Presence Of Diabetic Kidney Disease Research Articles

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

IntroductionDiabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality.Research design and methodsIn adults with type 1...

Association of thyroid autoantibodies and diabetic kidney disease in hospitalised patients with type 2 diabetes mellitus: a cross-sectional study from a Chinese university hospital

ObjectivesTo analyse and explore the association between thyroid autoantibodies and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).DesignA cross-sectional study.SettingPatients were from the inpatient unit at...

Pathophysiological features of thyroid dysfunction in patients with type 2 diabetes and chronic kidney disease (a literature review and own observations)

Background. Diabetes mellitus (DM) is a metabolic di­sease that causes disorders of all types of metabolism. Currently, there is an increasing prevalence of not only DM, but also its serious complications. One of the common chronic complications of DM is diabetic kidney disease (DKD). As of today, it is also known about the effect of DM on other endocrine organs, in particular thyroid gland. Thyroid dysfunction in combination with type 2 DM and DKD are interrelated conditions. In the literature review, the causes, theories of development, stages, course, and criteria for making a diagnosis of DKD are highlighted, probable mechanisms for the development of phenotypes are described. The impact of pathophysio­logical mechanisms of metabolic and secretory disorders on thyroid function has been demonstrated. PubMed and Google Scholar databases were used to search for literature data. The purpose of the study is to investigate the frequency and prevalence of phenoty­pic forms of DKD and the thyroid functional state. Materials and methods. We have analyzed the data of 1,874 patients with type 2 DM who were receiving inpatient treatment at the Lviv Regional Clinical Diagnostic Center, branch of the Center for Endocrinolo­gical Population Health, in 2022 and the first three quarters of 2023. Among them, 56 % were women, 44 % were men. The average age of the patients was 56.1 ± 8.2 years. The frequency and prevalence of phenotypic forms of DKD, the thyroid functional state in such patients were studied. Results. The share of patients with confirmed DKD was 26 % (n = 487). According to the results of the studies, DKD develops by a phenotype of non-albuminuric renal dysfunction in 288 patients (59 %), by an albuminuric phenotype — in 192 cases (39.6 %), and as a progressive decrease in kidney function — in 7 patients (1.4 %). Non-albuminuric renal dysfunction phenotype was 1.5 times more frequent than albuminuric one. Thyroid dysfunction was diagnosed in 166 patients with DKD (34 %). The obtained data confirm the greater prevalence of hypothyroidism as compared to hyperthyroidism in patients with DKD. This allows us to suspect that the structural and functional changes in the kidneys in type 2 DM, which lead to a decrease in the filtration capacity of the kidneys, may be independent of albuminuria. Conclusions. The presence of DKD, regardless of the stage of DM and phenotype, has a direct and indirect effect on the regulation and functioning of the thyroid gland. In turn, adequate production of thyroid hormones is necessary for a balanced metabolism, energy homeostasis and renoprotection. The presence of thyroid dysfunction can be a cause of unsatisfactory control of diabetes and lead to the development of complications.

Association of systemic immune-inflammation index with diabetic kidney disease in patients with type 2 diabetes: a cross-sectional study in Chinese population.

Systemic immune-inflammation index (SII), a novel inflammatory marker, has been reported to be associated with diabetic kidney disease (DKD) in the U.S., however, such a close relationship with DKD in other countries, including China, has not been never determined. We aimed to explore the association between SII and DKD in Chinese population. A total of 1922 hospitalized patients with type 2 diabetes mellitus (T2DM) included in this cross-sectional study were divided into three groups based on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR): non-DKD group, DKD stages 1-2 Alb group, and DKD-non-Alb+DKD stage 3 Alb group. The possible association of SII with DKD was investigated by correlation and multivariate logistic regression analysis, and receiver-operating characteristic (ROC) curves analysis. Moving from the non-DKD group to the DKD-non-Alb+DKD stage 3 Alb group, SII level was gradually increased (P for trend <0.01). Partial correlation analysis revealed that SII was positively associated with urinary ACR and prevalence of DKD, and negatively with eGFR (all P<0.01). Multivariate logistic regression analysis showed that SII remained independently significantly associated with the presence of DKD after adjustment for all confounding factors [(odds ratio (OR), 2.735; 95% confidence interval (CI), 1.840-4.063; P < 0.01)]. Moreover, compared with subjects in the lowest quartile of SII (Q1), the fully adjusted OR for presence of DKD was 1.060 (95% CI 0.773-1.455) in Q2, 1.167 (95% CI 0.995-1.368) in Q3, 1.266 (95% CI 1.129-1.420) in the highest quartile (Q4) (P for trend <0.01). Similar results were observed in presence of DKD stages 1-2 Alb or presence of DKD-non- Alb+DKD stage 3 Alb among SII quartiles. Last, the analysis of ROC curves revealed that the best cutoff values for SII to predict DKD, Alb DKD stages 1- 2, and DKD-non-Alb+ DKD stage 3 Alb were 609.85 (sensitivity: 48.3%; specificity: 72.8%), 601.71 (sensitivity: 43.9%; specificity: 72.3%), and 589.27 (sensitivity: 61.1%; specificity: 71.1%), respectively. Higher SII is independently associated with an increased risk of the presence and severity of DKD, and SII might be a promising biomarker for DKD and its distinct phenotypes in Chinese population.

