Normal Albuminuria Research Articles

Study the Possible Levels of Inflammatory Marker TNF-? and Microalbuminuria in Type 2 Diabetic Nephropathy Patients of Babylon Province/Iraq

Background: Diabetic nephropathy is referred to as the kidney damage that occurs in people with diabetes developing it over many years characterized by gradually increasing urinary albumin excretion (>300µg/ mg) from microalbuminuria to proteinuria, blood pressure, and declining in glomerular filtration rate (GFR) (thickening in glomerulus) which represents the late event. Aim: Study the relationship between the levels of urinary TNF-? and the progression of diabetic nephropathy in type2 diabetic patients. Objective: Fasting blood and urine samples were collected from seventy type2 diabetic patients with enrollment the age, duration, blood pressure, and Body Mass Index (BMI) of each patient. the levels of urine TNF-? were established by ELISA. Results: forty-patients have normal albuminuria (Albumin/Creatinine Ratio <30 µg/mg) and only thirtypatients have microalbuminuria (Albumin/Creatinine Ratio>300 µg/mg) with increased urinary TNF-? levels. Conclusions: A significant positive relationship between urinary TNF-? and sever microalbuminuria.

Risk Factors for Albuminuria in Normotensive Older Adults with Type 2 Diabetes Mellitus and Normal Renal Function: A Cross-Sectional Study.

IntroductionDiabetes mellitus (DM) is prevalent in developed and developing countries, including China. However, few studies have examined the potential risk factors for albuminuria in normotensive older adults with type 2 DM and normal renal function.MethodsWe recruited normotensive older adults (≥ 65 years) with type 2 DM and normal renal function from the First Affiliated Hospital of Soochow University from January to December 2019. We stratified participants according to their urine albumin to creatinine ratio (ACR) into the following groups: normal ACR (ACR1), microalbuminuria (ACR2), and macroalbuminuria (ACR3). Demographic characteristics, anthropometric parameters, and metabolic profiles were recorded. Creatinine clearance (Ccr) and homeostasis model assessment—insulin resistance (HOMA-IR) were calculated. Logistic regression was used to examine risk factors for albuminuria.ResultsA total of 250 older adults were enrolled during the study period, including 124, 82, and 44 with normal albuminuria, microalbuminuria, and macroalbuminuria, respectively. We found that an extended duration of DM (odds ratio [OR] 1.085, 95% confidence interval [CI] 1.012–1.164, P = 0.022), elevated systolic blood pressure (OR 1.049, 95%CI 1.018–1.081, P < 0.01), elevated glycated hemoglobin (OR 1.734, 95% CI 1.332–2.258, P < 0.01), low insulin (OR 0.871, 95% CI 0.804–0.944, P < 0.01), and low C-peptide (OR 0.365, 95% CI 0.239–0.588, P < 0.01) were independent risk factors for albuminuria.ConclusionElevated blood pressure, low insulin, low C-peptide, and poor glycemic control were significant risk factors for albuminuria. These parameters may serve as early indicators for intervention.

Relationship between serum Dickkopf-1 and albuminuria in patients with type 2 diabetes.

BACKGROUNDDiabetic kidney disease is a microvascular complication of diabetes with complex pathogenesis. Wingless signaling-mediated renal fibrosis is associated with diabetic kidney disease. Dickkopf-1, a negative regulator of Wingless, has been proven to participate in renal fibrosis, glucose metabolism, and inflammation. However, whether serum Dickkopf-1 levels are associated with diabetic kidney disease remains unclear. AIMTo assess the relationship between serum Dickkopf-1 levels and albuminuria in individuals with type 2 diabetes.METHODSSeventy-three type 2 diabetes patients and 24 healthy individuals were enrolled in this case-control study. Diabetic individuals were separated into normal albuminuria, microalbuminuria, and macroalbuminuria groups based on their urinary albumin/creatinine ratios (UACRs). Clinical characteristics and metabolic indices were recorded. Serum Dickkopf-1 levels were determined by enzyme-linked immunosorbent assay.RESULTSNo significant difference in serum Dickkopf-1 levels was found between healthy individuals and the normal albuminuria group. However, the levels in the microalbuminuria group were significantly lower than those in the normal albuminuria group (P = 0.017), and those in the macroalbuminuria group were the lowest. Bivariate analysis revealed that serum Dickkopf-1 levels were positively correlated with hemoglobin A1c level (r = 0.368, P < 0.01) and estimated glomerular filtration rate (r = 0.339, P < 0.01), but negatively correlated with diabetes duration (r = -0.231, P = 0.050), systolic blood pressure (r = -0.369, P = 0.001), serum creatinine level (r = -0.325, P < 0.01), and UACR (r = -0.459, P < 0.01). Multiple and logistic regression showed that serum Dickkopf-1 levels were independently associated with UACR (odds ratio = 0.627, P = 0.021).CONCLUSIONSerum Dickkopf-1 levels are negatively associated with UACR. Lower serum Dickkopf-1 levels could be a critical risk factor for albuminuria in diabetes.

