Activator of G protein signaling 3 promotes epithelial cell proliferation in PKD.

The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and autosomal dominant PKD. Increased AGS3 expression correlated with kidney size, which is an index of severity of cystic kidney disease. AGS3 expression localized exclusively to distal tubular segments in both normal and cystic kidneys. Short hairpin RNA-induced knockdown of endogenous AGS3 protein significantly reduced proliferation of cystic renal epithelial cells by 26 +/- 2% (P < 0.001) compared with vehicle-treated and control short hairpin RNA-expressing epithelial cells. In summary, this study suggests a relationship between aberrantly increased AGS3 expression in renal tubular epithelia affected by PKD and epithelial cell proliferation. AGS3 may play a receptor-independent role to regulate Galpha subunit function and control epithelial cell function in PKD.

Current State and Future of Private Practice Nephrology in the United States.

Chronic kidney disease remains highly prevalent and exerts a heavy economic burden. The practice of nephrology has come a long way in managing this disease, though there remains room for improvement. The private domain, where more than half of the adult nephrology workforce operates, faces serious challenges. Interest has decreased in the field, leading to diminished recruitment. There has been a reduction in both reimbursement rates and revenues. We discuss the current state of private practice nephrology and strategies to reinvigorate our discipline. There needs to be a focus on preparing fellows during training not only for academic careers, but also for effective functioning in the environment of private practice and development of pathways for growth. We believe that private practice nephrology must expand its frontiers to be fulfilling professionally, challenging academically, and successful financially. The United States government has recently announced the Advancing American Kidney Health Executive Order which seeks to prioritize optimal treatments for patients with kidney disease. We are optimistic that there is a renaissance afoot in nephrology and that our field is in the process of rediscovering itself, with its best days yet to come.