Diabetes Chronic Kidney Disease Stage Research Articles

Status and trends in epidemiologic characteristics of diabetic end-stage renal disease: an analysis of the 2021 Korean Renal Data System.

Korean Renal Data System (KORDS) is a nationwide end-stage renal disease (ESRD) registry database operated by the Korean Society of Nephrology (KSN). Diabetes mellitus is currently the leading cause of ESRD in Korea; this article provides an update on the trends and characteristics of diabetic ESRD patients. The KORDS Committee of KSN collects data on dialysis centers and patients through an online registry program. Here, we analyzed the status and trends in characteristics of diabetic chronic kidney disease stage 5D (CKD 5D) patients using data from 2001 to 2021. In 2021, the dialysis adequacy of hemodialysis (HD) was lower in diabetic CKD 5D patients than in nondiabetic CKD 5D patients, while that of peritoneal dialysis (PD) was similar. Diabetic CKD 5D patients had a higher proportion of cardiac and vascular diseases and were more frequently admitted to hospitals than nondiabetic CKD 5D patients, and the leading cause of death was cardiac disease. From 2001 to 2020, diabetic CKD 5D patients had a higher mortality rate than nondiabetic CKD 5D patients, but in 2021 this trend was reversed. Diabetic PD patients had the highest mortality rate over 20 years. The mortality rate of diabetic HD patients was higher than that of nondiabetic HD patients until 2019 but became lower starting in 2020. There was a decreasing trend in mortality rate in diabetic CKD 5D patients, but cardiac and vascular diseases were still prevalent in diabetic CKD 5D patients with frequent admissions to hospitals. More specialized care is needed to improve the clinical outcomes of diabetic CKD 5D patients.

The Association Between Red Blood Cell Distribution Width and the Severity of Diabetic Chronic Kidney Disease.

PurposeRed cell distribution width (RDW) has been evidenced to be related to various diabetes-associated macrovascular and microvascular complications. However, the studies on the association between RDW and diabetic chronic kidney disease (CKD) are still scarce. The aim of the study is to explore whether there is any association between RDW and the severity of diabetic CKD.Patients and MethodsThe study recruited 396 patients diagnosed with diabetic CKD at People’s Hospital of Gaochun from January 2006 to April 2021. Baseline characteristics were gathered and laboratory tests were performed to measure clinical indexes. Patients were also categorized into three groups based on their CKD stages. Correlation analysis and multivariate ordinal logistic regression were performed to investigate the association between RDW and the severity of diabetic CKD. The risk size was described as odds ratio (OR) and 95% confidence interval (CI).ResultsWe found a significant association between RDW and the severity of CKD, with a correlation coefficient of 0.32 (P < 0.01). We used three models for multivariate ordinal logistic regression to investigate the relationship between RDW and the severity of CKD. Results showed that RDW is an independent and significant risk factor of diabetic CKD after adjustment for demographic data, physiological indexes, and drug history [Model 3 OR (95% CI) = 1.225 (1.023–1.467)]. In subgroup analysis, RDW remained a significant risk factor in all three models for patients who had diabetes of 5–10 years [Model 3 OR (95% CI) = 1.480 (1.067–2.052)] and had a HbA1c level >7% [(Model 3 OR (95% CI) = 1.478 (1.184–1.845)].ConclusionRDW is significantly associated with the disease stages of diabetic CKD, and the risk is higher for people with 5–10 years of diabetes and for those who do not control the HbA1c level well. This study has implications for the diagnosis, monitoring, and timely treatment of the diabetic CKD.

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease.