Общие патогенетические аспекты развития диабетической ретинопатии и нефропатии. Трансплантация почки и течение диабетической ретинопатии

Epidemics of diabetes and its complications is a global threat to the health of human population. In 2040, the number of patients with diabetes is predicted to rise to 642 million. Diabetic retinopathy and nephropathy are the most dangerous complications. Chronic hyperglycemia is a major factor that determines the development and progression of microvascular complications of diabetes including retinopathy and nephropathy. Key biological pathogenic mechanisms of microvascular complications involve over-production of reactive oxygen species and activation of intracellular signaling pathways and their modulators. OCT angiography is a safe and informative early diagnostic tool to assess vascular retinal abnormalities and to monitor treatment efficacy. Proteinuria was long considered the gold standard to evaluate and monitor kidney functions. However, one-third of patients develop diabetic nephropathy in normal albuminuria. Degradation products of glomerular filtration barrier are thought to be perspective biomarkers of early diabetic nephropathy. End-stage renal disease requires kidney transplantation. In addition to the improvement of uremic syndrome, kidney transplantation favors the course of diabetic retinopathy. Keywords: diabetes, diabetic retinopathy, diabetic nephropathy, optical coherence tomography, OCT angiography, kidney transplantation. For citation: Vorobyeva I.V., Moshetova L.К., Pinchuk A.V. et al. Common pathogenic aspects of diabetic retinopathy and nephropathy. Kidney transplantation and the course of diabetic retinopathy. Russian Journal of Clinical Ophthalmology. 2021;21(2):90–95. DOI: 10.32364/2311- 7729-2021-21-2-90-95.

Features of the course of the nephropathy in patients with type 2 diabetes mellitus: genetic aspects and angiogenesis

Objective — to determine serum level of vascular endothelial growth factor (VEGF) in patients with diabetic nephropathy (DN) — carriers of different genotypes of Klotho gene polymorphism in different stages of the disease and in the treatment dynamics.Materials and methods. The examinations involved 84 patients (38 men and 46 women) with type 2 diabetes mellitus (DM 2). Depending on the functional state of kidneys, patients were divided into two groups: Group I — patients with normal glomerular filtration rate (GFR) and albuminuria (n = 46), group II — patients with the reduced GFR and albuminuria (n = 38). The control group consisted of 40 healthy individuals. DNA amplification and genotyping of the Klotho gene polymorphism were performed by real-time PCR. VEGF concentration was determined by enzyme-linked immunosorbent assay before and after 6 months of pathogenetic therapy, which included: antidiabetic drugs, ACE inhibitor or angiotensin II receptor blocker and coenzyme A reductase inhibitor.Results. In patients with DN, a significant increase of serum VEGF levels was determined, which was closely related to the functional state of the kidneys. The VEGF level was 162.63 ± 0.31 pg/ml in DN with albuminuria and normal GFR, 367.43 ± 36.15 pg/ml in DN with decreased GFR. The highest response to pathogenetic treatment was observed in the group with the initial stages of nephropathy — the level of VEGF decreased by 28 %, while in the group with low GFR — only by 16 %.Conclusions. It has been established that carriers of the heterozygous genotype of the F352V polymorphism of the Klotho gene had significantly lower serum VEGF levels when compared to the common F352F genotype. Blood VEGF levels in patients with DN can serve as an integral marker of endothelial dysfunction and pathological angiogenesis. After 6 months of pathogenetic nephroprotective therapy serum VEGF levels decreased significantly in all groups of patients with DN.

The Role of Circulating RBP4 in the Type 2 Diabetes Patients with Kidney Diseases: A Systematic Review and Meta-Analysis.

