trunk kidney than the head kidney. In conclusion, exposure to Cd affected precursor hematopoietic cells in C. macropomum.

  14. Robot-assisted "Santosh-Post Graduate Institute tubularized flap pyelovesicostomy" in a solitary functioning kidney with giant hydronephrosis: A minimally invasive salvage procedure

    PubMed Central

    Singh, Shivanshu; Kumar, Navneet

    2016-01-01

    We describe a case of a solitary functioning kidney with giant hydronephrosis secondary to ureteropelvic junction obstruction in a young girl who underwent successful robot-assisted tubularized flap pyelovesicostomy. The aim of this report was to highlight the feasibility and efficacy of this technique in salvaging such renal moieties and to present a brief review of the surgical options available for the management of giant hydronephrosis. PMID:26981597

  15. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine.

    PubMed

    van Hoek, I; Lefebvre, H P; Peremans, K; Meyer, E; Croubels, S; Vandermeulen, E; Kooistra, H; Saunders, J H; Binst, D; Daminet, S

    2009-01-01

    Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR. Serum total T4 (TT4), creatinine and blood urea nitrogen (BUN), blood pressure (BP), body weight (BW), GFR, urine specific gravity (USG), urinary protein/creatinine ratio (UPC) and retinol binding protein/creatinine ratio (uRBP/c) were evaluated before and 1, 4, 12 and 24 weeks post-treatment with radioiodine ((131)I) in 21 non-azotemic hyperthyroid cats. Cats were divided 24 weeks post-treatment into group A (normal kidney function, n=16) and group B (impaired kidney function, n=5). Serum TT4, GFR, UPC and uRBP/c decreased significantly after treatment for the complete group and group A (P<0.05), although GFR and uRBP/c did not change in group B. Serum creatinine and BW increased significantly from 1 week after treatment (P<0.05). There was no change in BUN, USG or BP. Pre-treatment serum TT4, GFR and USG differed significantly between group A and B (P<0.05). GFR at 4 weeks after treatment and maximum decrease in GFR could be partially predicted by a formula using pre-treatment GFR, serum TT4, serum creatinine, BUN and/or USG. Significant changes in kidney function occur within 4 weeks post-treatment and none thereafter. Pre-treatment measurement of GFR, USG and serum TT4 can have possible predictive value regarding the development of post-treatment renal azotemia. PMID:19010632

  16. Kidney biomarkers in cirrhosis.

    PubMed

    Francoz, Claire; Nadim, Mitra K; Durand, François

    2016-10-01

    Impaired renal function due to acute kidney injury (AKI) and/or chronic kidney diseases (CKD) is frequent in cirrhosis. Recurrent episodes of AKI may occur in end-stage cirrhosis. Differential diagnosis between functional (prerenal and hepatorenal syndrome) and acute tubular necrosis (ATN) is crucial. The concept that AKI and CKD represent a continuum rather than distinct entities, is now emerging. Not all patients with AKI have a potential for full recovery. Precise evaluation of kidney function and identification of kidney changes in patients with cirrhosis is central in predicting reversibility. This review examines current biomarkers for assessing renal function and identifying the cause and mechanisms of impaired renal function. When CKD is suspected, clearance of exogenous markers is the reference to assess glomerular filtration rate, as creatinine is inaccurate and cystatin C needs further evaluation. Recent biomarkers may help differentiate ATN from hepatorenal syndrome. Neutrophil gelatinase-associated lipocalin has been the most extensively studied biomarker yet, however, there are no clear-cut values that differentiate each of these conditions. Studies comparing ATN and hepatorenal syndrome in cirrhosis, do not include a gold standard. Combinations of innovative biomarkers are attractive to identify patients justifying simultaneous liver and kidney transplantation. Accurate biomarkers of underlying CKD are lacking and kidney biopsy is often contraindicated in this population. Urinary microRNAs are attractive although not definitely validated. Efforts should be made to develop biomarkers of kidney fibrosis, a common and irreversible feature of CKD, whatever the cause. Biomarkers of maladaptative repair leading to irreversible changes and CKD after AKI are also promising.

  17. EXPERIMENTAL NEPHRITIS IN THE FROG : IV. THE SIGNIFICANCE OF THE FUNCTIONAL RESPONSE TO VASCULAR AND TO PARENCHYMAL DISTURBANCES IN THE KIDNEY.

