Marker Of Kidney Disease Research Articles

501-P: Urinary C-Peptide Creatinine Ratio: A New Marker of Insulin Resistance and Diabetic Kidney Disease

Introduction: Urinary C-peptide creatinine ratio (UCPCR) is used to access β cell function, but rare study had explored UCPCR in conditions with insulin resistance (IR). Some studies indicated the positive correlation between diabetic kidney disease (DKD) and IR. This study aims to explore the correlation among UCPCR,IR and DKD. Methods: Chinese hospitalized patients with type 2 diabetes were included (n=1299). Fasting UCPCR was collected in the morning. We divided patients into three groups by the tertile of UCPCR, the characteristics of three groups were compared. Results: In patients with the highest tertile of UCPCR, they had the lowest percentage of male (223 [51.6%] vs.294 [68.1%] vs. 302 [70.1%], P<0.001), highest homoeostasis model assessment 2 estimates of insulin resistance (HOMA2-IR) (2.0 [1.5,2.6] vs. 1.6 [1.2,2.2] vs. 1.5 [1.0,2.0], P<0.001), urinary albumin creatinine ratio (9.58 [4.67,36.42] vs. 7.14 [4.10,22.43] vs. 6.87 [3.60,22.94]mg/g, P=0.003) level,highest percentage of diabetic kidney disease (DKD) (121 [27.9%] vs. 95 [21.9%] vs. 98 [22.7%], P=0.078), coronary heart disease (CHD) (75 [17.4%] vs. 61 [14.1%] vs. 36 [8.4%], P<0.001) and stroke (77 [17.8%] vs. 55 [12.7%] vs. 46 [10.7%], P=0.007). After the adjustment for sex, age, duration, SBP, DBP, BMI, UA,TG, LDL-c, HbA1c, the history of smoke, hypertension and hyperlipidemia, UCPCR level had a positive correlation with the risk of DKD (OR=1.207,95%CI [1.026,1.419], P=0.023) and CHD (OR=1.302, 95%CI [1.069,1.587], P=0.009). Conclusions: UCPCR is a practical and non-invasive marker of insulin resistance and associated with increased risk of DKD and CHD. Disclosure Y. Wang: None. X. Cai: None. L. Ji: None.

P0975EFFECT OF REGULATED INTRAMEMBRANE PROTEOLYSIS ON MEGALIN EXPRESSION DURING OXIDATIVE STRESS EXPOSURE

Abstract Background and Aims Megalin, an endocytic receptor in proximal tubular cells, plays a critical role in renal tubular protein reabsorption. We previously reported that oxidative stress induced the temporally increase in renal megalin expression through the PI3K/AKT signaling pathway, but that megalin elevation is normalized or decreased during long term exposure to oxidative stress (hydrogen peroxide). However, the underlying mechanisms are unclear. Studies have addressed that megalin is subjected to regulated intramembrane proteolysis (RIP). Intracellular megalin COOH-terminal fragment (MCTF) is produced by protein kinase C-regulated, metalloprotease-mediated ectodomain shedding and further cleavage by gamma-secretase to produce the soluble megalin intracellular domain (MICD). The MICD in turn translocates to the nucleus where it decreases expression of the Lrp2 gene encoding megalin. In the present study, we evaluated the effect of megalin RIP on the oxidative stress-regulated megalin expression. Method HK-2 cells were cultured with hydrogen peroxide (0.4 mmol/l) for 4.5 or 24 h, followed by treatment with gamma-secretase inhibitor, Compound E (5 mmol/L) or PKC activator, Phorbol 12-myristate 13-acetate (PMA, 0.5 mmol/L). Megalin expression was determined by performing western blotting or real-time PCR. The MCTF in medium was detected by western blotting. In animal experiments, Sprague-Dawley rats were randomly divided into two groups (n = 5): (i) STZ group (diabetic phenotype induced by streptozotocin administration) and (ii) sham group (vehicle). Urine was collected at two weeks after STZ administration, and the excretion of MCTF in urine was analyzed. Results Treatment of HK-2 cells with hydrogen peroxide (0.4 mmol/L) significantly increased megalin protein and mRNA levels at 4.5 h. Pretreatment of Compound E showed further increase in megalin expression in hydrogen peroxide-exposed cells. It was also found that presenilin-1 and -2, which are components of gamma-secretase, double knockdown with siRNA increased megalin expression in hydrogen peroxide treated-cells. On the other hand, PMA treatment inhibited the increase in both megalin protein and mRNA levels. In the cells treated with hydrogen peroxide for 24 h, megalin mRNA levels were normalized, but pretreatment of Compound E kept the elevation in megalin mRNA levels at 24 h after the treatment with hydrogen peroxide. Interestingly, megalin MCTF in the medium was increased by hydrogen peroxide treatment in a dose-dependent manner. Furthermore, megalin MCTF excretion in the urine of STZ-induced diabetes was significantly increased compared to sham rats. Conclusion These results suggested that oxidative stress-induced megalin upregulation was inhibited by RIP activation of megalin, suggesting that megalin RIP plays a role as a negative feedback system to oxidative stress-induced megalin upregulation. Furthermore, our data indicate that oxidative stress induces urinary excretions of MCTF in diabetic rats during the normoalbuminuric stage and potentially act as a marker of diabetic kidney disease.

