Diagnosis Of Diabetic Kidney Disease Research Articles

The Potential Value of Urinary Extracellular Vesicles VEGF-A165b in Diagnosis of Diabetic Kidney Disease

The Potential Value of Urinary Extracellular Vesicles VEGF-A165b in Diagnosis of Diabetic Kidney Disease

Predictive Role Of Neutrophil Gelatinase-Associated Lipocaline As An Early Marker For Kidney Injury In Patients With Diabetes Mellitus

Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus leading to increased cardiovascular morbidity and mortality, and a risk of developing an end-stage renal disease (ESRD). Diabetic nephropathy is a disease affecting mainly the glomerulus, however, a number of studies indicate the predictive role of tubulo-interstitial lesions in the development and the progression of diabetic nephropathy. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising tubular biomarkers in the diagnosis of kidney disease. The data in the literature determine NGAL as a marker with a good diagnostic profile in the diagnosis of DKD. Neutrophil gelatinase-associated lipocalin values correlate with the progression of the albumin excretion, with the decrease in the glomerular filtration rate and with the severity of renal impairment. Neutrophil gelatinase-associated lipocalin is defined as an early marker of DKD, which establishes the development of renal dysfunction before the increase in albumin excretion. The evaluated cut-off values demonstrate good to high efficacy of NGAL in discriminating DKD patients with normal albumin excretion from healthy individuals. Several studies have indicated NGAL as an indicator of DKD progression, stratifying the risk of developing ESRD, patients with diabetes with higher NGAL levels have a faster and earlier decline in renal function. However, NGAL is a modulator of insulin signalling and its levels are elevated in patients with diabetes without DKD. Elevated levels of NGAL may be the result of common concomitant diseases of diabetes—cardiovascular disease and urinary tract infections. Additional studies are needed to assess the clinical applicability of NGAL in the diagnosis of DKD.

Trajectories of kidney function in diabetes: a clinicopathological update.

Diabetic nephropathy has been traditionally diagnosed based on persistently high albuminuria and a subsequent decline in glomerular filtration rate (GFR), which is widely recognized as the classical phenotype of diabetic kidney disease (DKD). Several studies have emphasized that trajectories of kidney function in patients with diabetes (specifically, changes in GFR and albuminuria over time) can differ from this classical DKD phenotype. Three alternative DKD phenotypes have been reported to date and are characterized by albuminuria regression, a rapid decline in GFR, or non-proteinuric or non-albuminuric DKD. Although kidney biopsies are not typically required for the diagnosis of DKD, a few studies of biopsy samples from patients with DKD have demonstrated that changes in kidney function associate with specific histopathological findings in diabetes. In addition, various clinical and biochemical parameters are related to trajectories of GFR and albuminuria. Collectively, pathological and clinical characteristics can be used to predict trajectories of GFR and albuminuria in diabetes. Furthermore, cohort studies have suggested that the risks of kidney and cardiovascular outcomes might vary among different phenotypes of DKD. A broader understanding of the clinical course of DKD is therefore crucial to improve risk stratification and enable early interventions that prevent adverse outcomes.

Extracellular vesicle-derived AEBP1 mRNA as a novel candidate biomarker for diabetic kidney disease

BackgroundA novel and improved methodology is still required for the diagnosis of diabetic kidney disease (DKD). The aim of the present study was to identify novel biomarkers using extracellular vesicle (EV)-derived mRNA based on kidney tissue microarray data.MethodsCandidate genes were identified by intersecting the differentially expressed genes (DEGs) and eGFR-correlated genes using the GEO datasets GSE30528 and GSE96804, followed by clinical parameter correlation and diagnostic efficacy assessment.ResultsFifteen intersecting genes, including 8 positively correlated genes, B3GALT2, CDH10, MIR3916, NELL1, OCLM, PRKAR2B, TREM1 and USP46, and 7 negatively correlated genes, AEBP1, CDH6, HSD17B2, LUM, MS4A4A, PTN and RASSF9, were confirmed. The expression level assessment results revealed significantly increased levels of AEBP1 in DKD-derived EVs compared to those in T2DM and control EVs. Correlation analysis revealed that AEBP1 levels were positively correlated with Cr, 24-h urine protein and serum CYC and negatively correlated with eGFR and LDL, and good diagnostic efficacy for DKD was also found using AEBP1 levels to differentiate DKD patients from T2DM patients or controls.ConclusionsOur results confirmed that the AEBP1 level from plasma EVs could differentiate DKD patients from T2DM patients and control subjects and was a good indication of the function of multiple critical clinical parameters. The AEBP1 level of EVs may serve as a novel and efficacious biomarker for DKD diagnosis.

