Side effects of cyclosporin A treatment in patients with rheumatoid arthritis

Abstract

Cyclosporin A (CyA) and azathioprine (Aza) were compared with respect to renal side effects in an open controlled, randomized study of patients with rheumatoid arthritis. Twelve patients were treated with CyA (mean dose 7.8 +/- 1.2 mg/kg/day) and 12 with azathioprine for 26 weeks. All patients also received prednisolone 5 mg/day. The patients had normal serum creatinine (less than 120 mumoles/liter) and protein-free urine before the trial. CyA increased serum creatinine in nine out of the 11 patients followed for 26 weeks, the mean increase was approximately 50%. Creatinine clearance was reduced by 31%. Mean arterial pressure (MAP) and serum potassium were significantly increased by CyA. Urinary beta 2-microglobulin excretion was significantly increased by CyA, in five of the patients more than ten times. Urinary kallikrein excretion was reduced by more than 50% and urinary albumin excretion was doubled. All these parameters remained normal and unchanged in the azathioprine group. CyA was withdrawn in seven patients after 26 weeks. Urinary beta 2-microglobulin was still increased by 85% nine months after CyA treatment. The other parameters were gradually normalized after three to nine months except for one patient who developed renal failure. Urinary beta 2-microglobulin excretion was a very sensitive parameter for renal tubular damage in this study.

De novo hypertension after liver transplantation.

“…1719 In these reports, patients often have preexisting hypertension or a positive family history of essential hypertension. 17 Accelerated hypertension with serious vascular injury has been described, including microangiopathic hemolysis, encephalopathy, and seizures. 2023 Intracranial hemorrhage has occurred.…”

Long-term Treatment of Minimal-change Nephrotic Syndrome with Cyclosporin: A Control Biopsy Study

“…Thus, in non-fatal autoimmune diseases the risk and benefit of CsA therapy have to be evaluated. Dose-dependent nephrotoxicity is well known in all groups of patients treated with CsA including those with autoimmune diseases [15][16][17]. There was a slight increase of morphological scores in our control biopsies during treatment, but these findings were not so pronounced as to indicate CsA toxicity, and GFR remained unchanged during the observation period of 6-30 (mean 18) months.…”

“…CsA doses were considerably lower than in autoimmune patients in whom CsA toxicity has been reported [16,17].…”

Renal changes associated with cyclosporine in recent type I diabetes mellitus.

“…A CsAassociated decrease in PRA was also observed in renal transplant recipients 29 as well as patients with autoimmune diseases. 6 This contrasts with the direct stimulation of renin release by isolated rat juxtaglomerular cells 30 and the activation of the system usually occurring after acute or short-term administration of CsA in rats. 22 The presently observed fall in renin release associated with CsA, in the absence of an increase in sodium intake (as assessed by 24-hour urinary sodium excretion) may be the consequence of the rise in systemic arterial pressure per se, expansion of the extracellular fluid volume, 31 or a defect in the activation of prorenin.…”

“…1 ' 2 Nevertheless, the sustained benefits of CsA treatment are not clearly established. In most studies performed in recipients of renal 3 or cardiac 4 transplants, as well as in patients with autoimmune diseases such as uveitis, 5 rheumatoid arthritis, 6 psoriasis, 7 or primary biliary cirrhosis, 8 a significant impairment in renal function and an increase in arterial pressure were observed during short-term 5 and long-term 9 CsA therapy. In contrast with these results, no modification of renal function, as assessed by chromium-labeled ethylenediaminotetraacetic acid clearance, was reported in diabetic children receiving CsA.…”