{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:43:12Z","timestamp":1793256192981,"version":"4.5.0"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:sec id=\"ab-hoi230002-4\"><jats:title>Importance<\/jats:title><jats:p>Histologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi230002-5\"><jats:title>Objective<\/jats:title><jats:p>To assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE).<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi230002-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi230002-7\"><jats:title>Exposures<\/jats:title><jats:p>Semiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi230002-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi230002-9\"><jats:title>Results<\/jats:title><jats:p>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 m<jats:sup>2<\/jats:sup>, 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; <jats:italic>P<\/jats:italic>\u2009=\u2009.002), diabetic nephropathy (HR, 3.56; 95% CI, 1.62-7.83; <jats:italic>P<\/jats:italic>\u2009=\u2009.002), and kidney vascular diseases (HR, 2.86; 95% CI, 1.51-5.41; <jats:italic>P<\/jats:italic>\u2009=\u2009.001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98; 95% CI, 1.08-8.30; <jats:italic>P<\/jats:italic>\u2009=\u2009.04) and arteriolar sclerosis (HR, 1.68; 95% CI, 1.03-2.72; <jats:italic>P<\/jats:italic>\u2009=\u2009.04) 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; <jats:italic>P<\/jats:italic>\u2009=\u2009.04; moderate: HR, 1.66; 95% CI, 0.74-3.75; <jats:italic>P<\/jats:italic>\u2009=\u2009.22; mild: HR, 2.22; 95% CI, 1.01-4.89; <jats:italic>P<\/jats:italic>\u2009=\u2009.047) in fully adjusted models.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi230002-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2023.0056","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T16:04:58Z","timestamp":1678291498000},"page":"357","source":"Crossref","is-referenced-by-count":20,"title":["Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease"],"prefix":"10.1001","volume":"8","author":[{"given":"Leo F.","family":"Buckley","sequence":"first","affiliation":[{"name":"Department of Pharmacy Services, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insa M.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Medicine, Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Verma","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Medicine, Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ragnar","family":"Palsson","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Massachusetts General Hospital, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Adam","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amil M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anand","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois at Chicago"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushrut S.","family":"Waikar","sequence":"additional","affiliation":[{"name":"Section of Nephrology, Department of Medicine, Boston Medical Center and Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"hoi230002r1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1001\/jamacardio.2016.4652","article-title":"Absolute rates of heart failure, coronary heart disease, and stroke in chronic kidney disease: an analysis of 3 community-based cohort studies.","volume":"2","author":"Bansal","year":"2017","journal-title":"JAMA Cardiol"},{"issue":"10","key":"hoi230002r2","doi-asserted-by":"publisher","first-page":"2512","DOI":"10.1681\/ASN.2014101034","article-title":"Cause-specific deaths in non-dialysis-dependent CKD.","volume":"26","author":"Navaneethan","year":"2015","journal-title":"J Am Soc Nephrol"},{"issue":"10","key":"hoi230002r3","doi-asserted-by":"publisher","first-page":"2504","DOI":"10.1681\/ASN.2014070714","article-title":"Cause of death in patients with reduced kidney function.","volume":"26","author":"Thompson","year":"2015","journal-title":"J Am Soc Nephrol"},{"issue":"1","key":"hoi230002r4","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1053\/j.ajkd.2021.08.024","article-title":"Approach to kidney biopsy: Core Curriculum 2022.","volume":"80","author":"Najafian","year":"2022","journal-title":"Am J Kidney Dis"},{"issue":"8","key":"hoi230002r5","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1681\/ASN.2017121260","article-title":"The prognostic value of histopathologic lesions in native kidney biopsy specimens: results from the Boston Kidney Biopsy Cohort Study.","volume":"29","author":"Srivastava","year":"2018","journal-title":"J Am Soc Nephrol"},{"issue":"3","key":"hoi230002r6","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/ki.1993.292","article-title":"The increased risk of coronary heart disease associated with nephrotic syndrome.","volume":"44","author":"Ordo\u00f1ez","year":"1993","journal-title":"Kidney Int"},{"issue":"4","key":"hoi230002r7","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.kint.2017.01.002","article-title":"A proposal for standardized grading of chronic changes in native kidney biopsy specimens.","volume":"91","author":"Sethi","year":"2017","journal-title":"Kidney