History

Patients may present with hypertension, its complications (eg, heart failure, stroke), and/or symptoms of uremia. In most patients with nephrosclerosis, hypertension has been present for many years (usually > 10 y), with evidence of periods of accelerated or poorly controlled blood pressure (BP).

Features suggesting the diagnosis of hypertensive nephrosclerosis are as follows:

Black race
Hypertensive retinal changes
Left ventricular hypertrophy
Long-standing or very severe hypertension
Proteinuria less than 0.5 g/d
Hypertension diagnosed prior to the onset of proteinuria
Hypertension preceding kidney dysfunction
No evidence of another kidney disease
Biopsy findings compatible with the diagnosis

Physical

Upon physical examination, evidence of hypertension-related target organ damage includes hypertensive changes in the retinal vessels and signs of left ventricular hypertrophy.

On ophthalmologic examination, hemorrhages or exudates are characteristic of accelerated hypertension, and papilledema is a feature of malignant hypertension.

Causes

No specific causes for hypertensive nephrosclerosis are known.

A gene that predisposes to hypertensive kidney injury has been identified in rats. To date, however, no specific gene associated with hypertensive end-stage renal disease has been identified in humans. It must be noted that the APOL1 gene variant can increase the risk of kidney disease progression in African-American hypertensive patients, but the mechanism by which it causes progression of kidney disease is unknown andwhether the gene variant causes hypertension other than by causing kidney disease first remains unclear.

Correct identification of hypertensive nephrosclerosis susceptibility genes requires accurate hypertensive nephrosclerosis phenotyping. The major impediment to establishing a reliable hypertensive nephrosclerosis phenotype is the absence of strong clinical criteria to distinguish hypertensive nephrosclerosis from other kidney diseases. Genetic approaches to hypertensive nephrosclerosis require careful scrutiny of clinical diagnoses before assigning phenotypes to study subjects.

See also Pathophysiology.

