Determinants and burden of chronic kidney disease in the population-based CoLaus study: a cross-sectional analysis.

BACKGROUND: Chronic kidney disease (CKD) represents an increasing health burden. We present the population-based prevalence of CKD and compare the CKD Epidemiology collaboration (CKD-EPI) and modification of diet in renal disease (MDRD) equations to estimate the glomerular filtration rate, using the revised CKD classification with three albuminuria classes. We also explore factors associated with CKD. METHODS: The Swiss population-based, cross-sectional CoLaus study conducted in Lausanne (2003-2006) included 2810 men and 3111 women aged 35-75. CKD prevalence was assessed using CKD-EPI and MDRD equations and albuminuria estimated by the albumin-to-creatinine ratio in spot morning urine. Multivariate logistic regression was used to analyse determinants of CKD. RESULTS: Prevalence [95% confidence interval (CI)] of all stages CKD was 10.0% (9.2-10.8%) with CKD-EPI and 13.8% (12.9-14.6%) with MDRD. Using the revised CKD classification, the prevalence of low-, medium-, high- and very high-risk groups was 90.0, 8.46, 1.18 and 0.35% with CKD-EPI, respectively. With MDRD, the corresponding values were 86.24, 11.86, 1.55 and 0.35%. Using the revised classification, CKD-EPI systematically reclassified people in a lower risk category than MDRD. Age and obesity were more strongly associated with CKD in men [odds ratio (95% CI): 2.23(1.95; 2.56) per 10 years and 3.05(2.08;4.47), respectively] than in women [1.46 (1.29; 1.65) and 1.78 (1.30;2.44), respectively]. Hypertension, type 2 diabetes, serum homocysteine and uric acid were positively independently associated with CKD in men and women. CONCLUSIONS: One in 10 adults suffers from CKD in the population of Lausanne. CKD-EPI systematically reclassifies people in a lower CKD risk category than MDRD. Serum homocysteine and uric acid levels are associated with CKD independently of classical risk factors such as age, hypertension and diabetes.

Don de rein altruiste: enjeux psychologiques [Altruistic kidney deviation: psychological challenges].

Altruistic kidney donation challenges ethical principles, questions the anthropological meaning of donation and is associated with important psychological aspects. Obtaining free and informed consent is essential and requires a depth evaluation by a psychologist or a psychiatrist in order to identify the motivations which stimulate the desire of donation. By means of a psychodynamic understanding of a clinical case, we illustrate the complexity of the evaluation of consent and discuss the psychological issues associated with altruistic kidney donation.

Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism.

Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.

Sorting mechanisms regulating membrane protein traffic in the apical transcytotic pathway of polarized MDCK cells.

The transcytotic pathway followed by the polymeric IgA receptor (pIgR) carrying its bound ligand (dIgA) from the basolateral to the apical surface of polarized MDCK cells has been mapped using morphological tracers. At 20 degreesC dIgA-pIgR internalize to interconnected groups of vacuoles and tubules that comprise the endosomal compartment and in which they codistribute with internalized transferrin receptors (TR) and epidermal growth factor receptors (EGFR). Upon transfer to 37 degreesC the endosome vacuoles develop long tubules that give rise to a distinctive population of 100-nm-diam cup-shaped vesicles containing pIgR. At the same time, the endosome gives rise to multivesicular endosomes (MVB) enriched in EGFR and to 60-nm-diam basolateral vesicles. The cup-shaped vesicles carry the dIgA/pIgR complexes to the apical surface where they exocytose. Using video microscopy and correlative electron microscopy to study cells grown thin and flat we show that endosome vacuoles tubulate in response to dIgA/pIgR but that the tubules contain TR as well as pIgR. However, we show that TR are removed from these dIgA-induced tubules via clathrin-coated buds and, as a result, the cup-shaped vesicles to which the tubules give rise become enriched in dIgA/pIgR. Taken together with the published information available on pIgR trafficking signals, our observations suggest that the steady-state concentrations of TR and unoccupied pIgR on the basolateral surface of polarized MDCK cells are maintained by a signal-dependent, clathrin-based sorting mechanism that operates along the length of the transcytotic pathway. We propose that the differential sorting of occupied receptors within the MDCK endosome is achieved by this clathrin-based mechanism continuously retrieving receptors like TR from the pathways that deliver pIgR to the apical surface and EGFR to the lysosome.