We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5'-C-phosphate-G-3' (CpG) sites from this cohort to predict the progression of diabetic CKD. This cross-sectional study recruited 119 adults. DNA was extracted from blood using the Qiagen QIAampDNA Mini Spin Kit. Genome-wide methylation analysis was performed using Illumina Infinium MethylationEPIC BeadChips (HM850K). Intensity data files were processed and analysed using the minfi and MissMethyl packages for R. We examined the degree of methylation of CpG sites in early versus late diabetic CKD patients for CpG sites with an unadjusted P-value <0.01 and an absolute change in methylation of 5% (n = 239 CpG sites). Hierarchical clustering of the 239 CpG sites largely separated the two groups. A heat map for all 239 CpG sites demonstrated distinct methylation patterns in the early versus late groups, with CpG sites showing evidence of progressive change. Based on our differentially methylated region (DMR) analysis of the 239 CpG sites, we highlighted two DMRs, namely the cysteine-rich secretory protein 2 (CRISP2) and piwi-like RNA-mediated gene silencing 1(PIWIL1) genes. The best predictability for the two groups involved a receiver operating characteristics curve of eight CpG sites alone and achieved an area under the curve of 0.976. We have identified distinct DNA methylation patterns between early and late diabetic CKD patients as well as demonstrated novel findings of potential progressive methylation changes across all stages (1-5) of diabetic CKD at specific CpG sites. We have also identified associated genes CRISP2 and PIWIL1, which may have the potential to act as stage-specific diabetes-associated CKD markers, and showed that the use of a panel of eight identified CpG sites alone helps to increase the predictability for the two groups.

P0809LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN PATIENTS WITH DIABETIC CHRONIC KIDNEY DISEASE

Abstract Background and Aims Left ventricle diastolic dysfunction (LVDD) is common cardiac changes in diabetic patients without renal insufficiency. LVDD is also frequently occurs in chronic kidney disease (CKD). Diabetic patients with CKD are at increased risk of developing cardiovascular diseases. Therefore, early detection and prevention of risk factors are critical. The aim of this study was to evaluate the impact of type 2 diabetes on left ventricular (LV) diastolic function among CKD stage 3 and 5 patients, and whether markers of fluid balance can predict LVDD. Method A total of 409 patients (age and sex matched non-diabetic CKD stage 3 [nDMCKD3], n = 106; diabetic CKD stage 3 [DMCKD3], n = 106; non-diabetic CKD stage 5 [nDMCKD5], n = 73; diabetic CKD stage 5 [DMCKD5], n = 124) were analyzed. The stage 3 CKD patients were retrospectively reviewed, and stage 5 CKD patients were prospectively analyzed. All cohort patients with stage 5 CKD were hospitalized to plan their first dialysis treatment. The following exclusion criteria were applied: ejection fraction less than 45%, history of coronary artery disease and/or intervention treatment, history of angina or myocardial infarction, abnormalities of cardiac rhythm, moderate or severe valvular heart diseases, systemic immunologic diseases, liver cirrhosis, malignancy, infection, and previous renal transplantation. Coronary artery disease having regional wall motion abnormalities on echocardiographic examination was also ruled out. Clinical and echocardiographic parameters were compared among groups. Echocardiography, bioimpedance spectroscopy, and serum NT-proBNP were analyzed in patients with stage 5 CKD. The LVDD was defined as E/é ratio greater than 15. Extracellular water/total body water (ECW/TBW) and NT-proBNP were used as markers of fluid balance. Results Patients with E/é ratio &amp;gt; 15 presented with more advanced stages of CKD. Prevalence of LVDD in patients with diabetes was higher compared to those without diabetes. Patients in DMCKD5 group demonstrated higher E/é ratios compared to those with nDMCKD5, DMCKD3, and nDMCKD3 (16.63±5.04 vs. 14.12±4.60 vs. 14.69±4.65 vs. 13.07±3.76, p &amp;lt; 0.001). The E/é ratio in patients with DMCKD5 were significantly higher than those with DMCKD3 (16.63±5.04 vs. 14.69±4.65, p = 0.003). In contrast, the E/é ratio was not significantly different between nDMCKD3 and nDMCKD5 patients (13.07±3.76 vs. 14.12±4.60, p = 0.099). The ECW/TBW in patients with DMCKD5 were significantly higher than nDMCKD5 patients (0.51±0.04 vs. 0.48±0.05, p &amp;lt;0.001). In a multiple regression analysis, the presence of diabetes, serum albumin level, NT-proBNP, and ECW/TBW were significantly associated with LVDD in CKD5 patients. Conclusion Our results suggest that an echocardiographic examination and assessment of volume status should routinely be performed in patients with type 2 DMCKD. Early detection of LVDD before clinical symptoms are apparent is important, regardless of the stage of DMCKD. Fluid overload could be one of the aggravating factors of LVDD in DMCKD patients. Early evaluation of volume status and control of fluid overload should be considered important therapeutic approaches for LVDD in DMCKD patients, especially for those in advanced stages.

