Ciclosporin A in Lupus Nephritis

Dr. Yunus Erdem, Hacettepe Tip Fakültesi, Nefroloji Bölümü, Hacettepe, TR-06100 Ankara (Turkey) Dear Sir, Renal involvement is the major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) despite im-munosupressive therapy since up to 60-70% of patients with lupus nephritis progress to end-stage renal disease [1]. The most widely used therapeutic regimens include steroid plus azathioprine or cyclophosphamide [2]. The activation of disease under immunosup-pressive therapy poses a great problem. Certain clinical approaches had been proposed to improve the survival. Plasmapheresis seems to be ineffective and did not improve the prognosis of patients under standard im-munosuppressive treatment [3]. Ciclosporin A (CSA; Sandimmun®, Sandoz), by inhibiting interleukin-2 production, suppresses the helper T cells and has been shown to reduce anti-DNA production in an experimental animal model of SLE [4]. Ten patients (3 male, 7 female, mean age 29.5 ± 10.01 years, range 19-50) showing serologic or clinical activation of SLE under the immunosuppressive treatment with prednisolone and azathioprine were enrolled in the study. Patients with uncontrolled hypertension and a serum creatinine level above 2 mg/dl were excluded. All patients fulfilled 4 or more of the American Rheumatism Association revised criteria. In 2 patients, renal biopsy was performed showing diffuse proliferative nephritis. Daily protein excretion was above 0.5 g in all patients. CSA (3-5 mg/kg/day) divided into 2 doses, was added to treatment of patients and dosage was then adjusted according to serum CSA levels. The mean follow-up duration before and after CSA was 49 and 29 months, respectively. Each patient was followed regularly and at each visit blood pressure, serum creatinine, AST, ALT, 24-hour urinary protein excretion along with ANA and anti-DNA were recorded. An informed consent was obtained from all patients. In 5 patients, marked clinical and serologic improvements were seen and continued to the end of the study. One patient died because of CNS involvement, and another was initiated to a chronic hemodialysis program. In the remaining 3 patients clinical or serologic activation persisted. Hypertension was observed in 3 of 10 patients and controlled with antihypertensive therapy. Mean anti-DNA titers of patients were significantly decreased at the end of study (from 87.2 ± 9.8 to 49.6 ± 16.7 IU/ml, p < 0.05). There were no significant changes in proteinuria and serum creatinine levels.