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

Marius A Øvrehus; Tine S Oldereid; Aydin Dadfar; Rune Bjørneklett; Knut I Aasarød; Agnes B Fogo; Joachim H Ix; Stein I Hallan

doi:10.1016/j.ekir.2019.12.010

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

Kidney Int Rep. 2019 Dec 27;5(3):339-347. doi: 10.1016/j.ekir.2019.12.010. eCollection 2020 Mar.

Authors

Marius A Øvrehus^{1

2}, Tine S Oldereid¹, Aydin Dadfar¹, Rune Bjørneklett^{3

4}, Knut I Aasarød^{1

2}, Agnes B Fogo^{5

6}, Joachim H Ix^{7

8}, Stein I Hallan^{1

2}

Affiliations

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.

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: arterionephrosclerosis; diagnostic accuracy; hypertensive nephrosclerosis; renal biopsy.