Clinical features, diagnosis, and treatment of hypertensive nephrosclerosis
- Johannes FE Mann, MD
Johannes FE Mann, MD
- Professor of Medicine
- Friedrich Alexander University of Erlangen
- Karl F Hilgers, MD
Karl F Hilgers, MD
- Professor of Internal Medicine and Hypertension Research
- Friedrich-Alexander University, Erlangen-Nuremberg
- Vice Chair, Department of Nephrology and Hypertension
- Erlangen University Hospital
- Section Editors
- George L Bakris, MD
George L Bakris, MD
- Editor-in-Chief — Nephrology
- Section Editor — Hypertension
- Professor of Medicine
- The University of Chicago
- Norman M Kaplan, MD
Norman M Kaplan, MD
- Editor-in-Chief — Nephrology
- Section Editor — Hypertension
- Clinical Professor of Internal Medicine
- University of Texas Southwestern Medical Center
Hypertensive nephrosclerosis is a disorder that is usually associated with chronic hypertension. In addition to the level of blood pressure, it is clear that individual factors are involved. As an example, black patients have an approximate eight-fold elevation in the risk of hypertension-induced end-stage renal disease (ESRD) ; this increase in risk may persist even with "adequate" blood pressure control. Although low birth weight and bias in diagnosis based upon the patient's race may be involved, the recent recognition of an association between two independent sequence variants in the APOL1 gene on chromosome 22 and renal disease in African Americans, including focal segmental glomerular sclerosis and hypertension-related ESRD, provides a much more likely pathophysiologic mechanism  and suggests that hypertensive nephrosclerosis in blacks and whites may be distinct diseases. In addition, the histologic features of hypertensive nephrosclerosis may be observed in patients with normal blood pressure. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis", section on 'FSGS in African Americans'.)
Hypertensive nephrosclerosis is characterized histologically by vascular, glomerular, and tubulointerstitial involvement (picture 1) . The histologic pattern of renal injury in patients with malignant hypertension (ie, malignant nephrosclerosis) is different, and is discussed separately. (See "Evaluation and treatment of hypertensive emergencies in adults" and "Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults", section on 'Clinical manifestations and diagnosis'.)
Vascular disease — The vascular disease consists of intimal thickening and luminal narrowing of the large and small renal arteries and the glomerular arterioles. Two different processes appear to contribute to the development of the vascular lesions:
●A hypertrophic response to chronic hypertension that is manifested by medial hypertrophy and fibroblastic intimal thickening, leading to narrowing of the vascular lumen [4,5]. This response is initially adaptive by minimizing the degree to which the rise in systemic pressure is transmitted to the arterioles and capillaries .
●The deposition of hyaline-like material (plasma protein constituents, such as inactive C3b, part of the third component of complement) into the damaged, more permeable arteriolar wall .
- Toto RB. Hypertensive nephrosclerosis in African Americans. Kidney Int 2003; 64:2331.
- Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010; 329:841.
- Freedman BI, Iskandar SS, Appel RG. The link between hypertension and nephrosclerosis. Am J Kidney Dis 1995; 25:207.
- Harvey JM, Howie AJ, Lee SJ, et al. Renal biopsy findings in hypertensive patients with proteinuria. Lancet 1992; 340:1435.
- Zucchelli P, Zuccalà A. Primary hypertension--how does it cause renal failure? Nephrol Dial Transplant 1994; 9:223.
- Marcantoni C, Ma LJ, Federspiel C, Fogo AB. Hypertensive nephrosclerosis in African Americans versus Caucasians. Kidney Int 2002; 62:172.
- Keller G, Zimmer G, Mall G, et al. Nephron number in patients with primary hypertension. N Engl J Med 2003; 348:101.
- Hughson MD, Puelles VG, Hoy WE, et al. Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race. Nephrol Dial Transplant 2014; 29:1399.
- Ono H, Ono Y, Frohlich ED. L-arginine reverses severe nephrosclerosis in aged spontaneously hypertensive rats. J Hypertens 1999; 17:121.
- Thadhani R, Pascual M, Nickeleit V, et al. Preliminary description of focal segmental glomerulosclerosis in patients with renovascular disease. Lancet 1996; 347:231.
