正常白蛋白尿糖尿病患者的临床表现及肾组织损伤

Clinic and histologic changes in type 2 diabetic patients with normoalbuminuria

目的：观察正常白蛋白尿糖尿病患者肾组织损伤的特点,以及与尿白蛋白进展、肾小球滤过率（GFR）下降相关的临床和病理风险因素。方法：纳入尿白蛋白定量〈30 mg/24h,血清肌酐≤109.62μmol/L,并愿意接受肾活检的2型糖尿病患者41例。记录患者基线临床指标和病理指标,并与同期接受肾活检的39例微量白蛋白尿（MAU）早期糖尿病肾病（DN）患者进行比较。尿白蛋白进展定义：随访中连续两次尿白蛋白≥30mg/24h;eGFR下降定义为随访中eGFR下降≥3.3%/年。结果：41例正常白蛋白尿的2型糖尿病患者（NORUAE组）均表现出不同程度的肾小球体积增大、系膜增生及肾小球基膜（GBM）增厚,且与MAU组患者病理改变无统计学差异。肾小球超微结构测量显示NOR-UAE组裂孔膜分布频率显著高于MAU组（1.18±0.39个/μm vs0.83±0.35个/μm,P〈0.001）。随访中10例患者出现MAU,尿白蛋白进展组肾小球体积显著大于非进展组[（501.04±102.45）×104μm3vs（377.12±82.12）×104μm3,P=0.001],GBM厚度大于非进展组（604.54±194.96 nm vs 478.84±122.60 nm,P=0.041）;多因素COX回归分析显示,GBM厚度（P=0.017）和肾小球体积（P=0.017）是尿白蛋白进展的独立风险因素。随访中5例患者出现eGFR下降,其基线eGFR显著低于稳定组和升高组,GBM厚度和足突宽度大于eGFR稳定组,Logistic回归分析显示基线eGFR是eGFR下降的独立风险因素[HR0.774（0.615~0.973）,P=0.028]。结论：尿白蛋白正常的2型糖尿病患者已出现DN病理损伤特点,肾小球体积增大和GBM增厚是进展至MAU的独立风险因素;基线eGFR是eGFR下降的独立风险因素。

Objective： To investigate the histological injury of type 2 diabetic patients with normoalbuminuria,and to determine the risk factors for predicting the progression to microalbuminuria and eGFR decline. Methodology： Forty one type 2 diabetic patients with normoalbuminuria and serum creatinine ≤109. 62 mol / L who received renal biopsy were enrolled in this study. Clinical indicators and pathological indicators were recorded. The definition of progression of albuminuria was urinary albumin excretion≥ 30 mg /24 h during the follow-up. eGFR decline was defined as a rate of eGFR loss of ≥3. 3% per year. Results： The renal histological injuries such as glomerular enlargement,mesangial proliferation and thickening of GBM were found in all of 41 diabetic patients with normoalbuminuria,which have no significant difference with the 39 microalbuminuria diabetic patients. The slit diaphragm frequency was higher in NOR-UAE group than MAU group（ 1. 18 ± 0. 39 vs 0. 83 ± 0. 35 slits / μm,P〈0. 001）. 10 patients progressed to microalbuminuria during the followup,the glomerular volume and GBM width were larger in the progressive group than that in non-progressive group.Multivariate COX regression analysis indicated that greater width of GBM and larger glomerular volume were independent predictors of progression to microalbuminuria. eGFR was declined ≥ 3. 3% / year in 5 patients. Multivariate Logistic regression analysis indicated that lower baseline eGFR was the independent predictor of eGFR decline（ HR 0. 774（ 0. 615- 0. 973）,P = 0. 028）. Conclusion： Histological manifestations of DN have been existed in type 2 diabetic patients with normoalbuminuria. Greater width of GBM and larger glomrular volume were independent predictors of progression to microalbuminuria,and lower baseline eGFR was the independent predictor of eGFR decline.