Nephrosclerosis Follow-up

  • Author: Fernando C Fervenza, MD, PhD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Feb 25, 2010
 

Deterrence/Prevention

  • Hypertension complicating primary renal disease
    • Systemic hypertension clearly induces or accelerates the progression of renal disease in experimental models. In these models, BP control reduces proteinuria and prevents deterioration of renal function.
    • Similarly, in a variety of primary human renal diseases, BP strongly predicts a faster decline in the GFR.
    • As demonstrated by the MDRD study, even small differences in mean arterial pressure between the usual BP control group and the low-BP group had significant effects in reducing renal disease progression.
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Complications

  • Traditionally, nephrosclerosis was considered the consequence of long-term hypertension. This premise is based on observations of rapidly progressive renal failure developing in some patients with malignant hypertension. Such individuals demonstrate arterial and necrotizing lesions in the kidneys, which may be reversed with effective BP control. However, less severe hypertension, per se, is suggested to cause renal failure only rarely, and progressive renal impairment is usually secondary to undiagnosed primary renal disease.
    • Madhavan et al (1995) followed the cases of 2125 men with mild-to-moderate hypertension for 5 years and found no change in serum creatinine values.[22] Similarly, Tomson et al (1991) followed the cases of 176 patients with essential hypertension for more than 14 years and found no change in serum creatinine values, with none of the patients developing renal failure.[33]
    • In the Baltimore Longitudinal Study on Aging, the cases of 446 patients who are predominantly white and of middle or upper socioeconomic status were followed over a 13-year period. In this study, patients with hypertension had a decline in their GFRs at a faster rate than normotensive subjects (0.92 mL/min/y vs 0.75 mL/min/y). Although this study showed that patients with hypertension lost renal function at a faster rate with aging than normotensive subjects, the rate of decline in renal function was small and unlikely to result in ESRD. More importantly, this study failed to determine whether the decline in renal function was secondary to essential hypertension or was the result of undiagnosed primary renal disease.
    • In a review of the British Health System data on hypertension and nephrosclerosis, Beevers and Lip (1996) noted that baseline proteinuria or renal impairment was evident at presentation in all patients who later developed significant renal failure.[21] More importantly, these authors did not find any reported cases of patients who went on to develop renal failure who had benign essential hypertension with reference range serum creatinine levels and no evidence of proteinuria.
    • On the other hand, Rosansky et al (1990) reported on the cases of 56 patients with essential hypertension, all of whom had creatinine levels within the reference range and no proteinuria at the beginning of the observation, and compared them with 59 normotensive control patients.[34] At an average of 9.8 years, the rate of decline in renal function was significantly higher in the patients with hypertension than in the control patients; however, the authors stated that the diagnostic criteria for hypertensive renal disease often were not fulfilled.
    • Finally, Klag et al (1996), in the largest prospective trial to date, primarily intended to examine the cardiovascular risk associated with hypertension.[35] The MRFIT analyzed the cases of 332,544 men (90.4% white) whose cases were followed for an average of 16 years. This study showed a strong graded relationship between BP (the relative risk of developing ESRD varied from 2.8-12.4 as diastolic BP increased from 90-120 mm Hg) and the subsequent development of ESRD; however, most patients with progressive renal failure had a diagnosis other than essential hypertension. Furthermore, this tendency to develop an elevation in the serum creatinine level appears to have been largely a feature of the black population because no changes in the reciprocal creatinine slope were observed in white patients; however, a significant decline in renal function was observed in the black patients.
    • In 1997, the same group of authors (Brancati et al) reevaluated data from the MRFIT, this time aiming to determine the relative risk of ESRD related to diabetes.[36] Their conclusion was that diabetes mellitus is a strong independent risk factor for ESRD, even for ESRD ascribed to causes other than diabetes (by year 15 of follow-up, the cumulative ESRD incidence rate increased to 2.97% in diabetic men). However, if baseline diabetes mellitus is removed, the risk attributable to hypertension to cause ESRD is almost negligible (0.19%; this number may be actually lower because 8.4% of cases of ESRD in men without diabetes at baseline were classified as diabetic ESRD). Noted that a greater proportion of diabetic men, compared with nondiabetic men, were black (12.6% vs 6%). Diabetic men were also approximately 3 years older on average and had higher blood systolic and diastolic pressures than their nondiabetic counterparts.
    • The significant decline in renal function observed in black patients confirmed similar observations by the HDFP. In this study, of the 8000 patients with normal renal function at outset, only 110 had a significant increase in serum creatinine values over time; the increase was largely confined to black people. In further agreement with Beevers and Lip's observations outlined above, the patients with the highest serum creatinine levels at presentation had the largest reduction in renal function, implying that subclinical renal damage was present from the beginning. Neither the HDFP nor the MRFIT provide information regarding whether participants had proteinuria at presentation. In addition, these studies do not rule out the possibility that patients who progressed had some form of chronic glomerulonephritis because participants did not undergo renal biopsies.
    • Zucchelli and Zuccalà (1993) reviewed the cases of 136 patients who were originally diagnosed with benign nephrosclerosis but actually represented a heterogeneous group.[37] In these patients, a thorough diagnostic workup, including renal biopsy, reconfirmed nephrosclerosis as the correct diagnosis in many of the patients (44%), although 56% of the patients were reclassified as having cholesterol microembolism (29%) or renovascular hypertension (26.5%).
    • Schlessinger et al (1994) made a similar observation when they reviewed the cases of 233 patients undergoing evaluation as candidates for renal transplantation.[38] Schlessinger et al found that their referring physicians diagnosed 43 of these patients with ESRD secondary to hypertensive nephrosclerosis. After extensive review of the patients' medical histories, laboratory evaluations, and available renal biopsy results, the authors concluded that none of the 43 patients met the clinical criteria for hypertensive nephrosclerosis.
    • A further complication is that many patients already have advanced renal failure at presentation. Qualheim et al (1991) reported that at the time patients with presumed hypertensive nephrosclerosis first presented to a nephrologist, their serum creatinine values were close to 7 mg/dL in white patients and 9.4 mg/dL in black patients.[39] Diagnosing hypertensive nephrosclerosis in these patients can be difficult or impossible because of the inability to identify the initial process. However, in black patients, a closer correlation between clinical and histological diagnoses of hypertensive nephrosclerosis has been reported.
    • In the AASK, 88 black patients who did not have diabetes or hypertension but who had mild-to-moderate renal insufficiency and absent marked proteinuria were asked to undergo renal biopsy. Forty-six patients agreed, and 39 biopsies were performed. The mean arterial pressure of these patients was 109 mm Hg ± 15 mm Hg, and their mean GFR was 52 mL/min ± 13 mL/min. In nearly 85% of the cases, renal biopsy results showed arteriosclerosis and/or arteriolosclerosis, interstitial fibrosis, thickening of the basement membrane, and global glomerulosclerosis consistent with the clinical diagnosis of hypertensive nephrosclerosis. The conclusion of this study was that in black people who do not have diabetes or hypertension but who have decreased renal function and mild proteinuria, renal biopsy findings are likely to be consistent with the clinical diagnosis of hypertensive nephrosclerosis.
  • Considering that approximately 60 million individuals with hypertension live in the United States but only 19,000 (1 in 2200) develop ESRD, factors other than hypertension have been postulated to participate in the progression of renal failure. Hyperlipidemia, insulin resistance, hyperuricemia, immune-mediated factors, and other unrecognized mechanisms may play a role. In this context, hypertensive nephrosclerosis is possibly a disease primarily of the small renal vessels, with glomerular changes being secondary to the vascular process. Autopsy studies of patients with mild, moderate, and severe vascular disease found an independent correlation between glomerulosclerosis and atherosclerosis. Bleyer and Appel (1999) found that 52% of white patients diagnosed with hypertensive nephrosclerosis had at least one form of atherosclerosis at baseline.[40]
  • Clinical and experimental evidence indicates that histologic lesions indistinguishable from hypertensive nephrosclerosis occur in conditions associated with BP values within the reference range, such as in patients with Bartter syndrome. Nephrosclerosis is also observed spontaneously with aging, especially in patients older than 60 years. Diabetes mellitus markedly increases the presence and severity of nephrosclerosis in all age groups; as such, nephrosclerosis appears to be the common final pathway of several processes that cause injury to small intrarenal vessels.
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Prognosis

