Renal function after 10 years' treatment with cyclosporin for psoriasis

Abstract

Renal function was assessed by measuring serum creatinine and glomerular filtration rate (GFR) in two groups of patients with chronic plaque psoriasis who had been treated with cyclosporin A (CyA), average dose 2.8 mg/kg per day (range 1-5 mg/kg per day). Group I was our original cohort of nine patients, seven of whom had received CyA for an average period of 10 years (range 9.5-11 years). These seven patients showed a persistent increase in serum creatinine > 30% from baseline measurement and four of the seven had persistent increases > 50%. The GFR, which was first measured after 2.5 years of treatment, showed at 10 years a decrease of > 30% in two patients and of > 50% in one patient. Three of the seven showed stable renal function while two had repeat renal biopsy because of deteriorating renal function and histology showed further evidence of CyA nephrotoxicity compared with that after 5 years' treatment. Two of the nine patients in group I had discontinued CyA 5 years previously after 5 years of treatment because of CyA nephrotoxicity on renal biopsy and impaired renal function. This impairment of renal function showed improvement during the 5 years of follow-up, implying reversibility of CyA nephrotoxicity. The second group of 20 patients had received CyA for an average duration of 6 years (range 5-8 years). Nine of the 20 patients showed persistent increases in serum creatinine of > 30% from baseline and five showed persistent increases of > 50%. The GFR showed a persistent decrease of > 30% in seven patients and of > 50% in two patients. This study has shown that nephrotoxicity is associated with long-term treatment with CyA. However, there is patient variation as to when nephrotoxicity commences and its speed of progression. On discontinuing CyA the impairment of renal function improves with time. Providing renal function is monitored with GFR and renal biopsy in addition to serum creatinine then long-term (5-10 years) CyA treatment can be justified in severe psoriasis not responsive to other treatments.

Cyclosporin A Toxicity of the Renal Allograft – a Late Complication and Potentially Reversible

“…uveitis, psoriasis, rheumatoid arthritis, had comparable numbers of patients with cyclosporine A nephrotoxicity, e.g. 9 out of 20 patients [27]and 4 out of 15 patients treated with CsA for psoriasis [28]. …”

Cyclosporine A and its non-immunosuppressive derivative NIM811 induce apoptosis of malignant melanoma cells inin vitro andin vivo studies

“…Cyclosporine A and not related immunosuppressant tacrolimus (FK506) are effective against a broad range of inflammatory skin diseases, including widespread conditions such as psoriasis and atopic dermatitis. [33][34][35][36][37] When applied topically to either mouse or human skin, CsA transport across the cutaneous barrier may be facilitated by using short oligomers of arginine CsA. 38 It raises a possibility of topical application of concentrated CsA or its derivative directly on melanoma tissue to achieve a high dose of the drug that is necessary to exert cytostatic/cytotoxic effects.…”

Body-Weight-Independent Dosing of Cyclosporine Micro-Emulsion and Three Times Weekly Maintenance Regimen in Severe Psoriasis

“…However, there is also a weak correlation between weight and increased nephrotoxicity with conventional BWD dosing of CsA in psoriasis patients, especially in long-term treatment [15]. Therefore it was our hypothesis that BWI dosing might facilitate the treatment of severe plaque psoriasis and also improve the renal tolerability of the drug in obese patients, who may have an increased risk of developing side-effects if the BWD rule is applied without taking into account their ideal body weight.…”