Mechanisms of hydrogen peroxide-induced vasoconstriction in the isolated perfused rat kidney.

The vasoconstrictor effect of hydrogen peroxide (H(2)O(2)) on isolated perfused rat kidney was investigated. H(2)O(2) induced vasoconstriction in the isolated rat kidney in a concentration-dependent manner. The vasoconstrictor effects of H(2)O(2) were completely inhibited by 1200 U/ml catalase. Endothelium-removal potentiated the renal response to H(2)O(2). The H(2)O(2) dose-response curve was not significantly modified by administration of the NO inhibitor L-NAME (10(-4) mol/l), whereas it was increased by the non-specific inhibitor of K+-channels, tetraethylammonium (3.10(-3) mol/l). Separately, removal of extracellular Ca(2+), administration of a mixture of calcium desensitizing agents (nitroprusside, papaverine, and diazoxide), and administration of a protein kinase C (PKC) inhibitor (chelerythrine, 10(-5) mol/l) each significantly attenuated the vasoconstrictor response to H(2)O(2), which was virtually suppressed when they were performed together. The pressor response to H(2)O(2) was not affected by: dimethyl sulfoxide (7.10(-5) mol/l) plus mannitol (3.10(-5) mol/l); intracellular Ca(2+) chelation using BAPTA (10(-5) mol/l); calcium store depletion after repeated doses of phenylephrine (10(-5) g/g kidney); or the presence of indomethacin (10(-5) mol/l), ODYA (2.10(-6) mol/l) or genistein (10(-5) mol/l). We conclude that the vasoconstrictor response to H(2)O(2) in the rat renal vasculature comprises the following components: 1) extracellular calcium influx, 2) activation of PKC, and 3) stimulation of pathways leading to sensitization of contractile elements to calcium. Moreover, a reduced pressor responsiveness to H(2)O(2) in female kidneys was observed.

The significance of the amoebocyte-producing organ in Biomphalaria glabrata

In molluscs, internal defence against microorganisms is performed by a single cell type, i.e., the haemocyte or amoebocyte. The origin of these cells in Biomphalaria glabrata was initially thought to be localised within the vasculo-connective tissue. More recently, origin from a single organ, termed the amoebocyte-producing organ (APO), has been postulated based on the occurrence of hyperplasia and mitoses during Schistosoma mansoni infection. The present investigation represents a histological, immuno-histochemical and ultra-structural study of the B. glabrata APO, whereby histological identification was facilitated by means of collecting epithelial basophilic cells. These cells were comprised of single-cell layers that cover a portion of the stroma, which contains many small, round cells and haemolymph sinuses, as well as a small area of the pericardial surface of the reno-pericardial region. On occasion, this epithelial component vaguely resembled the vertebrate juxtaglomerular apparatus, which reinforces its presumed relationship to the kidney. Both in normal and infected molluscs, mitoses were only occasionally found. The present quantitative studies failed to demonstrate the presence of APO cellular hyperplasia, either in normal or schistosome-infected B. glabrata. Conversely, several structural details from the APO region in B. glabrata were found to be consistent with the hypothesis that the APO is a filtration organ, i.e., it is more closely related to the kidney rather than the bone marrow, as has been suggested in the literature.

Interprétation de la volémie dans l'insuffisance rénale aiguë [Interpretation of volemia in acute kidney injury].

Assessment of volume status is often challenging in daily clinical practice. One of the clinician's tasks is to prevent or to treat organ systems failures that arise from a mismatch between the transport of oxygen and metabolic needs. Renal failure is a frequently encountered in-hospital diagnosis that is known to alter significantly the prognosis. In patients with acute renal failure in particular, the consequences of an inadequate volume management further increase morbidity and mortality.