Background Diabetic nephropathy is a common and serious complication of diabetes mellitus (DM) and is one of the leading causes of end-stage renal disease worldwide. Although there have been many investigations on biomarkers for DN, there is no consistent conclusion about reliable biomarkers. The purpose of this study was to perform a systematic review and meta-analysis of the role of circulating retinol-binding protein 4 (RBP4) in the type 2 diabetes mellitus (T2DM) patients with kidney diseases. Materials and Methods We searched the PubMed, MEDLINE, EMBASE, and Web of Science databases for publications. For the 12 cross-sectional studies that we included in the review, we calculated standard mean differences (SMD) with 95% confidence intervals (CI) for continuous data when the applied scales were different. Risk of bias of included trials was assessed by using the Newcastle-Ottawa Scale. Results RBP4 concentrations in the micro-, macro-, or micro+macroalbuminuria groups were significantly higher than those in the normal albuminuria group of T2DM patients [P = 0.001, SMD 1.07, 95% CI (0.41, 1.73)]. The estimated glomerular filtration rate (eGFR) was negatively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher's Z = −0.48, 95% CI (-0.69, -0.26), P < 0.0001]. The albumin-to-creatinine ratio (ACR) was positively associated with circulating RBP4 concentrations in patients with T2DM [summary Fisher's Z = 0.20, 95% CI (0.08, 0.32), P = 0.001]. Conclusion The levels of circulating RBP4 were significantly higher both in T2DM subjects with micro/macroalbuminuria and in T2DM subjects with declined eGFR. The levels of circulating RBP4 were positively correlated with ACR but negatively correlated with eGFR. Circulating RBP4 could be a reliable biomarker for kidney diseases in T2DM.

Features of development of diastolic heart dysfunction in patients with comorbid pathology depending on the functional state of the kidney

The development of complications of diabetes mellitus and hypertension, in particular kidney and heart damage, mutually reinforcing each other, not only affect the quality of life, but also significantly reduce its average duration. One of the common problems in patients with comorbid pathology is the high prevalence of chronic heart failure. Very often chronic heart failure develops with a preserved left ventricular ejection fraction. These changes are associated with the diastolic phase of the heartbeat - diastolic dysfunction. The features of the development of diastolic dysfunction in patients with type 2 diabetes in combination with hypertension depending on the functional state of the kidneys were studied. After the initial examination, depending on the functional state of the kidneys, all examined patients were divided into three groups: first group consists of 25 patients with type 2 diabetes without signs of nephropathy; second group consists of 23 patients with type 2 diabetes with normal glomerular filtration rate and albuminuria; third group consists of 20 patients with type 2 diabetes with decreased glomerular filtration rate and albuminuria. The control group consisted of 20 healthy patients. To study the state of the heart, transthoracic echocardio­graphy was performed on a ULTIMA PA ultrasound machine (Radmir, Ukraine) with a sectoral phased transducer with a frequency range of 2-3 MHz, according to the standard technique according to the recommendations of the American Echocardiographie Society. The data obtained confirm the need for prevention, early diagnosis, clarification of mechanisms and adequate treatment of diastolic dysfunction in diabetic nephropathy patients even before the onset of renal failure. Structural changes in cardiomyocytes activate the processes of apoptosis, enhancing the production of extracellular matrix, and contribute to the formation of myocardial fibrosis. Fibrous changes lead to the progression of impaired contractile function and an increase in the stiffness of the left ventricle walls, which leads to diastolic and systolic dysfunction and the development of heart failure. Diastolic myocardial function in diabetic nephropathy is complicated with the progression of the disease. Keywords: diabetes mellitus, hypertonic disease, diabetic nephropathy diastolic dysfunction, chronic kidney disease.

Relationship between high-normal albuminuria and arterial stiffness in Chinese population.