2147-PUB: Change in Matrix Metalloproteinase Activity Is Associated with Zinc Level in the Development of Renal Changes in a Diabetic Preclinical Model

Zinc is required for activation of Matrix Metalloproteinases (MMPs). Circulating zinc levels are decreased in diabetes1 and decreased activity of some MMPs is associated with the development of diabetic nephropathy (DN). The association between MMP activity and zinc in the development of DN has not been investigated and was examined in a preclinical model in this study. In this study, diabetic (DM: STZ: 3x 65mg/kg) male BALB/c mice were euthanized after 5, 10 and 30wks of diabetes. Age-matched mice acted as controls. At termination, kidneys, plasma and urine were collected for histopathology, measurement of biochemical parameters, total MMP activity using a broad spectrum MMP fluorogenic substrate and zinc level by ICPMS. In DM mice, blood glucose levels were increased at 5, 10 and 30wks (P<0.01) as were kidney/body weight (P<0.05) and urinary albumin/creatinine ratios (P<0.05). After 5wks of diabetes histopathological changes were evident and albumin/creatinine ratio increased (P<0.05). Urinary MMP activity was decreased (P<0.001) at 5wks and preceded a decrease in kidney and plasma MMP activity at 10 and 30wks (both P<0.05). DM decreased plasma but not urinary zinc levels at 10 and 30wks (both P<0.05). In DM mice, the kidney MMP activity correlated positively with plasma MMP activity (r=0.3774, P<0.03) and diabetes duration. Plasma zinc correlated with plasma MMP activity (r=-0.77, P=0.04) but only at 30wks. These results suggest an association between plasma MMP activity and zinc but only after a long duration of diabetes. The early decrease in urinary total MMP activity suggests it may have utility as a marker of early kidney disease. Whether this is so for human kidney disease is currently not known and requires further study. 1 Chabosseau and Rutter, Archives of Biochemistry and Biophysics (2016). Disclosure A. Tao: None. R. McQuilty: None. S.S. Sutanto: None. L.A. Ban: None. S.M. Twigg: Advisory Panel; Self; Abbott, AstraZeneca, Sanofi. Speaker’s Bureau; Self; Abbott, AstraZeneca, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. S. McLennan: None.

P0670DIFFUSIONAL KURTOSIS IMAGING PREDICTS THE PROGNOSIS OF CHRONIC KIDNEY DISEASE

Abstract Background and Aims Renal fibrosis is the strongest prognosis predictor of ESRD in chronic kidney disease (CKD), but non-invasive and repeatable imaging markers are missing. Magnetic resonance imaging (MRI) has wide range of applications in renal parenchymal diseases, and diffusional kurtosis imaging (DKI) is a new promising noninvasive method of MRI which can provide more information about non-Gaussian diffusion using a polynomial model. We had successfully used DKI to assess renal fibrosis in IgA nephropathy in our previous work. This study aimed to evaluate the prognostic value of DKI in CKD. Method We prospectively enrolled forty-two CKD patients in our study in Jan. 2017. On recruitment, the basic clinical data were documented, and DKI was performed on a clinical 3T MR scanner. Region-of-interest (ROI) measurements were performed to determine apparent diffusion coefficient (ADC), kurtosis (K) and diffusivity (D) of the cortex of the kidneys. We had followed up these patients for 3 years, and collected all the clinical data and outcomes. The prognostic value of DKI metrics and clinical parameters were investigated. Results Forty-two patients consisted of 26 males and 16 females with mean age of 41.3±15.4 years. The most common etiology was IgA nephropathy (25/42, 59.5%). At baseline, the mean value of serum creatinine (SCr) was 224.4±156.2μmol/L. Among them, 18 patients had eGFR≥45ml/min and 24 patients had eGFR<45ml/min. According to the etiology and CKD classification, all the patients had received appropriate treatment. Besides supportive treatment and management of CKD complications, 21 patients (50%) had received corticosteroid and/or immunosuppressants treatment. After 36 months follow up, 12 patients had progressed to end stage renal disease (ESRD), and the mean value of SCr of the remaining 30 patients was 153.0±78.8umol/L. The Kaplan-Meyer survival regression showed that the patients with eGFR<45ml/min had worse clinical outcomes (p=0.0006). ROC analysis and Kaplan-Meyer survival regression showed that DKI metrics (K≥0.66 or ADC<1.35) not only predicted severe renal fibrosis, but also had worse clinical outcomes (p=0.01 and p<0.0001) (Figure 1). According to the COX regression analysis, both K (K≥0.66, HR 4.676, 95%CI 1.262-17.325) and ADC (ADC<1.35, HR 13.118, 95%CI 3.499-49.178) values, but not age, gender and eGFR group (cut-off value: 45ml/min), were the independent risk factors for the progression to ESRD. Conclusion Renal ADC and K values obtained from DKI showed significant predictive value for the prognosis of CKD, could be a promising non-invasive technique in patients follow-up.

