Powles A V, Hardman C M, Porter W M, Cook T, Hulme B, Fry L
Department of Dermatology, St Mary's Hospital, London, U.K.
Br J Dermatol. 1998 Mar;138(3):443-9. doi: 10.1046/j.1365-2133.1998.02122.x.
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.
通过测量血清肌酐和肾小球滤过率（GFR）来评估两组接受环孢素A（CyA）治疗的慢性斑块状银屑病患者的肾功能，平均剂量为每天2.8mg/kg（范围为每天1 - 5mg/kg）。第一组是我们最初的9名患者队列，其中7名患者接受CyA治疗的平均时间为10年（范围为9.5 - 11年）。这7名患者的血清肌酐较基线测量值持续升高>30%，其中4名患者的血清肌酐持续升高>50%。在治疗2.5年后首次测量的GFR显示，在10年时，2名患者下降>30%，1名患者下降>50%。7名患者中有3名肾功能稳定，2名因肾功能恶化进行了重复肾活检，组织学显示与5年治疗后相比，有更多环孢素A肾毒性的证据。第一组的9名患者中有2名在接受5年治疗后，因肾活检显示环孢素A肾毒性和肾功能受损，于5年前停用了CyA。在5年的随访期间，肾功能损害有所改善，这意味着环孢素A肾毒性具有可逆性。第二组20名患者接受CyA治疗的平均时长为6年（范围为5 - 8年）。20名患者中有9名患者的血清肌酐较基线持续升高>30%，5名患者的血清肌酐持续升高>50%。GFR显示7名患者持续下降>30%，2名患者持续下降>50%。这项研究表明，肾毒性与长期使用CyA治疗有关。然而，肾毒性何时开始及其进展速度存在个体差异。停用CyA后，肾功能损害会随着时间改善。如果除了血清肌酐外，还用GFR和肾活检来监测肾功能，那么对于对其他治疗无反应的重度银屑病患者，长期（5 - 10年）使用CyA治疗是合理的。