Real-World Diagnosis and Treatment of Diabetic Kidney Disease.

People with type2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD) have increased morbidity and mortality risk. Angiotensin-converting enzyme inhibitors (ACEi) or angiotensinII receptor blockers (ARB) are recommended to slow kidney function decline in DKD. This representative, real-world data analysis of patients with T2DM was performed to detect onset of DKD and determine methods and timing of DKD diagnosis and time to initiation of ACEi/ARB therapy. Patients diagnosed with T2DM before January1, 2016 who developed DKD between January1, 2017 and June30, 2019 were identified from a longitudinal ambulatory electronic health record (EHR) dataset (Veradigm Inc). Each record was analyzed using the CLinical INTelligence engine (CLINT™, HealthPals, Inc.) to identify delays and gaps in diagnosing DKD. DKD was diagnosed through two reduced estimated glomerular filtration rate (eGFR; < 60mL/min/1.73m2) measurements at least 90days apart, a single elevated urine albumin-to-creatinine ratio (UACR; > 30mg/g) measurement, or ICD-9/10 diagnosis codes for DKD and/or albuminuria. Time to diagnose (TTD), time to treat (TTT), and diagnosis to treatment time were assessed. Of 6,499,409 patients with T2DM before January 2016, 245,978 developed DKD between January1, 2017 and June30, 2019. In this DKD cohort, ca. 50% were first identified through EHR diagnosis and ca. 50% by UACR or eGFR lab-based diagnosis. In patients who had UACR/eGFR assessed, more than 90% exhibited DKD-level results on the first diagnostic test. Average TTD after eGFR labs was 2years; average TTT with ACEi/ARB was 6-9months after DKD lab evidence. The majority of patients who developed DKD received ACEi/ARB therapy 6-7months after diagnosis. In a contemporary, large national cohort of patients with T2DM, progression to DKD was common but likely underrepresented. The low rate of DKD-screening labs, along with sizable delays in diagnosis of DKD and initiation of ACEi/ARB therapy, indicates that many patients who progress to DKD are not being properly treated.

Clinical Predictors of Nondiabetic Kidney Disease in Patients with Diabetes: A Single-Center Study

Background Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients. Methods We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD. Results Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD. Conclusions After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD (alone or with concomitant DKD). Absence of DR and coexistence of a hematological condition (especially MGUS) were strong predictors of NDKD in our cohort.

Identification of differentially expressed genes in diabetic kidney disease by RNA-Seq analysis of venous blood platelets.

Diabetic kidney disease (DKD) is the leading cause of end‐stage renal disease. However, because of shared complications between DKD and chronic kidney disease (CKD), the description and characterization of DKD remain ambiguous in the clinic, hindering the diagnosis and treatment of early‐stage DKD patients. Although estimated glomerular filtration rate and albuminuria are well‐established biomarkers of DKD, early‐stage DKD is rarely accompanied by a high estimated glomerular filtration rate, and thus there is a need for new sensitive biomarkers. Transcriptome profiling of kidney tissue has been reported previously, although RNA sequencing (RNA‐Seq) analysis of the venous blood platelets in DKD patients has not yet been described. In the present study, we performed RNA‐Seq analysis of venous blood platelets from three patients with CKD, five patients with DKD and 10 healthy controls, and compared the results with a CKD‐related microarray dataset. In total, 2097 genes with differential transcript levels were identified in platelets of DKD patients and healthy controls, and 462 genes with differential transcript levels were identified in platelets of DKD patients and CKD patients. Through Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we selected 11 pathways, from which nine potential biomarkers (IL‐1B, CD‐38, CSF1R, PPARG, NR1H3, DDO, HDC, DPYS and CAD) were identified. Furthermore, by comparing the RNA‐Seq results with the GSE30566 dataset, we found that the biomarker KCND3 was the only up‐regulated gene in DKD patients. These biomarkers may have potential application for the therapy and diagnosis of DKD, as well aid in determining the mechanisms underlying DKD.

