Cutaneous changes of nephrogenic systemic fibrosis: Predictor of early mortality and association with gadolinium exposure

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Abstract
Objective: Nephrogenic systemic fibrosis (NSF) is a rapidly progressive, debilitating condition that causes cutaneous and visceral fibrosis in patients with renal failure. Little is known about its prevalence or etiology. The aim of this study was to establish the prevalence of NSF and associated risk factorsMethods: Two cohorts of patients were recruited from 6 outpatient hemodialysis centers and examined for cutaneous changes of NSF, which were defined using a scoring system based on hyperpigmentation, hardening, and tethering of skin on the extremities. Demographic data were gathered, mortality was followed up prospectively for 24 months, and gadolinium exposure was ascertained for a subgroup of patients in the second cohort.Results: Examination reproducibility was 97% in cohort 1. In cohort 2, 25 (13%) of 186 patients demonstrated cutaneous changes of NSF. Twenty‐four–month mortality following examination was 48% and 20% in patients with and those without cutaneous changes of NSF, respectively (adjusted hazard ratio 2.9, 95% confidence interval [95% CI] 1.4–5.9). Cutaneous changes of NSF were observed in 16 (30%) of 54 patients with prior exposure to gadopentetate dimeglumine contrast during imaging studies. Exposure to gadolinium‐containing contrast was associated with an increased risk of developing cutaneous changes of NSF (odds ratio 14.7, 95% CI 1.9–117.0) compared with nonexposed patients.Conclusion: In patients receiving hemodialysis, NSF is an underrecognized disorder that is associated with increased mortality. Exposure to gadolinium‐containing contrast material appears to be a significant risk factor for the development of NSF.