High-normal albuminuria is related to the morbidity and mortality of cardiovascular disease. Arterial stiffness has been regarded as a predictor of cardiovascular disease. However, the relationship between high-normal albuminuria and arterial stiffness is uncertain in Chinese population. A total of 1343 Chinese participants (aged 58.9±12.1years, 63.53% male) were included in this study. High-normal albuminuria was defined as urinary albumin-to-creatinine ratio (UACR) above the median within normal albuminuria. Based on the level of UACR, all participants were divided into low-normal albuminuria group (UACR<6.36mg/g, n=580), high-normal albuminuria group (6.36mg/g≤UACR<30mg/g, n=581), microalbuminuria (30mg/g≤UACR<300mg/g, n=162), and macroalbuminuria (UACR≥300mg/g, n=20). Arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV). With the increment of UACR, the level of cfPWV was increased gradually (P<.001). Stepwise multiple regression analysis showed that systolic blood pressure, age, serum creatinine, heart rate, logarithmic (LG)-transformed UACR, and fasting plasma glucose were independently associated with cfPWV in all subjects (P<.001). LG-UACR was found to be related to cfPWV in high-normal albuminuria and macroalbuminuria subjects. After further stratification in the high-normal albuminuria subjects, their relation remained in male, elderly over 65years old, or normotensives. In summary, UACR is associated with arterial stiffness in subjects with proteinuria excretion in high normal level. High-normal albuminuria might be an early indicator of arterial stiffness, especially in male, elderly, or normotensives in Chinese population. Furthermore, age and blood pressure are still observed to be the most important risk factor of arterial stiffness.

Early kidney damage in diabetic adolescents with increased blood pressure and glomerular hyperfiltration.

The early impact of type-1 diabetes mellitus (DM1), increased blood pressure and glomerular hyperfiltration (GHF) on kidney damage in adolescents using two urinary markers of kidney injury - neutrophil gelatinase-associated lipocalin (uNGAL) and transferrin (uTransf) was assessed. The study group consisted of 80 adolescents with DM1, of whom 42 were patients with increased blood pressure (IBP), and 38 were patients with normal blood pressure (NBP). Blood pressure was assessed by 24-hour ambulatory bloodpressure monitoring. All patients showed estimated glomerular-filtration rates (eGFRs) above 90 ml/min/1.73m2. The control group consisted of 19 healthy, age and gender-matched adolescents. All diabetic children showed a significant increase in uNGAL (p<0.001). This increase was not related to blood pressure. The uNGAL was elevated in all patients with normal albuminuria, normal eGFR and NBP. The concentration of uTransf was not increased in the entire studied group and was not related to blood pressure. Children with GHF had significantly higher levels of both uTransf (p=0.010) and uNGAL (p<0.001). In patients with GHF, blood pressure was normal. Patients with IBP showed a significantly higher value for triglycerides (r=0.247; p=0.032) and a longer duration of diabetes (r=0.264; p=0.019). Diabetes is the leading risk factor for early kidney injury. However, increased blood pressure does not lead to kidney damage, at least in the early stage of DM1. The uNGAL is the early indicator of kidney injury and increases in patients with normal albuminuria, normal glomerular filtration and normal blood pressure. Glomerular hyperfiltration seems to be a marker of diabetic-kidney involvement.

The correlation of circulating miR-29b and inflammatory markers with albuminuria in hypertensive patients

ABSTRACT Aims Circulating miR-29b and inflammatory process play a vital role in hypertension and hypertensive nephropathy. The aim of the present study was to investigate the association of circulating miR-29b and inflammatory markers with albuminuria and assess the predictive value of circulating miR-29b for albuminuria in essential hypertension. Methods This cross-sectional study was continuously enrolled 150 subjects and were divided into three groups based on random urinary albumin/creatinine ratio (UACR, mg/g), the patients with ACR<30 mg/g were classified as normal albuminuria, the values of 30< ACR<300 was defined as micro-albuminuria while the group with ACR over 300 mg/g are macro-albuminuria. Circulating miR-29b was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Multivariate logistic regression and area under the ROC curve (AUC) were used. Results We found miR-29b, C-reactive protein, and transforming growth factor-β1 (TGF-β1) in macro-albuminuria group were significantly higher than those in the micro-albuminuria and normal albuminuria group. The level of miR-29b was positively associated with TGF-β1, C-reactive protein, and UACR, while negatively related to glomerular filtration rate. Circulating miR-29b was a significant independent determinant factor for albuminuria. Conclusion Our results provided a clinical evidence of a positive association between circulating miR-29b, inflammatory markers, and UACR, and implied miR-29b was a significant independent determinant factor for albuminuria.

Evaluation of early biomarkers of renal dysfunction in diabetic patients.