English

About one-third of diabetes mellitus (DM) patients are complicated by diabetic nephropathy. It is even more challenging in type 2 DM in which this complication may occur before presentation. Microalbuminuria which is the traditional marker of early diabetic nephropathy is limited in its usefulness because it is detected when significant renal damage has already occurred. The aim of this study was to evaluate and compare urinary fibronectin and laminin with microalbuminuria as markers of glomerular injury in type 2 DM patients. A cross-sectional study with 120 consenting non-hypertensive type 2 DM, consisting of 57 (47.5%) males and 63 (52.5%) females; and 120 non-diabetic/non-hypertensive controls, consisting of 51 (42.5%) males and 69 (57.5%) females. Urinary albumin, fibronectin and laminin as well as plasma glucose were measured. The mean albumin –creatinine ratio was significantly higher (p<0.001) among type 2 DM (1.990.78 mg/mmol) compared to the control (0.120.01 mg/mmol). Also, urinary fibronectin (1.290.35 µg/mL) and laminin (1251.34+234.61 pg/mL) were significantly higher (p<0.001) in type 2 DM patients than in controls (0.290.07 µg/mL and 127.8114.07 pg/mL respectively). The sensitivity test for urinary fibronectin and laminin was 93.9% each while their specificities were 8.0 and 13.8% respectively. The negative predictive values (NPV) for urinary fibronectin and laminin were 77.8 and 85.7% respectively while the positive predictive values (PPV) were 27.9 and 29.2% respectively. This study suggests that assay for urinary fibronectin and laminin, which showed high sensitivities and high negative predictive values are useful as markers of early diabetic kidney disease and can substitute microalbuminuria in the routine evaluation of type 2 DM patients. The slightly higher PPV and NPV for urinary laminin suggest that it is a better marker than urinary fibronectin. Key words: Diabetes mellitus, microalbuminuria, urinary fibronectin, urinary laminin. &nbsp

The TGF-β profibrotic cascade targets ecto-5′-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease

Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-β and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We evaluated the role of TGF-β on NT5E gene expression coding for the ecto-5`-nucleotidase CD73, the limiting enzyme in extracellular adenosine production. We showed that high d-glucose may predispose HK-2 cells towards active transcription of the proximal promoter region of the NT5E gene while additional TGF-β results in full activation. The epigenetic landscape of the NT5E gene promoter was modified by concurrent TGF-β with occupancy by the p300 co-activator and the phosphorylated forms of the Smad2/3 complex and RNA Pol II. Transcriptional induction at NT5E in response to TGF-β was earlier compared to the classic responsiveness genes PAI-1 and Fn1. CD73 levels and AMPase activity were concomitantly increased by TGF-β in HK-2 cells. Interestingly, we found increased CD73 content in urinary extracellular vesicles only in diabetic patients with renal repercussions. Further, CD73-mediated AMPase activity was increased in the urinary sediment of DN patients. We conclude that the NT5E gene is a target of the profibrotic TGF-β cascade and is a traceable marker of progressive DN.

