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.

Superior vena cava syndrome complicating calcific uremic arteriolopathy in an ESRD male patient on maintenance hemodialysis following failed kidney transplantation

“…In a recent multivariable conditional logistic regression analysis, diabetes mellitus, higher body mass index (BMI), higher levels of serum calcium, phosphorous, and parathyroid hormone (PTH), and nutritional vitamin D, cinacalcet, and also warfarin treatments were associated with increased odds of subsequent calciphylaxis development (11). Clearly our patient had very elevated levels of phosphorus, PTH and Ca×P product.…”

Calciphylaxis in peritoneal dialysis patients: a single center cohort study

“…24,25 It is likely that in our study, a statistically significant difference between PD patients with and without calciphylaxis was not noted due to limited sample size and one-time assessment (at PD initiation) of certain covariates such as medications. This is particularly important as the pathogenesis of calciphylaxis is likely multifactorial, as supported by larger studies 3,6 in the HD population that noted multiple calciphylaxis risk factors, including diabetes mellitus and advanced age. Small sample size also limited us from conducting multivariable adjusted analyses to examine whether associations observed in univariate analyses …”

“…20 Furthermore, prevalence of well-described calciphylaxis risk factors such as warfarin therapy and obesity was higher in PD patients who developed calciphylaxis compared to previously published prevalence of these risk factors in HD patients who developed calciphylaxis. 3,[5][6][7]18 Thus, it is possible that it is these risk factors and not dialysis modality that dictates calciphylaxis risk. Previous studies have shown that PD is associated with more abnormalities in phosphorous and albumin than HD, especially once residual renal function has deteriorated.…”

“…These data suggest that the incidence of calciphylaxis in HD patients is approximately 3.5 cases per 1,000 patient-years and it may be on the rise. 3,4 Diabetes mellitus, obesity, abnormalities in mineral bone parameters, and warfarin therapy have been described as calciphylaxis risk factors for HD patients. 3,[5][6][7] Cinacalcet has been reported to reduce the risk…”

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis

“…Moreover, CPX is associated with significant mortality. In a recent study of a large cohort of patients from the USA, mortality rates were 27 and 45% at 6 and 12 months, respectively, after diagnosis, and median time to death was 151 days [8]. …”