Differential Diagnoses

Carriazo S, Vanessa Perez-Gomez M, Ortiz A. Hypertensive nephropathy: a major roadblock hindering the advance of precision nephrology. Clin Kidney J. 2020 Aug. 13 (4):504-509. [QxMD MEDLINE Link]. [Full Text].
Zuccalà A, Zucchelli P. Is nephroangiosclerosis a hypertension-induced nephropathy?. Contrib Nephrol. 1996. 119:110-4. [QxMD MEDLINE Link].
Rule AD, Amer H, Cornell LD, Taler SJ, Cosio FG, Kremers WK, et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med. 2010 May 4. 152(9):561-7. [QxMD MEDLINE Link]. [Full Text].
Meyrier A. Nephrosclerosis: a term in quest of a disease. Nephron. 2015. 129 (4):276-82. [QxMD MEDLINE Link]. [Full Text].
Tracy RE, Ishii T. What is 'nephrosclerosis'? lessons from the US, Japan, and Mexico. Nephrol Dial Transplant. 2000 Sep. 15(9):1357-66. [QxMD MEDLINE Link].
Wang G, Lai FM, Kwan BC, et al. Podocyte loss in human hypertensive nephrosclerosis. Am J Hypertens. 2009 Mar. 22(3):300-6. [QxMD MEDLINE Link].
Wang G, Kwan BC, Lai FM, et al. Intrarenal expression of miRNAs in patients with hypertensive nephrosclerosis. Am J Hypertens. 2010 Jan. 23(1):78-84. [QxMD MEDLINE Link].
Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet. 2008 Oct. 40(10):1185-92. [QxMD MEDLINE Link]. [Full Text].
Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet. 2008 Oct. 40(10):1185-92. [QxMD MEDLINE Link]. [Full Text].
Freedman BI, Sedor JR. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010 Dec 23. 363(26):2565; author reply 2565-6. [QxMD MEDLINE Link].
Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010 Aug 13. 329(5993):841-5. [QxMD MEDLINE Link]. [Full Text].
Appel LJ, Wright JT Jr, Greene T, Agodoa LY, Astor BC, Bakris GL, et al. Intensive blood-pressure control in hypertensive chronic kidney disease. N Engl J Med. 2010 Sep 2. 363(10):918-29. [QxMD MEDLINE Link]. [Full Text].
Freedman BI, Murea M. Target organ damage in African American hypertension: role of APOL1. Curr Hypertens Rep. 2012 Feb. 14(1):21-8. [QxMD MEDLINE Link]. [Full Text].
Fung MM, Chen Y, Lipkowitz MS, et al. Adrenergic beta-1 receptor genetic variation predicts longitudinal rate of GFR decline in hypertensive nephrosclerosis. Nephrol Dial Transplant. 2009 Dec. 24(12):3677-86. [QxMD MEDLINE Link]. [Full Text].
US Renal Data System. National Institute of Diabetes and Digestive and Kidney Disease. USRDS 2016 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, Md: National Institutes of Health,; 2016. [Full Text].
United States Renal Data System. 2020 Annual Data Report. USRDS. Available at https://adr.usrds.org/2020/end-stage-renal-disease/1-incidence-prevalence-patient-characteristics-and-treatment-modalities. Accessed: June 4, 2021.
Moutzouris DA, Herlitz L, Appel GB, et al. Renal biopsy in the very elderly. Clin J Am Soc Nephrol. 2009 Jun. 4(6):1073-82. [QxMD MEDLINE Link]. [Full Text].
Rimmer JM, Gennari FJ. Atherosclerotic renovascular disease and progressive renal failure. Ann Intern Med. 1993 May 1. 118(9):712-9. [QxMD MEDLINE Link].
Appel RG, Bleyer AJ, Reavis S, et al. Renovascular disease in older patients beginning renal replacement therapy. Kidney Int. 1995 Jul. 48(1):171-6. [QxMD MEDLINE Link].
Hansen KJ, Edwards MS, Craven TE, et al. Prevalence of renovascular disease in the elderly: a population-based study. J Vasc Surg. 2002 Sep. 36(3):443-51. [QxMD MEDLINE Link].
Pillay WR, Kan YM, Crinnion JN, et al. Prospective multicentre study of the natural history of atherosclerotic renal artery stenosis in patients with peripheral vascular disease. Br J Surg. 2002 Jun. 89(6):737-40. [QxMD MEDLINE Link].
Olin JW. Atherosclerotic renal artery disease. Cardiol Clin. 2002 Nov. 20(4):547-62, vi. [QxMD MEDLINE Link].
US Food and Drug Administration. Information for Healthcare Professionals. Gadolinium-Based Contrast Agents for Magnetic Resonance Imaging. http://www.fda.gov/cder/drug/InfoSheets/HCP/gcca_200705.htm.
Dorros G, Jaff M, Mathiak L, et al. Multicenter Palmaz stent renal artery stenosis revascularization registry report: four-year follow-up of 1,058 successful patients. Catheter Cardiovasc Interv. 2002 Feb. 55(2):182-8. [QxMD MEDLINE Link].
Wheatley K, Ives N, Gray R, Kalra PA, Moss JG, Baigent C, et al. Revascularization versus medical therapy for renal-artery stenosis. N Engl J Med. 2009 Nov 12. 361(20):1953-62. [QxMD MEDLINE Link].
Cooper CJ, Murphy TP, Cutlip DE, Jamerson K, Henrich W, Reid DM, et al. Stenting and medical therapy for atherosclerotic renal-artery stenosis. N Engl J Med. 2014 Jan 2. 370 (1):13-22. [QxMD MEDLINE Link]. [Full Text].
Garovic VD, Textor SC. Renovascular hypertension and ischemic nephropathy. Circulation. 2005 Aug 30. 112(9):1362-74. [QxMD MEDLINE Link].
Textor SC. Atherosclerotic renal artery stenosis: overtreated but underrated?. J Am Soc Nephrol. 2008 Apr. 19(4):656-9. [QxMD MEDLINE Link].
Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol. 1998 Jan. 9(1):133-42. [QxMD MEDLINE Link].
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec. 42(6):1206-52. [QxMD MEDLINE Link].
Innes A, Johnston PA, Morgan AG, et al. Clinical features of benign hypertensive nephrosclerosis at time of renal biopsy. Q J Med. 1993 Apr. 86(4):271-5. [QxMD MEDLINE Link].