How to Assess Diabetic Kidney Disease Progression? From Albuminuria to GFR.

Diabetic kidney disease (DKD) is one of the most relevant complications of type 2 diabetes and dramatically increases the cardiovascular risk in these patients. Currently, DKD is severely infra-diagnosed, or its diagnosis is usually made at advanced stages of the disease. During the last decade, new drugs have demonstrated a beneficial effect in terms of cardiovascular and renal protection in type 2 diabetes, supporting the crucial role of an early DKD diagnosis to permit the use of new available therapeutic strategies. Moreover, cardiovascular and renal outcome trials, developed to study these new drugs, are based on diverse cardiovascular and renal simple and composite endpoints, which makes difficult their interpretation and the comparison between them. In this article, DKD diagnosis is reviewed, focusing on albuminuria and the recommendations for glomerular filtration rate measurement. Furthermore, cardiovascular and renal endpoints used in classical and recent cardiovascular outcome trials are assessed in a pragmatic way.

Expert consensus on early prediction and diagnosis of diabetic kidney disease

Diabetic kidney disease (DKD) is a type of chronic kidney disease (CKD) caused by diabetes. The clinical diagnosis of DKD is usually based on the presence of increased albuminuria and/or decreased estimated glomerular filtration rate (eGFR), and exclusion of other causes of CKD. The clinical features of DKD are proteinuria, gradual decline in renal function, and severe renal failure in the later stages, which is one of the main causes of death in patients with diabetes. Any single biomarker might be insufficient to evaluate renal injury; thus, multiple methods and markers are needed. In addition, diabetic patients should be paid more attention to the kidney, and kidney damage should be evaluated with standardized assessment aimed at strengthening the early prediction and diagnosis of DKD.