Distribution of urinary gamma-glutamyltransferase activity in 40- to 74-year-old Japanese women

Urinary gamma-glutamyltransferase (u-γGT) concentration (U/L) and excretion (urinary creatinine-corrected u-γGT; u-γGT/u-Cre, U/g creatinine) are useful markers for kidney disease. However, there is limited information available on u-γGT and u-γGT/u-Cre distribution in the elderly Japanese population. In this study, we investigated the distribution of u-γGT and u-γGT/u-Cre in 113 Japanese women aged 40–74 years. The u-γGT was assessed from spot urine samples (collected from 09:00 to 14:00) spectrophotometrically according to the Japan Society of Clinical Chemistry reference measurement procedure using l-γ-glutamyl-3-carboxy-4-nitroanilide as the substrate. The u-Cre was measured enzymatically using creatininase, creatinase, sarcosine oxidase, and peroxidase. None of the participants was diagnosed with any kidney disease. Median u-γGT and u-γGT/u-Cre values (central 95% interval values) were 29.7 (5.3–144.0) U/L and 57.9 (32.9–122.7) U/g creatinine, respectively. The distribution of u-γGT tended to decline with age. There was a statistically significant difference in the u-γGT value between the 40-59- and 60-74-year-old groups. In contrast, there was no significant difference in the u-γGT/u-Cre between each age group. The u-Cre level also declined with age. It is suggested that the decline of u-γGT with aging would be masked by the u-Cre correction.

Oral supplementation with omega-3 fatty acids and inflammation markers in patients with chronic kidney disease in hemodialysis

Chronic kidney disease (CKD) is an increasingly common public health problem that increases the risk of death because of cardiovascular complications by 2-3 times compared with the general population. This research concerns a prospective, randomized, double-blind study in patients with CKD undergoing hemodialysis. The participants were assigned to 1 of 2 groups: the study group (group A; 46 patients) received 4 capsules (2.4 g) of omega-3 fatty acids daily during the 12-week intervention, while patients in the control group (group B; 47 patients) received 4 capsules of paraffin oil. The patients' general characteristics, nutritional indicators, renal disease markers and inflammatory markers (C-reactive protein, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF-α)) were evaluated. No differences were found between the general characteristics of the patients (P < 0.05), and no differences were shown in the nutritional indicators and markers of kidney disease (P < 0.05). Patients in group A showed significant decreases in levels of C-reactive protein, IL-6, TNF-α, and the IL-10/IL-6 ratio after 12 weeks of supplementation (P < 0.05). Patients in group B did not show any significant changes in concentrations of inflammatory markers during the intervention (P < 0.05). In conclusion, oral supplementation with omega-3 fatty acids produces a significant decrease in the concentrations of inflammation markers in patients with chronic kidney disease on hemodialysis. Novelty Oral supplementation with omega-3 fatty acids produced significant decreases in the concentrations of inflammation markers. This supplementation could be given to patients with uremic syndrome and coronary heart disease to reduce cardiovascular risk.

Blood pressure control and kidney damage in hypertension: Results of a three-center cross-sectional study in North Central Nigeria.

Hypertension is one of the commonest cause of chronic kidney disease (CKD) in Nigerians. We describe blood pressure (BP) control and kidney disease markers in patients with hypertension as part of measures to curb the burden of this chronic debilitating disease. Patients with hypertension in the main tertiary hospitals in three states in north central Nigeria were evaluated for indicators of CKD, including proteinuria and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Patients had their early morning first void urine tested for proteinuria using Combi-10 test strips. eGFR was estimated using the MDRD equation. A total of 1063 subjects (63.1% females and 36.8% males) with a mean age of 55 ± 11 years were studied. Diabetes mellitus (DM) was present in 214 (20.6%) and 422 (39.7%) had optimal BP control. The median duration of hypertension was 6 years (range 1-44 years). Proteinuria occurred in 130 (12.2%), while 212 (19.9%) had reduced eGFR and 46 (4.3%) had proteinuria and reduced eGFR. The use of calcium channel blockers [adjusted odds ratio (AOR): 0.70, 95% Confidence Interval (CI) 0.50-0.99] and the use of more than two antihypertensive medications (AOR: 0.62, 95% CI 0.40-0.96) were associated with reduced odds of optimal BP control. Male sex (AOR: 1.75, 95% CI 1.14-2.70) and the use of renin-angiotensin-aldosterone system blocking medications (AOR: 2.07, 95% CI 1.18-3.64) were independently associated with proteinuria while DM (AOR: 1.69, 95% CI 1.06-2.55) and treatment with more than two medications (AOR: 1.86, 95% CI 1.09-3.17) were more likely to have reduced eGFR. A large proportion of hypertensive patients in north-central Nigeria have poorly controlled BP. Kidney damage is common among these patients.