Burden and predictors of diabetic kidney disease in an adult Ugandan population with new-onset diabetes

BackgroundDespite the growing evidence of diabetic kidney disease (DKD) in adult patients with long-standing diabetes in sub-Saharan Africa, data on its burden and correlates in adult African patients with new-onset diabetes are limited. We, therefore, undertook this study to determine the burden and predictors of DKD in an adult population with new-onset diabetes in Uganda.MethodsWe collected data on the relevant sociodemographic, clinical, anthropometric, and metabolic characteristics in 519 participants with newly diagnosed diabetes recruited from seven tertiary hospitals. A spot mid-stream urine sample was collected for determination of the urine albumin creatinine ratio (UACR) using Clinitek® microalbumin strips and a point-of-care Clinitek® status analyser. The estimated glomerular filtration rate (e-GFR) was determined using the Chronic Kidney Disease Epidemiology formula. The presence of DKD was defined as a spot UACR ≥ 3 mg/mmol with or without an e-GFR < 60 ml/min/1.73m2.ResultsThe median (IQR) age, UACR, and e-GFR of the participants were 48 years (39–57), 2.27 mg/mmol (1.14–3.41), and 121.8 ml/min/1.73m2 (105.4-133.9). UACR ≥ 3 mg/mmol and e-GFR < 60 ml/min/1.73m2 was noted in 175 (33.7%) and 7 (1.4%) participants, respectively. DKD was documented in 175 participants (33.7%). Compared with those without DKD, participants with DKD were more likely to be ≥ 50 years of age (53.7% vs. 43%, p = 0.02) and to have co-existing hypertension at the time of diagnosis (40.6% vs. 30.1%, p = 0.02). On multivariate analysis, self-reported hypertension comorbidity (OR 1.76 95% CI 1.24–2.48, p = 0.002) and body mass index (BMI) ≥ 30 kg/m2 (OR 0.61 95% CI 0.41–0.91, p = 0.02) were noted to independently predict DKD.ConclusionIn this study population, DKD was relatively common and was independently associated with self-reported hypertension comorbidity and BMI ≥ 30 kg/m2.

The glycemic profile in patients with non-alcoholic steatohepatitis and type 2 diabetes depending on diabetic kidney disease

Background. State of carbohydrate metabolism and severity of insulin resistance in the comorbid course of non-alcoholic steatohepatitis (NASH) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (DM2) is due to the cascade of possible transformation of NASH into liver cirrhosis. The purpose is to study the interaction of changes in glucose and insulin homeostasis, the degree of insulin resistance and insulin sensitivity, the degree of hemoglobin glycosylation on the clinical course of NASH associated with DM depending on the presence of DKD and its stage. Materials and methods. One hundred and eight patients with NASH and comorbid DM2 were examined. The average age of patients was 58.2 ± 6.1 years. There were 63 women (58.3 %) and 45 men (41.7 %). Depending on the presence of DKD, 4 groups of patients were formed, who were randomized by age, sex, activity of cytolytic syndrome. The comparison group consisted of 30 healthy individuals of the appropriate age and sex. The degree of hepatic steatosis and its nature were determined using SteatoTest, ASH and NASH-Test kits (BioPredictive, France). The stage of liver fibrosis was determined using FibroTest (BioPredictive, France), a set of markers for quantitative biochemical evaluation of fibrosis. Results. In patients with NASH, DM2 and DKD stage I–II, we found a significant decrease in serum albumin by 9.0 % (p &lt; 0.05); glomerular filtration rate (GFR) and urine albumin, on the contrary, increased significantly, by 1.5 times (p &lt; 0.05) compared to those in the control group, which indicates the phenomenon of hyperfiltration and is specific to the initial stage of DKD. When NASH is combined with DM2 and DKD stage III, a significant decrease in serum albumin by 1.2 times (p &lt; 0.05) is reported; GFR and albuminuria were significantly increased, by 1.4 and 11.7 times (p &lt; 0.05), respectively, compared to the control group. In patients with NASH, DM2 and DKD stage IV, we found a significant decrease in serum albumin by 1.4 times (p &lt; 0.05), it was significantly increased by 30.2 times (p &lt; 0.05) compared to the indicator in the control group, and the GFR, on the contrary, was significantly reduced by 1.7 times (p &lt; 0.05), which indicates the progression of DKD. Conclusions. Disorders of glucose homeostasis due to insulin resistance are one of the probable risk factors for the progression of non-alcoholic steatohepatitis and type 2 diabetes mellitus in the presence of stage I–IV diabetic kidney disease.

