Renal arteriolar hyalinosis, not intimal thickening in large arteries, is associated with cardiovascular events in people with biopsy‐proven diabetic nephropathy

• Published in: Diabetic medicine Vol. 37; no. 12; pp. 2143 - 2152
• Main Authors: Morimoto, K., Matsui, M., Samejima, K., Kanki, T., Nishimoto, M., Tanabe, K., Murashima, M., Eriguchi, M., Akai, Y., Iwano, M., Shiiki, H., Yamada, H., Kanauchi, M., Dohi, K., Tsuruya, K., Saito, Y.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2020
• Subjects: Biopsy; Cardiovascular diseases; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetic nephropathy; Diuretics; Lesions; Microvasculature; Nephropathy; Risk factors; Veins & arteries
• DOI: 10.1111/dme.14301
• ISSN: 0742-3071

Aims Diabetic nephropathy, a pathologically diagnosed microvascular complication of diabetes, is a strong risk factor for cardiovascular events, which mainly involve arteries larger than those affected in diabetic nephropathy. However, the association between diabetic nephropathy pathological findings and cardiovascular events has not been well studied. We aimed to investigate whether the pathological findings in diabetic nephropathy are closely associated with cardiovascular event development. Methods This retrospective cohort study analysed 377 people with type 2 diabetes and biopsy‐proven diabetic nephropathy, with a median follow‐up of 5.9 years (interquartile range 2.0 to 13.5). We investigated how cardiovascular events were impacted by two vascular diabetic nephropathy lesions, namely arteriolar hyalinosis and arterial intimal thickening, and by glomerular and interstitial lesions. Results Of the 377 people with diabetic nephropathy, 331 (88%) and 295 (78%) had arteriolar hyalinosis and arterial intimal thickening, respectively. During the entire follow‐up period, those with arteriolar hyalinosis had higher cardiovascular event rates in the crude Kaplan–Meier analysis than those without these lesions (P = 0.005, log‐rank test). When fully adjusted for clinically relevant confounders, arteriolar hyalinosis independently predicted cardiovascular events [hazard ratio (HR) 1.99; 95% confidence interval (CI) 1.12, 3.86], but we did not find any relationship between arterial intimal thickening and cardiovascular events (HR 0.89; 95% CI 0.60, 1.37). Additionally, neither glomerular nor interstitial lesions were independently associated with cardiovascular events in the fully adjusted model. Conclusions Arteriolar hyalinosis, but not intimal thickening of large arteries, was strongly associated with cardiovascular events in people with diabetic nephropathy. What’s new? In diabetic nephropathy, the relationship between two histological vascular lesions in kidney tissues and future cardiovascular events is unclear. We evaluated hyalinosis in small arterioles of < 150 µm diameter, and intimal thickening in double‐layered large arteries of 150–300 µm diameter. Arteriolar hyalinosis was significantly associated with cardiovascular events, whereas intimal thickening in large arteries was not. Systolic blood pressure was strongly related to arteriolar hyalinosis but not to intimal thickening in large arteries, suggesting that hypertensive injury of smaller arterioles in the kidneys was more strongly associated with cardiovascular events and mortality than that of larger arteries in diabetic nephropathy.