Ultrastructural changes of platelets in patients with diabetes mellitus type 1 and 2 depending on the state of renal function at different stages of chronic renal failure

The aim of our study was to study the ultrastructural changes of platelets in patients with diabetes mellitus type 1 (T1DM) and type 2 (T2DM) depending on estimated glomerular filtration rate (eGFR) and to assess the possibility of their use as an early marker of diabetic kidney disease progression.Materials and methods. The study included 37 people: 15 patients with T1DM, 15 with T2DM, 7 healthy volunteers. Patients were divided into three groups depending on eGFR: group 1 – eGFR ≥90 ml/min/1.73 m²; group 2 – eGFR 89–60 ml/min/1.73 m²; group 3 – eGFR 59–45 ml/min/1.73 m². Transmission electron microscope PEM-100-01 “SELMI” (Ukraine) was used to determine the ultrastructural changes of platelets.Results. We studied ultrastructural changes of platelets in patients with T1DM and T2DM depending on eGFR and determined the changes in platelet hemostasis in patients with eGFR ≥90 ml/min/1.73 m². We proved that the higher damage degree of kidneys filtration function leads to the worse platelets membrane structures damage, increased number of platelet hyperactivation signs, higher proportion of irreversibly transformed cells.Conclusion. Morphological substrate of platelet hemostasis damage in patients with T1DM and T2DM is increased destabilization of the platelet membranes, massive agglutination with a predominance of various sizes condensed aggregates, the involvement of irreversibly deformed erythrocytes and activated leukocytes in their composition, imbalance of density packing of alpha-, delta-, and lambda- granules. This ultrastructural complex can be considered as an early marker of diabetic kidney disease progression in patients with T1DM and T2DM.

Vasopressin and Copeptin in health and disease.

Arginine Vasopressin (AVP) and copeptin derive from the same precursor molecule. Due to the equimolar secretion, copeptin responds as rapidly as AVP to osmotic, hemodynamic and unspecific stress-related stimuli and both peptides show a very strong correlation. The physiological functions of AVP are homeostasis of fluid balance, vascular tonus and regulation of the endocrine stress response. In contrast, the exact function of copeptin remains unknown. Since copeptin, in contrast to AVP, can easily be measured with a sandwich immunoassay, its main function so far that it indirectly indicates the amount of AVP in the circulation. Copeptin has emerged as a useful measure in different diseases. On one hand, through its characteristics as a marker of stress, it provides a unique measure of the individual stress burden. As such, it is a prognostic marker in different acute diseases such as ischemic stroke or myocardial infarction. On the other side, it has emerged as a promising marker in the diagnosis of AVP-dependent fluid disorders. Copeptin reliably differentiates various entities of the polyuria polydipsia syndrome; baseline levels >20pmol/L without prior fluid deprivation identify patients with nephrogenic diabetes insipidus, whereas levels measured upon osmotic stimulation with hypertonic saline or upon non-osmotic stimulation with arginine differentiate primary polydipsia from central diabetes insipidus. In patients with hyponatremia, low levels of copeptin together with low urine osmolality identify patients with primary polydipsia, but copeptin levels overlap in all other causes of hyponatremia, limiting its diagnostic use in hyponatremia. Copeptin has also been put forward as predictive marker for autosomal dominant polycystic kidney disease and for diabetes mellitus, but more studies are needed to confirm these findings.

Associations of Chronic Kidney Disease Markers with Cognitive Function: A 12-Year Follow-Up Study.

Background:The role of chronic kidney disease (CKD) as a risk factor for cognitive impairment independent of their shared antecedents remains controversial.Objective:To determine whether kidney damage (indicated by albuminuria) or kidney dysfunction (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) predict future (12-year) cognitive function independently of their shared risk factors.Methods:We studied 4,128 individuals from the 1999/00 population-based Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study who returned in 2011/12 for follow-up cognitive function testing. Albuminuria was defined by urinary albumin:creatinine≥3.5 (women) or≥2.5 mg/mmol (men). Kidney dysfunction was indicated by eGFR <60 ml/min/1.73 m2. Cognitive function domains assessed included memory (California Verbal Learning Test [CVLT]) and processing speed (Symbol Digit Modalities Test [SDMT]).Results:Baseline albuminuria and kidney dysfunction were identified in 142 (3.4%) and 39 (0.9%) individuals, respectively, with minimal overlap (n = 7). Those with albuminuria demonstrated concurrently reduced 12-year SDMT (p = 0.084) and CVLT scores (p = 0.005) following adjustment for age, sex, and education. However, only CVLT performance remained worse (p = 0.027) following additional adjustment for myocardial infarction, stroke, and related risk factors (hypertension, diabetes, dyslipidemia, smoking, BMI, physical activity, and alcohol intake). Indeed, these collective covariates were responsible for 47% of the effect of albuminuria on SDMT, but only 21% of its effect on CVLT. Kidney dysfunction was not associated with either SDMT or CVLT performance (p > 0.10).Conclusions:Albuminuria predicted worse memory function at 12 years follow-up, whereas its effect on processing speed was driven largely by differences in cardiovascular risk. Kidney dysfunction based on eGFR predicted neither cognitive domain.

