A genotype-to-phenotype approach suggests under-reporting of single nucleotide variants in nephrocystin-1 (NPHP1) related disease (UK 100,000 Genomes Project).

Autosomal recessive whole gene deletions of nephrocystin-1 (NPHP1) result in abnormal structure and function of the primary cilia. These deletions can result in a tubulointerstitial kidney disease known as nephronophthisis and retinal (Senior-Løken syndrome) and neurological (Joubert syndrome) diseases. Nephronophthisis is a common cause of end-stage kidney disease (ESKD) in children and up to 1% of adult onset ESKD.

Hemizygous loss of function mutations in causing end-stage kidney disease without Dent disease phenotype.

Dent disease type 1 is suspected in the presence of a complete phenotype of low molecular weight (LMW) proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, nephrolithiasis, haematuria, hypophosphatemia or chronic kidney disease (CKD). We present two brothers who presented with CKD alone. In the absence of typical clinical features, further assessment of LMW proteinuria and hypercalciuria was not undertaken.

Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease.

Background: Autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by mutations in the UMOD gene (ADTKD-UMOD) is considered rare and often remains unrecognised. We aimed to establish the prevalence of genetic kidney diseases, ADTKD and ADTKD-UMOD in adult chronic kidney disease (CKD) patients, and to investigate characteristic features.

Methods: We sent questionnaires on family history to all patients with CKD stages 3-5 in our tertiary renal centre to identify patients with inherited renal disease.

From juvenile hyperuricaemia to dysfunctional uromodulin: an ongoing metamorphosis.

Familial juvenile hyperuricaemic nephropathy (FJHN) is a diagnosis that is easily missed. It has taken a long time to clarify the pathophysiology and prevalence of this disease entity which has been shown to be genetically identical to medullary cystic kidney disease (MCKD) type II. The initial suspicion that uric acid was the noxious agent has been replaced by the recognition that a mutant uromodulin (UMOD) is the real culprit-although the exact mechanisms of pathogenicity remain uncertain.

Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis.

Background: Multiple genes underlying focal segmental glomerulosclerosis (FSGS) and/or steroid-resistant nephrotic syndrome (SRNS) have been identified, with the recent inclusion of collagen IV mutations responsible for Alport disease (AD) or thin basement membrane nephropathy (TBMN). We aimed to investigate the distribution of gene mutations in adult patients with primary FSGS/SRNS by targeted next generation sequencing (NGS).

Methods: Eighty-one adults from 76 families were recruited; 24 families had a history of renal disease.

Statins prevent oxidized low-density lipoprotein- and lysophosphatidylcholine-induced proliferation of human endothelial cells.

The proliferation of endothelial cells is induced by oxidized low-density lipoprotein (oxLDL) and its major component, lysophosphatidylcholine (LPC). The aim of this study was to investigate the effect of statins on the proliferation of endothelial cells derived from human umbilical cord veins (HUVEC). Cerivastatin, simvastatin and fluvastatin caused a dose-dependent inhibition of endothelial cell growth (n=12; P<.

Cerivastatin activates endothelial calcium-activated potassium channels and thereby modulates endothelial nitric oxide production and cell proliferation.

Statins are known to counteract the process of arteriosclerosis by exerting direct pleiotropic effects on vascular endothelium. The aim of this study was to investigate a possible effect of cerivastatin on endothelial Ca(2+)-activated K+ channels (BK(Ca)) and to assess their contribution to cerivastatin-mediated changes of endothelial nitric oxide (NO) production and proliferation. Membrane potential was measured using bis-1,3-dibutylbarbituric acid-trimethine oxonol-fluorescence imaging.