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Observational Study
. 2023 Apr 1;8(4):357-365.
doi: 10.1001/jamacardio.2023.0056.

Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease

Affiliations
Observational Study

Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease

Leo F Buckley et al. JAMA Cardiol. .

Abstract

Importance: Histologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events.

Objective: To assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE).

Design, setting, and participants: This prospective observational cohort study included participants without a history of myocardial infarction, stroke, or heart failure from the Boston Kidney Biopsy Cohort recruited from 2 academic medical centers in Boston, Massachusetts. Data were collected from September 2006 and November 2018, and data were analyzed from March to November 2021.

Exposures: Semiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories.

Main outcomes and measures: The main outcome was the composite of death or incident MACE, which included myocardial infarction, stroke, and heart failure hospitalization. All cardiovascular events were independently adjudicated by 2 investigators. Cox proportional hazards models estimated associations of histopathologic lesions and scores with cardiovascular events adjusted for demographic characteristics, clinical risk factors, estimated glomerular filtration rate (eGFR), and proteinuria.

Results: Of 597 included participants, 308 (51.6%) were women, and the mean (SD) age was 51 (17) years. The mean (SD) eGFR was 59 (37) mL/min per 1.73 m2, and the median (IQR) urine protein to creatinine ratio was 1.54 (0.39-3.95). The most common primary clinicopathologic diagnoses were lupus nephritis, IgA nephropathy, and diabetic nephropathy. Over a median (IQR) of 5.5 (3.3-8.7) years of follow-up, the composite of death or incident MACE occurred in 126 participants (37 per 1000 person-years). Compared with the reference group of individuals with proliferative glomerulonephritis, the risk of death or incident MACE was highest in individuals with nonproliferative glomerulopathy (hazard ratio [HR], 2.61; 95% CI, 1.30-5.22; P = .002), diabetic nephropathy (HR, 3.56; 95% CI, 1.62-7.83; P = .002), and kidney vascular diseases (HR, 2.86; 95% CI, 1.51-5.41; P = .001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98; 95% CI, 1.08-8.30; P = .04) and arteriolar sclerosis (HR, 1.68; 95% CI, 1.03-2.72; P = .04) were associated with an increased risk of death or MACE. Compared with minimal chronicity, greater chronicity was significantly associated with an increased risk of death or MACE (severe: HR, 2.50; 95% CI, 1.06-5.87; P = .04; moderate: HR, 1.66; 95% CI, 0.74-3.75; P = .22; mild: HR, 2.22; 95% CI, 1.01-4.89; P = .047) in fully adjusted models.

Conclusions and relevance: In this study, specific kidney histopathological findings were associated with increased risks of CVD events. These results provide potential insight into mechanisms of the heart-kidney relationship beyond those provided by eGFR and proteinuria.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Buckley has received research grants from the National Heart, Lung, and Blood Institute, American Society of Nephrology/KidneyCure, and Brigham and Women’s Hospital Khoury Innovation Fund as well as personal fees from Kiniksa Pharmaceuticals outside the submitted work. Dr Shah has received research support from Novartis as well as personal fees from Philips Ultrasound and Janssen outside the submitted work. Dr Srivastava has received grants from the National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases as well as personal fees from Horizon Therapeutics, CVS Caremark, AstraZeneca, Bayer, Foundation for the National Institutes of Health, and Tate & Latham outside the submitted work. Dr Waikar has received grants from Johnson & Johnson, Pfizer, and Vertex as well as personal fees from GlaxoSmithKline, Sironax, Bain, Wolters Kluwer, Ikena, Senda Biosciences, BioMarin, Metro Biotechnology, Regeneron, Oxidien, and Kantum outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Association of Kidney Histopathologic Lesion Severity and Death or Major Adverse Cardiovascular Events
This forest plot summarizes adjusted hazard ratios (aHRs) and 95% CIs derived from Cox proportional hazards regression models of the association between semiquantitative scores for 10 kidney histopathologic lesions and the composite of death, incident myocardial infarction, incident stroke, or incident heart failure hospitalization. Hazard ratios are adjusted for age, sex, race, estimated glomerular filtration rate, urine protein to creatinine ratio, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, and body mass index.

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