[ADPKD treatment: Tolvaptan and Octreotide].

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent monogenic hereditary disease as well as the most studied inherited kidney disease. Two drugs have recently been authorized that can slow down the progression of the disease: Tolvaptan (vasopressin receptor antagonist) and Octreotide-LAR (long-acting somatostatin analogue); they both are able to reduce the activity of cyclic adenosine monophosphate (cAMP) and therefore have anti-proliferative and anti-secretory effects. This review analyzes the main trials published to date demonstrating the effects on disease progression in patients with ADPKD and illustrates the indications for identifying subjects eligible for therapy.

[Renal manifestation of Autosomal Dominant Polycystic Kidney Disease].

Autosomal dominant polycystic kidney disease affects over 12 million people in the world and is the fourth cause of ESRD. It is the main monogenic kidney disease and causes the progressive formation of cysts leading to renal failure after a few decades. The main manifestations of the disease are observed even at a young age. The early sign of ADPKD is impaired urinary concentrating capacity, due to medullary alteration by cysts, and resistance to vasopressin. These anatomical alterations determine hyperfiltration, altered ammonium transport, nephrolithiasis, and, above all, hypertension even in pediatric age. Activation of the renin-angiotensin-aldosterone system has been shown responsible for the maintenance of high pressure values as well as the growth of cysts and renal fibrosis. Arterial hypertension would be responsible for ventricular hypertrophy. Many recent studies have confirmed the role of pressure control, especially if rigorous, in decreasing the progression of renal disease, and the use of ACE inhibitors seems to have higher efficacy than other antihypertensive drugs. The progression of renal disease is evidenced by the reduction of glomerular filtration which may be minimal in the early years, due to hyperfiltration, but, then, may even exceed 5 ml / min per year, especially when the total kidney volume (TKV) exceeds 1500 ml. In more rapid progression forms, ESRD may appear at about 55 years of age. The main risk factors are age, genetic mutation, familiarity with ESRD, macrohematuria episodes, and early onset hypertension. Some authors have proposed both genetic and clinical scores that can provide guidance on the probability of rapid progression. Other renal manifestations include kidney pain, nephrolithiasis, urinary tract infections and cyst hemorrhage. Renal cell carcinoma is a very rare event.

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.