Abstracts Nephrology Dialysis Transplantation 3.1560.28 vs. -0.7460.09, P<0.05) and CAT (-34.863.17 vs. -9.5761.24, P<0.01) compared to control group. Reductions from baseline to week 12 in ACR were 24.163.6% for L-arginine and -10.562.7% for standard therapy (P<0.01). No serious adverse event was detected in the both groups. CONCLUSIONS: The addition of L-arginine to standard treatment improves the oxidative stress markers and reduces albuminuria in patients with DKD. SP438 DECREASING SPEED OF KINDEY FUNCTION IN PATIENTS WITH BIOPSY-PROVEN DIABETIC NEPHROPATHY Kengo Furuichi2, Yukio Yuzawa1, Yoshifumi Ubara3, Miho Shimizu2, Tadashi Toyama2, Yasunori Iwata2, Norihiko Sakai2, Takashi Wada2 1 Department of Nephrology Fujita Health University Hospital Toyoake Japan, 2Division of Nephrology Kanazawa University Hospital Kanazawa Japan and 3Nephrology Center Toranomon Hospital Minato Japan SP439 PARTICULAR PROFILES OF URINARY MICRO-RNAs MAY EXPLAIN PODOCYTE INJURY AND PROXIMAL TUBULE DYSFUNCTION IN NORMOALBUMINURIC PATIENTS WITH TYPE 2 DIABETES MELLITUS Ligia Petrica8, Florica Gadalean4, Adrian Vlad3, Victor Dumitrascu6, Cristina Gluhovschi4, Gheorghe Gluhovschi4, Silvia Velciov4, Roxana Popescu2, Flaviu Bob4, Maxim Petrica5, Catalin Jianu5, Petru Matusz1, Oana Milas4, Alina Secara4, Anca Simulescu4, Sorin Ursoniu7, Daliborca Vlad6 1 Anatomy and Embryology "Victor Babes"University of Medicine and Pharmacy Timisoara Romania, 2Cellular and Molecular Biology "Victor Babes"University of Medicine and Pharmacy Timisoara Romania, 3Diabetes and Metabolic Diseases "Victor Babes"University of Medicine and Pharmacy Timisoara Romania, 4Nephrology "Victor Babes"University of Medicine and Pharmacy Timisoara Romania, 5Neurology "Victor Babes"University of Medicine and Pharmacy Timisoara Romania, 6Pharmacology "Victor Babes"University of Medicine and Pharmacy Timisoara Romania, 7Public Health Medicine "Victor Babes"University of Medicine and Pharmacy Timisoara Romania and 8 Nephrology ’’Victor Babes’’ University of Medicine and Pharmacy Timisoara Romania INTRODUCTION AND AIMS: MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression. The aim of the study was to establish a potential explanation of podocyte damage and proximal tubule (PT) dysfunction induced by deregulated miRNAs expression in the course of type 2 diabetes mellitus (DM). METHODS: A total of 68 patients with type 2 DM and 11 healthy subjects were enrolled in a cross-sectional study and were assessed concerning urinary albumin: creatinine ratio (UACR), urinary N-acetyl-b-D-glucosamininidase (NAG), urinary kidney injury molecule-1 (uKIM-1), urinary nephrin, podocalixin, synaptopodin, eGFR, and urinary miRNAs: miRNA21, miRNA124, miRNA192. SP440 UINARY EXCRETION OF NEPHRIN, PODOCIN AND MENDIN AS EARLY MARKERS OF DIABETIC NEPHROPATHY (DN) Anna Schukina1, Irina Bobkova2, Natalia Chebotareva1, Marina Shestakova1, Elena Kamyshova1 1 Nephrology I.M. Sechenov First Moscow State Medical University Moscow Russian Federation and 2Nephrology I.M. Sechenov First Moscow State Medical University Nephrology Russian Federation INTRODUCTION AND AIMS: Albuminuria (AU) level remains available noninvasive predictor of DN risk, regularly measured according to established guidelines. However, as shown by recent studies, both sensitivity and specificity of AU are not high enough for detecting the initial stage of DN. At the same time there is an exciting increase in our understanding that much of the early inciting events in DN stem from podocytes (Pds) pathology. Cytoskeletal Pds changes and foot process effacement are