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Background: PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort., Study Design: Case series, January 2010 to March 2016., Settings & Participants: Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease., Outcomes: Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate., Results: The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD., Limitations: Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers., Conclusions: Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.

Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFH+IF mutations). Age <3 mo at onset seems to be characteristic of CFH and IF mutation-associated aHUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within <1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group.

The central neurotoxicity of cyclosporin A (CsA) has been abundantly documented in pediatric and adult recipients of bone marrow or organ transplants, with variations in the rate of occurrence from 0.5% to 35%. We report two cases of central neurotoxicity ascribable to CsA in children with nephrotic syndrome due to lipoid nephrosis. The manifestations of CsA-related central neurotoxicity include confusion, aphasia, dystonias, akinetic mutism, parkinsonism, palsies, seizures, catatonia, coma, brain hemorrhage, and cortical blindness. Decreased density of the cerebral white matter is visible by computed tomography (CT) in 50% of cases, with the most commonly involved sites being the occipital cortex, the cerebellum, the periventricular substance, and the brainstem. Magnetic resonance imaging is more sensitive and more specific than CT for investigating the white matter. High-signal lesions are seen on T2-weighted sequences in the areas that are abnormal by CT. Many risk factors have been reported, including hypomagnesemia, hypocholesterolemia, high-dose glucocorticoid therapy, arterial hypertension, and infections. We present two patients with central neurotoxicity both of whom have elevated cholesterol levels.

We report a case of reversible myoclonic encephalopathy which appeared after intravenous acyclovir treatment in a patient in CAPD for which pharmacological dosages have been made in serum, peritoneal dialysate and cerebrospinal fluid (CSF). Encephalopathy appeared after two intravenous doses of 7.33 mg/kg (doses higher than recommended), administered on admission and 16 hours later. Pharmacological dosages indicated that acyclovir peritoneal clearance was negligible, and that acyclovir persisted a long time in plasma and CSF. Neurological symptoms persisted although serum concentrations returned to normal value. The diagnostic value of pharmacological dosages in serum and CSF is discussed. In addition, neurological symptoms disappeared following two consecutive hemodialysis procedures. Hence we suggest that hemodialysis could be used for drug removal in case of acyclovir overdose in CAPD patients.

Antipyrine metabolic clearance and BSP fractional (K1) clearance relationship in liver disease is the object of this study. 47 patients have been examined (liver cirrhosis: 17, liver disease without cirrhosis: 15, patients with no liver disease: 15). Results are as follows: antipyrine metabolic clearance is significantly lower in patients with cirrhosis; BSP fractional clearance is significantly lower in liver disease with and without cirrhosis; the clearances are significantly linked in liver cirrhosis patients, but not in the other patient groups. The role of liver cell deficiency and blood flow decrease is discussed with result interpretation.

Fourteen patients with polyarteritis nodosa complicated by histologically confirmed glomerulopathies were included in a prospective multi-center study comparing corticotherapy (group 1, n = 8) with combined cyclophosphamide and steroids (group 2, n = 6). Plasma exchanges were associated on a routine basis. The two groups were comparable apart from initially more severe renal impairment in group 1 (p less than 0.05). Initial control of the disease was obtained in 11 patients (7 from group 1, 4 from group 2) including the patients with oligoanuria. Six patients recovered, 3 had recurrence requiring chronic hemodialysis and 5 patients died from group 1 (p less than 0.05). These preliminary findings suggest that plasma exchange can contribute to control of polyarteritis nodosa with renal complications.