Objectives:To evaluate 2 renal tubular enzymes; urinary neutrophil gelatinase-associated lipocalin (uNGAL), and urinary N-acetyl-beta-D-glucosaminidase (uNAG), and serum Cystatin C as candidate biomarkers for early diagnosis of early stage of diabetic nephropathy (DB) in patients with type 2 diabetes mellitus (T2DM).Methods:This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia during the period between May 2017 and May 2018 and was conducted on 86 patients with T2DM. Patients were classified according to their albumin/creatinine ratio (ACR) into 3 groups; a normal albuminuria group with ACR <30 mg/g creatinine, a moderately increased albuminuria group with ACR: 30-299 mg/g creatinine, and a severely increased albuminuria group with ACR ≥300 mg/g. Healthy adults were recruited as a control group. Urine uNGAL, uNAG, and serum Cystatin C were measured in all patients.Results:Compared with healthy control, diabetic patients with normal albuminuria excreted significantly higher levels of uNGAL (p<0.001). In addition, significantly elevated uNGAL, uNAG and cystatin C levels were observed in moderately increased albuminuria and severely increased albuminuria groups when compared to the control and normoalbuminuric groups (p<0.001). urinary neutrophil gelatinase-associated lipocalin, urinary N-acetyl-beta-D-glucosaminidase and Cystatin C showed a positive correlation with fasting blood glucose (FBG), HbA1c, duration of diabetes, urea, creatinine, and ACR.Conclusion:Our results indicated that uNGAL could be a sensitive biomarker for early renal dysfunction in diabetic patients while uNAG and serum Cystatin C might have prognostic value.

Serum Klotho protein level in type 2 diabetic patients depending on the renal function

The study aimed to assess serum Klotho protein level in type 2 diabetic patients depending on kidney function.&#x0D; Methods. This observational study included 72 patients with diabetes mellitus (DM) and 26 patients with acute coronary syndrome. The control group consisted of 20 healthy subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR), the diabetics were divided into the following groups: group I included the patients with normal GFR and without albuminuria (n = 25); group ІІ consisted the patients with normal GFR and albuminuria (n = 23); group III – the patients with reduced GFR and albuminuria (n = 24) and group ІV included the patients with acute coronary syndrome (n = 26).&#x0D; The GFR was calculated using the CKD EPI formula (KDIGO 2012). The concentration of Klotho protein was determined by enzyme-linked immunosorbent assay.&#x0D; Results. The development of diabetic nephropathy in type 2 diabetic patients accompanied by a significant decrease of soluble Klotho compared with the controls and the patients of the1-st group. The level of Klotho protein in the group of patients with albuminuria decreased to (490.66 ± 58.76) pg/ml (p &lt;0.05). The lowest concentration of Klotho (443.58 ± 46.92) pg/ml was found in the advanced stages of diabetic nephropathy, namely in patients with albuminuria and impaired renal function. Moreover, a significantly decreased serum Klotho was observed in acute coronary syndrome group in comparison with the control group (p &lt;0.05). There were inverse correlations of Klotho concentration with urinary albumin and blood creatinine levels and a direct correlation between Klotho and GFR.&#x0D; Conclusions. The obtained data indicated the key role of Klotho protein in the formation of renal pathology in type 2 diabetes and the feasibility of practical use of Klotho determination as an early diagnostic marker of renal disorders and cardiovascular risk assessment. The strategies improving Klotho production may be useful in the reduction of both renal and vascular lesions progression in type 2 diabetic patients.