    PubMed

    Oliver, J

    1932-01-31

    A summary of our findings is briefly made. A functional examination of the kidneys did not allow any differentiation between the results of vascular and parenchymal damage. This was true, as is emphasized in the arrangement of Charts 1 and 2, in the case of both glomerular and tubular dysfunction for it is seen that the type of functional derangement is identical in the two types of damage. Anatomical examination of the kidneys on the other hand showed definite differences in the state of the kidneys in the two types of damage, whether the dysfunction was glomerular or tubular. Certain points should be emphasized here. First, the validity of these results is not dependent on any particular interpretation of the significance of the functional phenomena observed. Whatever the anatomical relations between the two circulations in the kidney, whether urea, salts, dyes or water is excreted by one mechanism or another, no matter what part "filtration" or "absorption" may play in the elaboration of the final urine, the fact remains that the status of the function of these kidneys was identical, no matter how its functional state came into being, when an anatomical examination showed their actual condition to be significantly different. The fact that vascular disturbances, if of sufficient duration may in turn produce parenchymal changes complicates the problem still further, for in lesions that spontaneously develop in the kidney the mixture of vascular and parenchymal disturbances is so intimate that the functional results become infinitely more difficult of interpretation. Our previous studies have shown that even in the controlled extravital experiment conditions and relations of functional and structural response may thus become exceedingly complex (2). These complications were purposely avoided in the present study, however, by making the period of vascular disturbance short. Also, and again for the purpose of simplification, the toxic agent which caused the

  18. Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species.

    PubMed

    Han, Sang Jun; Jang, Hee-Seong; Kim, Jee In; Lipschutz, Joshua H; Park, Kwon Moo

    2016-02-29

    The length of primary cilia is associated with normal cell and organ function. In the kidney, the change of functional cilia length/mass is associated with various diseases such as ischemia/reperfusion injury, polycystic kidney disease, and congenital solitary kidney. Here, we investigate whether renal mass reduction affects primary cilia length and function. To induce renal mass reduction, mice were subjected to unilateral nephrectomy (UNx). UNx increased kidney weight and superoxide formation in the remaining kidney. Primary cilia were elongated in proximal tubule cells, collecting duct cells and parietal cells of the remaining kidney. Mn(III) Tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, reduced superoxide formation in UNx-mice and prevented the elongation of primary cilia. UNx increased the expression of phosphorylated ERK, p21, and exocyst complex members Sec8 and Sec10, in the remaining kidney, and these increases were prevented by MnTMPyP. In MDCK, a kidney tubular epithelial cell line, cells, low concentrations of H2O2 treatment elongated primary cilia. This H2O2-induced elongation of primary cilia was also prevented by MnTMPyP treatment. Taken together, these data demonstrate that kidney compensation, induced by a reduction of renal mass, results in primary cilia elongation, and this elongation is associated with an increased production of reactive oxygen species (ROS).

  19. Unilateral nephrectomy elongates primary cilia in the remaining kidney via reactive oxygen species

    PubMed Central

    Han, Sang Jun; Jang, Hee-Seong; Kim, Jee In; Lipschutz, Joshua H.; Park, Kwon Moo

    2016-01-01

    The length of primary cilia is associated with normal cell and organ function. In the kidney, the change of functional cilia length/mass is associated with various diseases such as ischemia/reperfusion injury, polycystic kidney disease, and congenital solitary kidney. Here, we investigate whether renal mass reduction affects primary cilia length and function. To induce renal mass reduction, mice were subjected to unilateral nephrectomy (UNx). UNx increased kidney weight and superoxide formation in the remaining kidney. Primary cilia were elongated in proximal tubule cells, collecting duct cells and parietal cells of the remaining kidney. Mn(III) Tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, reduced superoxide formation in UNx-mice and prevented the elongation of primary cilia. UNx increased the expression of phosphorylated ERK, p21, and exocyst complex members Sec8 and Sec10, in the remaining kidney, and these increases were prevented by MnTMPyP. In MDCK, a kidney tubular epithelial cell line, cells, low concentrations of H2O2 treatment elongated primary cilia. This H2O2-induced elongation of primary cilia was also prevented by MnTMPyP treatment. Taken together, these data demonstrate that kidney compensation, induced by a reduction of renal mass, results in primary cilia elongation, and this elongation is associated with an increased production of reactive oxygen species (ROS). PMID:26923764

  20. Cytotoxicity, intracellular localization and exocytosis of citrate capped and PEG functionalized gold nanoparticles in human hepatocyte and kidney cells.

