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      Clinical Phenotypes and Long-term Prognosis in White Patients With Biopsy-Verified Hypertensive Nephrosclerosis

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          Hypertensive nephrosclerosis is considered the second most common cause of end-stage renal disease (ESRD), but it is still an insufficiently studied and controversial disease entity. More information on the phenotype and prognosis is needed to improve clinical diagnostics and treatment.


          We included all Norwegian patients with chronic kidney disease (CKD) referred for kidney biopsy between 1988 and 2012 whose clinical presentation was consistent with, but not primarily suspicious for, hypertensive nephrosclerosis (n = 4920); follow-up continued until 2013.


          A total of 918 patients (19%) had biopsy-verified hypertensive nephrosclerosis (i.e., arterionephrosclerosis). Their most common biopsy indications were proteinuria (57%), low estimated glomerular filtration rate (eGFR) (44%), hematuria (34%), or combinations of these indications. Multivariable logistic regression analysis revealed that arterionephrosclerosis was significantly associated with higher age, male sex, not having diabetes, higher blood pressure, lower proteinuria, and not having hematuria ( P < 0.01 for all). Body mass index, cholesterol, high-density lipoprotein cholesterol, and eGFR were not significantly associated with arterionephrosclerosis ( P > 0.05 for all). The most common biopsy-verified diagnoses in patients fulfilling the clinical criteria for hypertensive nephrosclerosis were arterionephrosclerosis (40%), glomerulonephritis (22%), and interstitial nephritis (14%), reflecting that the criteria had low sensitivity (0.17) and high specificity (0.94). ESRD and mortality risks did not differ in patients with arterionephrosclerosis compared to patients with glomerulonephritis, interstitial nephritis, or other relevant diagnoses ( P > 0.1 for both), whereas patients with diabetic kidney disease had a 2-fold higher risk ( P < 0.001 for both).


          Arterionephrosclerosis is a high-risk disease, often with an atypical phenotype with proteinuria and hematuria contributing to low accuracy for current clinical criteria for hypertensive nephrosclerosis.

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          Blood pressure and end-stage renal disease in men.

          End-stage renal disease in the United States creates a large burden for both individuals and society as a whole. Efforts to prevent the condition require an understanding of modifiable risk factors. We assessed the development of end-stage renal disease through 1990 in 332,544 men, 35 to 57 years of age, who were screened between 1973 and 1975 for entry into the Multiple Risk Factor Intervention Trial (MRFIT). We used data from the national registry for treated end-stage renal disease of the Health Care Financing Administration and from records on death from renal disease from the National Death Index and the Social Security Administration. During an average of 16 years of follow-up, 814 subjects either died of end-stage renal disease or were treated for that condition (15.6 cases per 100,000 person-years of observation). A strong, graded relation between both systolic and diastolic blood pressure and end-stage renal disease was identified, independent of associations between the disease and age, race, income, use of medication for diabetes mellitus, history of myocardial infarction, serum cholesterol concentration, and cigarette smoking. As compared with men with an optimal level of blood pressure (systolic pressure or = 210 mm Hg or diastolic pressure > or = 120 mm Hg) was 22.1 (P < 0.001). These relations were not due to end-stage renal disease that occurred soon after screening and, in the 12,866 screened men who entered the MRFIT study, were not changed by taking into account the base-line serum creatinine concentration and urinary protein excretion. The estimated risk of end-stage renal disease associated with elevations of systolic pressure was greater than that linked with elevations of diastolic pressure when both variables were considered together. Elevations of blood pressure are a strong independent risk factor for end-stage renal disease; interventions to prevent the disease need to emphasize the prevention and control of both high-normal and high blood pressure.
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            The association between age and nephrosclerosis on renal biopsy among healthy adults.