Harvey JM, Howie AJ, Lee SJ, et al. Renal biopsy findings in hypertensive patients with proteinuria. Lancet. 1992 Dec 12. 340(8833):1435-6. [QxMD MEDLINE Link].
Freedman BI, Iskander SS, Buckalew VM Jr, et al. Renal biopsy findings in presumed hypertensive nephrosclerosis. Am J Nephrol. 1994. 14(2):90-4. [QxMD MEDLINE Link].
Momoki K, Kataoka H, Moriyama T, Mochizuki T, Nitta K. Hyperuricemia as a Predictive Marker for Progression of Nephrosclerosis: Clinical Assessment of Prognostic Factors in Biopsy-Proven Arterial/Arteriolar Nephrosclerosis. J Atheroscler Thromb. 2017 Jun 1. 24 (6):630-642. [QxMD MEDLINE Link]. [Full Text].
Hallan SI, Øvrehus MA, Bjørneklett R, Aasarød KI, Fogo AB, Ix JH. Hypertensive nephrosclerosis: wider kidney biopsy indications may be needed to improve diagnostics. J Intern Med. 2021 Jan. 289 (1):69-83. [QxMD MEDLINE Link].
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 Jan. 51(1):244-52. [QxMD MEDLINE Link].
Beevers DG, Lip GY. Does non-malignant essential hypertension cause renal damage? A clinician's view. J Hum Hypertens. 1996 Oct. 10(10):695-9. [QxMD MEDLINE Link].
Madhavan S, Stockwell D, Cohen H, et al. Renal function during antihypertensive treatment. Lancet. 1995 Mar 25. 345(8952):749-51. [QxMD MEDLINE Link].
Zucchelli P, Zuccala A. Progression of renal failure and hypertensive nephrosclerosis. Kidney Int Suppl. 1998 Dec. 68:S55-9. [QxMD MEDLINE Link].
Rostand SG, Brown G, Kirk KA, et al. Renal insufficiency in treated essential hypertension. N Engl J Med. 1989 Mar 16. 320(11):684-8. [QxMD MEDLINE Link].
Whelton PK, Klag MJ. Hypertension as a risk factor for renal disease. Review of clinical and epidemiological evidence. Hypertension. 1989 May. 13(5 Suppl):I19-27. [QxMD MEDLINE Link].
Toto RD, Mitchell HC, Smith RD, et al. "Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis. Kidney Int. 1995 Sep. 48(3):851-9. [QxMD MEDLINE Link].
Hsu CY. Does non-malignant hypertension cause renal insufficiency? Evidence-based perspective. Curr Opin Nephrol Hypertens. 2002 May. 11(3):267-72. [QxMD MEDLINE Link].
Ruilope LM, Salvetti A, Jamerson K, et al. Renal function and intensive lowering of blood pressure in hypertensive participants of the hypertension optimal treatment (HOT) study. J Am Soc Nephrol. 2001 Feb. 12(2):218-25. [QxMD MEDLINE Link].
Cushman WC, Evans GW, Byington RP. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. April. 17:1575-85. [QxMD MEDLINE Link].
Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008 May 1. 358(18):1887-98. [QxMD MEDLINE Link].
Bhatnagar V, O'Connor DT, Brophy VH, et al. G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions. Am J Hypertens. 2009 Mar. 22(3):332-8. [QxMD MEDLINE Link]. [Full Text].
Ruilope LM, Alcazar JM, Hernandez E, et al. Long-term influences of antihypertensive therapy on microalbuminuria in essential hypertension. Kidney Int Suppl. 1994 Feb. 45:S171-3. [QxMD MEDLINE Link].
Bianchi S, Bigazzi R, Campese VM. Microalbuminuria in essential hypertension: significance, pathophysiology, and therapeutic implications. Am J Kidney Dis. 1999 Dec. 34(6):973-95. [QxMD MEDLINE Link].
Kunz R, Wolbers M, Glass T, et al. The Cooperate trial: a letter of concern. Lancet. 2008 May 10. 371(9624):1575-6. [QxMD MEDLINE Link].
Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008 Aug 16. 372(9638):547-53. [QxMD MEDLINE Link].
Collier DJ, Poulter NR, Dahlöf B, Sever PS, Wedel H, Buch J, et al. Impact of amlodipine-based therapy among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). J Hypertens. 2011 Mar. 29(3):583-91. [QxMD MEDLINE Link].
Jamerson K, Weber MA, Bakris GL, Dahlöf B, Pitt B, Shi V, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008 Dec 4. 359(23):2417-28. [QxMD MEDLINE Link].
Tomson CR, Petersen K, Heagerty AM. Does treated essential hypertension result in renal impairment? A cohort study. J Hum Hypertens. 1991 Jun. 5(3):189-92. [QxMD MEDLINE Link].
Rosansky SJ, Hoover DR, King L, et al. The association of blood pressure levels and change in renal function in hypertensive and nonhypertensive subjects. Arch Intern Med. 1990 Oct. 150(10):2073-6. [QxMD MEDLINE Link].
Klag MJ, Whelton PK, Randall BL, et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996 Jan 4. 334(1):13-8. [QxMD MEDLINE Link].
Brancati FL, Whelton PK, Randall BL, et al. Risk of end-stage renal disease in diabetes mellitus: a prospective cohort study of men screened for MRFIT. Multiple Risk Factor Intervention Trial. JAMA. 1997 Dec 17. 278(23):2069-74. [QxMD MEDLINE Link].
Zucchelli P, Zuccala A. The diagnostic dilemma of hypertensive nephrosclerosis: the nephrologist's view. Am J Kidney Dis. 1993 May. 21(5 Suppl 2):87-91. [QxMD MEDLINE Link].
Schlessinger SD, Tankersley MR, Curtis JJ. Clinical documentation of end-stage renal disease due to hypertension. Am J Kidney Dis. 1994 May. 23(5):655-60. [QxMD MEDLINE Link].
Qualheim RE, Rostand SG, Kirk KA, et al. Changing patterns of end-stage renal disease due to hypertension. Am J Kidney Dis. 1991 Sep. 18(3):336-43. [QxMD MEDLINE Link].
Bleyer AJ, Appel RG. Risk factors associated with hypertensive nephrosclerosis. Nephron. 1999. 82(3):193-8. [QxMD MEDLINE Link].
Meyrier A. Renal vascular lesions in the elderly: nephrosclerosis or atheromatous renal disease?. Nephrol Dial Transplant. 1996. 11 Suppl 9:45-52. [QxMD MEDLINE Link].