P1037EFFECT OF VITAMIN D SUPPLEMENTATION ON PROTEINURIA, LIPID STATUS, GLICOREGULATION, C-REACTIVE PROTEIN, VEGF-A, TGF-BETA1 AND NEPHRIN IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Abstract Background and Aims: Vitamin D insufficiency/deficiency is often present in patients with Type-2 diabetes mellitus and could present a risk factor for rapid progression of diabetic nephropathy and higher incidence of cardiovascular events. The aim of this study was to examine the influence of vitamin D supplementation on glucoregulation, inflammation, cholesterol, triglycerides, albuminuria and biomarkers of renal injury – nephrin, VEGF-A and TGF- β1 in patients with Type-2 diabetes mellitus and vitamin D insufficiency/deficiency. Method: We included 90 patients with Type-2 diabetes mellitus and vitamin D insufficiency/deficiency in this prospective, cohort study. Patients are divided in 3 equal groups: 30 patients with normal albuminuria, 30 with microalbuminuria and 30 with macroalbuminuria. Therapy included 6 months of supplementation with cholecalciferol drops: first 2 months with 20000 IU twice weekly, than if vitamin D level remained below normal range, we procedeed with same dose next 4 months. If the level of vitamin D normalized, we proceeded with 5000 IU twice weekly. At the beginning and at the end of the study we measured levels of albumin, hemoglobin, serum iron, urea, creatinine, fasting blood glucose, hemoglobin A1c, calcium, phosphorus, total cholesterol, triglycerides, C-reactive protein, intact parathyroid hormone, and urine analysis: 24-hour urine protein, albumin/creatinine ratio and creatinine clearance. Biomarkers are measured in serum and urine. Levels of calcium, phosphorus and vitamin D are also checked 2 months after beginning of therapy due to possible correction of cholecalciferol dose. Results are analysed according to the vitamin D level at the beginning and at the end of the study. Results: The lowest level of vitamin D, before therapy, is found in patients with macroalbuminuria, while at the end of the study we found significantly higher level of vitamin D in all three groups. After 6 months of therapy we found significant decrease of 24-hour urine protein, total cholesterol, triglycerides, hemoglobin A1c and VEGF-A in urine, in all three groups, and C-reactive protein in patients with normal albuminuria and microalbuminuria, nephrin in urine in patients with microalbuminuria and TGF- β1 in urine in patients with macroalbuminuria. Conclusion: vitamin D supplementation with high-dose cholecalciferol in patients with Type-2 diabetes mellitus (with or without albuminuria) decreases C-reactive protein, hemoglobin A1c, total cholesterol, triglycerides in serum, and albumin/creatinine ratio, 24-hour urine protein, VEGF-A, TGF- β1 and nephrin in urine.

P1038NEPHROPROTECTIVE EFFECT OF SGLT2 INHIBITORS DURING FIRST YEAR OF TREATMENT

Abstract Background and Aims SGLT2 inhibitors, the most recent glucose-lowering oral agents, have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects. Recent studies demonstrate this effect with decreased albuminuria and lowering the progression of chronic kidney disease. The aim of our study was to evaluate the effect of iSGLT2 on glomerular filtration rate and albuminuria during the first year of treatment. Method This was a retrospective cross-sectional study that included patients diagnosed with DM2 and treated with an iSGLT2 during 1 year in a Diabetic Clinic. Demographic and clinical variables were collected, including HbA1c, disease duration and cardiovascular risk factors (CVRF). Patient glucose-control therapy as well as RAAS inhibitor drugs were gathered. The estimated Glomerular Filtration Rate (eGFR) by the formula CKD-EPI and albuminuria, using the urinary albumin-to-creatinine ratio, were evaluated at the iSGLT2 introduction date and at 3, 6, 9 and 12 months of treatment. Results We analyzed 208 patients, 53.8% male, mean age 65.5 years, median baseline HbA1c 8.4% and median duration of DM2 14 years. Of all patients, 94.2% had at least 1 CVRF, 71.6% were hypertensive, 83.2% had dyslipidemia, 48.1% were obese, and 25.2% had past/current smoking habits. Regarding glucose-control therapy, only 20.2% were treated with one oral drug class and the remaining with 2 or more classes, with 81.7% of the patients receiving metformin and 51.4% being on insulin therapy. Overall, 63.5% of patients received dapaglifozin therapy and 36.5% empaglifozin. Also, 56.3% were on a RAAS inhibitor. Regarding eGFR, 15.6% patients had an eGFR between 30 and 60 and 84.4% patients had an eGFR greater than 60 ml/min/1.73m2. As for albuminuria, 37 patients had normal albuminuria (&amp;lt;30mg/g), 18 patients had moderate albuminuria (30-300mg/g) and 6 patients had severe albuminuria (&amp;gt;300mg/g). In 12 months, there was a significant reduction in HbA1c (mean variation 0.5%) (p&amp;lt;0.001). Evaluating eGFR throughout the year, a decrease was observed in the first 6 months from an average of 81.6 to 78.5 ml/min/1.73m2 (p=0,001). Although on the second semester, there was an increase in eGFR to 83.4 ml/min/1.73m2 (p&amp;lt;0.001). These were similar in patints treated with dapagliflozin and empagliflozin. In patients with eGFR &amp;lt;60ml/min at the admission, there was an increase in eGFR from 49.6 to 53.4ml/min/1.73m2 after one year of treatment (p=0,260). A decrease in albuminuria levels was observed in the first year of iSGLT2 use, either in the case of moderate albuminuria (initial median of 80.52mg/g to 54.88mg/g) (p=0,758) or severe albuminuria (initial mean 650.40mg/g to 420.28mg/g) (p=0,213). Conclusion This data shows that after an initial reduction in eGFR during the first 6 months of treatment, the use of iSGLT2 after one year improved the eGFR, promoting a nephroprotective effect in type 2 diabetic patients.

