Assessing renal graft function in clinical trials: Can tests predicting glomerular filtration rate substitute for a reference method?

Assessing renal graft function in clinical trials: Can tests predicting glomerular filtration rate substitute for a reference method?BackgroundIn clinical trials, comparison of renal graft function needs a rigorous determination of glomerular filtration rate (GFR). Since reference methods to measure GFR cannot be easily implemented, a number of tests predicting GFR are usually used. However, little is known about their validity in renal transplant patients. We aimed to compare the performances of six GFR tests with inulin clearance in this population.MethodsFive hundred consecutive inulin clearances performed in 294 renal transplant recipients with stable renal function were retrospectively selected. For each of them, we computed six estimates: the 24-hour creatinine clearance, the Cockcroft-Gault, Walser, Jelliffe, Nankivell, and Levey formulas. Their respective performance was assessed by correlation (simple linear regression), accuracy (dispersion of true error), and agreement (Bland and Altman method).ResultsEach GFR test closely correlated with inulin clearance (P < 0.0001). Comparisons between pairs of GFR tests did not show any significant difference in accuracy between the Levey, Jelliffe, and Walser formulas. Conversely, each of these formulas demonstrated a significant lower dispersion (P < 0.005) than the others. Nevertheless, all GFR tests displayed considerable lack of agreement with limits of agreement over 40mL/min/1.73m2 apart. The proportion of predicted GFR differing from inulin clearance by ± 10mL/min/1.73m2, ranged from 34% for the Jelliffe formula to 53% for the Nankivell's one.ConclusionNone of these formulas seems to be able to safely substitute for inulin clearance. In clinical trials, renal graft function should be preferably assessed using a reference method of GFR measurement

Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis

Peer reviewe

Spectrum of ANCA-Associated Disorders According to Serological Phenotype in Routine Care: Retrospective Case Series of 209 Patients

Objective: To summarize the experience of three years of positive ANCA (anti-neutrophil cytoplasmic antibodies) testing in a single university based hospital. We describe the clinical features according to ANCA phenotype of patients who did and did not have ANCA- associated vasculitis (AAV).Methods: We did a review of all samples tested for ANCA in a 3 year-period (2005-2007). Each sample was tested by indirect immunofluorescence (IIF) and enzyme-linked-immunosorbent assay (ELISA). Sera were considered as positive for ANCA testing if either IIF or ELISA for MPO or PR3 antigen specificity was positive. Patients were considered as having AAV on established diagnostic criteria and algorithms.Results: The positive ANCA population consisted in 209 patients, 54 were classified in the AAV group and 155 patients constituted the “Others†group. The typically most relevant ANCA phenotypes (C-ANCA/anti-PR3+ and P-ANCA/anti-MPO+) were detected in 90 % (49/54) of patients in the AAV group and only 10% (15/155) of the “Others†group (p &lt; 0.001). Among the latter none developed AAV during follow-up. Positive IIF alone was found in 4% (2/54) of the AAV group and in 68% (105/155) of the “Others†group (p &lt; 0.001). In patients without AAV, positive IIF alone or positive ELISA with negative IIF represented the main ANCA pattern.Conclusion: In routine clinical practice, most patients with positive ANCA testing do not have AAV. The typical ANCA pattern (C-ANCA/anti-PR3+ or P-ANCA/anti-MPO+) remains a strong predictor of AAV in patients with a high level of suspicion for systemic vasculitis. In other cases, ANCA positivity should be interpreted with extreme caution

Le dosage de l'inuline: mise au point

L’inuline, polymère de fructose, reste le marqueur de référence du débit de filtration glomérulaire (DFG). Popularisé par les études de Smith et Shannon, son dosage n’en demeure pas moins complexe et sujet à des interférences dont celle du glucose est la plus importante. Il existe deux grands types de dosages de l’inuline : les méthodes de dosage « acide » et enzymatiques. Le dosage « acide » consiste en un dosage colorimétrique du fructose obtenu après hydrolyse de l’inuline en milieu très acide. Le dosage du fructose englobe différentes méthodes de dosage dont la plus utilisée est la réaction à l’anthrone. Toutes ces méthodes présentent des interférences au glucose. Différentes méthodes « enzymatiques » ont été décrites au cours du temps. Celles-ci apparaissent plus précises et sans doute moins sujettes aux interférences même si peu d’études comparatives sont disponibles. Plusieurs auteurs ont également développé des dosages de type CLHP. Cette méthode spécifique et précise demeure cependant moins adaptée à la routine. Ainsi, si l’utilisation de l’inuline comme marqueur de référence n’est pas remise en cause, son dosage reste délicat, sujet aux interférences et à une certaine interprétation. Des études supplémentaires restent nécessaires pour valider analytiquement et comparativement les techniques de dosage de l’inuline

Estimated glomerular filtration rate as an end point in kidney transplant trial: where do we stand?