critically involved in the pathogenesis of DN. The aim of the study was to assess urinary excretion of Pds proteins nephrin, podocin (an important slit diaphragm components) and mindin (integrin ligand for foot process fixation to the GBM) in DM patients with different levels of AU and renal dysfunction, to clarify their significance as an early markers of DN. METHODS: 74 DM pts were studied (type1 DM (T1DM) -30, type2 DM (T2DM) 44), including 41 pts with AU 10-30 mg/gCr (AU1), 13 pts with c AU 30-300 mg/gCr (AU2), 20 pts with proteinuria (PU). GFR>90 ml/min was revealed in 41pts, GFR 9060 ml/min - in 25 pts, GFR<60 ml/min - in 8 pts. Urinary Pds biomarkers levels were measured by ELISA. RESULTS: Not detected in healthy high nephrinuria (NU) >5,84ng/ml and podocinuria (PdU) >1,73ng/ml were revealed in 63% and 78% DM pts with AU1. The frequency of high NU and PdU increased gradually with AU growth, reaching maximum values (80 and 83%) in DN with PU. The mean NU level in overt DN was significantly higher than in AU1 and AU2 (p<0,05). Direct correlation was obtained between NU and AU (R=0,47 p=0,03), it was more strong in pts with AU2 (R=0,947 p=0,01). The mean urinary mindin (Mnd) level in DM with AU1 has a tendency to increase compared to healthy; it increased significantly in pts with AU2 and PU and directly correlated with NU and PdU (R=0,97 p< 0,001 and R=0,984 p< 0,001). Correlation between urinary Mnd and PdU was detected even in short DM duration (R= 0,998 < 0,001). In DM course <5years NU and urinary Mnd correlated directly with dff1c (R=0,84 p=0,00196 and R= 0,64 p=0,01), reflecting the key role of a hyperglycemia in Pds dysfunction and importance of glycemic control in DM pts. NU and PdU in T1DM correlated directly with serum Cr level (R=0,489 p=0,009 and R=0,468 p=0,02) and indirectly with GFR (R=-0,461 p=0,02), emphasizing the role of Pds damage not only in glomerular permeability, but also in glomerulosclerosis formation. In DM pts with GFR<60 ml/min there was direct relationship between the NU and DM duration (R=0,73 p=0,037). Systolic hypertension and NU correlated directly in T2DM pts (R=0,53 p=0,029), and strong correlation was obtained between urinary Mnd and arterial hypertension duration (R= 0,97 p=0,009), reflecting also the hemodynamic mechanism of Pds injury in DM. CONCLUSIONS: Our data suggest that determination of such urinary Pds biomarkers as nephrin, podocin, mindin can can be useful tests for early identification and noninvasive monitoring of DN. SP441 VALIDATION OF A DIFFERENTIAL DIAGNOSTIC MODEL OF DIABETIC KIDNEY DISEASE AND NON-DIABETIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS Hui Zhuan Tan2, Jia Liang Kwek2, Stephanie Fook-Chong1, Choong Meng Chan2, Jason Chon Jun Choo2 1 Department of Clinical Research Singapore General Hospital Singapore Singapore and 2 Renal Medicine Singapore General Hospital Singapore Singapore INTRODUCTION AND AIMS: Renal injuries in patients with diabetes include diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD). The predictability of diagnosing of DKD versus NDKD from clinical data remains inconclusive. Liu et al. (J Diabetes, 2014) established a differential diagnostic model to provide a non-invasive method for predicting DKD in clinical practice. We aimed to identify predictive factors of DKD in diabetic patients with kidney disease and to externally validate this differential diagnostic model in our multiethnic Asian population. METHODS: We retrospectively analyzed clinical and laboratory data from 102 patients with Type 2 Diabetes Mellitus (T2DM) who underwent