2149-PUB: The Changes in the Panel of Circulating Cytokines Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes

Aim: To estimate the differences in the panel of circulating cytokines mediating low-grade inflammation and fibrosis in patients with type 2 diabetes (T2D) and chronic kidney disease.Methods: We examined 130 patients with T2D duration ≥10 years. Among them, 65 individuals had reduced estimated glomerular filtration rate (eGFR; 15-59 ml/min/1.73 m2) and 64 patients had increased albuminuria. Thirty healthy subjects were acted as control. Serum IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17A, bFGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF were assessed by multiplex analysis. Urinary nephrin and podocin, as podocyte injury markers, and WFDC-2, a marker of tubulointerstitial fibrosis, were assessed by ELISA. Results: Patients with T2D and reduced eGFR had increased levels of IL-1ra, IL-8, IL-13 and decreased IL-7, IL-9 and IL-15 concentrations when compared to those with preserved renal function and control (all p&amp;lt;0.05). Excretion of WFDC-2, but not podocyte markers, was increased in these patients (p≤0.02). The elevation of albuminuria was associated with enhanced excretion of nephrin and podocin (p&amp;lt;0.0001), but no differences were found in the levels of all measured cytokines between patients with normal and elevated albuminuria. The levels of IL-2, IL-4, IL-5, IL-17A, bFGF, G-CSF, IP-10 and MIP-1α correlated negatively with eGFR. No correlations were found between measured cytokines and glomerular markers. There was positive correlation between WFDC-2 and MIP-1α. The levels of IL-10 and IL-15, two anti-inflammatory cytokines, correlated negatively with WFDC-2. Conclusion: The obtained results demonstrate that decreased eGFR and increased urinary excretion of WFDC-2, a marker of tubulointerstitial fibrosis, are associated with a predominance of pro-inflammatory and fibrogenic molecules in the panel of circulating cytokines in T2D subjects. Disclosure A.I. Korbut: None. O. Fazullina: None. V. Klimontov: None.

Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative correlation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=-0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbuminuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients.

Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study.

This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR < 30 mg/g, n = 136, NA), microalbuminuria (UACR at 30-300 mg/g, n = 132, MA), and clinical albuminuria (UACR > 300 mg/g, n = 122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects (P < 0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR (P < 0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.

Effect of vitamin D on proteinuria, lipid status, glicoregulation and C-reactive protein in patients with type-2 diabetes mellitus

Background/Aim. Vitamin D insufficiency/deficiency is often present in patients with type-2 diabetes mellitus (DM) and could present a risk factor for rapid progression of diabetic nephropathy and for higher incidence of cardiovascular events. The aim of this study was to examine the influence of vitamin D supplementation on proteinuria, cholesterol, triglycerides, C-reactive protein (CRP) and hemoglobin A1c in patients with type-2 DM and vitamin D insufficiency/ deficiency. Methods. This prospective, cohort study included 90 patients with type-2 DM and vitamin D insufficiency/ deficiency divided into 3 equal groups: with normal proteinura, with microproteinuria and with macroproteinuria. Therapy included six months of supplementation with cholecalciferol drops: first two months with 20,000 IU twice weekly, than if level of vitamin D was below normal the same dose was given next four months. If the level of vitamin D was normal 5,000 IU was given twice weekly. At the begining and at the end of the study the levels of urea, creatinine, fasting blood glucose, calcium, phosphorus, cholesterol, triglycerides, CRP, hemoglobin A1c, intact parathyroid hormone, 24-hour urine protein and creatinine clearance were determined. Levels of calcium, phosphorus and vitamin D were also checked 2 months after beginning of therapy due to possible correction of cholecalciferol dose. Results. The lowest level of vitamin D before therapy was found in patients with macroproteinuria, while at the end of the study the significantly higher level of vitamin D was found in all three groups. After 6 months of therapy a significant decrease of 24-hour urine protein, cholesterol, triglycerides, hemoglobin A1c in all three groups, and CRP in patients with normal proteinuria and microproteinuria were found. Significantly negative correlation between vitamin D and 24-hour urine protein, cholesterol and CRP was found in patients with macroproteinuria. Also, significantly negative correlation was found between vitamin D and hemoglobin A1c, in patients with normal proteinuria, vitamin D and CRP in patients with microproteinuria. Conclusion. A preventive use of high-dose cholecalciferol supplementation in patients with type-2 DM (with or without proteinuria) decreases cholesterol, triglycerides, proteinuria, CRP and hemoglobin A1c.