Urinary metabolites associate with the presence of diabetic kidney disease in type 2 diabetes and mediate the effect of inflammation on kidney complication

AimsDiabetic kidney disease (DKD) is the one of the leading causes of end-stage kidney disease. Unraveling novel biomarker signatures capable to identify patients with DKD is favorable for tackle the burden. Here, we investigated the possible association between urinary metabolites and the presence of DKD in type 2 diabetes (T2D), and further, whether the associated metabolites improve discrimination of DKD and mediate the effect of inflammation on kidney involvement was evaluated.MethodsTwo independent cohorts comprising 192 individuals (92 DKD) were analyzed. Urinary metabolites were analyzed by targeted metabolome profiling and inflammatory cytokine IL-18 were measured by ELISA. Differentially expressed metabolites were selected and mediation analysis was carried out.ResultsSeven potential metabolite biomarkers (i.e., S-Adenosyl-L-homocysteine, propionic acid, oxoadipic acid, leucine, isovaleric acid, isobutyric acid, and indole-3-carboxylic acid) were identified using the discovery and validation design. In the pooled analysis, propionic acid, oxoadipic acid, leucine, isovaleric acid, isobutyric acid, and indole-3-carboxylic acid were markedly and independently associated with DKD. The composite index of 7 potential metabolite biomarkers (CMI) mediated 32.99% of the significant association between the inflammatory IL-18 and DKD. Adding the metabolite biomarkers improved the discrimination of DKD.ConclusionsIn T2D, several associated urinary metabolites were identified to improve the prediction of DKD. Whether interventions aimed at reducing CMI also reduce the risk of DKD especially in patients with high IL-18 needs further investigations.

Circulating 18-Glycosyl Hydrolase Protein Chitiotriosidase-1 is Associated with Renal Dysfunction and Systemic Inflammation in Diabetic Kidney Disease.

Chitotriosidase-1 (CHIT-1) is a marker of macrophage activation and recently attributed to type 2 diabetes mellitus (T2DM). However, its role in the development and progression of diabetic kidney disease (DKD) has been sparsely discussed in the recent literature. In this cross-sectional exploratory study, 81 participants with T2DM were classified into two groups based on the presence of DKD. Their anthropometric, biochemical, and pathological profiles were estimated. Circulatory CHIT-1 concentration was determined using the enzyme-linked immuno-sorbent assay (ELISA) in plasma. CHIT-1 was significantly elevated in diabetic nephropathy, independent of age and gender. It is associated with severity of kidney disease, as assessed using urinary protein-creatinine ratio (uPCR) in a multiple linear regression model, independent of age, gender, diabetes duration, and insulin resistance. CHIT-1 positively predicted the likelihood of DKD in the study population (area under the curve = 0.724, P < 0.05). The duration of diabetes correlated positively with uPCR and negatively with estimated glomerular-filtration rate. Neutrophil-Lymphocyte ratio was elevated in participants with DKD. This well-established marker of systemic inflammation exhibited significant positive association with CHIT-1. Plasma CHIT-1 protein is elevated in DKD and associated with disease progression. It is capable of reflecting disease severity and is closely related to systemic inflammation possibly caused by pro-inflammatory circulatory immune cells.