    PubMed

    Tlotleng, Nonhlanhla; Vetten, Melissa A; Keter, Frankline K; Skepu, Amanda; Tshikhudo, Robert; Gulumian, Mary

    2016-08-01

    Surface-modified gold nanoparticles (AuNPs) are nanomaterials that hold promise in drug delivery applications. In this study, the cytotoxicity, uptake, intracellular localization, and the exocytosis of citrate-stabilized (Cit-AuNP) and polyethylene glycol (PEG)-modified gold nanoparticles with the carboxyl (COOH) terminal functional group were assessed in human embryonic kidney (HEK 293) and the human caucasian hepatocytes carcinoma (Hep G2) cell systems, representing two major accumulation sites for AuNPs. The zeta (ζ)-potential measurements confirmed the negative surface charge of the AuNPs in water and in cell growth medium. The transmission electron microscopy confirmed the size and morphology of the AuNPs. Both types of AuNPs were shown to induce cytotoxic effects in cells. The Hep G2 cells were more sensitive cell type, with the COOH-PEG-AuNPs inducing the highest toxicity at higher concentrations. Dark field microscopy and TEM images revealed that the AuNPs were internalized in cells, mostly as agglomerates. TEM micrographs further revealed that the AuNPs were confined as agglomerates inside vesicle-like compartments, likely to be endosomal and lysosomal structures as well as in the cytosol, mostly as individual particles. The AuNPs were shown to remain in cellular compartments for up to 3 weeks, but thereafter, clearance of the gold nanoparticles from the cells by exocytosis was evident. The results presented in this study may therefore give an indication on the fate of AuNPs on long-term exposure to cells and may also assist in safety evaluation of AuNPs. PMID:27184667

  1. Bone kidney interactions.

    PubMed

    Nickolas, Thomas L; Jamal, Sophie A

    2015-06-01

    The fact that bone disease and kidney disease co-exist is well known. Formally, this inter-relationship is called chronic kidney disease mineral bone disorder or CKD-MBD. Traditionally, it was thought that bone played a passive role in CKD-MBD - specifically that kidney disease caused disordered mineral metabolism which resulted in bone disease and ultimately fractures. More recently however our understanding of bone function in general and the role that bone plays in CKD-MBD in particular, has changed. This chapter will briefly review epidemiology of fractures in chronic kidney disease (CKD) and the roles that imaging and measuring markers of mineral metabolism can play in assessing fracture risk. We will then review more recent data consistent with the concept MBD occurs early in the course of CKD and, via the secretion of novel molecules and/or signalling pathways, the bone can influence other organ systems. PMID:26156535

  2. Perception of affective prosody in major depression: a link to executive functions?

    PubMed

    Uekermann, Jennifer; Abdel-Hamid, Mona; Lehmkämper, Caroline; Vollmoeller, Wolfgang; Daum, Irene

    2008-07-01

    Major depression is associated with impairments of executive functions and affect perception deficits, both being linked to dysfunction of fronto-subcortical networks. So far, little is known about the relationship between cognitive and affective deficits in major depression. In the present investigation, affect perception and executive functions were assessed in 29 patients with a diagnosis of major depression (Dep) and 29 healthy controls (HC). Both groups were comparable on IQ, age, and gender distribution. Depressed patients showed deficits of perception of affective prosody, which were significantly related to inhibition, set shifting, and working memory. Our findings suggest a significant association between cognitive deficits and affect perception impairments in major depression, which may be of considerable clinical relevance and might be addressed in treatment approaches. Future studies are desirable to investigate the nature of the association in more detail.

  3. Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis.

    PubMed

    Grove, Tyler B; Tso, Ivy F; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Ellingrod, Vicki L; McInnis, Melvin G; Deldin, Patricia J

    2016-09-30

    Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychosis not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms.

  4. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    ERIC Educational Resources Information Center

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  5. Determining place and process: functional traits of ectomycorrhizal fungi that affect both community structure and ecosystem function.

    PubMed

    Koide, Roger T; Fernandez, Christopher; Malcolm, Glenna

    2014-01-01

    There is a growing interest amongst community ecologists in functional traits. Response traits determine membership in communities. Effect traits influence ecosystem function. One goal of community ecology is to predict the effect of environmental change on ecosystem function. Environmental change can directly and indirectly affect ecosystem function. Indirect effects are mediated through shifts in community structure. It is difficult to predict how environmental change will affect ecosystem function via the indirect route when the change in effect trait distribution is not predictable from the change in response trait distribution. When response traits function as effect traits, however, it becomes possible to predict the indirect effect of environmental change on ecosystem function. Here we illustrate four examples in which key attributes of ectomycorrhizal fungi function as both response and effect traits. While plant ecologists have discussed response and effect traits in the context of community structuring and ecosystem function, this approach has not been applied to ectomycorrhizal fungi. This is unfortunate because of the large effects of ectomycorrhizal fungi on ecosystem function. We hope to stimulate further research in this area in the hope of better predicting the ecosystem- and landscape-level effects of the fungi as influenced by changing environmental conditions.

