Specific histopathologic renal lesions may be associated with increased risk of cardiovascular disease

1. Risk of major adverse cardiac events increased amongst patients with a specific glomerular disease, including non-proliferative glomerulopathy, renal vascular disease and diabetic nephropathy.

2. Specific pathologic characteristics, including mesangial expansion and arteriolar sclerosis, were associated with an increased risk of major adverse cardiac events or death.

Level of Evidence Rating: 2 (Good)

Study Rundown: Chronic kidney disease is a known risk factor for major adverse cardiac events, although the relationship between the cardiac-renal system is not fully understood. Furthermore, the specific etiology causing chronic kidney disease may affect the risk and severity of adverse cardiac outcomes. The Boston Kidney Biopsy Cohort study sought to evaluate the relationship between various renal histopathologic diagnoses and subsequent risk of adverse cardiovascular events.

597 patients with chronic kidney disease were included. The most common histopathologic diagnoses were lupus nephritis (14.4%), IgA nephropathy (10.7%), diabetic nephropathy (7.2%), vascular disease (6.7%), membranous nephropathy (6.5%) and secondary focal segmental glomerulosclerosis (5.7%). Over 5.5 years, the incidence of the primary outcome was 37 per 1000 person-years overall. The highest incidence rate was 113.8/1000 person-years amongst patients with diabetic nephropathy and was lowest amongst patients with proliferative glomerulonephritis (16/1000 person-years). Patients with non-proliferative glomerulopathy, diabetic nephropathy and vascular disease had a significantly higher risk of major adverse cardiovascular events or death than patients with proliferative glomerulopathy. Finally, the following histopathologic characteristics were associated with a significantly increased risk of experiencing the primary outcome: mesangial expansion, moderate-severe interstitial fibrosis, tubular atrophy, and global glomerulosclerosis.

This article by Buckley et al. demonstrated a variable risk of adverse cardiovascular events and death in individuals with different etiologies of chronic kidney disease based on the histopathological diagnosis. This research provides important information about the relationship between cardiac and renal physiology. A strength of this study includes the large sample size of histologic data and the prospective nature of data collection. However, one limitation of this work is low external validity, as comparatively fewer patients had diabetic and hypertensive kidney disease than the general population.

Click here to read this study in JAMA Cardiology

Relevant reading: Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options

In-Depth [prospective cohort]: A prospective cohort study was conducted in the United States. Adult patients undergoing clinically-indicated renal biopsies were prospectively evaluated for inclusion; patients who were anemic or pregnant were excluded.  Biopsies were reviewed for histopathologic diagnosis by two study pathologists amongst 72% of participants, while the remainder of diagnoses were abstracted from clinical pathology reports. A standardized scoring system was used to quantify fibrotic, atrophic and sclerotic pathologic changes. The eight clinical diagnostic categories were as follows: proliferative glomerulonephritis, nonproliferative glomerulopathy, paraprotein-associated disease, diabetic nephropathy, vascular disease, tubulointerstitial disease, advanced chronic changes, and others. The study’s primary outcome was the incidence of major adverse cardiovascular events or death; outcome data were abstracted retrospectively.

Of the 597 patients included, 126 (37 per 1000 person-years, 95% confidence interval [CI] 31-44%) developed the primary outcome over a median follow-up time of 5.5 years (3.3-8.7). The highest incidence rate was 113.8/1000 person-years (95% CI 10.3-24.9) amongst patients with diabetic nephropathy and was lowest amongst patients with proliferative glomerulonephritis (16/1000 person-years, 95% CI 73.4-176.4). Patients with non-proliferative glomerulopathy (hazard ratio 2.61, 95% CI 1.30-5.22), diabetic nephropathy (3.56,1.62-7.83) and vascular disease (2.86, 1.51-5.41) had a significantly higher risk of major adverse cardiovascular event or death than patients with proliferative glomerulopathy. Finally, the following histopathologic characteristics were associated with a significantly increased risk of experiencing the primary outcome: mesangial expansion (hazard ratio 2.94, 95% CI .07-8.07) and moderate-severe interstitial fibrosis/tubular atrophy (1.67, 1.02-2.73), and global glomerulosclerosis (1.48, 1.01-2.17).

Image: PD

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