487-P: AI Prediction of Chronic Kidney Disease Stage Progression Combinations for Type 2 Diabetes Mellitus

Chronic Kidney Disease (CKD) for type 2 diabetes mellitus (T2DM) is an increasingly serious issue worldwide. CKD stage is known to progress in stages where 1 is normal and 5 is the worst case of hemodialysis. We have previously reported on the accuracy of AI technology to target CKD stage 1 patients and predict the progression to stages 2 and above. Such prediction is targeted to help identify patients who require intensive care. Such study showed maximum 0.75 AUC score. In this study, we have extended our study to investigate all other stage combinations. For example, we can set our goal to answer questions such as: "Can AI technology accurately predict stage 2 patients progressing into stage 5 (hemodialysis)?" We have investigated the EMR (Electronic Medical Record) of 64,059 type-2 diabetes patients who have visited the hospital. We have extracted 36 features, where 12 sources (e.g., Urine protein, albuminuria and eGFR) were selectively chosen by extraction from known literature and 3 types of values (mean, latest, SD) were calculated for each source. Period of 180 days range was scanned within 20% range (i.e., 180 days * 0.2 = 36 days). We balanced the label transition of each stage evenly by the number of data for each good label (no progress from current target stage) and bad label (progress from target to worse stage). We created a new prediction model for each combination (i.e., 1 to 2, 1 to 3, 1 to 4, 1 to 5, etc.) and performed cross validation by Logistic Regression to calculate the accuracy, F-Score and AUC. All the combinations showed relatively good results. The range and average of each measurements were: Accuracy 0.653 through 0.753 Average: 0.708. F-Score 0.673 through 0.754 Average:0.719. AUC 0.705 through 0.826 Average 0.770. We applied AI techniques to create new predictive model which can detect the progression for all combinations of type-2 diabetes CKD stage progression. This model may contribute by a more effective and accurate intervention to reduce hemodialysis and cardiovascular events. Disclosure K. Miyamoto: None. A. Koseki: Employee; Self; IBM. M. Kudo: Employee; Self; IBM. M. Makino: None. A. Suzuki: Research Support; Self; Chugai Pharmaceutical Co., Ltd., Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.

Decreased Bioimpedance Phase Angle in Patients with Diabetic Chronic Kidney Disease Stage 5

Early detection and regular monitoring of the nutritional status of patients with diabetic chronic kidney disease (DMCKD) with reliable tools are necessary. We aimed to determine the clinical significance of the phase angle (PhA) in patients with DMCKD stage 5 not undergoing dialysis. A total of 219 patients (non-diabetic CKD stage 5 [nDMCKD5], n = 84; diabetic CKD stage 5 [DMCKD5], n = 135) were analyzed. The nDMCKD5 group had a significantly higher PhA (p = 0.001), intracellular water/body weight (p = 0.001), and albumin level (p = 0.010) than the DMCKD5 group. The DMCKD5 group experienced significantly more overhydration (p < 0.001). The PhA was positively associated with the lean tissue index (LTI) (r = 0.332; p < 0.001), hemoglobin level (r = 0.223; p = 0.010), albumin level (r = 0.524; p < 0.001), and estimated glomerular filtration rate (eGFR; r = 0.204; p = 0.018) in the DMCKD5 group. Multivariate logistic regression analysis showed the eGFR (odds ratio [OR]: 0.824, 95% confidence interval [CI]: 0.698–0.974); p = 0.023), LTI (OR: 0.771, 95% CI: 0.642–0.926; p = 0.005), and albumin level (OR: 0.131, 95% CI: 0.051–0.338; p < 0.001) were significantly associated with undernutrition (PhA < 4.17°) in the DMCKD5 group. Our observations suggest that the PhA could be used as a marker to reflect the nutritional status in patients with DMCKD5.

