Systemic hypertension causes permanent damage to the kidneys in about 6% of patients with elevated blood pressure. As many as 27% of patients with end-stage kidney disease have hypertension as a primary cause. Although there is not a clear correlation between the extent or duration of hypertension and the risk of end-organ damage, hypertensive nephrosclerosis is fivefold more frequent in African Americans than whites. Risk alleles associated with APOL1, a functional gene for apolipoprotein L1 expressed in podocytes, substantially explains the increased burden of ESRD among African Americans. Associated risk factors for progression to end-stage kidney disease include increased age, male gender, race, smoking, hypercholesterolemia, duration of hypertension, low birth weight, and preexisting renal injury. Kidney biopsies in patients with hypertension, microhematuria, and moderate proteinuria demonstrate arteriolosclerosis, chronic nephrosclerosis, and interstitial fibrosis in the absence of immune deposits (see Fig. A3-21). Today, based on a careful history, physical examination, urinalysis, and some serologic testing, the diagnosis of chronic nephrosclerosis is usually inferred without a biopsy. Recent studies suggest, in the absence of diabetes, adults with hypertension and cardiovascular risk factors benefit from achieving a systolic BP <120 mmHg compared to <140 mmHg. In the presence of kidney disease, most patients begin antihypertensive therapy with two drugs, classically a thiazide diuretic and an ACE inhibitor; most will require three drugs. There is strong evidence in African Americans with hypertensive nephrosclerosis that therapy initiated with an ACE inhibitor can slow the rate of decline in renal function independent of effects on systemic blood pressure. Malignant acceleration of hypertension complicates the course of chronic nephrosclerosis, particularly in the setting of scleroderma or cocaine use (see Fig. A3-24). The hemodynamic stress of malignant hypertension leads to fibrinoid necrosis of small blood vessels, thrombotic microangiography, a nephritic urinalysis, and acute renal failure. In the setting of renal failure, chest pain, or papilledema, the condition is treated as a hypertensive emergency.

Aging patients with clinical complications from atherosclerosis sometimes shower cholesterol crystals into the circulation—either spontaneously or, more commonly, following an endovascular procedure with manipulation of the aorta—or with use of systemic anticoagulation. Spontaneous emboli may shower acutely or shower subacutely and somewhat more silently. Irregular emboli trapped in the microcirculation produce ischemic damage that induces an inflammatory reaction. Depending on the location of the atherosclerotic plaques releasing these cholesterol fragments, one may see cerebral transient ischemic attacks; livedo reticularis in the lower extremities; Hollenhorst plaques in the retina with visual field cuts; necrosis of the toes; and acute glomerular capillary injury leading to FSGS sometimes associated with hematuria, mild proteinuria, and loss of renal function, which typically progresses over a few years. Occasional patients have fever, eosinophilia, or eosinophiluria. A skin biopsy of an involved area may be diagnostic. Since tissue fixation dissolves the cholesterol, one typically sees only residual, biconvex clefts in involved vessels (see Fig. A3-22). There is no therapy to reverse embolic occlusions, and steroids do not help. Controlling blood pressure and lipids and cessation of smoking are usually recommended for prevention.