The Evaluation of SCUBE-1 and sCD40L Levels in Diabetic Nephropathy

Aim: There is a close link between diabetic nephropathy and atherosclerotic heart disease. We aimed to evaluate the changes of SCUBE-1 and sCD40L, which play role in the course of atherosclerosis, with the progression of nephropathy in patients with type 2 diabetes.Material and Methods: Thirty healthy subjects (group 1) and 74 patients with type 2 diabetes (divided into 3 groups as normal albuminuria group (group 2, n=33), moderately increased albuminuria group (group 3, n=22) and severely increased albuminuria group (group 4, n=19)) were enrolled in the study. Plasma SCUBE-1 and sCD40L levels were measured using the enzyme-linked immunosorbent assay technique.Results: Mean SCUBE-1 levels were significantly higher in group 4 compared to group 1 and group 2 (p=0.005 and p=0.014, respectively) and in group 3 compared to group 1 and group 2 (p=0.011 and p=0.028, respectively). Mean sCD40L levels were significantly higher in group 4 than in other three groups (all p&amp;lt;0.001), and in group 3 than in group 1 and group 2 (p=0.001 and p=0.016, respectively). Furthermore, SCUBE-1 level was positively correlated with total cholesterol level (r=0.212, p=0.031) and triglyceride (r=0.194, p=0.049). Likewise, sCD40L level was positively correlated with only creatinine level (r=0.297, p=0.002).Conclusion: SCUBE-1 and sCD40L levels increased with the progression of nephropathy in type 2 diabetes. This increment suggested that SCUBE-1 and sCD40L may play key role in the course of atherosclerosis due to diabetic nephropathy and, diabetic nephropathy may affect the levels of these parameters.

The short-term effects of angiotensin II receptor blockers on albuminuria and renal function in Korean patients.

Each angiotensin II receptor blocker (ARB) asserts independent molecular effects. No study has compared the renoprotective potency of different types of ARBs in Korea. This study evaluated the differences among medications for treating albuminuria. Data were obtained from electronic medical records of adult patients who underwent albuminuria test and received treatment with either angiotensin-converting enzyme inhibitors (ACEIs) or ARBs between January 2009 and June 2016. Patients' albuminuria and renal function data were observed for three months after treatment initiation. In total, 1475 patients were included. Patients treated with ACEIs had no significant changes in albuminuria (from 127.7±55.1mg/g to 46.7±18.7mg/g, P=.127), but those treated with ARBs showed significant improvement (from 491.2±33.2mg/g to 372.0±28.0mg/g, P<.001). The ARB group had significantly more patients with normal albuminuria after treatment (from 55.8% to 59.3% for normal albuminuria, from 16.7% to 18.5% for moderately increased albuminuria and from 27.5% to 22.2% for severely increased albuminuria, P=.005), but renal function did not change significantly. Subgroup analysis of ARB types showed that candesartan (from 712.5±71.1 to 489.8±57.8mg/g, P<.001) and irbesartan (from 522.6±65.7 to 352.6±54.3mg/g, P<.001) had significant effects. Candesartan improved albuminuria in patients older than 60years (from 506.9±84.2 to 371.9±70.6mg/g, P=.004) and irbesartan improved albuminuria in patients with glomerular filtration rate <60 (from 551.6±100.0 to 392.4±76.2, P=.007). Only irbesartan and candesartan could reduce albuminuria, suggesting that all ARBs do not have the same outcome. This indicates the importance of optimizing ARB selection, considering both patient condition and organ-specific characteristics of medications.