allopurinol and Glomerulosclerosis--Focal-Segmental

The relationship between hypertension and chronic kidney disease (CKD) has long been the subject of controversy. The pathogenetic mechanisms of nephropathy in non-diabetic individuals with hypertension, as well as optimal hypertension treatment targets in populations with nephropathy remain important clinical concerns. This manuscript reviews breakthroughs in molecular genetics that have clarified the complex relationship between hypertension and kidney disease, answering the question of which factor comes first. An overview of the potential roles that hyperuricemia plays in the pathogenesis of hypertension and CKD and current blood pressure treatment guidelines in populations with CKD are discussed. The ongoing National Institutes of Health-sponsored Systolic Blood Pressure Intervention Trial (SPRINT) is underway to help answer these important questions. Enrollment of 9250 hypertensive SPRINT participants will be completed in 2013; important results on ideal blood pressure control targets for reducing nephropathy progression, cardiovascular disease end-points, and preserving cognitive function are expected. As such, many of the controversial aspects of hypertension management will likely be clarified in the near future.

Topics: Allopurinol; Animals; Antihypertensive Agents; Apolipoprotein L1; Apolipoproteins; Black People; Causality; Chronic Disease; Diabetic Angiopathies; Diabetic Nephropathies; Disease Management; Disease Models, Animal; Genetic Predisposition to Disease; Glomerulosclerosis, Focal Segmental; Goals; Humans; Hypertension; Hypertension, Renal; Hyperuricemia; Kidney Diseases; Lipoproteins, HDL; Multicenter Studies as Topic; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Rats

The role of superoxide in adriamycin-induced nephropathy (single dose; i.v. 3 mg/kg) has been studied by blocking superoxide synthesis through the administration of allopurinol (500 mg/L in drinking water). In Experiment I (EI), allopurinol administration was started 3 days prior to nephropathy induction and continued until day 14. In Experiment II (EII) allopurinol administration was started 2 weeks after nephropathy induction and was maintained until the end of the experiment (26 weeks). Affected glomeruli frequency and tubulointerstitial lesion index (TILI) were determined at Weeks 2 and 4 (EI) and Week 26 (EII). In EI, the 24 h mean proteinuria in the nephrotic control group (NCG-I) differed from that of the treated nephrotic group (TNG-I) at Week 1 (TNG = 33.3 +/- 6.39 mg/24 h; NCG = 59.8 +/- 6.3 mg/24 h; p < 0.05) and 2 (NCG-I = 80.0 +/- 17.5 mg/24 h; TNG-I = 49.1 +/- 8.4 mg/24 h; p < 0.05). No glomerular alterations were observed and TILI medians were not different in both nephrotic groups at week 2 (NCG-I = 1+: TNG = 1+) and 4 (NCG = 4+; TNG = 4+). In EII, NCG-II and TNG-II presented different 24 h proteinuria values only at Week 6, (136.91 +/- 22.23 mg/24 h and 72.66 +/- 10.72 mg/24 h, respectively; p < 0.05). Between nephrotic groups, there was no statistical difference in the median of affected glomeruli (CNG-II = 56%; TNG-II = 48%) and TILI (NCG-II = 8+; TNG-II = 9+). Thus, allopurinol was associated with a transient reduction in proteinuria and it did not alter the progression of the nephropathy.

Topics: Allopurinol; Animals; Antineoplastic Agents; Biopsy; Disease Models, Animal; Disease Progression; Doxorubicin; Follow-Up Studies; Free Radical Scavengers; Glomerulosclerosis, Focal Segmental; Kidney Glomerulus; Kidney Tubules; Male; Nephritis, Interstitial; Proteinuria; Random Allocation; Rats; Rats, Wistar; Ultrasonography