The Association Between Kidney Disease and Diabetes Remission in Bariatric Surgery Patients With Type 2 Diabetes

The association between bariatric surgery, type 2 diabetes, and chronic kidney disease (CKD) is poorly understood. We studied whether remission of type 2 diabetes induced by bariatric surgery influences markers of kidney disease, if CKD is associated with remission of diabetes after bariatric surgery, and if baseline levels of gut hormones and peptides modify these associations. Prospective observational study. 737 bariatric surgery patients with type 2 diabetes who participated in a multicenter cohort study for up to 5 years. Demographics, blood pressure, medications, type of bariatric surgery, anthropometrics, markers of kidney disease, and circulating levels of gut hormones and peptides. Estimated glomerular filtration rate (eGFR), urinary albumin excretion, prognostic risk for CKD, and remission of diabetes. Linear mixed models for eGFR; generalized linear mixed models with logit link for albuminuria, prognostic risk for CKD, and diabetes remission. Remission of diabetes at 5 years post-bariatric surgery was not independently associated with eGFR but was associated with lower risk for moderate/severe increase in albuminuria (risk ratio, 0.66; 95% CI, 0.48-0.90) and stabilization in prognostic risk for CKD. These findings were modified by baseline ghrelin level. Lower preoperative eGFR and greater prognostic risk for CKD were independently associated with reduced likelihood of diabetes remission. The association with preoperative GFR was modified by C-peptide level. Higher baseline circulating ghrelin level was independently associated with a lower prognostic risk for CKD. A minority of participants had baseline CKD; lack of comparison group; no information on duration of diabetes, other clinical end points, or kidney biopsy results. Remission of type 2 diabetes 5 years after bariatric surgery was associated with improvements in albuminuria and stabilized prognostic risk for CKD, but not with eGFR. Lower kidney function and greater prognostic risk at the time of bariatric surgery was linked to a lower likelihood of diabetes remission. These results highlight the need to identify the mechanisms through which bariatric surgery may delay the long-term progression of CKD in type 2 diabetes.

Evaluation of Kidney Function Parameters in Diabetic Rats Following Virgin Coconut Oil Diet.

Diabetes mellitus (DM) leads to disruption of kidney function parameters (KFPs) which are markers of kidney diseases, especially nephropathy. Virgin coconut oil (VCO) has been implicated in playing a significant role in DM management. However, its role on KFPs in DM is scarce. To evaluate the kidney function parameters following VCO diet in diabetic rats. Twenty-five (25) male rats of 150 - 200 g were divided into 5 groups (n=5): Non-diabetic control (Group 1), diabetes control (Group 2), diabetes + metformin (Group 3), diabetes + 10% VCO (Group 4) and diabetes + 20% VCO (Group 5). Apart from Group 1, other groups were given intraperitone-ally 50 mg/kg of streptozotocin to induce diabetes mellitus. After 72 hours, fasting hyperglycaemia was confirmed by glucose oxidase method. All the rats were fed normal rat chow for 8 weeks. At 8th week, serum and urine samples were analysed for biochemical analysis. After 8 weeks, Group 1 and Group 2 continued to be fed on normal rat chow while other groups were treated with diets (VCO) or drug (metformin) for 4 weeks. At 12th week, urine samples were collected for biochemical analysis, the rats were sacrificed, and blood samples were collected by cardiac puncture. There were significant differences in some KFPs in diabetes control (Group 2) compared to other experimental groups. However, there was no significant difference in glomerular filtration rate (GFR) and serum sodium in all the groups. VCO supplementary diet improved the altered KFPs and could be a therapy for kidney problems.