Association Between High-Sensitivity C-Reactive Protein and Diabetic Kidney Disease in Patients With Type 2 Diabetes Mellitus

ObjectiveHigh-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker. This study aimed to identify the correlation between hs-CRP levels and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM).Materials/MethodsThis cross-sectional and observational study included 927 patients with T2DM. We collected the data of patients based on their medical data, including sociodemographic characteristics, concomitant diseases, laboratory results, and medical therapy. Multivariate logistic regression analysis was conducted to assess the relationship between hs-CRP levels and DKD. A restricted cubic spline (RCS) was used to assess the correlation of hs-CRP levels on a continuous scale with the DKD.ResultsIn total, 927 patients were recruited in our study. The median age of the recruited patients was 55 years, and there were 346 female patients and 581 male patients. The hs-CRP levels were evidently higher in patients with DKD than those without DKD. After adjusting for age, sex, diastolic blood pressure, systolic blood pressure, body mass index, neck circumference, waist circumference, hypertension, duration of diabetes, common carotid artery plaque, fasting plasma glucose, glycated hemoglobin, hemoglobin, erythrocyte, leukocyte, γ-glutamyl transferase, albumin, urea nitrogen, uric acid and triglyceride, a significant increase in the odds ratios (ORs) for DKD in the fourth hs-CRP quartile compared with the first quartile was observed (P value for trend= 0.003), and the ORs (95% confidence intervals) in the fourth quartile of hs-CRP were 1.968 (1.244–3.114) for DKD compared to the first quartile.. Moreover, the RCS curves presented a positive association between hs-CRP and DKD in total subjects, male subjects and female subjects, respectively.ConclusionsThe results of our study indicated that hs-CRP levels were significantly and positively correlated with the presence of DKD, which may provide predictive and diagnostic values in clinical practice.

Association of chemotactic cytokine receptor 5 (CCR5) gene polymorphism (59029 A/G, rs1799987) with diabetic kidney disease in patients with type 2 diabetes from Poland.

Diabetic kidney disease (DKD) pathogenesis is multifactorial and is a combination of metabolic, genetic, and environmental factors. Due to a long period of asymptomatic course, it is often diagnosed late when advanced stages of the disease are present. Among patients with diabetes, the presence of chemotactic cytokine receptor 5 (CCR5) gene polymorphism is suspected to be associated with the risk of DKD occurrence; however, the results of the research conducted so far are inconclusive. The aim of this study was to evaluate the CCR5 gene polymorphism (rs1799987, 59029 A/G) association with DKD among patients with type 2 diabetes mellitus (T2DM), who are residents of the Upper Silesia region of Poland. CCR5 gene polymorphism (rs1799987, 59029 A/G) was assessed among consecutive patients with type 2 diabetes mellitus (T2DM) treated in a single outpatient diabetology clinic in Upper Silesia, Poland. Its association with DKD was examined. Additionally, selected clinical and demographic data were included in the analysis. Among 467 eligible study patients, there was no association between examined CCR5 gene polymorphism and the presence of DKD in relation both to the American Diabetes Association definition (p = 0.6) and to the National Kidney Foundation definition (p = 0.3) of this complication. The presented study did not confirm the association between the examined gene polymorphism and the risk of DKD; further studies in this area are needed in order to establish or explicitly exclude this association.

The Goto Kakizaki rat: Impact of age upon changes in cardiac and renal structure, function.

Patients with diabetes are at a high risk for developing cardiac dysfunction in the absence of coronary artery disease or hypertension, a condition known as diabetic cardiomyopathy. Contributing to heart failure is the presence of diabetic kidney disease. The Goto-Kakizaki (GK) rat is a non-obese, non-hypertensive model of type 2 diabetes that, like humans, shares a susceptibility locus on chromosome 10. Herein, we perform a detailed analysis of cardio-renal remodeling and response to renin angiotensin system blockade in GK rats to ascertain the validity of this model for further insights into disease pathogenesis. Study 1: Male GK rats along with age matched Wistar control animals underwent longitudinal assessment of cardiac and renal function for 32 weeks (total age 48 weeks). Animals underwent regular echocardiography every 4 weeks and at sacrifice, early (~24 weeks) and late (~48 weeks) timepoints, along with pressure volume loop analysis. Histological and molecular characteristics were determined using standard techniques. Study 2: the effect of renin angiotensin system (RAS) blockade upon cardiac and renal function was assessed in GK rats. Finally, proteomic studies were conducted in vivo and in vitro to identify novel pathways involved in remodeling responses. GK rats developed hyperglycaemia by 12 weeks of age (p<0.01 c/w Wistar controls). Echocardiographic assessment of cardiac function demonstrated preserved systolic function by 48 weeks of age. Invasive studies demonstrated left ventricular hypertrophy, pulmonary congestion and impaired diastolic function. Renal function was preserved with evidence of hyperfiltration. Cardiac histological analysis demonstrated myocyte hypertrophy (p<0.05) with evidence of significant interstitial fibrosis (p<0.05). RT qPCR demonstrated activation of the fetal gene program, consistent with cellular hypertrophy. RAS blockade resulted in a reduction blood pressure(P<0.05) cardiac interstitial fibrosis (p<0.05) and activation of fetal gene program. No significant change on either systolic or diastolic function was observed, along with minimal impact upon renal structure or function. Proteomic studies demonstrated significant changes in proteins involved in oxidative phosp4horylation, mitochondrial dysfunction, beta-oxidation, and PI3K/Akt signalling (all p<0.05). Further, similar changes were observed in both LV samples from GK rats and H9C2 cells incubated in high glucose media. By 48 weeks of age, the diabetic GK rat demonstrates evidence of preserved systolic function and impaired relaxation, along with cardiac hypertrophy, in the presence of hyperfiltration and elevated protein excretion. These findings suggest the GK rat demonstrates some, but not all features of diabetes induced "cardiorenal" syndrome. This has implications for the use of this model to assess preclinical strategies to treat cardiorenal disease.

