A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors

Abstract

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

Keywords: clinical epidemiology; diabetes mellitus; end stage kidney disease; hemodialysis; obesity; vascular calcification.

Figure 1.

Multivariable conditional logistic regression model showing ORs of future CUA development by patient characteristics at hemodialysis initiation. Filled diamond denotes point estimate of ORs and error bars represent 95% CI. ACEi/ARB, angiotensin converting enzyme inhibitor/angiotensin receptor blocker; ESA, erythropoiesis-stimulating agents; sPKtV, single pool KtV.

Figure 2.

ORs of future CUA involving lower abdomen and/or upper thigh areas by number of insulin injections per day at hemodialysis initiation. Model 1 is an unadjusted model; model 2 is adjusted for age, race, and sex; model 3 is adjusted for covariates independently associated with increased risk of CUA involving lower abdomen and/or upper thigh areas in patients with diabetes mellitus. *P<0.05 (significant difference from reference values; zero insulin injections per day).