CYCLOSPORINE-ASSOCIATED LESIONS IN NATIVE KIDNEYS OF DIABETIC PANCREAS TRANSPLANT RECIPIENTS
CYCLOSPORINE-ASSOCIATED LESIONS IN NATIVE KIDNEYS OF DIABETIC PANCREAS TRANSPLANT RECIPIENTS
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DOI：
10.1038/ki.1995.318
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发表时间：
1995-08-01
影响因子：
19.6
通讯作者：
MAUER, M
中科院分区：
文献类型：
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作者：
FIORETTO, P;STEFFES, MW;MAUER, M
胰腺移植（PT）后5年的正常血糖不能改善具有自身肾脏和长期胰岛素依赖型糖尿病（IDDM）的患者的肾小球病变（Lancet 342：1193，1993）。所有这些患者接受环孢素（CsA）作为其免疫抑制的一部分。在这里，我们研究了CsA剂量和血药浓度与这些PT患者中CsA相关肾脏病变的存在和严重程度以及肾功能变化的关系。在PT之前（0）和PT之后2年和5年，从13名非尿毒症性IDDM患者中进行肾活检，并与10名IDDM对照的基线和5年活检进行比较（C）。CsA剂量从PT后第1个月的10 +/- 3 mg/kg/天降至第5年的5 +/- 2 mg/kg/天。在PT后1年，肌酐清除率（C-Cr）下降了34%，此后保持稳定，而C没有变化。0 ~ 1年C-Cr下降与1年CsA血药浓度和剂量有关（P < 0.005）。皮质间质体积分数[Vv（Int/Cortex）]、肾小管萎缩指数和肾小球硬化百分比从PT后0年至5年显著增加（分别为P < 0.005、0.01和0.001），但C组无变化。PT后0至2年，这些病变无显著变化，而2至5年有明显进展。PT后第一年的平均CsA剂量和血液水平与5年时Vv（Int/Cortex）的增加（Delta）相关（两者均P < 0.05）。Delta Vv（Int/Cortex）的最佳预测因子是PT后第一年C-Cr的变化（P < 0.003）。总之，在5年内，严重的肾小管间质和肾小球硬化病变发生在接受CsA治疗的PT受者中，而不是在IDDM C中。这些病变最好通过PT后第一年C-Cr和CsA血液水平和剂量的下降来预测。尽管早期CsA剂量减少，C-Cr稳定，结构性病变从PT后2年至5年进展。
Five years of normoglycemia following pancreas transplantation (PT) does not ameliorate glomerular lesions in patients with their own kidneys and with long-term insulin-dependent diabetes (IDDM) (Lancet 342:1193, 1993). All these patients received cyclosporine (CsA) as part of their immunosuppression. Here we examined the relationship of CsA dose and blood levels to the presence and severity of CsA-associated renal lesions and changes in renal function in these PT patients. Renal biopsies were taken before (0) and two and five years after PT from 13 non-uremic IDDM patients and were compared with baseline and five year biopsies from 10 IDDM controls (C). CsA dose was reduced from 10 +/- 3 mg/kg/day in the first month to 5 +/- 2 in the fifth year post-PT. Creatinine clearance (C-Cr) decreased by 34% at one year post-PT and was stable thereafter, and did not change in C. The decline in C-Cr from 0 to one year was related to CsA blood levels and dose (P < 0.005) at one year. Cortical interstitial volume fraction [Vv(Int/Cortex)], the index of tubular atrophy, and % sclerotic glomeruli increased significantly from 0 to five years post-PT (P < 0.005, 0.01 and 0.001, respectively), but did not change in C. There was no significant change from 0 to two years post-PT in these lesions, while there was a clear progression from two to five years. Mean CsA dose and blood levels in the first year post-PT correlated with the increase (Delta) in Vv(Int/Cortex) at five years (P < 0.05 for both). The best predictor of Delta Vv(Int/Cortex) was the change in C-Cr over the first year post-PT (P < 0.003). In conclusion, in five years serious tubulointerstitial and glomerulosclerotic lesions developed in PT recipients on CsA therapy, but not in IDDM C. These lesions were best predicted by the decline in C-Cr and CsA blood levels and dose during the first year post-PT. Despite early CsA dose reductions, and stabilization of C-Cr, structural lesions progressed from two to five years post-PT.