Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension

Hypertension is the largest risk factor for cardiovascular disease, the leading cause of mortality worldwide. As blood pressure regulation is influenced by multiple physiological systems, hypertension cannot be attributed to a single identifiable etiology. Three decades of research into Mendelian forms of hypertension implicated alterations in the renal tubular sodium handling, particularly the distal convoluted tubule (DCT)-native, thiazide-sensitive Na-Cl cotransporter (NCC). Altered functions of the NCC have shown to have profound effects on blood pressure regulation as illustrated by the over activation and inactivation of the NCC in Gordon's and Gitelman syndromes respectively. Substantial progress has uncovered multiple factors that affect the expression and activity of the NCC. In particular, NCC activity is controlled by phosphorylation/dephosphorylation, and NCC expression is facilitated by glycosylation and negatively regulated by ubiquitination. Studies have even found parvalbumin to be an unexpected regulator of the NCC. In recent years, there have been considerable advances in our understanding of NCC control mechanisms, particularly

Etiology of graft dysfunction in renal transplant recipients

Background: Kidney transplantation is the preferred mode of renal replacement therapy for the endstage renal disease, with dramatic improvements in patient and graft survival over the last 50 years. In the modern era of immunosuppression, 1-year patient survival is close to 98%, and 1-year allograft survival rates have improved to 90% for deceased donor kidney transplants and 95 % for living donor kidney transplants with some inter-center variability. The aim of the study: To elucidate the etiology of graft dysfunction among renal transplant recipients. Materials and methods: A retrospective study was conducted among 155 patients who underwent both cadavers and live donor transplant from October 2009 to March 2011 at a tertiary care center in Chennai, South India. All the transplant recipients were regularly followed with serum urea and creatinine, urine routine, calcineurin inhibitor drug levels in the serum, USG Abdomen, urine culture depending on the graft status. Graft dysfunction defined by a rise in the creatinine more than 25% or 0.3 to 0.5 mg per dl from the baseline. Those who developed graft dysfunction were presented for graft biopsy and managed based on the report accordingly. S. Thirumavalavan, Krishna Kumar, S. A. K. Noor Mohamed, R Vijaya Kumar. Etiology of graft dysfunction in renal transplant recipients. IAIM, 2019; 6(3): 313-318. Page 314 Results: Among the 155 transplant recipient patients, 66 (44%) patients developed graft dysfunction and underwent renal biopsy. The graft dysfunction was due to chronic allograft dysfunction (interstitial fibrosis and tubular atrophy) in 24 (15.4%) patients, acute cellular rejection in 13 (8.4%) patients, acute antibody-mediated rejection in 2 (1.3%) patients, acute tubular necrosis in 9 (5.8%) patients, calcineurin toxicity in 6 (3.9%) patients, thrombotic microangiopathy in 6 (3.9%) patients, IgA nephropathy in 3 (1.9%) patients and transplant renal artery stenosis in 1(0.6%) patient. Conclusion: Among the various causes, acute cellular, acute antibody rejection and chronic allograft nephropathy holds nearly 25% of the incidence of graft dysfunction. It indicates appropriate immunological evaluation, appropriate immunosuppression, use of induction agents in high-risk patients and protocol renal biopsy to identify early rejection in high-risk patient and appropriate early intervention is important to improve long-term term graft and patient survival.