Correlation of serum intact parathyroid hormone and alkaline phosphatase in diabetic chronic kidney disease stage 3 to 5 patients with mineral bone disorders

Introduction: Chronic kidney disease (CKD) amongst diabetic patients is a worldwide public health problem. It is associated with cardiovascular disease and CKD mineral bone disorder (CKD-MBD). Cardiovascular and MBD are important contributors of morbidity and mortality in CKD patients. Serum intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP) are two important markers to identify and mange CKD-MBD. This study was designed to evaluate the relationship between serum iPTH and alkaline phosphatase in diabetic CKD stages 3-5 patients with MBD.&#x0D; Methods: This cross-sectional study was conducted in BIRDEM General Hospital, Dhaka, Bangladesh from January 2013 to December 2014. Diabetic patients suffering from stage 3-5 CKD with MBD and not on dialysis, were consecutively and purposively included in this study. Along with base-line characteristics, clinical and laboratory data including serum alkaline phosphatase and iPTH levels were recorded for all patients. Data were analyzed by using SPSS version 20.0 and Pearson’s correlation test was applied to evaluate the relationship between iPTH and serum ALP.&#x0D; Results: Total patients were 306, of which 166 (54.2%) were males and 140 females (45.8%). Mean age of the study population was 56.5±11.3 years. Mean duration of diabetes mellitus (DM) and CKD were 12.8±7.6 and 2.9±1.7 years respectively. Among the study population, 49 (16.0%) were in CKD stage 3, 90 (29.4%) in stage 4 and rest 167 (54.6%) in stage 5. The mean HbA1c level did not differ significantly (p&gt;0.05 by ANOVA) amongst CKD-MBD stage 3, 4 and 5 cases. Mean±SE values of glycated haemoglobin (HbAlc %), serum creatinine (mg/dl), urea (mg/dl), calcium (mg/dl), phosphate (mg/dl), ALP (U/L) and iPTH (pg/ml) of total study population were 7.77±0.12, 6.8±0.17, 141.1±4.33, 8.1±0.07, 5.2±0.11, 164.1±7.74 and 229.7±8.64 respectively. Out of total cases, serum ALP was raised in only 53.9% CKD-MBD cases compared to 76.8% for iPTH. Serum iPTH level was found elevated in 79.6%, 83.3% and 72.5% CKD-MBD stage 3, 4 and 5 cases respectively while in comparison, serum ALP was found raised in 44.8%, 54.4% and 56.2% cases respectively. On correlation analysis between serum iPTH and ALP, the r values observed were 0.074, 0.231 and 0.046 for stage 3, 4 and 5 CKD-MBD cases respectively.&#x0D; Conclusion: The results of current study showed that most diabetic stage 3-5 pre-dialysis CKD-MBD patients had raised serum iPTH. In comparison, significantly low number of cases had raised serum ALP.&#x0D; IMC J Med Sci 2018; 12(2): 80-85

Prediction of prevalence of chronic kidney disease in diabetic patients in countries of the European Union up to 2025.