504-P: TGF-ß1 and VCAM-1 as Early Diagnostic Biomarkers of Diabetic Kidney Disease Progression

Aim: To evaluate the significance of using transforming growth factor beta 1 (TGF-β1) and vascular adhesion molecule -1 (VCAM-1) as early prognostic markers of diabetic kidney disease (DKD) progression in patients with DM type 1 and 2. Materials and Methods: The study included 66 patients with T1DM, 58 with T2DM and 20 healthy volunteers. Diabetic patients were divided into three groups depending on the estimated glomerular filtration rate. All patients were equal for age and sex. The endothelial function was determined by TGF-β1 and VCAM-1 levels. Recognitive Operating Characteristic - was used to assess the discrimination ability (diagnostic test value) to be a predictor of DKD progression. Results: Patients of all study groups had significantly higher (p˂0,05) levels of TGF-b1 and VCAM-1 versus control group. That’s present endothelial dysfunction in DM patients. The diagnostic value of TGF-b1 and VCAM-1 was compared with diagnostic value of AU. The highest test’s sensitivity and specificity has TGF-b1, its predictive ability concerning DKD progression can be assessed as “excellent” for both types of DM (Se = 100.0; Sr = 100.0; AUC = 1.000; p &amp;lt; 0.001). VCAM-1 has “excellent” operating characteristics for predicting DKD progression in T2DM (Se = 100,0; SP = 88,89; AUC = 0,923; p &amp;lt;0.001) and “very good” in T1DM (Se = 86,36; Sp = 90.48; AUC = 0.866; p &amp;lt;0.001). AU has “good” operating characteristics concerning DKD progression: Se = 57,50; Sd = 97.44; AUC = 0.785; p &amp;lt;0,001 for type1 and 2 DM. That’s shows us evaluation of AU in DM has a high specificity, but low sensitivity of the prognosis DKD progression for both types of DM. Conclusion: We provide evidences that TGF-β1 and VCAM-1 can be used for prediction of DKD progression in patients with type 1 and type 2 DM. Diagnostic capabilities of VCAM-1 and TGF-β1 significantly exceed the diagnostic capabilities of AU, which determines them as early markers. Disclosure C. Daria: None. N. Pertseva: None.

NF-κB gene expression in peripheral blood and urine in early diagnosis of diabetic nephropathy – A liquid biopsy approach

Abstract Diabetic nephropathy (DN) is a pathological condition that affects diabetic patients around the world, and it is the main cause of chronic kidney diseases. It is known that the inflammatory pathway is activated in diabetic patients. Thus, the aims of this study were to evaluate the gene expression of Nuclear factor-κappa B (NF-κB) in liquid samples (urine and blood), then to evaluate the correlation between NF-κB gene expression with classical biochemical markers of kidney disease to investigate if the gene expression of this molecule can be used as a biomarker of loss of kidney function in diabetic patients. We recruited 35 patients with type 2 diabetes mellitus for at least 5 years and 29 healthy donors and collected samples of urine and blood to quantify the NF-κB expression. It was found higher expression of NF-κB in both samples in diabetes patients. We verified elevated levels of microalbuminuria, serum creatinine, urea and BMI in diabetic patients, as well as a fall in GFR, without alteration in serum creatinine and proteinuria levels. Our data suggest that overexpression of NF-κB participates in the onset of diabetic nephropathy and that it is possible to quantify these changes in liquid biopsy (blood and urine) through gene expression of this molecule. The NF-κB expression is correlated with increased BMI data.

Urine Albumin Creatinine Ratio May Predict Graft Function After Kidney Transplant

BackgroundThe albumin to creatinine ratio (ACR) has been shown to be an important prognostic marker in kidney disease. The ACR has been shown to predict graft failure and patient death after kidney transplant. MethodsFrom March 1, 2011, to December 31, 2013, we checked the urine ACR and blood for highly sensitive C-reactive protein in 93 kidney recipients who regularly follow up at out institute. We tested the linear correlations of these parameters with estimated glomerular filtration rate. Furthermore, we used multivariate linear regression to examine its value in predicting graft function. Finally, we used receiver operating characteristic curve analysis to validate their predictive value on creatinine clearance > 45 mL/min. ResultsWith multivariate linear regression, the latest estimated glomerular filtration rate has a strong linear relationship with initial ACR (B = −0.032; P = .02), suggesting each unit rise in ACR with a decrease in creatinine clearance by 0.032 mL/min. To investigate their value in predicting good functional graft defined as creatinine clearance >45 mL/min, a receiver operating characteristic curve analysis was applied on these parameters. The area under curve for age is 0.496, for body weight is 0.539, and for highly sensitive C-reactive protein is 0.582, which are all around the chance of 0.5 by flipping coins. The area under ACR curve is 0.825, better than above parameters, and only second to serum creatinine level. ConclusionsUrine ACR is a simple and effective measure to predict graft function after a kidney transplant. It has similar independent strong correlations to creatinine clearance comparing with serum creatinine without requirement of a blood draw.

