Progressive Renal Disease: A Disorder of Adaptation

Abstract

Chronic renal insufficiency generally progresses to end-stage renal failure, suggesting that, after a certain point, reduction in functioning nephron number leads to failure of the remaining units. A well-recognized risk factor contributing to acceleration of renal disease is systemic hypertension, which may be both cause and consequence of chronic renal disease. However, clinical studies have not uniformly demonstrated slowing of progressive renal disease with antihypertensive therapy. Recent studies in animal models of hypertensive renal disease have provided insight into this apparent paradox by clarifying the complex and variable relationship between systemic and glomerular hypertension. Recognition that systemic and glomerular hypertension do not necessarily coexist, and that therapeutic interventions may affect systemic and glomerular capillary pressures independently, helps to explain the renal responses to systemic hypertension and to antihypertensive therapy in a number of different circumstances. In contrast to the classic notion that ischemia mediates hypertensive glomerular injury, recent studies suggest that it is in fact glomerular capillary hyperperfusion and hypertension which initiate glomerular structural injury