Diabetes and chronic kidney disease (CKD) are a growing burden for health-care systems. The prevalence of diabetes has increased constantly during the last decade, although a slight flattening of end-stage renal disease as a result of diabetes has been observed recently in some European countries. In this study, we project the prevalence of CKD in patients with diabetes in European countries up to the year 2025. We analysed the population with diabetes and development of nephropathy in 12 European countries, which we computed from models published previously and on data from the annual reports of the European Renal Association (1998-2011). The prevalence of CKD stage 5 in patients with diabetes up to the year 2025 was projected by the Lee-Carter algorithm. Those for stage 3 and 4 were then estimated by applying the same ratios of CKD prevalences as estimated in the Austrian population with diabetic nephropathy. The estimated prevalence of CKD in patients with diabetes is expected to increase in all 12 countries up to the year 2025. For CKD stage 3, we estimate for Austria in 2025 a prevalence of 215 000 per million diabetic population (p.m.p.) (95% confidence interval 169 000, 275 000), for CKD4 18 600 p.m.p. (14 500, 23 700) and for CKD5 6900 p.m.p. (5400, 8900). The median prevalence in the considered countries is 132 900 p.m.p. (IQR: 118 500, 195 800), 11 500 (10 200, 16 900) and 4300 (3800, 6300) for CKD stages 3, 4 and 5, respectively. Altogether, these data predict in the years 2012-25 an annual increase of 3.2% in the prevalence of diabetic CKD stage 5. Due to the increase in prevalence of diabetes and CKD5, the costs of renal therapy are expected to rise. We believe that these data may help health-care policy makers to make informed decisions.

Ergocalciferol and microcirculatory function in chronic kidney disease and concomitant vitamin d deficiency: an exploratory, double blind, randomised controlled trial.

Background and ObjectivesVitamin D deficiency and endothelial dysfunction are non-traditional risk factors for cardiovascular events in chronic kidney disease. Previous studies in chronic kidney disease have failed to demonstrate a beneficial effect of vitamin D on arterial stiffness, left ventricular mass and inflammation but none have assessed the effect of vitamin D on microcirculatory endothelial function.Study DesignWe conducted a randomised controlled trial of 38 patients with non diabetic chronic kidney disease stage 3–4 and concomitant vitamin D deficiency (<16 ng/dl) who received oral ergocalciferol (50,000 IU weekly for one month followed by 50,000 IU monthly) or placebo over 6 months. The primary outcome was change in microcirculatory function measured by laser Doppler flowmetry after iontophoresis of acetylcholine. Secondary endpoints were tissue advanced glycation end products, sublingual functional capillary density and flow index as well as macrovascular parameters. Parallel in vitro experiments were conducted to determine the effect of ergocalciferol on cultured human endothelial cells.ResultsTwenty patients received ergocalciferol and 18 patients received placebo. After 6 months, there was a significant improvement in the ergocalciferol group in both endothelium dependent microcirculatory vasodilatation after iontophoresis of acetylcholine (p = 0.03) and a reduction in tissue advanced glycation end products (p = 0.03). There were no changes in sublingual microcirculatory parameters. Pulse pressure (p = 0.01) but not aortic pulse wave velocity was reduced. There were no significant changes in bone mineral parameters, blood pressure or left ventricular mass index suggesting that ergocalciferol improved endothelial function independently of these parameters. In parallel experiments, expression of endothelial nitric oxide synthase and activity were increased in human endothelial cells in a dose dependent manner.ConclusionsErgocalciferol improved microcirculatory endothelial function in patients with chronic kidney disease and concomitant vitamin D deficiency. This process may be mediated through enhanced expression and activity of endothelial nitric oxide synthase.Trial RegistrationClinical trials.gov NCT00882401

Visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease.