            Chronic kidney disease is common with older age and is characterized on renal biopsy by global glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. To see whether the prevalence of these histologic abnormalities in the kidney increases with age in healthy adults and whether histologic findings are explained by age-related differences in kidney function or chronic kidney disease risk factors. Cross-sectional study. Mayo Clinic, Rochester, Minnesota, from 1999 to 2009. 1203 adult living kidney donors. Core-needle biopsy of the renal cortex obtained during surgical implantation of the kidney, and medical record data of kidney function and risk factors obtained before donation. The prevalence of nephrosclerosis (> or =2 chronic histologic abnormalities) was 2.7% (95% CI, 1.1% to 6.7%) for patients aged 18 to 29 years, 16% (CI, 12% to 20%) for patients aged 30 to 39 years, 28% (CI, 24% to 32%) for patients aged 40 to 49 years, 44% (CI, 38% to 50%) for patients aged 50 to 59 years, 58% (CI, 47% to 67%) for patients aged 60 to 69 years, and 73% (CI, 43% to 90%) for patients aged 70 to 77 years. Adjustment for kidney function and risk factor covariates did not explain the age-related increase in the prevalence of nephrosclerosis. Kidney donors are selected for health and lack the spectrum or severity of renal pathologic findings in the general population. Kidney function and chronic kidney disease risk factors do not explain the strong association between age and nephrosclerosis in healthy adults. National Institutes of Health, U.S. Public Health Service.
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              Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease.

              Many cases of end-stage renal disease (ESRD) are ascribed to hypertension. However, because renal disease itself can raise blood pressure, some investigators argue that ESRD seen in patients with hypertension is due to underlying primary renal disease. Previous cohort studies of the relationship between blood pressure and ESRD did not uniformly screen out baseline kidney disease. We conducted a historical cohort study among members of Kaiser Permanente of Northern California, a large integrated health care delivery system. The ESRD cases were ascertained by matching with the US Renal Data System registry. A total of 316 675 adult Kaiser members participated in the Multiphasic Health Checkups from 1964 to 1985. All subjects had estimated glomerular filtration rates of 60 mL /min per 1.73 m(2) or higher and negative dipstick urinalysis results for proteinuria or hematuria. During 8 210 431 person-years of follow-up, 1149 cases of ESRD occurred. Compared with subjects with a blood pressure less than 120/80 mm Hg, the adjusted relative risks for developing ESRD were 1.62 (95% confidence interval [CI], 1.27-2.07) for blood pressures of 120 to 129/80 to 84 mm Hg, 1.98 (95% CI, 1.55-2.52) for blood pressures of 130 to 139/85 to 89 mm Hg, 2.59 (95% CI, 2.07-3.25) for blood pressures of 140 to 159/90 to 99 mm Hg, 3.86 (95% CI, 3.00-4.96) for blood pressures of 160 to 179/100 to 109 mm Hg, 3.88 (95% CI, 2.82-5.34) for blood pressures of 180 to 209/110 to 119 mm Hg, and 4.25 (95% CI, 2.63-6.86) for blood pressures of 210/120 mm Hg or higher. Similar associations between blood pressure level and ESRD risk were seen in all subgroup analyses. Even relatively modest elevation in blood pressure is an independent risk factor for ESRD. The observed relationship does not appear to be due to confounding by clinically evident baseline kidney disease.

                Author and article information

                Kidney Int Rep
                Kidney Int Rep
                Kidney International Reports
                27 December 2019
                March 2020
                27 December 2019
                : 5
                : 3
                : 339-347
                [1 ]Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
                [2 ]Department of Nephrology, St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway
                [3 ]Faculty of Medicine and Dentistry, University of Bergen, Institute of Clinical Medicine, Bergen, Norway
                [4 ]Department of Nephrology, Haukeland University Hospital, Bergen, Norway
                [5 ]Division of Renal Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
                [6 ]Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
                [7 ]Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California, USA
                [8 ]Division of Nephrology-Hypertension, University of California San Diego, San Diego, California, USA
                Author notes
                [] Correspondence: Stein I. Hallan, Norwegian University of Science and Technology, Department of Cancer Research and Molecular Medicine, Prinsesse Kristinas gate 1, Gastro-senteret, 7000 Trondheim, Norway. stein.hallan@

                TO and AD contributed equally to this work.

                © 2019 International Society of Nephrology. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (

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