Analyse fonctionnelle et moléculaire d'un nouveau gène (VIT32) impliqué dans le mécanisme d'action de la vasopressine

Résumé Les mécanismes de régulation de la réabsorption fine du sodium dans la partie distale (tube distal et tube collecteur) du néphron ont un rôle essentiel dans le maintien de l'homéostasie de la composition ionique et du volume des fluides extracellulaires. Ces mécanismes permettent le maintien de la pression sanguine. Dans la cellule principale du tube collecteur cortical (CCD), le taux de réabsorption de sodium dépend essentiellement de l'activité du canal épithélial à sodium (ENaC) à la membrane apicale et de la pompe sodium-potassium-adénosine-triphosphatase (Na+-K±ATPase) à la membrane basolatérale. L'activité de ces deux molécules de transport est en partie régulée par des hormones dont l'aldostérone, la vasopressine et l'insuline. Dans les cellules principales de CCD, la vasopressine régule le transport de sodium en deux étapes : une étape précoce dite « non-génomique » et une étape tardive dite « génotnique ». Durant l'étape précoce, la vasopressine régule l'expression de gènes, dont certains peuvent être impliqués dans le transport de sodium, comme ENaC et la Na+ -K+ATP ase. Le but de mon travail a été d'étudier l'implication d'une protéine appelée VIP32 (vasopressin induced protein : VIP) dans le transport de sodium. L'expression de VIP32 est augmentée par la vasopressine dans les cellules principales de CCD. Dans l'ovocyte de Xenopus laevis utilisé comme système d'expression hétérologue, nous avons montré que l'expression de VIP32 provoque la maturation méiotique de l'ovocyte par l'activation de la voie des MAPK (mitogen-activated protein kinase : MAPK) et du facteur de promotion méiotique (MPF). La co-expression d'ENaC et de VIP32 diminue l'activité d'ENaC de façon sélective, par l'activation de la voie des MAPK, sans affecter l'expression du canal à la surface membranaire. Nous avons également montré que la régulation de l'activité d'ENaC par la voie des MAPK est dépendante du mécanisme de régulation d'ENaC lié à un motif du canal appelé PY. Ce motif est impliqué dans le contrôle de la probabilité d'ouverture ainsi que l'expression à la surface membranaire d'ENaC. Dans les cellules principales, VIP32 par l'activation de la voie des MAPK peut être impliqué dans la régulation négative du transport transépithélial qui a lieu après plusieurs heures de traitement à la vasopressine. Le tube collecteur de reins normaux présente un taux basal significatif d'activité de la voie MAPK MEK1/2-ERK1/2. Dans la lignée mpkCCDc14 de cellules principales de CCD de souris, que nous avons utilisé pour cette partie du travail, nous avons montré la présence d'un taux basal d'activité d'ERK1/2 (pERK1/2). L'aldostérone et la vasopressine, connus pour stimuler le courant sodique transépithélial dans le CCD, ne changeaient pas le taux basal de pERK1/2. Le transport de sodium transépithélial basal, ou stimulé par l'aldostérone ou la vasopressine est diminué par l'effet de PD98059, un inhibiteur de MEK1/2 qui diminue parallèlement le taux de pERK1/2. Nous avons également montré dans des cellules non stimulées, ou stimulées par de l'aldostérone ou de la vasopressine, que l'activité de la Na+-K+ ATPase, mais pas celle d'ENaC est inhibée par des traitements avec différents inhibiteurs de MEK1/2. Par un marquage de la Na±-K+ATPase à la surface membranaire nous avons montré que la voie d'ERK1/2 contrôle l'activité intrinsèque de la Na+-K+ ATPase, plutôt que son expression à la surface membranaire. Ces données ont montré que l'activité de la Na+-K+ATPase et le transport transépithélial de sodium sont contrôlés par l'activité basal et constitutive de la voie d'ERK1/2. Summary The regulation of sodium reabsorption in the distal nephron (distal tubule and cortical collecting duct) in the kidney plays an essential role in the control of extracellular fluids composition and volume, and thereby blood pressure. In the principal cell of the collecting duct (CCD), the level of sodium reabsorption mainlly depends on the activity of both epithlial sodium channel (ENaC) and sodium-potassium-adenosine-triphosphatase (Na+-K+ATPase). The activity of these