糖尿病肾病病理分型临床应用的评估

Prediction of renal outcome in patients with diabetic nephropathy using the pathological classification

目的:评估糖尿病肾病(DN)病理分型对判断2型糖尿病肾病(T2DN)患者肾脏预后的意义。方法:选取2003年1月至2011年11月在南京军区南京总医院全军肾脏病研究所经肾活检明确诊断为DN且随访>1年的T2DN患者414例,回顾性分析其临床病理特点,探讨病理特征与肾脏预后的联系。所有患者均按照Tervaet等提出的病理分型标准进行分型,并对其他DN常见的病理改变进行评估。随访终点定义为估算的肾小球滤过率(eGFR)<15 ml/(min·1.73 m2)。结果:本研究共纳入Ⅰ期患者63例,Ⅱa期95例,Ⅱb期32例,Ⅲ期168例,Ⅳ期56例。各期5年肾脏生存率分别为100%、90.2%、75.4%、39.0%和15.3%。单因素回归分析显示该分型中的肾小球病变分级、肾小管萎缩与间质纤维化(IFTA)、间质炎症均对肾脏预后有显著影响,但血管病变指标(动脉透明变性、动脉硬化)与肾脏预后无相关性,75.4%的DN患者普遍存在>1个部位的动脉透明变性,对于指导分型意义不大,如将血管指标重新定义为根据动脉透明变性程度及有无动脉硬化进行评分,则可对肾脏预后产生影响。此外,对不同病理指标的单因素回归分析表明结节样病变、微血管瘤、无肾小管的肾小球、节段硬化、透明滴和纤维蛋白帽、纤维素样渗出、袢内泡沫细胞、肾小球炎、新月体、节段内皮增生对肾脏预后均有显著影响。多因素回归分析显示校正临床指标(蛋白尿、血压、eGFR)后,肾小球病变分级及IFTA是进展至终末期肾病的独立危险因素。结论:肾小球病变分级及IFTA对预测T2DN患者肾脏预后具有指导意义,但现有的血管指标对于反映病变严重程度、指导预后作用不佳,如能根据动脉透明变性程度及有无动脉硬化进行评分,对预后则有更好的指导作用。

Objective：To evaluate the predictive power of the pathologic classification in type 2 diabetes mellitus （T2DM）.Methodology：Four hundred and fourteen T2DM patients who had biopsy-confirmed DN and followed for at least a year after biopsy from January 2003 to November 2011 at Jinling Hospital were enrolled in this retrospective study.The relevancies between pathological findings and renal outcome were assessed.All cases were categorized according to the pathologic classification of Tervaert having reported.Some common pathological changes of DN were also examined.A renal event was defined as eGFR ＜ 15 ml/（min· 1.73m2）.Results：They were 260 male and 154 female with an average age of （50.0 ±9.10） years old.Among them,there were 63 in Class Ⅰ,95 Class Ⅱ a,32 Class Ⅱ b,168 Class Ⅲ,and 56 Class IV.The 5-year renal survival rates were 100％,90.2％,75.4％,39.0％ and 15.3％,respectively.Cox regression showed that the glomerular classes,interstitial fibrosis and tubular atrophy （IFTA） and interstitial inflammation can significantly influence renal survival in these patients.Scores of arteriolar hyalinosis and arteriosclerosis were not significant variables.More than one area of arteriolar hyalinosis was commonly found in 95.4％ of these patients,indicating that this index may not be suitable for classification.The patient with nodule lesions,glomerular microaneurysms,atubular glomeruli,segmental sclerosis,hyaline caps,fibrinoid exudation,foam cells within loops,glomerular inflammation,crescents,and segmental endothelial proliferation had a worse renal survival.Multivariate COX analysis showed that the glomerular classes,IFTA and acute tubular injury were independent risk factors for renal prognosis,even when adjusted for proteinuria,blood pressure and eGFR.Conclusion：The glomerular classification and IFTA are significantly associated with renal outcome in patients with T2DM,independently of proteinuria,blood pressure and eGFR.However,the vascular indexes in the classification are incapable to reflect the difference in vascular lesion severity of the patients and can＇t be used for renal prognosis,suggesting a necessity to redefine them.