Search

To test the association between bilateral nephrectomies in patients with autosomal recessive polycystic kidney disease (ARPKD) and long-term clinical outcome and to identify risk factors for severe outcomes, a dataset comprising 504 patients from the international registry study ARegPKD was analyzed for characteristics and complications of patients with very early (? 3 months; VEBNE) and early (4–15 months; EBNE) bilateral nephrectomies. Patients with very early dialysis (VED, onset ? 3 months) without bilateral nephrectomies and patients with total kidney volumes (TKV) comparable to VEBNE infants served as additional control groups. We identified 19 children with VEBNE, 9 with EBNE, 12 with VED and 11 in the TKV control group. VEBNE patients suffered more frequently from severe neurological complications in comparison to all control patients. Very early bilateral nephrectomies and documentation of severe hypotensive episodes were independent risk factors for severe neurological complications. Bilateral nephrectomies within the first 3 months of life are associated with a risk of severe neurological complications later in life. Our data support a very cautious indication of very early bilateral nephrectomies in ARPKD, especially in patients with residual kidney function, and emphasize the importance of avoiding severe hypotensive episodes in this at-risk cohort. © 2020, The Author(s)., Marga und Walter Boll-Stiftung Universität zu Köln, UoC Bundesministerium für Bildung und Forschung, BMBF: 01GM1903, 01GM1515 PKD Foundation, PKDF European Paediatric Neurology Society, EPNS, We thank the German Society for Pediatric Nephrology (GPN) and the ESCAPE Network for their support. ML was supported by grants of the GPN, the European Society for Paediatric Nephrology (ESPN), the German PKD foundation, the Koeln Fortune program, the GEROK program of the Medical Faculty of University of Cologne, and the Marga and Walter Boll-Foundation. FS and ML are supported by the the German Federal Ministry of Research and Education (BMBF grant 01GM1515 and 01GM1903). KB was supported by the Koeln Fortune program of the Medical Faculty of University of Cologne and the Marga and Walter Boll-Foundation. This work was generated within the European Reference Network for Rare Kidney Disorders (ERKNet). Open Access funding provided by Projekt DEAL.

International audience; Membranous nephropathy results from subepithelial antigen-antibody complex deposition along the glomerular basement membrane. Although PLA2R, THSD7A, and NELL-1 account for a majority (about 80%) of the target antigens, the target antigen in the remaining cases is not known. Using laser microdissection of PLA2R-negative glomeruli of patients with membranous nephropathy followed by mass spectrometry we identified a unique protein, Semaphorin 3B, in three cases. Mass spectrometry failed to detect Semaphorin-3B in 23 PLA2R-associated cases of membranous nephropathy and 88 controls. Semaphorin 3B in all three cases was localized to granular deposits along the glomerular basement membrane by immunohistochemistry. Next, an additional eight cases of Semaphorin 3B-associated membranous nephropathy were identified in three validation cohorts by immunofluorescence microscopy. In four of 11 cases, kidney biopsy also showed tubular basement membrane deposits of IgG on frozen sections. Confocal microscopy showed that both IgG and Semaphorin 3B co-localized to the glomerular basement membrane. Western blot analysis of five available sera showed reactivity to reduced Semaphorin 3B in four of four patients with active disease and no reactivity in one patient in clinical remission; there was also no reactivity in control sera. Eight of the 11 cases of Semaphorin 3B-associated membranous nephropathy were pediatric cases. Furthermore, in five cases, the disease started at or below the age of two. Thus, Semaphorin 3B-associated membranous nephropathy appears to be a distinct type of disease; more likely to be present in pediatric patients.

Study question:Is azoospermia in male cystinosis patients obstructive or nonobstructive in origin?Summary answer: Azoospermia in male cystinosis patients is obstructive in origin.What is known already: Cystinosis is a rare autosomal recessive metabolic disorder caused by mutations in the lysosomal membrane protein cystinosin (CTNS), which leads to intracellular lysosomal cystine accumulation. Depending on the disease severity, three forms are distinguished: infantile (most severe), juvenile (intermediate), and ocular (benign) form. The main clinical presentation in infantile cystinosis is the renal Fanconi syndrome, leading to end stage renal disease (ESRD) by the age of ten, if the patient is left untreated. Cysteamine, a cystine-depleting agent, beside renal replacement therapy, has improved the life expectancy of cystinosis patients. In contrast to females, male infantile cystinosis patients suffer from infertility.Study design, size, duration: Three groups were included in a prospective case control study; adult cystinosis patients (three infantile, two juvenile, and one ocular male patients), control group (seven adult fertile male subjects), and a positive control group for obstructive azoospermia (ten adult vasectomized males who underwent vasectomy 4-8 weeks prior to enrollment). In addition, clinical data and testicular sections for five adult infantile male cystinosis patients were retrospectively included in the study (in total, eight infantile cystinosis patients).Participants/materials, setting,methods:Scrotal ultrasound for screening for soft biomarkers of obstruction and semen analysis were performed in all prospectively included subjects, while sexual hormonal levels were evaluated only in the cystinosis patients. In addition, clinical data, semen analysis results, percutaneous epididymal sperm aspiration (PESA) results, sexual hormonal profile, and testicular sections from the retrospectively included cystinosis patients were analyzed. For the testicular sections, morphological evaluation and immunohistochemistry were performed.Main results and the role of chance:All testicular sections taken from three infantile cystinosis patients (3/3) showed the presence of testicular sperm and normal spermatogenesis, with a Johnsen’s score of 7 to 9. Besides, epididymal sperm was present in two other infantile cystinosis patients (2/2), obtained by PESA procedure, which was only performed in those two patients. Hence, all of the five investigated infantile cystinosis patients showed either testicular or epididymal sperm (5/5 or 100%), indicating that testicular function was preserved in those patients. In contrast, seven out of the total eight infantile cystinosis patients underwent semen analysis, and they all presented with azoospermia (7/7 or 100%), including four out of the five patients that showed testicular or epididymal sperm, while a semen sample from one infantile patient, who underwent testicular biopsy, could not be retrieved. Meanwhile, the two juvenile cystinosis patients (2/2) showed a reduced sperm count (15.9 and 6.4 million/ml), and the ocular cystinosis patient (1/1) showed normal sperm count (71.6 million/ml). Remarkably, the scrotal ultrasound results revealed a significant higher epididymis caput diameter (normalized to the testis volume) in infantile cystinosis group compared with healthy controls (1.63±0.66 mm/cm3 for infantile cystinosis vs 0.50±0.18 mm/cm3 for controls, p