304-OR: Association of Eating Patterns and Diabetic Kidney Disease in Type 2 Diabetes

Evaluation of association of eating patterns with diabetes kidney disease (DKD) in patients with type 2 diabetes (T2DM) was performed. Cross-sectionally, T2DM patients underwent clinical, laboratory, and nutritional assessments. Dietary information was evaluated by a quantitative food frequency questionnaire validated for diabetes and converted into daily intakes. The eating patterns were identified by cluster analysis. DKD was defined as estimated glomerular filtration rate &amp;lt;60 mL/min/1.73m2 and persistently elevated urinary albumin excretion (≥14 mg/dL). A chi-square test, one-way analysis of variance (ANOVA/Bonferroni’s post hoc test) and Kruskal-Wallis test (Bonferroni post hoc correction) were used to test differences across the eating patterns. Poisson regression analysis was used to investigate the associations between eating patterns and DKD. IBM SPSS Statistics 25.0 (p&amp;lt;0.05). A total of 329 T2DM patients were evaluated: 10 years (5-19) diabetes duration; HbA1c=8.7±2.0%; 62±10 years old; BMI=30.9±4.2kg/m². Four eating patterns were identified: (1) high intake of dairy products, fruits, and vegetables; (2) ultra-processed foods; (3) high intake of refined carbohydrates, processed meats, and solids fats; and (4) high intake of red meat and sugary beverages. Age, sex, sedentary lifestyle, maximum doses of anti-glycemic agent in addition to fasting plasma glucose levels were different among the patterns. Poisson regression models confirmed the association of Pattern 2 (PR=1.48; 95% CI=1.10-1.99; P=0.010) and Pattern 4 (PR=1.93; 95% CI=1.29-2.89; P=0.001) with presence of DKD after adjusting for confounders. In conclusion, eating patterns with higher consumption of ultra-processed foods or red meat and sugary beverages were associated with the presence of DKD when compared to patterns rich in dairy products, fruits, and vegetables in this sample of T2DM outpatients. Disclosure C. C. R. Rodrigues: None. B. P. Riboldi: None. T. C. Rodrigues: None. R. A. Sarmento: None. J. P. Antonio: None. R. A. Borba: None. A. P. Vieira: None. I. S. Pasini: None. J. C. De almeida: None.

Biochemical Urine Testing of Medication Adherence and Its Association With Clinical Markers in an Outpatient Population of Type 2 Diabetes Patients: Analysis in the DIAbetes and LifEstyle Cohort Twente (DIALECT)