FC 085SERUM INTERLEUKIN-6 LEVELS PREDICT RENAL DISEASE PROGRESSION IN DIABETIC KIDNEY DISEASE

Abstract Background and Aims Inflammation is a main mechanism for the pathogenesis and progression of diabetic kidney disease (DKD). Interleukin-6 (IL-6) is an important inflammatory mediator and different studies have suggested its involvement in the pathogenesis of DKD. The aim of our study was to evaluate the association between IL-6 levels and progression of DKD in patients with type 2 diabetes. We also tested whether the use of optimal doses of RAS blockade in monotherapy had an influence on the levels of IL-6 in comparison with dual blockade. Method IL-6 levels were measured at baseline and after 4 and 12 months in 70 patients included in the PRONEDI trial (EUDRACT 2004-002470-31), a multicenter, randomized controlled clinical trial. The study included type 2 diabetes patients with a clinical diagnosis of DKD, stage 2 or 3 CKD, and a urinary protein/creatinine ratio (UPCR) &amp;gt;300 mg/g (morning urine spot) on 2 separate opportunities. The primary composite endpoint was a &amp;gt;50% increase in baseline serum creatinine, end stage kidney disease (ESKD) or death. Cox regression model was adjusted for potential confounders or modifiers including eGFR calculated using the CKD-EPI equation and UPCR. Mixed models were adjusted to study longitudinal data. Results The recruitment period was 18 months and the median follow-up was 36 (IQR: 20-48) months, after which 27 patients (38.6%) reached the primary endpoint. At baseline mean IL-6 levels in the whole cohort were 4.58 ± 2.90, at 4 months 4.61 ± 3.10 and at 12 months: 6.14 ± 4.97. Patients were further divided into three groups according to the tertiles of baseline IL-6 levels (tertile 1: 0.65–2.65 pg/mL; tertile 2: 2.66–4.83 pg/mL and tertile 3: 4.84–13.30 pg/mL). There were no differences among the groups in demographic characteristics, cardiovascular risk factors, serum creatinine or proteinuria among the groups. Correlation analyses for IL6 and other inflammatory parameters were carried out for all subjects. The results showed that inflammatory parameters had a significant correlation between them. IL-6 levels correlated with TNFα (r: 0.29; 95% CI: 0.05 - 0.49 p= 0.02), C-reactive protein (r= 0.61; 95%CI: 0.44 - 0.74 p&amp;lt;0.01), and PTH (r: 0.30, 95% CI: 0.03-0.54, p=0.03). However, in the univariate analysis only IL-6 tertiles were associated with the primary outcome (OR: 2.41; 95% CI 1.25-4.64, p=0.008). Patients with the highest IL-6 levels (&amp;gt;4.84 pg/ml) experienced a significantly faster evolution to endpoint (mean survival: 33.2 months, CI 95%: 25.2-41.3) than the other 2 groups. In the multivariate Cox regression analysis, the highest levels of IL-6 (Tertile 3) were significantly associated with the primary outcome (HR:3.86; 95%CI: 1.08-13.86) after being adjusted for baseline serum creatinine and proteinuria. The time-dependent area under the ROC curve at two years of follow-up was 0.88 (95% CI: 0.79 - 0.97). The best cut-off IL-6 level was found at 4.68 pg/ml (sensitivity: 100%, specificity: 78.7%) Generalized linear mixed model analysis showed no effect on subsequent IL-6 levels either with RAS blockade monotherapy or dual blockade. Conclusion In conclusion, our results show that higher levels of IL-6 are independently associated with progression of DKD in patients with type 2 diabetes, and that treatment with RAS blockade does not influence these levels. Serum IL-6 may be used as a noninvasive biomarker of progression to ESKD. Since our results show that higher IL-6 levels are associated with a worse renal prognosis, anti- inflammatory drugs that modulate IL-6 could be promising therapeutic agents to improve outcomes. Further studies focusing on the potential applications of anti-IL6 treatment in DKD are warranted.

MO637THE HIDDEN PREVALENCE OF DIABETIC KIDNEY DISEASE IN A HOSPITAL-BASED REAL-WORLD DATA ANALYSIS

Abstract Background and Aims Correct identification of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients is crucial to implement therapeutic interventions to prevent disease progression and premature death. Method We have analyzed the prevalence of DKD according to lab criteria and the rate of identification of DKD and/or chronic kidney disease (CKD) on 516,578 hospital care electronic medical records (EMR) in a tertiary hospital-based population using Savana Manager®. Results Out of 24,129 T2DM patients, 15,304 met inclusion criteria. DKD was defined as eGFR&amp;lt;60 ml/min/1.73m2 or urinary albumin to creatinine ratio (UACR) &amp;gt;30 mg/g or urinary protein to creatinine ratio (UPCR) &amp;gt;0.3 g/g after excluding acute kidney injury (AKI). A total of 4,526 (29.6%) T2DM patients had DKD according to lab criteria. However, the terms “CKD” or “DKD” were only present in 33.1% and 7.5% of the 4,526 EMR, with a hidden prevalence of CKD and DKD of 66.9% and 92.5%, respectively. Less severe kidney disease (lower UACR or UPCR, higher eGFR values), female sex, and lack of insulin prescription were associated with the absence of “DKD” or “CKD” terms in EMR (p&amp;lt;0.001) in the patients fulfilling laboratory criteria for DKD. However, while younger age (&amp;lt;70 years) was associated with a missing CKD diagnosis, older age (≥70 years) was associated with a missing DKD diagnosis in EMR. Conclusion In conclusion, the prevalence of DKD among T2DM patients according to laboratory data is higher than prevalence based on specific diagnosis written in EMR. This could imply underdiagnosis of DKD, especially in patients with less severe disease who may benefit the most from optimized therapy

Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes

BackgroundPatients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. ObjectivesThis work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. MethodsPatients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin–angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. ResultsOf 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53–0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). ConclusionsIn patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993)

Targeted metabolomics as a tool for the diagnosis of kidney disease in Type II diabetes mellitus

ABSTRACT Background: Diabetic kidney disease (DKD) is an increasing health problem and an extra burden to health services. The study of characteristic metabolic alterations of DKD is crucial for a better understanding of pathogenesis to identify new potential biomarkers and drug targets. We hypothesized that metabolic profiling of amino acids, acylcarnitines, and organic acids are useful new biomarkers for the diagnosis of the early stages of DKD Methods: The hypothesis was testing in a case-control study of 232 patients with type 2 diabetes mellitus and 150 healthy controls. Patients were classified according to urinary albumin and estimated glomerular filtration rate (eGFR) into 100 with normoalbuminuria and 132 with microalbuminuria group. Eighteen AcylCNs and 17 amino acids were measured in the blood by tandem mass spectrometry while 17 urinary organic acids were quantitatively measured by gas chromatography – mass spectrometry. Results: Regression analysis found that dodecanoylcarnitines C12 (effect size 2.03 [95%CI 1.73–2.32]), triglylcarnitine C5:1 (2.01 [1.70–2.30]), and isovalerylcarnitine C5 (1.78 [1.48–2.07]) were stronger predictors of albumin/creatinine ratio than HbA1c (1.50 [1.20–1.78]) and hence they could serve as potential biomarkers for the diagnosis of the early stages of DKD. Conclusions: Targeted metabolic profiling offers a new, non-invasive approach for detecting biomarkers for the early diagnosis of DKD suggesting new pathogenetic phases that might be new targets for treatment.

Особливості перебігу діабетичної хвороби нирок у хворих на латентний автоімунний діабет дорослих

Актуальність. Латентний автоімунний діабет дорослих (LADA) є гетерогенним типом цукрового діабету (ЦД), що поєднує ознаки цукрового діабету 1-го (ЦД1) та 2-го типу (ЦД2). Дані щодо частоти і структури мікросудинних ускладнень при LADA малочисельні й доволі суперечливі, практично відсутня інформація про особливості їх перебігу, що вказує на необхідність проведення досліджень у цьому напрямку. Мета дослідження: з’ясувати особливості перебігу діабетичної хвороби нирок у хворих на латентний автоімунний діабет дорослих порівняно з класичними типами цукрового діабету. Матеріали та методи. Обстежено 112 хворих на ЦД із діабетичною хворобою нирок (ДХН). Пацієнтів розподілили на три групи: І— 54 особи з LADA, ІІ— 30 хворих на ЦД1, ІІІ— 28 пацієнтів із ЦД2. Особливості перебігу ДХН вивчали на підставі оцінки даних анамнезу, клінічного обстеження, значень швидкості клубочкової фільтрації (ШКФ), альбумінурії, відношення альбуміну до креатиніну в сечі. Результати. За даними анамнезу діагноз ДХН у пацієнтів із LADA встановлювався в середньому через 3 роки після маніфестації ЦД, при цьому на 4,5 року раніше, ніж при ЦД1, але на 1,3 року пізніше, ніж при ЦД2. Аналіз показників ШКФ показав, що при LADА найбільш часто (у 63% пацієнтів) реєструвалась категорія G3 (G3а— у 46%, G3b— у 17% пацієнтів). Решта обстежених мали категорію G1 (7%), G2 (24%), і тільки в 6% пацієнтів виявлено стадію G4. У пацієнтів усіх груп переважали категорії альбумінурії А1 та А2 (при LADА— по 43% осіб у кожній категорії), водночас категорія A3 при LADA реєструвалась удвічі частіше, ніж при ЦД1. При LADA переважаючими фенотипами ДХН були неальбумінурійне порушення функції нирок (НАПН) (43%) і альбумінурійний фенотип (АФ) (35%), при ЦД1— АФ (50%) і НАПН (40%), а при ЦД2 усі три фенотипи реєструвалися майже з однаковою частотою (АФ— у 32%, НАПН— у 29% пацієнтів, прогресуюче зниження функції нирок — у 39% хворих). Висновки. Перебіг діабетичної хвороби нирок в осіб із латентним автоімунним діабетом дорослих відрізняється від такого при класичних типах цукрового діабету, що вказує на необхідність розробки специфічного алгоритму ведення цієї категорії пацієнтів.

