Anti-PKD2 monoclonal antibody, clone 5D9

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited disorders. It is the fourth leading cause of renal replacement and renal failure worldwide. Mutations in PKD1 or PKD2 cause ADPKD. Patients with ADPKD show progressive growth of renal cysts filled with cystic fluid, leading to end-stage renal disease (ESRD) and renal failure by their sixth decade of life. Currently, there are no curative treatments for ADPKD. Therefore, patients require dialysis or kidney transplantation. To date, researchers have elucidated many of the mechanisms that cause ADPKD and developed many methods to diagnose the disease. ADPKD is related to growth factors, signaling pathways, cell proliferation, apoptosis, inflammation, the immune system, structural abnormalities, epigenetic mechanisms, microRNAs, and so on. Various therapies have been reported to slow the progression of ADPKD and alleviate its symptoms.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD), the commonest inherited kidney disease, is generally caused by heterozygous mutations in PKD1, PKD2, or GANAB (PKD3).MethodsWe performed mutational analyses of PKD genes to identify causative mutations. A set of 90 unrelated families with ADPKD were subjected to mutational analyses of PKD genes. Genes were analysed using long-range PCR (LR-PCR), direct PCR sequencing, followed by multiplex ligation-dependent probe amplification (MLPA) or screening of GANAB for some patients. Semen quality was assessed for 46 male patients, and the correlation between mutations and male infertility was analysed.ResultsA total of 76 mutations, including 38 novel mutations, were identified in 77families, comprising 72 mutations in PKD1 and 4 in PKD2, with a positive detection rate of 85.6%. No pathogenic mutations of GANAB were detected. Thirty-seven patients had low semen quality and were likely to be infertile. No association was detected between PKD1 mutation type and semen quality. However, male patients carrying a pathogenic mutation in the Ig-like repeat domain of PKD1 had a high risk of infertility.ConclusionOur study identified a group of novel mutations in PKD genes, which enrich the PKD mutation spectrum and might help clinicians to make precise diagnoses, thereby allowing better family planning and genetic counselling. Men with ADPKD accompanied by infertility should consider intracytoplasmic sperm injection combined with preimplantation genetic diagnosis to achieve paternity and obtain healthy progeny.