Apheresis in Adult With Refractory Idiopathic Nephrotic Syndrome on Native Kidneys.

BACKGROUND: Apheresis is the gold standard for idiopathic nephrotic syndrome (INS) relapse after transplantation, but it remains unknown whether such treatment is useful for adults with refractory INS on native kidneys. METHODS: This retrospective study included patients older than 16 years with biopsy-proven refractory (persistent nephrotic syndrome on corticosteroids plus at least 1 immunosuppressive drug) INS treated by apheresis and followed for at least 3 months. RESULTS: Between September 1997 and January 2020, 21 patients (focal segmental glomerulosclerosis: 12, minimal change nephrotic syndrome: 9, men: 67%, median age: 34 years) were identified. At last follow-up (12 months), 7 of 21 patients were in complete or partial remission. Remission was associated with older age (51 vs. 30 years, P = 0.05), lower proteinuria (3.9 vs. 7.3 g/d, P = 0.03), and lower estimated glomerular filtration rate (eGFR) (28.0 vs. 48.5 ml/min per 1.73 m2, P = 0.05) at apheresis. The need for dialysis before apheresis (odds ratio [OR] 22.0 [1.00-524], P = 0.026), age ≥50 years (OR: 22.6 [1.00-524], P = 0.006), a marked (>4.5 g/d) decrease in proteinuria (OR: 9.17 [1.15-73.2], P = 0.041), and a short (<12 months) time between diagnosis and apheresis (OR: 10.8 [1-117], P = 0.043) were significantly associated with remission. Three of 7 patients in remission who were initially on dialysis became dialysis-free; by contrast, none of the 14 patients without remission was initially on dialysis, but 5 of 14 had become dialysis-dependent (P = 0.01). CONCLUSION: Apheresis may result in remission in adult patients with refractory INS, particularly in those at risk of renal failure, with limited sensitivity to medical treatments, if apheresis is initiated within a year of diagnosis.

Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome.

Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the α3α4α5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis.

Endoplasmic reticulum stress in UMOD-related kidney disease: a human pathologic study.

Mutations of the UMOD gene, which encodes the uromodulin protein, are associated with tubulointerstitial nephritis and hyperuricemia. UMOD mutations impair uromodulin folding, resulting in its retention within the endoplasmic reticulum (ER) of renal tubular cells. The aim of this study was to investigate whether mutant uromodulin accumulation in epithelial tubular cells is associated with ER stress. We characterized tubular expression of uromodulin and the ER stress surrogate marker Grp78 by immunohistochemistry in kidney biopsy specimens from 7 patients with UMOD-related kidney disease. We compared this population with 5 patients with familial tubulointerstitial nephritis not related to UMOD mutation. All biopsy specimens from patients carrying the UMOD mutation showed strong heterogeneous cytoplasmic expression of uromodulin in cells of the thick ascending limb of the loop of Henle. In the same tubules, Grp78 was highly expressed in a perinuclear pattern. In contrast, in all kidney biopsy specimens from patients without UMOD mutations, uromodulin staining showed normal apical expression and Grp78 expression was not increased. Our observations support the hypothesis that ER accumulation of mutant uromodulin may cause ER stress, providing a potential mechanism for the progression of UMOD-related kidney disease.

Peritoneal dialysis in polycystic kidney disease patients. Report from the French peritoneal dialysis registry (RDPLF).

BACKGROUND: It is commonly believed that polycystic kidney disease (PKD) patients on peritoneal dialysis (PD) are over-exposed to technique failure and peritonitis compared with other patients. This study was carried out to assess whether PKD is associated with technique failure and to evaluate the outcome of PKD patients on PD. METHODS: This was a retrospective cohort study based on the data of the French Language Peritoneal Dialysis Registry. We analysed 4162 incident non-diabetic patients who started PD between January 2002 and December 2007. The end of the observation period was 31 December 2008. RESULTS: Among 4162 patients, there were 344 PKD patients and 3818 patients who had another underlying nephropathy. PKD patients were younger, had a lower Charlson comorbidity index, were more frequently treated by automated PD and were less frequently assisted than other patients. For the PKD patients, the main reason for PD cessation was renal transplantation. In the multivariate analysis, comorbidities and centre size were associated with technique survival, and no association between PKD and technique failure was observed. There was no statistically significant association between PKD and peritonitis or between PKD and enteric peritonitis. On multivariate analysis, patient survival was associated with PKD and with patient age, comorbidities and the modality of assistance. Centre size was not associated with patient survival. CONCLUSION: PD is a suitable method for at least a subgroup of PKD patients reaching end-stage renal disease in a country where renal transplantation is available.