Type 2 Diabetes, Kidney Damage And Its Clinical Pathological Significance

BackgroundNephropathy is a severe complication of diabetes mellitus. Being the major cause of ESRD in developed countries, it also presents as a rising cause of kidney failure in China. The underline mechanism of kidney injury in diabetes remains unclear. At the same time, the pathological classification/grading criteria of diabetic nephropathy are still under debate, due to the lack of widely recognized, highly predictive systems. Type2diabetes mellitus kidney disease has revealed a highly heterogeneous nature in clinical, pathological and prognostic dimensions, which lead to the concept of "atypical diabetes related renal disease". It is characterized by short diatetes histories, fewer retinopathies, heavier metabolic disturbance, slower renal function loss, and specific pathological features manifested by disproportionally severe tubulal,thterstitial and vascular lesions and distinguished from classical glomerulopathy represented by type1diabetes mellitus patients. Whoever, cohort study in this field is largely insufficient especially on relationship between pathological classification and prognosis. Therefore, it is necessary to perform clinical and pathological researches on T2DM kidney disease in China.ObjectivesFurther explore relationship between pathological classification and clinical features in T2DM kidney disease; explore the predictive value of the classification for renal outcome events and renal function decreasing speed; search for efficient predictive pathological and clinical factors for renal prognosis in T2DM kidney disease.MethodsCase selection:We enrolled a cohort of119T2DM patients who were diagnosed by1997WHO criteria and underwent renal biopsy in PUMCH hospital between2001and2011, with intact clinical and pathological data and no evidence for NDKD. Patients with follow-up time shorter than6months are ruled out for final analysis.Pathological data:Patients are divided into typical diabetic glomerulopathy (DG, n=51) and atypical diabetes-related renal disease (ADRD,n=41) according to findings under LM, and evaluated for glomerular, vascular, tubular and interstitial lesion and podocyte density quantitative/semi-quantitatively, according to LM, EM and immunohistochemistry findings.Clinical data:Clinical data within2weeks from biopsy date are collected and compared.Prognostics:Through follow-up research by medical documents and telephone inquiry, prognosis related events (death, need for regular renal replacement therapy, double of SCr, diabetic ophthalmic event, CVD, etc.) are collected for regression analysis.Results1. Patients in DG group are characterized by older age, lower Hb and ALB, longer diabetes history, more severe DR, higher PBG and SBP, as well as more severe hematuria, proteinuria and kidney function damage; ADRD patients show significantly higher BMI, TG,2. Mesangial functional volume, GBM width are significantly higher and relative podocyte density is significantly lower in DG group; and scores for tubular atrophy, interstitial lesion and vascular lesion are also significantly higher in DG group.3. During follow-up, SCr increasing speed is significantly faster than ADRD group. In DG group,29renal outcome events,12death events,31DR renal events and4CVD events are observed, and median survival time and median non-events renal survival time are23(6,40) and32(19,45) months. No renal outcome events are observed in ADRD group and2DR renal events and4CVD events are observed. Survival rates are significantly different between two groups.4. Cox regression model indicates that the classified as DG, thicker GBM width and heavier vascular, tubular and interstial lesion are risk factors for renal outcome events adjusted for CKD stage. Only high mesangial fractional volume is the renal outcome risk factor independent from CKD stage, proteinuria and age.Conclusions1. T2DM kidney disease can be divided into DG and ADRD, according to features typical of T1DM kidney disease. 2. ADRD is largely distinguished from DG by significantly milder pathological manifestation and renal lesions, worse metabolic disturbance, fewer DR, indicating a essentially different pathophysiological mechanism.3. Renal survival rates are significant different between two groups, and mesangial fractional volume is the renal outcome predictive factors independent of CKD stage, proteinuria and age.