Int"},{"issue":"9","key":"hoi230002r8","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate.","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"hoi230002r9","doi-asserted-by":"publisher","first-page":"b2393","DOI":"10.1136\/bmj.b2393","article-title":"Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls.","volume":"338","author":"Sterne","year":"2009","journal-title":"BMJ"},{"issue":"10302","key":"hoi230002r10","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/S0140-6736(21)00519-5","article-title":"Chronic kidney disease.","volume":"398","author":"Kalantar-Zadeh","year":"2021","journal-title":"Lancet"},{"issue":"2","key":"hoi230002r11","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1161\/CIRCULATIONAHA.107.716951","article-title":"High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study.","volume":"117","author":"Mahmoodi","year":"2008","journal-title":"Circulation"},{"issue":"6","key":"hoi230002r12","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1053\/j.ajkd.2022.04.005","article-title":"The risk of cardiovascular events in individuals with primary glomerular diseases.","volume":"80","author":"Canney","year":"2022","journal-title":"Am J Kidney Dis"},{"issue":"9","key":"hoi230002r13","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1681\/ASN.2020111583","article-title":"Primary nephrotic syndrome and risks of ESKD, cardiovascular events, and death: the Kaiser Permanente Nephrotic Syndrome Study.","volume":"32","author":"Go","year":"2021","journal-title":"J Am Soc Nephrol"},{"issue":"7","key":"hoi230002r14","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.2337\/db08-1543","article-title":"The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes.","volume":"58","author":"Groop","year":"2009","journal-title":"Diabetes"},{"issue":"11","key":"hoi230002r15","doi-asserted-by":"publisher","first-page":"2312","DOI":"10.1007\/s00125-010-1860-3","article-title":"In the absence of renal disease, 20 year mortality risk in type 1 diabetes is comparable to that of the general population: a report from the Pittsburgh Epidemiology of Diabetes Complications Study.","volume":"53","author":"Orchard","year":"2010","journal-title":"Diabetologia"},{"issue":"2","key":"hoi230002r16","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1681\/ASN.2012070718","article-title":"Kidney disease and increased mortality risk in type 2 diabetes.","volume":"24","author":"Afkarian","year":"2013","journal-title":"J Am Soc Nephrol"},{"issue":"9","key":"hoi230002r17","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/nrneph.2014.114","article-title":"Inflammatory processes in renal fibrosis.","volume":"10","author":"Meng","year":"2014","journal-title":"Nat Rev Nephrol"},{"issue":"6","key":"hoi230002r18","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1681\/ASN.2008050549","article-title":"The mesangial cell revisited: no cell is an island.","volume":"20","author":"Schl\u00f6ndorff","year":"2009","journal-title":"J Am Soc Nephrol"},{"issue":"1","key":"hoi230002r19","doi-asserted-by":"publisher","first-page":"4703","DOI":"10.1038\/s41598-019-41253-7","article-title":"Amelioration of diabetic nephropathy by SGLT2 inhibitors independent of its glucose-lowering effect: a possible role of SGLT2 in mesangial cells.","volume":"9","author":"Maki","year":"2019","journal-title":"Sci Rep"},{"issue":"2","key":"hoi230002r20","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1159\/000505144","article-title":"Renal anti-fibrotic effect of sodium glucose cotransporter 2 inhibition in angiotensin II-dependent hypertension.","volume":"51","author":"Castoldi","year":"2020","journal-title":"Am J Nephrol"},{"issue":"7","key":"hoi230002r21","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1007\/s00125-019-4859-4","article-title":"Canagliflozin reduces inflammation and fibrosis biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease.","volume":"62","author":"Heerspink","year":"2019","journal-title":"Diabetologia"},{"issue":"1","key":"hoi230002r22","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41581-021-00490-8","article-title":"Mineralocorticoid receptor antagonists in diabetic kidney disease - mechanistic and therapeutic effects.","volume":"18","author":"Barrera-Chimal","year":"2022","journal-title":"Nat Rev Nephrol"},{"key":"hoi230002r23","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1159\/issn.0302-5144","article-title":"Renal vasculature in essential hypertension: a review of some contrarian evidence.","volume":"169","author":"Tracy","year":"2011","journal-title":"Contrib Nephrol"},{"issue":"5","key":"hoi230002r24","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/sj.ki.5000163","article-title":"Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension.","volume":"69","author":"Hill","year":"2006","journal-title":"Kidney Int"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2802372\/jamacardiology_buckley_2023_oi_230002_1681233024.22873.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T15:08:31Z","timestamp":1681312111000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2802372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,1]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2023.0056","relation":{},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2023,4,1]]}}}