Early podocyte injury and elevated levels of urinary podocyte-derived extracellular vesicles in swine with metabolic syndrome: role of podocyte mitochondria.

Metabolic syndrome (MetS) is associated with nutrient surplus and kidney hyperfiltration, accelerating chronic renal failure. The potential involvement of podocyte damage in early MetS remains unclear. Mitochondrial dysfunction is an important determinant of renal damage, but whether it contributes to MetS-related podocyte injury remains unknown. Domestic pigs were studied after 16 wk of diet-induced MetS, MetS treated with the mitochondria-targeted peptide elamipretide (ELAM; 0.1 mg·kg-1·day-1 sc) for the last month of diet, and lean controls (n = 6 pigs/group). Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured using multidetector computed tomography, and podocyte and mitochondrial injury were measured by light and electron microscopy. Urinary levels of podocyte-derived extracellular vesicles (pEVs; nephrin positive/podocalyxin positive) were characterized by flow cytometry. Body weight, blood pressure, RBF, and GFR were elevated in MetS. Glomerular size and glomerular injury score were also elevated in MetS and decreased after ELAM treatment. Evidence of podocyte injury, impaired podocyte mitochondria, and foot process width were all increased in MetS but restored with ELAM. The urinary concentration of pEVs was elevated in MetS pigs and directly correlated with renal dysfunction, glomerular injury, and fibrosis and inversely correlated with glomerular nephrin expression. Additionally, pEV numbers were elevated in the urine of obese compared with lean human patients. Early MetS induces podocyte injury and mitochondrial damage, which can be blunted by mitoprotection. Urinary pEVs reflecting podocyte injury might represent early markers of MetS-related kidney disease and a novel therapeutic target.

Biochemical evaluation of kidney disease.

Different biochemical markers exist in both blood and urine for assessing renal function. Most of these biomarkers have advantages and limitations associated with their use, which is important to consider when ordering and utilising them in the clinical setting. The ideal marker should be able to detect acute kidney injury (AKI) at the onset and be used for the diagnosis and ongoing monitoring and management of kidney disease. The search for such a marker is ongoing, as all potential candidates thus far are associated with certain limitations. This article will attempt to compare and contrast established and emerging kidney disease markers.

Physical component quality of life reflects the impact of time and moderate chronic kidney disease, unlike SF‐6D utility and mental component SF‐36 quality of life: An AusDiab analysis

Assessing the impact of interventions on the patient experience requires measures that are plausibly responsive to change. In a community cohort of people with and without chronic kidney disease (CKD) markers at baseline, we aimed to evaluate change in commonly used measures of quality of life (QOL) over the passage of 5 years. Included were 6400 participants in the Australian Diabetes, Obesity and Lifestyle (AusDiab) surveys with baseline and 5-year CKD and QOL measures. Changes in SF-6D utility, and the Medical Outcomes Study 36-Item Short Form (SF-36) physical (PCS) and mental (MCS) component summary scores, were evaluated with regression analyses according to the baseline presence of reduced estimated glomerular filtration rate (eGFR) (CKD-Epidemiology Collaboration eGFR ≤60 m/min per 1.73 m2 ) or albuminuria (urine albumin:creatinine ratio ≥3.4 mg/mmol). At baseline, eGFR was reduced in 2.4% of participants and 5.1% had albuminuria. Participants with reduced eGFR had a lower SF-6D and PCS, and those with albuminuria a lower PCS, compared with those without, but the differences were explained by known confounders. MCS scores were not affected by the presence of reduced eGFR or albuminuria. Over 5 years all groups exhibited stable SF-6D and MCS scores but declining unadjusted PCS scores. PCS decline was greater for those with reduced eGFR, and remained significant after adjustment (-2.7 (-4.1 to -1.3) vs. -0.8 (-1.1 to -0.6, P < 0.01). Analyses according to CKD stages were essentially unchanged. Utility and mental QOL appears stable over 5 years, unaffected by time or markers of CKD health. Physical QOL appeared to deteriorate with time, especially for those with CKD, making it a more likely candidate assessment measure for intervention and health service evaluations.