POS-253 THE DETECTION OF PLASMID-MEDIATED ESBLS AND PMQR GENES IN UROPATHOGENS ISOLATED FROM DIABETIC KIDNEY DISEASE PATIENTS WITH UTI

IDF has estimated that approximately 463 million adults (20-79 years) were living with diabetes; by 2045 this will rise to 700 million. Diabetes caused 4.2 million deaths. Diabetes is one of the leading causes of chronic kidney disease (CKD). DM induces a wide range of kidney damage that can be classified as follows: diabetic nephropathy (DN), diabetic kidney disease (DKD) and non-diabetic renal disease (NDRD). The spectrum of NDRD includes kidney diseases such as IgA nephropathy, membranous nephropathy, urinary tract infections etc., that are requiring specific treatments. Urinary tract infections is the most common bacterial infections, which occur at rates 3 to 4 times more often in diabetic patients than in general population. Moreover, infection is an importаnt cause of mоrbidity and mоrtality amоng patients with kidney failurе and is the sеcond lеading causе of death following CVD. The effectiveness of treatment UTI is limited due to the antibiotic resistance development. By 2050, it is estimated that antibiotic resistance will cause 10 million deaths every year. A cross-sectional study of 105 adult patients, who were admitted in Kharkiv City Clinical Emergency Hospital, Ukraine, was carried out. The diagnosis of DKD has been stated in accordance with the criteria established by KDIGO. UTIs were diagnosed according to EAU 2020 guidelines. Antimicrobial susceptibility of bacterial isolates was determined by the Kirby Bauer disk diffusion method and screening for PMRG was performed by the polymerase chain reaction (table 1). From 105 observed patients, 21 (20 %), 28 (26.7 %), 27 (25.7 %) and 29 (27.6 %) were identified to have CKD G1, CKD G2, CKD G3 and CKD G4, respectively. The patients were hospitalized when they have following signs/symptoms: chills, rigors or warmth associated with fever; flank pain; nausea or vomiting; dysuria, urinary frequency or urinary urgency; costo-vertebral angle tenderness on physical examination. Out of 105 patients, 31 (29.5%) were infected with PMRG-producing bacteria. Among 81 gram negative bacterial isolates, 39 (48.1 %) were identified to carry different types of PMRG, among which 27 (69.2 %) were found to be extended spectrum beta-lactamases producers (ESBLs), and 12 (30.8 %) – were positive for plasmid-mediated quinolone resistance genes (PMQR), table 2. The most active antimicrobial agents against isolated strains were meropenem, nitroxolinum, fosfomycin and cefepime. Susceptibility rates of isolated uropathogens depending on expression of different types of PMRG are presenting in figure 1. According to multivariate analysis, chronic heart failure (OR 3.20; 95% CI: 1.27-8.07), coronary artery disease (OR 3.57; 95% CI: 1.42-9.02), age > 55 years (OR 3.05; 95% CI: 1.12-8.32), atrial hypertension (OR 2.57; 95% CI: 0.94-7.04), chronic kidney disease stage ІІІ (OR 2.03; 95% CI: 0.80-5.10) and stage ІV ст. (OR 1.1; 95% CI: 0.40-2.60), hospital admission (OR 2.02; 95% CI: 0.78-5.23), use of an antibiotic in the preceding year (OR 1.41; 95% CI: 0.60-3.33) were found to be associated with plasmid-mediated genes existence (figure 2). Further clinical studies are needed to establish the guideline for the management of DKD patients with resistant UTI and to expand the number of options available for empiric therapy of these multi-drug resistance infections.

