Fioretto P, Steffes M W, Sutherland D E, Goetz F C, Mauer M
Department of Internal Medicine and the Center for the Study of Aging of the National Research Council, University of Padua Medical School, Italy.
N Engl J Med. 1998 Jul 9;339(2):69-75. doi: 10.1056/NEJM199807093390202.
In patients with type I diabetes mellitus who do not have uremia and have not received a kidney transplant, pancreas transplantation does not ameliorate established lesions of diabetic nephropathy within five years after transplantation, but the effects of longer periods of normoglycemia are unknown.
We studied kidney function and performed renal biopsies before pancreas transplantation and 5 and 10 years thereafter in eight patients with type I diabetes but without uremia who had mild to advanced lesions of diabetic nephropathy at the time of transplantation. The biopsy samples were analyzed morphometrically.
All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the comparison of values at base line and at 5 years; P=0.11 for the comparison between base line and 10 years). The mean (+/-SD) creatinine clearance rate declined from 108+/-20 ml per minute per 1.73 m2 of body-surface area at base line to 74+/-16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74+/-14 ml per minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570+/-64 and 928+/-173 nm, respectively) and at base line (594+/-81 and 911+/-133 nm, respectively) but had decreased by 10 years (to 404+/-38 and 690+/-111 nm, respectively; P<0.001 and P=0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33+/-0.07) to 5 years (0.39+/-0.10, P=0.02) but had decreased at 10 years (0.27+/-0.02, P=0.05 for the comparison with the baseline value and P=0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix.
Pancreas transplantation can reverse the lesions of diabetic nephropathy, but reversal requires more than five years of normoglycemia.
在未患尿毒症且未接受肾移植的I型糖尿病患者中，胰腺移植在移植后五年内并不能改善已有的糖尿病肾病病变，但长期血糖正常的影响尚不清楚。
我们对8例I型糖尿病但无尿毒症且在移植时患有轻度至重度糖尿病肾病病变的患者进行了研究，在胰腺移植前、移植后5年和10年分别评估肾功能并进行肾活检。对活检样本进行形态计量分析。
所有患者移植后糖化血红蛋白值持续正常。移植前尿白蛋白排泄率中位数为每日103mg，移植后5年为每日30mg，移植后10年为每日20mg（基线值与5年值比较，P = 0.07；基线值与10年值比较，P = 0.11）。平均（±标准差）肌酐清除率从基线时的每1.73m²体表面积每分钟108±20ml降至5年时的每1.73m²每分钟74±16ml（P<0.001），10年时为每1.73m²每分钟74±14ml（P<0.001）。肾小球和肾小管基底膜厚度在5年时（分别为570±64和928±173nm）与基线时（分别为594±81和911±133nm）相似，但到10年时有所下降（分别降至404±38和690±111nm；与基线值比较，P<0.001和P = 0.004）。系膜分数体积（系膜占据肾小球的比例）从基线时的0.33±0.07增加到5年时的0.39±0.10（P = 0.02），但在10年时有所下降（0.27±0.02，与基线值比较，P = 0.05；与5年值比较，P = 0.006），主要是由于系膜基质减少。
胰腺移植可逆转糖尿病肾病病变，但逆转需要超过五年的血糖正常。