The authors previously reported that the visit-to-visit variability of blood pressure is correlated with renal function decline in nondiabetic chronic kidney disease. Little is known about the association between visit-to-visit variability and renal function decline in patients with diabetic chronic kidney disease. The authors retrospectively studied 69 patients with diabetic chronic kidney disease stage 3a, 3b, or 4. The standard deviation and coefficient of variation of blood pressure in 12 consecutive visits were defined as visit-to-visit variability of blood pressure. The median observation period was 32 months. In univariate correlation, the standard deviation and coefficient of variation of blood pressure were not significantly associated with the slope of estimated glomerular filtration rate. There was no significant association between the visit-to-visit variability of blood pressure and renal function decline in patients with diabetic chronic kidney disease, in contrast with our previous study of nondiabetic patients with chronic kidney disease.

Combined Therapy with Renin-Angiotensin System and Calcium Channel Blockers in Type 2 Diabetic Hypertensive Patients with Proteinuria

Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin-3 (PTX3) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). This study tested the hypothesis that the improvement in endothelial function after initiation of angiotensin II receptor blocker (valsartan), calcium channel blocker (amlodipine) therapy, or a combination of both is directly linked to the normalization of sTWEAK and PTX3. One-hundred-eight diabetic CKD stage I patients with hypertension (56% men, 46.7+/-5.3 years) were allocated to a 12-week intervention with amlodipine (10 mg/d), valsartan (160 mg/d), or their combination. Plasma levels of sTWEAK, PTX3, and flow-mediated dilation (FMD) were studied during the interventions. All treatment strategies effectively increased FMD and reduced proteinuria, confirming a more prone reduction with the combined therapy. These improvements were followed by significant PTX3 reductions. Valsartan alone and in combination with amlodipine achieved significant incremental raises in sTWEAK plasma levels. More importantly, the changes observed in sTWEAK (beta=0.25, P=0.006) or PTX3 (beta=-0.24, P=0.007) plasma levels were independently associated with the improvement in ultrasonographically measured FMD. This study shows that treatment with antihypertensive drugs improves FMD and normalizes proteinuria, PTX3, and sTWEAK in diabetic CKD stage I patients with hypertension. The improvement in FMD was independently associated with PTX3 and sTWEAK normalization. Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570.

Reduced proteinuria using ramipril in diabetic CKD stage 1 decreases circulating cell death receptor activators concurrently with ADMA. A novel pathophysiological pathway?

Renin-angiotensin system (RAS) blockade improves proteinuria and the endothelial functions in diabetic nephropathy. Plasma asymmetric dimethylarginine (ADMA), abundant in the cell than in the plasma, is also improved by RAS blockage. We hypothesized that RAS blockade may reduce ADMA by reducing injurious cell death. In a hypothesis-generating study, we assessed circulating levels of apoptotic signalling peptides in incident chronic kidney disease (CKD) stage 1 patients (aged >18 years with diabetes mellitus type 2 as the only cause of nephropathy) not previously prescribed statins or RAS blockade. Ninety-three (29 M, 47 ± 5 years) patients with CKD 1 diabetic nephropathy and 38 healthy subjects (20 M, 47 ± 5 years) were enrolled. Ramipril was given (5 mg daily for 12 weeks), and circulating ADMA, soluble Fas (sFas), myostatin and endothelial function [flow-mediated vasodilation (FMD); ultrasound)] were measured. After the study, ADMA, sFas, myostatin, insulin resistance, high-sensitive C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), blood pressure and proteinuria levels were decreased, and FMD and serum albumin levels increased (P < 0.05 for all). ADMA and sFas levels were independently related to FMD levels both before (rho = -0.33; P < 0.005 and rho = -0.26; P < 0.02, respectively) and after (rho = -0.39; P < 0.001 and rho = -0.28; P < 0.002, respectively) ramipril treatment. Changes in sFas and ADMA were related to the change in FMD (-0.32; P > 0.004 and -0.31; P < 0.004, respectively). A reduction of proteinuria in CKD 1 diabetic kidney disease is accompanied by lower circulating sFas, myostatin and ADMA, suggesting that increased cell death may contribute to ADMA formation and endothelial dysfunction in diabetic CKD.