POS-364 TO STUDY THE CLINICAL PHENOTYPE OF NON - PROTEINURIC KIDNEY DISEASE IN TYPE 2 DIABETIC PATIENTS

Type-2 Diabetes mellitus (T2DM) is the leading cause of CKD and ESRD across the world. Albuminuria is widely accepted as the earliest marker of nephropathy and is used for early diagnosis of diabetic kidney disease (DKD). Classically, the development of overt proteinuria mark the initiation of GFR decline. However, in the last few years growing evidence has shown that a significant proportion of T2DM patients has decreased GFR without albuminuria.

Duration of diabetes-related complications and mortality in type 1 diabetes: a national cohort study.

People with type 1 diabetes often live for many years with different combinations of diabetes-related complications. We aimed to quantify how complication duration and total complication burden affect mortality, using data from national registers. This study included 33396 individuals with type 1 diabetes, registered in the Swedish National Diabetes Register at any time between 2001 and 2012. Each individual was followed and classified according to their time-updated diabetes-related complication status. The main outcomes were all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Poisson models were used to estimate the rate of these outcomes as a function of the time-updated complication duration. Overall, 1748 of the 33396 individuals died during 198872 person-years of follow-up. Overall, the time-updated all-cause mortality rate ratio (MRR) was 2.25 [95% confidence interval (CI): 1.99-2.54] for patients with diabetic kidney disease, 0.98 (0.82-1.18) for patients with retinopathy and 4.00 (3.56-4.50) for patients with cardiovascular disease relative to individuals without complications. The excess rate was highest in the first period after a diagnosis of CVD, with an 8-fold higher mortality rate, and stabilized after some 5 years. After diagnosis of diabetic kidney disease, we observed an increase in all-cause mortality with an MRR of around 2 compared with individuals without diabetic kidney disease, which stabilized after few years. In this cohort we show that duration of diabetes-related complications is an important determinant of mortality in type 1 diabetes, for example the MRR associated with CVD is highest in the first period after diagnosis of CVD. A stronger focus on time-updated information and thorough consideration of complication duration may improve risk stratification in routine clinical practice.

Evaluation of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as markers of diabetic kidney disease in Bangladeshi patients with type 2 diabetes mellitus

Background: The roles of neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as novel surrogate markers of diabetic kidney disease (DKD) are promising. Objective: The aim of this study was to evaluate whether NLR and PLR can predict DKD in type 2 diabetes mellitus (T2DM). Subjects and Methods: This cross‑sectional study was conducted from July 2018 to June 2019, among 312 patients with T2DM recruited from eight tertiary hospitals throughout Bangladesh. Complete blood count (CBC) was performed in fully automated hematology analyzers, and NLR and PLR were calculated. The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. The diagnosis of DKD was made based on the presence of albuminuria (ACR ≥30 mg/g) and/or reduced estimated glomerular filtration rate (eGFR <60mL/min/1.73 m2) in the absence of signs or symptoms of other primary causes of kidney damage. Results: Among 312 study subjects, 150 (48.1%) had DKD. The mean age (51.9 ± 11.9 vs. 48.6 ± 9.6 years), fasting plasma glucose (10.3 ± 4.1 vs. 9.2 ± 3.0 mmol/L), 2-h postprandial plasma glucose (14.6 ± 5.6 vs. 12.8 ± 4.5 mmol/L), glycated hemoglobin (HbA1c) (9.2 ± 2.1 vs. 8.4 ± 1.9%), and serum triglyceride (213.6 ± 109.9 vs. 185.5 ± 100.8) were higher (P ≤0.05 in each instance) in subjects with DKD in comparison to those without DKD. DKD group had higher mean absolute neutrophil count (6.0 ± 2.0 vs. 5.4 ± 1.9 ×109/L, P = 0.022), platelet count (310.4 ± 87.3 vs. 287.0 ± 78.7 ×109/L, P = 0.013), NLR (2.16 ± 1.1 vs. 1.92 ± 0.96, P = 0.040), and PLR (115.45 ± 57.07 vs. 101.02 ± 40.06, P = 0.010). The levels of hemoglobin, total leukocyte count, absolute lymphocyte count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width were similar in the two groups. Conclusion: In this study, we found higher NLR and PLR in subjects with DKD than those without DKD. NLR and PLR may be considered as cheap, readily available alternative markers of DKD in resource-poor settings.