  • With regard to the target BP, the Working Group Report on Hypertension and Diabetes recommended a BP goal of less than 130/80 mm Hg to preserve renal function and to reduce cardiovascular events in patients with hypertension and diabetes. Lower BPs are recommended for patients with proteinuria greater than 1 g/d and renal insufficiency, regardless of etiology. The optimal BP goal to slow the progression of renal failure in patients with hypertensive nephrosclerosis currently is unknown.
  • Hypertensive nephrosclerosis remains a poorly defined entity. Researchers continue to search for a clear definition, a pathophysiologic mechanism, and optimal treatment for patients with this condition. As suggested by Meyrier (1996), hypertensive nephrosclerosis may conceivably be a primary microvascular nephropathy.[41]
  • Uncontrolled hypertension can accelerate the decline of renal function in patients with primary renal disease; however, whether mild-to-moderate essential hypertension can cause ESRD in white people is uncertain. The available data do not support the hypothesis that high BP is the only factor determining ESRD in these patients.
  • Medical treatment is indicated in patients younger than 80 years with BP higher than 140/90 mm Hg. In these patients, antihypertensive treatment has proven to reduce the risk of stroke and cardiovascular mortality. Data from the Hypertension in the Very Elderly (HYVET) trial showed decreased strokes, heart failure, and all-cause mortality from the treatment of patients older than 80 years with BP less than 160 mm Hg. However, the effect of treatment on renal function was not assessed, and patients with a creatinine value of greater than 1.7 mg/dL were excluded from the trial.
  • Evidence for the beneficial effect of hypertension treatment on patients with hypertensive nephrosclerosis is lacking, and many questions regarding the ability of these drugs to protect renal function in the long term remain unanswered.
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Patient Education

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Contributor Information and Disclosures
Author

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

Disclosure: Nothing to disclose.

Coauthor(s)

Stephen C Textor, MD  Professor of Medicine, Mayo Clinical College of Medicine; Consultant, Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic; Participating Author, Joint National Commission Guidelines VI

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, and International Society of Nephrology

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

Chike Magnus Nzerue, MD  Associate Dean for Clinical Affairs, Meharry Medical College

Chike Magnus Nzerue, MD 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, and National Kidney Foundation

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Eleanor Lederer, MD  Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, 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, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN 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, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

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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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