Eculizumab (anti-C5) has been sporadically reported as an efficient therapy for atypical hemolytic uremic syndrome (aHUS). However, the lack of series precludes any firm conclusion about the optimal use of anti-C5 for preventing or treating aHUS posttransplant aHUS recurrence. We thoroughly studied 22 renal transplant recipients with aHUS who received offlabel therapy with anti-C5, including 12 cases, which have not been reported yet. Nine patients, all carrying a complement genetic abnormality associated with a high risk of aHUS recurrence, received prophylactic anti-C5 therapy to prevent posttransplant recurrence. Eight of them had a successful recurrencefree posttransplant course and achieved a satisfactory graft function, while the remaining patient experienced early arterial thrombosis of the graft. Thirteen renal transplant recipients were given anti-C5 for posttransplant aHUS recurrence. A complete reversal of aHUS activity was obtained in all of them. Importantly, the delay of anti-C5 initiation after the onset of the aHUS episode inversely correlated with the degree of renal function improvement. Three patients in whom anti-C5 was subsequently stopped experienced a relapse. Altogether these data suggest that long-term eculizumab is highly effective for preventing and treating posttransplant aHUS recurrence. Our study also indicates that anti-C5 should be promptly started if a recurrence occurs.

Background and objectives Cystinuria is an autosomal recessive disorder affecting renal cystine reabsorption; it causes 1% and 8% of stones in adults and children, respectively. This study aimed to determine epidemiologic and clinical characteristics as well as comorbidities among cystinuric patients, focusing on CKD and high BP.Design, setting, participants, & measurements This retrospective study was conducted in France, and involved 47 adult and pediatric nephrology and urology centers from April 2010 to January 2012. Data were collected from 442 cystinuric patients.Results Median age at onset of symptoms was 16.7 (minimum to maximum, 0.3-72.1) years and median diagnosis delay was 1.3 (0-45.7) years. Urinary alkalinization and cystine-binding thiol were prescribed for 88.8% and 52.2% of patients, respectively, and 81.8% had at least one urological procedure. Five patients (1.1%, n=4 men) had to be treated by dialysis at a median age of 35.0 years (11.8-70.7). Among the 314 patients aged $16 years, using the last available plasma creatinine, 22.5% had an eGFR$90 ml/min per 1.73 m 2 (calculated by the Modification of Diet in Renal Disease equation), whereas 50.6%, 15.6%, 7.6%, 2.9%, and 0.6% had an eGFR of 60-89, 45-59, 30-44, 15-29, and ,15, respectively. Among these 314 patients, 28.6% had high BP. In multivariate analysis, CKD was associated with age (odds ratio, 1.05 [95% confidence interval, 1.03 to 1.07]; P,0.001), hypertension (3.30 [1.54 to 7.10]; P=0.002), and severe damage of renal parenchyma defined as a past history of partial or total nephrectomy, a solitary congenital kidney, or at least one kidney with a size ,10 cm in patients aged $16 years (4.39 [2.00 to 9.62]; P,0.001), whereas hypertension was associated with age (1.06 [1.04 to 1.08]; P,0.001), male sex (2.3 [1.3 to 4.1]; P=0.003), and an eGFR,60 ml/min per 1.73 m 2 (2.7 [1.5 to 5.1]; P=0.001).Conclusions CKD and high BP occur frequently in patients with cystinuria and should be routinely screened.

Functional properties of the paracellular pathway depend critically on the set of claudins expressed at the tight junction. Two syndromes are causally linked to loss-of-function mutations of claudins: HELIX syndrome caused by genetic variations in the CLDN10 gene, and Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis caused by genetic variations in the CLDN16 or the CLDN19 gene. All three genes are expressed in the kidney, particularly in the thick ascending limb (TAL). However, localization of these claudins in humans and rodents remains to be delineated in detail. We studied the segmental and subcellular expression of CLDN10, 16 and 19 in both paraffin-embedded and frozen kidney sections from adult human, mouse and rat, using immunohistochemistry and immunofluorescence, respectively. Here CLDN10 was present in a subset of medullary and cortical TAL cells, localizing to basolateral domains and tight junction in human and rodent kidney. A weak expression was detected at the tight junction of proximal tubular cells. CLDN16 was primarily expressed in a subset of TAL cells in cortex and outer stripe of outer medulla, restricted to basolateral domains and tight junctional structures in both human and rodent kidney. CLDN19 predominantly colocalized with CLDN16 in tight junctions and basolateral domains of TAL but was also found in basolateral and junctional domains in more distal sites. CLDN10 expression at tight junction almost never overlapped with that of CLND16 and CLDN19, consistent with distinct junctional pathways with different permeation profiles in both human and rodent kidney.