Hypertensive nephrosclerosis: update

PURPOSE OF VIEW: A major clinical trial and a meta-analysis completed within the past year addressed the issue of renal disease progression after blood pressure-lowering treatment in patients with hypertension and diminished renal function. Important human and animal studies have addressed mechanistic issues regarding renal disease progression. These advances warrant detailed discussion.

The African American Study of Kidney Disease and Hypertension Study Group trial found that an angiotensin-converting enzyme inhibitor was superior to a calcium antagonist or beta-blocker in ameliorating renal disease progression in African-Americans. An attempt to show an advantage of lowering blood pressure to less than 130/80 compared with 140/90 mmHg showed no additional benefit. However, a meta-analysis of 2000 non-diabetic hypertensive patients suggested that lower blood pressures are beneficial, particularly in individuals with proteinuria. An autopsy study of hypertensive and normotensive individuals dying in motor vehicle accidents supported the theory that hypertensive individuals have fewer, albeit larger, glomeruli than normotensive individuals. An animal study in sheep showed similar findings in sheep born to dams given dexamethasone compared with placebo. Animal studies involving stress, immunity, and cytokines shed further light on the mechanisms. The transfer of Smad7 ameliorated renal damage in rats with ureteral obstruction and fibrosis.

Guidelines suggest prescribing angiotensin-converting enzyme inhibitor or angiotensin 1 receptor blocker therapy to all patients with decreased renal function and hypertension with or without diabetes. The possibility that essential hypertension involves reduced glomerular numbers received support, as well as the theory of prenatal imprinting. Progress is being made regarding basic mechanisms and novel therapies.