Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
The Use of Calcium-Channel Blockers May Prevent the Development of Scleroderma Renal Crisis.
Montanelli, Gaia, Beretta, Lorenzo, Santaniello, Alessandro, Scorza, Raffaella
Scleroderma renal crisis (SRC) is one of the most severe complications of systemic sclerosis (SSc), with high mortality and morbidity rates. Past studies were conducted to determine which factors may precipitate or protect from the development of SRC. The use of corticosteroids, the diffuse cutaneous subset (dcSSc), the presence of friction tendon rubs, the presence of certain autoantibodies and an aggravating skin score were shown to be risk-factors for SRC. Apart from corticosteroids, which were associated with the onset of SRC, the role of other therapies, including vasodilators or Iloprost, in the progression of or in the protection from SRC is not clear.
A retrospective study was conducted in all the patients referred to our outpatient clinic between 1990 and 2010, with a disease duration < 5 years at referral. The development of SRC, defined as either hypertensive renal crisis or normotensive renal crisis, up to 5 years (20 trimesters) from referral was sought. Medical records were reviewed to determine whether the patients had been treated with calcium-channel blockers (CCB), Iloprost or steroids. The dose of steroids (expressed as the medium dose Prednisione/day/trimester) was also reviewed.
Univariate Cox regression analysis with or without time-dependent covariates was used to assess the individual risk for SRC for baseline demographic and clinical characteristics and for therapies. Meaningful variables were inserted in a multivariate Cox regression model.
Two-hundred-ninety-one patients (females=89.7%; dcSSc=25.8%) with a disease duration of 13 months at referral (interquartile range [IQR]: 4 29), were considered. Fifteen SRC (5.2%; 12 hypertensive, 3 normotensive) were observed, the median time-to-onset of SRC was 6 months (IQR: 3 12 months). Overall, 165 patients were treated with steroids with a median maximum dose of 25 mg/day/trimester (IQR: 14 50 mg); 260 subjects (89.3%) received CCB and 100 (34.4%) Iloprost, prior or concurrently to corticosteroids. On univariate analysis, gender, disease subset and the use of steroids were associated with a positive risk of SRC, whilst FVC, disease duration prior to referral and the use of CCB were negatively associated with SRC. On multivariate analysis the use of CCB was negatively associated with SRC (HR=0.118, CI95=0.0380.362, p<0.0001), whilst steroids (HR=1.014, CI95=1.0021.026, p<0.035) and dcSSc (HR=6.75, CI95=1.98822.195, p<0.003) increased the risk for SRC.
SRC is a relatively rare event in Italian patients. We confirmed that the use of steroids increases the risk for SRC, albeit this risk is relatively low (1.4% for every milligram of Prednisone used in the trimester prior to SRC). Conversely, the use of CCB is highly protective against the development of SRC. In our centre, the vast majority of patients is prescribed first-second generation dihydropyridine agents (Nifedipine or Nicardipine), that acting on L-type calcium channels may favour afferent renal arterioles vasodilatation, and counteract angiotensin II vasoconstrictive effects thus increasing or stabilising the glomerular filtration rate and glomerular filtration fraction.
To cite this abstract, please use the following information:
Montanelli, Gaia, Beretta, Lorenzo, Santaniello, Alessandro, Scorza, Raffaella; The Use of Calcium-Channel Blockers May Prevent the Development of Scleroderma Renal Crisis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1235