FP246KIDNEY OUTCOME IN DIABETIC SUBJECTS WITH PRIMITIVE GLOMERULOPATHIES COMPARED TO DIABETIC NEPHROPATHY

INTRODUCTION: Kidney involvement secondary to diabetes mellitus is the first cause of renal replacement therapy (RRT) initiation worldwide. However, other biopsy-proven glomerulopathies, alone or superimposed on diabetic nephropathy (DN), were reported with variable frequencies. Since the type of histologic lesion, conclusively identified only by kidney biopsy, might influence the patients’ prognosis, we aimed to comparatively assess the kidney outcome in diabetic subjects with chronic kidney disease (CKD) according to biopsy findings. METHODS: This single-center, retrospective study enrolled 133 diabetic adults with CKD who underwent a native kidney biopsy, were histologically diagnosed as isolated diabetic nephropathy (iDN), primary glomerulopathy (GP) or DN associated with GP, between 1st Jan 2010 – 31st Dec 2016 and followed till 30th June 2018 for 29.5 (95%CI 22-55.5) months. Patients (pts) with inadequate biopsy specimen were excluded. The time to RRT initiation was the primary end-point. The subjects were divided in two groups: an iDN group (89 pts) and a mixed group with 44 subjects having GP, either isolated (37 pts) or associated with DN (7 pts). Indications for kidney biopsy and patients’ characteristics suggesting iDN at presentation were assessed by multivariate logistic regression. Only subjects who were alive at the end of follow-up (52 in iDN group and 32 in mixed group) entered the kidney survival analysis. RESULTS: Membranous nephropathy (13.5%) and IgA nephropathy (6%) were the most common types of primary GP. The iDN subjects were younger (53±12 vs. 59±11 years, p= 0.03), had higher systolic blood pressure [160 (95%CI 137-170) vs 140 (95%CI 128-160) mmHg, p=0.04], lower glomerular filtration rate (eGFR [28 (95%CI 18-47) vs. 47 (95%CI 25-64) mL/min/1.73m2, p=0.007], and less frequently microscopic hematuria (64% vs. 46%, p=0.04). Proteinuria was similar in both groups. The risk of iDN was 7-folds higher (95%CI 2.7-17.9, p<0.0001) when the reason of biopsy was unexplained kidney failure and 11-folds higher (95%CI 1.4-85.2, p=0.02) in case of isolated proteinuria. The presence of microvascular complications (OR 6.4; 95%CI 2.4-17.1, p<0.001), higher serum albumin (OR 2.2; 95%CI 1.1-4.4, p=0.02), lower serum cholesterol (OR 0.14; 95%CI 0.04-0.46, p=0.001) and elevated systolic blood pressure (OR 4.3; 95%CI 1.1-17.1, p=0.02) were other independent predictors of iDN in the multivariate analysis. During the follow-up period, 41.6% from iDN group reached the end-point, compared to 27.3% from mixed group. The mean time to RRT was shorter in iDN group [47 (95%CI 38-56) vs. 80 (95%CI 70-91) months, p<0.001]. In an adjusted Cox-model, only eGFR at biopsy predicted RRT initiation (HR=0.38; 95%CI 0.21-0.66, p<0.0001). CONCLUSIONS: As one third of the investigated subjects had non-diabetic glomerular lesions, kidney biopsy seems to be useful both to assess prognosis and to guide therapy in diabetic patients with CKD. Isolated diabetic nephropathy seems associated with a worse kidney survival and the initial reduction in kidney function remained the most powerful predictor of RRT initiation.