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
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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.