two transporters is regulated by hormones especially aldosterone, vasopressin and insuline.In the principal cell of the CCD, vasopressin regulates sodium transport via a short-term effect and a late genomic effect. During the genomic effect vasopressin activates a complex network of vasopressin-dependent genes involved in the regulation of sodium transport as ENaC and Na+-K+ATPase. We were interested in the role of a recently identified vasopressin induced protein (VIP32) and its implication in the regulation of sodium transport in principal cell of the CCD. The Xenopus oocyte expression system revealed two functions : expressed alone VIP32 rapidly induces oocyte meiotic maturation through the activation of the mitogen-activated protein kinase (MAPK) pathway and the meiotic promoting factor and when co-expressed with ENaC, V1P32 selectively dowrn-egulates channel activity, but not channel cell surface expression. We have shown that the ENaC downregulation mediated by the activation of the MAPK pathway is related to the PY motif of ENaC. This motif is implicated in ENaC cell surface expression and open probability regulation. In the kidney principal cell, VIP32 through the activation of MAPK pathway may be involved in the downregulation of transepithelial sodium transport observed within a few hours after vasopressin treatment. The collecting duct of normal kidney exhibits significant activity of the MEK1/2-ERK1/2 MAPK pathway. Using in vitro cultured mpkCCDc14 principal cells we have shown a significant basal level of ERK1/2 activity (pERK1/2). Aldosterone and vasopressin, known to upregulate sodium reabsorption in CCDs, did not change ERK1/2 activity. Basal and aldosterone- or vasopressin-stimulated sodium transport were downregulated by the MEK1/2 inhibitor PD98059 in parallel with a decrease in pERK1/2 in vitro. The activity of Na+-K+ATPase but not that of ENaC was inhibited by MEK1/2 inhibitors in both, unstimulated and aldosterone- or vasopressin-stimulated CCDs in vitro. Cell surface labelling showed that intrinsic activity rather than cell surface expression of Na+-K+ATPase was controlled by pERK1/2. Our data demonstrate that basal constitutive activity of ERK1/2 pathway controls Na+-K+ATPase activity and transepithelial sodium transport in the principal cell. Résumé tout public Les mécanismes de régulation de la réabsorption fine du sodium dans la partie distale du néphron (l'unité fonctionnelle du rein) ont un rôle essentiel dans le maintien de l'homéostasie de la composition et du volume des fluides extracellulaires. Ces mécanismes permettent de maintenir une pression sanguine effective. Dans les cellules principales du tube collecteur, une région spécifique du néphron distal, le transport de sodium dépend essentiellement de l'activité de deux transporteurs de sodium : le canal épithélial à sodium (ENaC) et la pompe sodium-potassium-adénosine-triphosphatase (Na+-K+ATPase). Afin de répondre aux besoins de l'organisme, l'activité de ces deux molécules de transport est en partie régulée par des hormones dont l'aldostérone, la vasopressine et l'insuline. Dans les cellules principales du tube collecteur, la vasopressine régule le transport de sodium en deux étapes : une étape rapide et une étape lente dite « génomique ». Durant l'étape lente, la vasopressine régule l'expression de gènes pouvant être impliqués dans le transport de sodium, dont notamment ceux d'ENaC et de la Na+-K+ATPase. Parmi les gènes dont l'expression est augmentée par la vasopressine, celui de VIP32 (vasopressin induced protein : VIP) fait l'objet de cette étude. Le but de mon travail a été d'étudier, dans un système d'expression hétérologue (l'ovocyte de Xenopus leavis), l'implication de VIP32 dans le transport de sodium. Nous avons montré que VIP32 est capable d'activer un mécanisme moléculaire en cascade appelé MAPK (mitogen-activated protein kinase : MAPK) et est aussi capable de diminuer l'activité d'ENaC. Parallèlement, dans une lignée de cellules principales de tube collecteur les mpkCCDc14, nous avons montré que le taux basal d'activité de la cascade MAPK est capable de réguler l'activité de la Na+-K+ATPase, tandis qu'il n'influence pas l'activité d'ENaC.