To assess adherence to the three main drug classes in real-world patients with type 2 diabetes using biochemical urine testing, and to determine the association of nonadherence with baseline demographics, treatment targets, and complications. Analyses were performed of baseline data on 457 patients in the DIAbetes and LifEstyle Cohort Twente (DIALECT) study. Adherence to oral antidiabetics (OADs), antihypertensives, and statins was determined by analyzing baseline urine samples using liquid chromatography-tandem mass spectrometry. Primary outcomes were microvascular and macrovascular complications and treatment targets of LDL cholesterol, HbA1c, and blood pressure. These were assessed cross-sectionally at baseline. Overall, 89.3% of patients were identified as adherent. Adherence rates to OADs, antihypertensives, and statins were 95.7%, 92.0%, and 95.5%, respectively. The prevalence of microvascular (81.6% vs. 66.2%; P = 0.029) and macrovascular complications (55.1% vs. 37.0%; P = 0.014) was significantly higher in nonadherent patients. The percentage of patients who reached an LDL cholesterol target of ≤2.5 mmol/L was lower (67.4% vs. 81.1%; P = 0.029) in nonadherent patients. Binary logistic regression indicated that higher BMI, current smoking, elevated serum LDL cholesterol, high HbA1c, presence of diabetic kidney disease, and presence of macrovascular disease were associated with nonadherence. Although medication adherence of real-world type 2 diabetes patients managed in specialist care was relatively high, the prevalence of microvascular and macrovascular complications was significantly higher in nonadherent patients, and treatment targets were reached less frequently. This emphasizes the importance of objective detection and tailored interventions to improve adherence.

Association of Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio with Diabetic Kidney Disease among Adult Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies

Objective. This meta-analysis aimed to evaluate the association of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the presence of diabetic kidney disease (DKD) among adult patients with Type 2 diabetes mellitus (T2DM). Methods. A systematic search of articles was performed in various databases. Studies must have fulfilled the following criteria for inclusion: 1) Randomized controlled trial or observational study; 2) Included adults diagnosed with T2DM; 3) Reported data associating NLR or PLR with the presence of DKD; and 4) Controlled for confounders using logistic regression. Data analysis was performed using Review Manager 5.4 software. The estimates were derived using the generic inverse variance method and pooled using the random effects model. Results were presented as odds ratios (OR) and standard errors (SE) with 95% confidence intervals (CI), and graphically shown as forest plots. The I2 value and Chi-square test were used to assess heterogeneity across studies. Results. Seven studies were included in the review, totaling 1,486 patients. All were cross-sectional studies and had satisfactory methodological quality as evaluated using the Newcastle-Ottawa Quality Assessment Scale. Pooled analysis from six studies showed a statistically significant association between increased NLR and the presence of DKD, defined as either the presence of albuminuria (95% CI, OR 1.68 [1.28, 2.19], p<0.01); or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (95% CI, OR 1.56 [1.09, 2.23], p=0.01). In both analyses, there was no significant heterogeneity across studies (I2=0%, Chi2=3.54; and I2=28%, Chi2=2.76 respectively). On the other hand, pooled analysis from two studies did not show a statistically significant association between PLR and albuminuria (95% CI, OR 1.75 [0.85, 3.60], p=0.13), although both studies were homogeneous (I2=0%, Chi2=0.57). Conclusion. We found a statistically significant association between increased NLR and the presence of DKD. However, a similar association was not found with PLR. Larger studies with more robust designs are recommended.

Diabetic Nephropathy and Diabetic Kidney Disease

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) in the United States and worldwide. Alterations in glomerular hemodynamics, inflammation, and fibrosis are primary mediators of kidney tissue damage, although the relative contribution of these mechanisms likely varies between individuals and over the course of the natural history of diabetic kidney disease. The presence of DKD is also strongly associated with cardiovascular morbidity/mortality and has a major influence on survival. Clinical presentation and prognosis of DKD are heterogeneous and vary between individuals, although the severity of albuminuria, particularly when combined with elevated blood pressure, remains an important marker of those at higher risk of progression. Management of DKD requires a holistic approach that combines cardiovascular risk reduction with elements to slow the progression of kidney disease, namely glycemic control, RAAS inhibition and blood pressure lowering. Effective delivery of these interventions in combination reduces the risks of DKD progression, as well as other microvascular complications, cardiovascular events, and mortality. Several international groups have issued clinical guidelines that largely agree on recommended targets, and in clinical practice these should be tailored for each individual patient. SGLT2 inhibitors are exciting new options now available to slow the progression of diabetic nephropathy.

2150-PUB: Chemotactic Cytokine Receptor 5 (CCR5) Gene Promoter Polymorphism (rs1799987) Is Associated with the Risk of Diabetic Kidney Disease in Polish Patients with Type 2 Diabetes

