BackgroundAtypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade–based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.MethodsTo evaluate this strategy’s effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.ResultsThe first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.ConclusionsResults from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

BackgroundDetecting impaired glomerular filtration rate (GFR) is important in intensive care units (ICU) in order to diagnose acute kidney injuries and adjust the dose of renally excreted drugs. Whether serum Cystatin C (SCysC) may better reflect glomerular filtration rate than serum creatinine (SCr) in the context of intensive care medicine is uncertain.MethodsWe compared the performance of SCysC and SCr as biomarkers of GFR in 47 critically ill patients (median SOFA (Sepsis-related Organ Failure Assessment) score of 5) for whom GFR was measured by a reference method (urinary clearance of iohexol).ResultsMean Iohexol clearance averaged 96 ± 54 mL/min and was under 60 mL/min in 28% of patients. Mean SCr and SCysC concentrations were 0.70 ± 0.33 mg/dL and 1.26 ± 0.61 mg/L, respectively. Area under the ROC curve for a GFR threshold of 60 mL/min was 0.799 and 0.942 for SCr and SCysC, respectively (p = 0.014).ConclusionsWe conclude that ScysC significantly outperfoms SCr for the detection of an impaired GFR in critically ill patients.Trial registrationClinicalTrials.gov: B7072006347

Activation of complement through the alternative pathway has a key role in the pathogenesis of IgA nephropathy (IgAN). Large, international, genome-wide association studies have shown that deletion of complement factor H-related genes 1 and 3 () is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown. Here, we compared the renal outcomes of patients with IgAN according to their genotype. This retrospective, monocentric cohort study included 639 white patients with biopsy-proven IgAN since 1979 (mean age at diagnosis, 40.1 years; median follow-up, 132 months). We determined the number of and gene copies by quantitative PCR and collected clinical and biologic data by reviewing the patients' medical records. In all, 30.5% of the patients were heterozygous and 4% were homozygous for We did not detect an association between and age, eGFR, urinary protein excretion rate, or the presence of hypertension or hematuria at the time of diagnosis. The mean intensities of immune IgA, IgG, and C3 deposits were lower in the group with heterozygous or homozygous gene deletions than in those with no deletion. However, did not associate with progression to stage 3 CKD or renal death. In conclusion, the genotype did not associate with progression toward CKD stages 3 and 5 in our white population of patients with IgAN, although it did associate with a reduced level of glomerular immune deposits.