- Schmieder RE, Veelken R, Gatzka CD, et al. Predictors for hypertensive nephropathy: results of a 6-year follow-up study in essential hypertension. J Hypertens 1995; 13:357.
- Palatini P, Mormino P, Dorigatti F, et al. Glomerular hyperfiltration predicts the development of microalbuminuria in stage 1 hypertension: the HARVEST. Kidney Int 2006; 70:578.
- Regina S, Lucas R, Miraglia SM, et al. Intrauterine food restriction as a determinant of nephrosclerosis. Am J Kidney Dis 2001; 37:467.
- Truong LD, Farhood A, Tasby J, Gillum D. Experimental chronic renal ischemia: morphologic and immunologic studies. Kidney Int 1992; 41:1676.
- Mai M, Geiger H, Hilgers KF, et al. Early interstitial changes in hypertension-induced renal injury. Hypertension 1993; 22:754.
- Rule AD, Amer H, Cornell LD, et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med 2010; 152:561.
- Lindeman RD, Tobin JD, Shock NW. Association between blood pressure and the rate of decline in renal function with age. Kidney Int 1984; 26:861.
- Westhoff JH, Hilgers KF, Steinbach MP, et al. Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a. Hypertension 2008; 52:123.
- Fogo A, Breyer JA, Smith MC, et al. Accuracy of the diagnosis of hypertensive nephrosclerosis in African Americans: a report from the African American Study of Kidney Disease (AASK) Trial. AASK Pilot Study Investigators. Kidney Int 1997; 51:244.
- Messerli FH, Frohlich ED, Dreslinski GR, et al. Serum uric acid in essential hypertension: an indicator of renal vascular involvement. Ann Intern Med 1980; 93:817.
- Mujais SK, Emmanouel DS, Kasinath BS, Spargo BH. Marked proteinuria in hypertensive nephrosclerosis. Am J Nephrol 1985; 5:190.
- Madhavan S, Stockwell D, Cohen H, Alderman MH. Renal function during antihypertensive treatment. Lancet 1995; 345:749.
- Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996; 334:13.
- Schlessinger SD, Tankersley MR, Curtis JJ. Clinical documentation of end-stage renal disease due to hypertension. Am J Kidney Dis 1994; 23:655.
- Parsa A, Kao WH, Xie D, et al. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med 2013; 369:2183.
- Beevers DG, Lip GY. Does non-malignant essential hypertension cause renal damage? A clinician's view. J Hum Hypertens 1996; 10:695.
- Zarif L, Covic A, Iyengar S, et al. Inaccuracy of clinical phenotyping parameters for hypertensive nephrosclerosis. Nephrol Dial Transplant 2000; 15:1801.
- Perneger TV, Whelton PK, Klag MJ, Rossiter KA. Diagnosis of hypertensive end-stage renal disease: effect of patient's race. Am J Epidemiol 1995; 141:10.
- Jafar TH, Stark PC, Schmid CH, et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med 2003; 139:244.
- Agodoa LY, Appel L, Bakris GL, et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001; 285:2719.
- Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 2002; 288:2421.
- Lewis J, Greene T, Appel L, et al. A comparison of iothalamate-GFR and serum creatinine-based outcomes: acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension. J Am Soc Nephrol 2004; 15:3175.
- Wright JT Jr, Agodoa L, Contreras G, et al. Successful blood pressure control in the African American Study of Kidney Disease and Hypertension. Arch Intern Med 2002; 162:1636.
- Appel LJ, Wright JT Jr, Greene T, et al. Long-term effects of renin-angiotensin system-blocking therapy and a low blood pressure goal on progression of hypertensive chronic kidney disease in African Americans. Arch Intern Med 2008; 168:832.
- Appel LJ, Wright JT Jr, Greene T, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med 2010; 363:918.
- Hu B, Gadegbeku C, Lipkowitz MS, et al. Kidney function can improve in patients with hypertensive CKD. J Am Soc Nephrol 2012; 23:706.
- Vascular disease
- Interstitial nephritis
- CLINICAL MANIFESTATIONS
- Incidence of renal failure
- Choice of antihypertensive agent
- - AASK trial
- Goal blood pressure
- Progression despite blood pressure control
- Improvement of renal function
- SUMMARY AND RECOMMENDATIONS