Diabetic kidney disease: update on clinical management and non-glycaemic effects of newer medications for type 2 diabetes.

Type 2 diabetes is a leading cause of chronic kidney disease worldwide and continues to increase in prevalence. This in turn has significant implications for healthcare provision and the economy. In recent years there have been multiple advances in the glucose-lowering agents available for the treatment of diabetes, which not only modify the disease itself but also have important benefits in terms of the associated cardiovascular outcomes. The cardiovascular outcome trials of agents such as glucagon-like peptide-1 receptor agonists (GLP-RAs) and sodium glucose cotransporter 2 inhibitors (SGLT-2) have demonstrated significant benefits in reducing major adverse cardiovascular events, admissions for heart failure and in some cases mortality. Secondary analysis of these trials has also indicated significant renoprotective benefit. Canagliflozin and Renal Outcomes in Type 2 Diabetes Mellitus and Nephropathy (CREDENCE) a renal-specific trial, has shown major benefits with canagliflozin for renal outcomes in diabetic kidney disease, and similar trials with other SGLT-2 inhibitors are either underway or awaiting analysis. In this article we review current goals of treatment of diabetes and the implications of advancing renal impairment on choice of treatments. Areas discussed include the diagnosis of diabetic kidney disease and current treatment strategies for diabetic kidney disease ranging from lifestyle modifications to glycaemic control. This review focuses on the role of GLP-RAs and SGLT-2 inhibitors in treating those with diabetes and chronic kidney disease with some illustrative cases. It is clear that these agents should now be considered first choice in combination with metformin in those with diabetes and increased cardiovascular risk and/or reduced renal function, and in preference to other classes such as dipeptidyl peptidase-4 (DPP-4) inhibitors or sulphonylureas.

The Role of Diffusion-Weighted MRI and Apparent Diffusion Coefficient in Assessment of Diabetic Kidney Disease: Preliminary Experience Study.

BackgroundDiabetic kidney disease is the most common cause of ESRD. There is poor correlation between the degree of renal fibrosis and current screening markers. A noninvasive imaging technique is needed to assess the degree of structural changes in the kidney. The aim of this study was to assess the role of apparent diffusion coefficient (ADC) in the diagnosis of diabetic kidney disease. Forty adult diabetic patients with chronic kidney disease as well as 20 age- and sex-matched adult healthy controls were recruited from Nephrology Department of our University Hospital. All patients underwent renal MR-DWI and ADC mapping on a 1.5-T scanner (Philips Achieva) using phased array body coil.ResultsAmong the studied 40 diabetic patients, five groups of patients were resulted 8 patients for each and the ADC values were inversely correlated with advancement in renal parenchymal affection, ie, in late stages of the disease the ADC values were lower than in early stages. The mean ADC values of renal parenchyma in patients with diabetic kidney disease were considerably lower than that of healthy controls with normal renal function (2.1±0.3x10−3 mm2/s vs 2.4±0.1x10−3 mm2/s with p<0.001).ConclusionADC value is a possible noninvasive technique in evaluating the stage of renal dysfunction with assessment of disease progression.