Systemic sclerosis medications and risk of scleroderma renal crisis

S M Gordon,J B Hughes,D J Little,R S Stitt,S W Olson,R Nee,J D Edison,W T Bailey

doi:10.1186/s12882-019-1467-y

S M Gordon, J B Hughes + Show 6 more

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https://doi.org/10.1186/s12882-019-1467-y

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Journal: BMC Nephrology	Publication Date: Jul 25, 2019
Citations: 15	License type: open-access

Affiliation: Walter Reed National Military Medical Center

Abstract

BackgroundScleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC.MethodsIn this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the use of ACEi, ARB, CCB, NSAID, ERB, fluticasone, and MMF after SSc diagnosis for 31 cases who subsequently developed SRC to 322 SSc without SRC disease controls.ResultsACEi was associated with an increased risk for SRC adjusted for age, race, and prednisone use [odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6–10.2, P = 0.003]. On stratified analyses, ACEi was only associated with SRC in the presence [OR 5.3, 95% CI 1.1–29.2, p = 0.03], and not the absence of proteinuria. In addition, a doubling of ACEi dose [61% vs. 12%, p < 0.001) and achieving maximum ACEi dose [45% vs. 4%, p < 0.001] after SSc diagnosis was associated with future SRC. CCB, ARB, NSAIDs, ERB, fluticasone, and MMF use were not significantly associated with SRC.ConclusionACEi use at SSC diagnosis was associated with an increased risk for SRC. Results suggest that it may be a passive marker of known SRC risk factors, such as proteinuria, or evolving disease. SSC patients that require ACEi should be more closely monitored for SRC.

Highlights

Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality
The SRC cases were more frequently prescribed an ace inhibitor (ACEi) between systemic sclerosis (SSc) diagnosis and SRC than the SSc without SRC cases during the 5 years after SSc diagnosis [77% vs. 33%, Table 2]
ACEi was a significant predictor for SRC in models that accounted for prednisone use [OR-4.1]; thrombocytopenia and anemia [OR-6.6]; cardiac involvement, pulmonary hypertension and elevated erythrocyte sedimentation rate (ESR) [OR-4.9]; chronic kidney disease (CKD) [OR-7.3], and RNAPOL3-Ab and Ro-Ab [OR-7.1] (Table 3)

Summary

Introduction

Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC. Scleroderma Renal Crisis (SRC) develops abruptly in systemic sclerosis (SSc) and is associated with significant morbidity and mortality [1,2,3,4]. Previous case series and small cohort studies found no benefit for initiation of an ACEi at SSc diagnosis to prevent SRC [9,10,11,12].

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