International audienc

Vitamin D deficiency during late pregnancy mediates placenta-associated complications

International audienceAbstract During pregnancy, maternal vitamin D insufficiency could increase the risk of preeclampsia. Aim of the study was to evaluate the relationship between vitamin D status and the occurrence of placenta-mediated complications (PMCs) in a population at high risk. A prospective multicenter cohort study of 200 pregnant patients was conducted. The vitamin D level of patients with placenta-mediated complications was lower at 32 weeks compared to uncomplicated pregnancies ( P = 0.001). At 32 weeks, the risk of occurrence of PMCs was five times higher in patients with vitamin D deficiency (RR: 5.14 95% CI (1.50–17.55)) compared to patients with normal vitamin D levels. There was a strong, inverse relationship between serum 25(OH)D levels at 32 weeks and the subsequent risk of PMCs ( P = 0.001). At 32 weeks, the vitamin D level of patients with late-onset PMCs was lower than the one of patients with early-onset PMCs and of patients without PMCs ( P < 0.0001). These results suggest a role of vitamin D in the maintenance of placental performance and therefore in the prevention of the onset of late PMC

Cystatin C-based equations in renal transplantation: moving toward a better glomerular filtration rate prediction?

International audienceCreatinine-based glomerular filtration rate (GFR) estimators perform poorly in renal transplant recipients. Cystatin C might be a better alternative to serum creatinine in assessing renal graft function. We compared several cystatin C-based equations with the modification diet renal disease (MDRD) equation in 120 adult renal transplant recipients for whom the GFR was measured by the gold standard inulin clearance. Mean inulin-measured GFR was 52.6 mL/min/1.73 m (range, 13-119). The Hoek, Rule, Le Bricon, and Filler cystatin C-based formulas showed significantly better performances (accuracy 30% of 82%, 81%, 78%, and 71%), than the MDRD equation (58%, Mac Nemar test, P<0.01). Sensitivity to detect a GFR below 60 mL/min/1.73 m was significantly higher for the Hoek and the Rule equations (0.95, 95% CI 0.91-1) than for the MDRD equation (0.76, 95% CI 0.67-0.85). These data confirm that cystatin C as a GFR marker offers significant advantages over creatinine in renal transplantation

GFR Estimation Using Standardized Cystatin C in Kidney Transplant Recipients

Background: The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients. Study Design: Study of diagnostic test accuracy. Setting & Participants: 670 kidney transplant recipients from 3 centers undergoing glomerular filtration rate (GFR) measurements from December 2006 to November 2012. Index Test: Estimated GFR (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysCbased CKD-EPI equations (eGFRcys and eGFRcr-cys, respectively) and the 2009 SCr-based CKD-EPI equation (eGFRcr), with SCysC and SCr measured at a single laboratory between April 2011 and June 2011. Reference Test: Measured GFR (mGFR) using urinary clearance of inulin. Results: Bias (the difference between mGFR and eGFR) was significantly smaller for eGFRcys and eGFRcr-cys versus eGFRcr ( 2.82 and 0.54 vs 4.4 mL/min/1.73 m2, respectively; P 0.001). Precision (standard deviation of the mean bias) also was better for eGFRcys and eGFRcr-cys versus eGFRcr (12 and 11 vs 13 mL/min/1.73 m2 [P 0.001 for both comparisons]). Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for eGFRcys and eGFRcr-cys versus eGFRcr (81% and 86% vs 75%, respectively [P 0.004 and P 0.001]). Net reclassification index with respect to mGFR of 30 mL/min/1.73 m2 for eGFRcr-cys and eGFRcys versus eGFRcr was 18.8% [95% CI, 8.6%-28.9%] and 22.5% [95% CI, 10.2%-34.9%]. Limitations: Patients were exclusively of European descent; association with transplant outcome was not evaluated. Conclusions: Our data validate the use of both the newly developed SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant recipients. Both equations perform better than the SCr-based CKD-EPI equation (2009)

UMOD polymorphism rs12917707 is not associated with severe or stable IgA nephropathy in a large Caucasian cohort.

Genetic factors are suspected in the pathogenesis of IgA nephropathy, as well as in the course of IgA nephropathy progression towards end stage renal failure. UMOD polymorphism rs12917707 is known to associate with end stage renal failure of mixed aetiologies.SCOPUS: ar.jinfo:eu-repo/semantics/publishe