The Link Between Hypertension and Nephrosclerosis

Nephrosclerosis is literally defined as hardening of the kidneys (Greek derivation: nephros, kidney; sklerosis, hardening). It is the result of scarring or replacement of the normal renal parenchyma by dense collagenous tissue. In practice, nephrosclerosis refers to diseases with predominant pathologic changes occurring in the preglomerular microvasculature and secondarily involving the glomeruli and interstitium. The relationship between mild to moderate hypertension and either nephrosclerosis or end-stage renal disease (ESRD) remains circumstantial, although these syndromes have long been associated in the medical literature. Nephrologists credit hypertension as the etiology of nephrosclerosis in 25% of patients initiating Medicare-supported renal replacement therapy, even though other processes may cause similar renal pathologic findings. Strikingly, serum creatinine values infrequently increase in patients with long-standing mild to moderate hypertension. Patients classified as having hypertensive ESRD typically present with advanced disease, making the processes that initiated the renal disease difficult to detect. Nephrologists are twice as likely to label an African-American patient as having hypertensive nephrosclerosis, compared with a white patient, when presented with identical clinical histories. This review proposes that many patients classified as having hypertensive nephrosclerosis actually have intrinsic renal parenchymal diseases, renal artery stenosis, unrecognized episodes of accelerated hypertension, or a primary renal microvascular disease. The familial clustering of ESRD attributed to hypertension in African-Americans and the identification of genes associated with renal injury in animals support the concept that inherited factors may predispose to renal failure. African-American families often have members with ESRD from disparate etiologies, including hypertensive ESRD. This suggests that common mechanisms, be they inherited or environmental, underlie the development of progressive renal failure in diverse forms of nephropathy. Identification of the mechanisms producing susceptibility to progressive renal disease would support the concept that mild to moderate elevations in blood pressure per se are uncommon causes of nephrosclerosis.