Background and Aims: The environmental risk factors of diabetic kidney disease (DKD) do not allow identification of people at higher risk of it. A lot of expectations are being placed to the genetic predisposition. Among patients with diabetes, the presence of CCR5 gene polymorphism is suspected to be associated with DKD, yet the results are inconclusive. The aim of this study was to evaluate its association with DKD among Polish patients with type 2 (T2DM). Materials and Methods: CCR5 gene polymorphism (rs1799987, 59029 A/G) was assessed among 467 consecutive patients with T2DM visiting one outpatient diabetology clinic in Upper Silesia, Poland. DKD diagnosis was based on urinary albumin creatinine ratio &amp;gt;300 mg/g and the presence of diabetic retinopathy. Information related to time of diabetes duration and HbA1c were collected. Results: Clinical characteristic of studied patients is presented in Table 1. We found that both GG genotype (p=0.035) and allele G (p=0.02) were significantly associated with DKD occurrence and G allele was present in all of the DKD patients. Conclusion: A significant association between rs1799987 polymorphism of CCR5 gene and the presence of DKD in the group of Polish patients with T2DM was found what is in accordance with some previous studies. Further studies are needed in this area to confirm this association. Disclosure K. Nabrdalik: None. P.S. Pokrzywnicka: None. H. Kwiendacz: None. P. Adamczyk: None. D. Moczulski: None. H. Moczulska: None. K. Drozdz: None. W. Grzeszczak: None. J. Gumprecht: Consultant; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier. Speaker’s Bureau; Self; Astra, Bioton, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk A/S, Polfa Tarchomin S.A., Sanofi, Servier.

Diabetic retinopathy and its association with low glomerular filtration rate: a cross-sectional analysis of diabetes patients of community clinics across India

To determine the prevalence of diabetic retinopathy (DR) in patients with T2DM having low estimated glomerular filtration rate (eGFR). A cross-sectional retrospective data analysis of T2DM patients’ records who were screened for DR across Apollo Sugar Clinics from June 2016 to December 2016. DR was diagnosed through fundus examination; patients having eGFR values were grouped into eGFR < 60 and eGFR ≥ 60 mg/ml/1.73 m2. Appropriate statistical tests were applied to identify the association of eGFR and DR, and significance was set at 2-tailed p ≤ 0.05. A total of 1547 T2DM patients were screened; mean (SD) age was 56.7 (10.0) years. Among them, data of 443 patients with eGFR were included in the analysis. Mean eGFR was 91.2 mg/ml/1.73 m2; 12.5% patients had eGFR ≤ 60 mg/ml/1.73 m2 and 87.5% had ≥ 60 mg/ml/1.73 m2. DR was observed in 79 (17.8%) patients; it was higher in males (62%) than in females (38%). Further, the proportion of patients with DR was significantly higher in patients with eGFR ≤ 60 mg/ml/1.73 m2 compared with that in patients with eGFR ≥ 60 mg/ml/1.73 m2 (38% vs. 15%; p < 0.001). Association of DR with low eGFR in patients with T2DM may suggest presence of diabetes kidney disease in a community, thus reaffirming the significance of DR screening in community diabetes practices.

Prevalence and Associated Factors of Diabetic Kidney Disease in Senegalese Patients: A Cross-Sectional Study in Saint-Louis

Introduction: Diabetes is a leading cause of chronic kidney disease in the world. During the next decade, its burden is expected to increase in Africa with potential complications such as chronic kidney disease. However, epidemiology and risk factors of diabetic kidney disease are poorly described at population level. This study aimed to determine prevalence of diabetic kidney disease (DKD) in adult diabetics living in Saint-Louis, northern Senegal. Methods: A cross-sectional study including diabetic patients followed-up aged ≥18 years during a five-year period (2013-2018) in Saint-Louis. Clinical and biological parameters were collected during annual community-based mass screening. Diabetes was defined as fasting blood glucose ≥ 1.26 g/L confirmed by a second lab dosage. DKD was defined as persistence of albuminuria ≥ 30 mg/24h and/or estimated glomerular filtration rate (eGFR) 2. Data were analyzed with Stata 12.0. Results: We included a total of 1310 diabetic patients among whom 3.7% (95% CI = 1.4% - 9.8%) presented DKD. Their mean age was 46.2 ± 11.8 years and sex-ratio was 0.7. Micro-albuminuria and macro-albuminuria were present respectively in 59.2% and 18.4% of patients with DKD and half of them had a normal eGFR. Before the survey 89.8% of patients with DKD were not aware of their renal disease and only four of them had seen a nephrologist. After multivariate analysis, age (OR = 1.5; 95% CI = 1.1 - 3.4), duration of diabetes (OR = 1.2; 95% CI = 1.6 - 4.4) and hypertension (OR = 2.5; 95% CI = 1.4 - 4.6) were associated with the presence of DKD in diabetic patients while no significant association was not found with gender, blood glucose level, smoking and familial history. Conclusion: DKD is a frequent complication in diabetic adult population living in Saint-Louis. Early detection and management should be promoted in order to prevent progression to end-stage renal disease.