JC polyomavirus infection in candidates for kidney transplantation living in the Brazilian Amazon Region

This study evaluated the relative occurrences of BK virus (BKV) and JC virus (JCV) infections in patients with chronic kidney disease (CKD). Urine samples were analysed from CKD patients and from 99 patients without CKD as a control. A total of 100 urine samples were analysed from the experimental (CKD patients) group and 99 from the control group. Following DNA extraction, polymerase chain reaction (PCR) was used to amplify a 173 bp region of the gene encoding the T antigen of the BKV and JCV. JCV and BKV infections were differentiated based on the enzymatic digestion of the amplified products using BamHI endonuclease. The results indicated that none of the patients in either group was infected with the BKV, whereas 11.1% (11/99) of the control group subjects and 4% (4/100) of the kidney patients were infected with the JCV. High levels of urea in the excreted urine, low urinary cellularity, reduced bladder washout and a delay in analysing the samples may have contributed to the low prevalence of infection. The results indicate that there is a need to increase the sensitivity of assays used to detect viruses in patients with CDK, especially given that polyomavirus infections, especially BKV, can lead to a loss of kidney function following transplantation.

Donors/recipients representations about living-kidney donation : P-527

Living-kidney donation offers an option to patients awaiting renal transplantation. Representations about giving-receiving are explored retrospectively in a qualitative study. Questionnaires with open questions were sent to thirty donor-recipient dyads. Interviews were also conducted, during which participants were invited to propose an image representing donation. Thematic analysis was performed on the questionnaires (twenty-nine donors; twenty-five recipients), and on the comments of ten images selected by five donors and five recipients. Percentages are given regarding each part (donors; recipients). In the questionnaires, life (34.5%; 12%), love (27.6%; 40%), quality of life (27.6%; 8%) and generosity (6.9%; 24%) are common grounds regarding giving-a-kidney. Obviousness, hope, personal benefits or duty are expressed by donors. Recipients explain donation through emphatic sentences, qualify it as a gift or refer to the donor's courage or risk-taking. Regarding receiving-a-kidney, life (31%; 60%), gift (10.3%; 28%) and debt (3.4%; 4%) are common grounds. Donors refer to generosity or love. Quality of life, donor's risk-taking or emphatic sentences are characteristic of recipients, who highlight that nobody had to die. Preliminary data on the comments of the images underline that live-donation represents life and love. Mutual help, sharing-act, obviousness and personal benefits are expressed by donors. Recipients use emphatic sentences or refer to quality of life, gift or the difficulty to accept donation. Life and love are common grounds in live-donation. Improvement in quality of life is underlined by recipients, who stress the donor's courage or risk-taking. Donors describe donation as obvious, sometimes accompanied by personal benefits. Feelings of duty (donors) and of debt (recipients) are less discussed. Representations about giving and receiving differ between donors and recipients. These data show the specificity of each perspective. This analysis provides valuable information in order to adapt individual or dyad psychological support in live-donation.

Prevalence of occult hepatitis B virus infection in kidney transplant recipients

In this cross-sectional study, 207 hepatitis B surface antigen (HBsAg)-negative kidney transplant recipients were evaluated based on demographic and epidemiological data and on the levels of serological markers of hepatitis B virus (HBV) and hepatitis C virus infection and liver enzymes. Patients with HBV or human immunodeficiency virus infection were excluded. Sera were analysed for the presence of HBV-DNA. HBV-DNA was detected in two patients (1%), indicating occult hepatitis B (OHB) infection (the HBV-DNA loads were 3.1 and 3.5 IU/mL in these patients). The results of the liver function tests were normal and no serological markers indicative of HBV infection were detected. The prevalence of OHB infection was low among kidney transplant recipients, most likely due to the low HBsAg endemicity in the general population of the study area.

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

BACKGROUND: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). METHODS: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. RESULTS: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. CONCLUSIONS: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patients.

Minimization of calcineurin inhibitors to improve long-term outcomes in kidney transplantation.

Long-term outcomes after kidney transplantation remain suboptimal, despite the great achievements observed in recent years with the use of modern immunosuppressive drugs. Currently, the calcineurin inhibitors (CNI) cyclosporine and tacrolimus remain the cornerstones of immunosuppressive regimens in many centers worldwide, regardless of their well described side-effects, including nephrotoxicity. In this article, we review recent CNI-minimization strategies in kidney transplantation, while emphasizing on the importance of long-term follow-up and patient monitoring. Finally, accumulating data indicate that low-dose CNI-based regimens would provide an interesting balance between efficacy and toxicity.