kidney biopsy from doi:10.1093/ndt/gfx149 | iii271 Downloaded from https://academic.oup.com/ndt/article/32/suppl_3/iii271/3853376 by guest on 10 July 2022 INTRODUCTION AND AIMS: Declining speed of kidney function in patients with diabetic nephropathy is now discussing. In this study, declining speed of kidney function in 422 patients with biopsy proven diabetic nephropathy were investigated. METHODS: Kidney biopsies and clinical data were collected retrospectively from 13 centers across Japan for 422 patients with type 2 diabetes. Rate of decrease in kidney function was evaluated using eGFR data at renal biopsy and follow up data. From the subsequent eGFR values, the slope was determined by the method of least squares, and it was defined as the declining speed. Decreased percent of eGFR at the second year of the renal biopsy was calculated by the eGFR at biopsy and decreasing speed. The data were evaluated based on Japanese classification of diabetic nephropathy, and CKD heat map. RESULTS: Median declining speed of estimated GFR (eGFR) in all cases was 5.61 mL/ min/1.73m2/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. Declining rate of eGFR within 2 years after kidney biopsy increased as the stage of Japanese classification of diabetic nephropathy and CKD heat map increased; Stage 1, 2, 3, 4; -0.9, 10.7, 26.5, 38.8 %, respectively, and Green and Yellow, Orange, Red; 3.7, 17.9, 34.3 %, respectively. Event rate of 30% reduction of the eGFR in two years was 41.9% (Stage 1, 2, 3, 4; 4.0, 3.8, 47.1, 61.7 %, respectively, and Green and Yellow, Orange, Red; 5.9, 30.6, 53.6 %, respectively), and that of 40% reduction was 33.2% (Stage 1, 2, 3, 4; 4.0, 0, 37.6, 49.4 %, respectively, and Green and Yellow, Orange, Red; 2.0, 25.0, 42.6 %, respectively). Sensitivity of 30% reduction of the eGFR in two years as a surrogate end point for kidney death was 56.7% (Stage 1, 2, 3, 4; 0, 0, 84.2, 11.1 %, respectively, and Green and Yellow, Orange, Red; 0, 80.0, 56.5 %, respectively) and specificity of it was 58.8% (Stage 1, 2, 3, 4; 95.0, 93.5, 57.3, 32.1 %, respectively, and Green and Yellow, Orange, Red; 91.2, 73.8, 46.9 %, respectively).Similarly, Sensitivity of 40% reduction of the eGFR in two years as a surrogate end point for kidney death was 40.0% (Stage 1, 2, 3, 4; 0, 0, 57.9, 11.1 %, respectively, and Green and Yellow, Orange, Red; 0, 60.0, 39.1 %, respectively) and specificity of it was 68.0 % (Stage 1, 2, 3, 4; 95.0, 100, 66.8, 44.6 %, respectively, and Green and Yellow, Orange, Red; 97.1, 78.8, 58.3 %, respectively). CONCLUSIONS: Decreasing rate of eGFR increased in advanced stages of diabetic nephropathy, and sensitivity and specificity of surrogate end point (30% reduction of the eGFR in two years) was relatively high in Stage 3 Japanese classification of diabetic nephropathy, and Orange in CKD heat map. RESULTS: In multivariate regression analysis, urinary nephrin, podocalixin, and synaptopodin correlated with UACR (p<0.0001; p=0.005; p=0.007), miRNA21, miRNA192 (p=0.003; p<0.0001; p<0.0001), eGFR (p=0.006; p<0.001; p<0.001), whereas NAG and uKIM-1 correlated with UACR (p<0.0001; p<0.001), miRNA124 (p<0.001; p<0.001), miRNA192 (p<0.0001; p<0.001), eGFR (p=0.008; p<0.001). The expression of miRNA192 was down-regulated, and that one of miRNA21 and miRNA124 was up-regulated. CONCLUSIONS: In patients with type 2 DM there is an association between podocyte injury and PT dysfunction, and miRNA excretion, even in the normoalbuminuria stage. This observation documents a potential role of the miRNAs profiles of miRNA21, miRNA124, miRNA192 in early DN.