Disturbances in angiogenesis and vascular maturation in the skin are associated with diabetic kidney disease in type 1 diabetes

Introduction. The skin, as one of the most accessible tissues, is frequently used for investigations of microcirculation and angiogenesis. The aim of this study was to assess the relationship between the dermal microvessel density (MVD) and maturity and the presence of diabetic kidney disease (DKD) in adults with type 1 diabetes (T1D). Skin as the most accessible organ served as a model for the study of angiogenesis. Materials and methods. 148 consecutive T1D patients (87 men), median age of 41 [interquartile range (IQR): 31–49] years and diabetes duration of 21 (17–30) years, participated in the study. The patients were under the care of the Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences. Diabetic kidney disease was diagnosed in patients with increased albuminuria and at least 10-year duration of diabetes or evidence of diabetic retinopathy. The skin biopsy was performed on distal part of lower leg, using a sterile, disposable 3 mm biopsy punch with plunger (Disposable Biopsy Punches, Integra™ Miltex ® ). In the immunohistochemical analyses, we used: anti-CD133, anti-CD34, anti-CD31, and anti-von Willebrand factor (vWF) autoantibodies. Microvessel density measurement in all specimens was performed using “hot spots technique”. Slides were scanned using the MiraxMidi scanner (Carl Zeiss) and were viewed using CaseViewer (3DHISTECH Ltd. Budapest, Hungary). Data were analyzed using Statistica v. 13 software. Results. In the study group 21 patients with diagnosis DKD+, as compared to 127 subjects withaout DKD–, had longer duration of diabetes [30 (IQR: 21–36) vs. 21 (16–28) years, p = 0.002], higher prevalence of hypertension [14 (67%) vs. 37 (29%), p = 0.002], lower estimated glomerular filtration rate (eGFR) [66 (55–88) vs. 94 (83–106) mL/min/1.73 m 2 , p < 0.001]. Median MVD compared between groups with and without DKD, was similar for CD34+ vessels/1 mm 2 [123 (100–170) vs. 121 (100–170), p = 0.775], CD133+ vessels/1 mm2 [79 (50–100) vs. 79 (63–93), p = 0.823], and for CD31+ vessels/ 1 mm 2 [29 (21–46) vs. 38 (17–58), p = 0.454]. Median MVD vWF+ vessels/1 mm 2 was lower in the group with than without DKD: 42 (25–54) vs. 54 (43–71), p = 0.009. The values given above were calculated for both layers of the dermis (papillary and reticular dermis). In multivariate logistic regression analysis presence of diabetic kidney disease was associated with lower median vWF+ MVD [odds ratio: 0.97 (95% confidence interval: 0.95–0.99), p = 0.017], with adjustment for age, gender, eGFR value, diabetes duration and presence of hypertension. MVD did not differ significantly between chronic kidney disease stages. Conclusion. In patients with type 1 diabetes and diabetic kidney disease the disturbances in the angiogenesis and vascular maturation are present. The number of mature blood vessels (vWF+) in the skin is reduced. Disturbances in the angiogenesis occur at early stages of diabetic kidney disease.

Protective factors for diabetic retinopathy in Type 2 diabetes mellitus patients: Long duration of no less than 10 years

AimTo study the factors protecting against diabetic retinopathy (DR) in patients with over a decade-long history of type 2 diabetes mellitus. MethodsA total of 490 patients with type 2 diabetes mellitus lasting for ≥10 years were divided into DR and no diabetic retinopathy (no DR) groups. Their basic information was collected, including age, sex, and duration of diabetes mellitus, as well as pertinent laboratory data. Potential correlations between these factors and DR were evaluated using multivariate analysis. ResultsOverall, 208 patients met the diagnostic criteria for DR. Multivariate logistic regression was used to evaluate factors with P < 0.10 after univariate analysis. Age, total bilirubin, and total cholesterol were found to be protective factors against DR. Presence of diabetic kidney disease and diabetic peripheral neuropathy, duration of diabetes mellitus, apolipoprotein B, blood urea nitrogen, and prothrombin time were found to be risk factors for DR. ConclusionsWe conclude that total cholesterol is a protective factor against DR. Specifically, it was confirmed that high levels of total cholesterol reduce the risk of DR. These findings may provide a basis for new diet and lifestyle guidelines for patients with diabetes mellitus.