Media Gallery

Nephrosclerosis. The glomerular tuft is shrunken, with wrinkling of the capillary walls (asterisk), global glomerular sclerosis (arrow), and complete obliteration of the capillary loops and glomerular ischemia (periodic acid-Schiff stain at 250X magnification).
Nephrosclerosis. Glomerulus with wrinkling of glomerular basement membranes accompanied by reduction of capillary lumen diameter (silver stain at 400X magnification).
Nephrosclerosis. Hyaline arteriosclerosis with hyaline deposits (arrows) (trichrome stain at 250X magnification).
Nephrosclerosis. Fibrointimal proliferation of the arcuate artery (periodic acid-Schiff stain at 150X magnification).

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Author

Fernando C Fervenza, MD, PhD Professor of Medicine, Mayo Graduate School of Medicine; Consulting Staff, Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic

Fernando C Fervenza, MD, PhD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Stephen C Textor, MD Professor Emeritus, Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic College of Medicine and Science

Stephen C Textor, MD is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Ladan Zand, MD Fellow in Nephrology, Department of Internal Medicine, Division of Nephrology, Mayo Medical School

Ladan Zand, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology, Canadian Medical Association, Ontario Medical Association

Disclosure: Nothing to disclose.

David Rosenthal, MD Staff Nephrologist, Department of Nephrology, Kaiser Permanente

David Rosenthal, MD is a member of the following medical societies: American Society of Hypertension

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.

Chief Editor

Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Interim Chair, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Chike Magnus Nzerue, MD, FACP Professor of Medicine, Associate Dean for Clinical Affairs, Meharry Medical College

Chike Magnus Nzerue, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.