  6. Chronic Kidney Diseases

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  7. Kidney disease - resources

    MedlinePlus

    Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Kidney Disease Education Program -- www.nkdep.nih.gov National Kidney Foundation -- www.kidney.org National ...

  8. RAAS-mediated Redox effects in Chronic Kidney Disease

    PubMed Central

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

    2009-01-01

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

  9. Brain–kidney crosstalk

    PubMed Central

    2014-01-01

    Encephalopathy and altered higher mental functions are common clinical complications of acute kidney injury. Although sepsis is a major triggering factor, acute kidney injury predisposes to confusion by causing generalised inflammation, leading to increased permeability of the blood–brain barrier, exacerbated by hyperosmolarity and metabolic acidosis due to the retention of products of nitrogen metabolism potentially resulting in increased brain water content. Downregulation of cell membrane transporters predisposes to alterations in neurotransmitter secretion and uptake, coupled with drug accumulation increasing the risk of encephalopathy. On the other hand, acute brain injury can induce a variety of changes in renal function ranging from altered function and electrolyte imbalances to inflammatory changes in brain death kidney donors. PMID:25043644

  10. A novel proteoglycan from Ganoderma lucidum fruiting bodies protects kidney function and ameliorates diabetic nephropathy via its antioxidant activity in C57BL/6 db/db mice.

    PubMed

    Pan, Deng; Zhang, Dan; Wu, Jiasheng; Chen, Congheng; Xu, Zhixue; Yang, Hongjie; Zhou, Ping

    2014-01-01

    Diabetic nephropathy (DN) is the major cause of morbidity among diabetic patients. Thus, antidiabetic drugs with protection potential in the kidneys would have a higher therapeutic value. The effects of a novel proteoglycan, named FYGL, isolated from G. lucidum fruiting bodies, on the kidney function were investigated systematically in present work. FYGL (250 mg/kg) not only dosedependently reduced the blood glucose concentration (23.5%, p<0.05), kidney/body weight ratio (23.6%, p<0.01), serum creatinine (33.1%, p<0.01), urea nitrogen (24.1%, p<0.01),urea acid contents (35.9%, p<0.01) and albuminuria (30.7%, p<0.01)of DN mice compared to the untreated DN mice but also increased the renal superoxide dismutase (75.3%, p<0.01), glutathione peroxidase (35.0%, p<0.01) and catalase activities (58.5%, p<0.01) compared to the untreated DN mice. The decreasing of renal malondialdehyde content (34.3%, p<0.01) and 8-hydroxy-2'-deoxyguanosine expression (2.5-fold, p<0.01) were also observed in FYGL-treated DN mice compared to the untreated DN mice, along with an amelioration of renal morphologic abnormalities. We conclude that FYGL confers protection against the renal functional and morphologic injuries by increasing activities of antioxidants and inhibiting accumulation of oxidation, suggesting a potential nutritional supplement for the prevention and therapy of DN.

  11. High Intensity Interval Training Favourably Affects Angiotensinogen mRNA Expression and Markers of Cardiorenal Health in a Rat Model of Early-Stage Chronic Kidney Disease

    PubMed Central

    Tucker, Patrick S.; Scanlan, Aaron T.; Dalbo, Vincent J.

    2015-01-01

    The majority of CKD-related complications stem from cardiovascular pathologies such as hypertension. To help reduce cardiovascular complications, aerobic exercise is often prescribed. Emerging evidence suggests high intensity interval training (HIIT) may be more beneficial than traditional aerobic exercise. However, appraisals of varying forms of aerobic exercise, along with descriptions of mechanisms responsible for health-related improvements, are lacking. This study examined the effects of 8 weeks of HIIT (85% VO2max), versus low intensity aerobic exercise (LIT; 45–50% VO2max) and sedentary behaviour (SED), in an animal model of early-stage CKD. Tissue-specific mRNA expression of RAAS-related genes and CKD-related clinical markers were examined. Compared to SED, HIIT resulted in increased plasma albumin (p = 0.001), reduced remnant kidney weight (p = 0.028), and reduced kidney weight-body weight ratios (p = 0.045). Compared to LIT, HIIT resulted in reduced Agt mRNA expression (p = 0.035), reduced plasma LDL (p = 0.001), triglycerides (p = 0.029), and total cholesterol (p = 0.002), increased plasma albumin (p = 0.047), reduced remnant kidney weight (p = 0.005), and reduced kidney weight-body weight ratios (p = 0.048). These results suggest HIIT is a more potent regulator of several markers that describe and influence health in CKD. PMID:26090382

  12. Risk Factors for Chronic Kidney Disease

    MedlinePlus