Progression Of Kidney Disease In Type Research Articles

Associations between triglyceride-glucose index and risk of diabetic kidney disease progression in type 2 diabetes mellitus

Associations between triglyceride-glucose index and risk of diabetic kidney disease progression in type 2 diabetes mellitus

Triglyceride-glucose index is associated with the risk of chronic kidney disease progression in type 2 diabetes.

The study aimed to investigate the association of TyG index with chronic kidney disease (CKD) progression in type 2 diabetes mellitus (T2DM). A total of 179 T2DM patients with CKD were retrospectively included. CKD progression was defined as a doubling of baseline serum creatinine or onset of end-stage kidney disease (ESKD). Internal validation was performed by the Kidney Failure Risk Equation (KFRE) model and Net reclassification improvement (NRI). The optimal cut-off value of the TyG index was 9.17. The cumulative incidence of kidney outcomes was significantly higher in the high-TyG group (v.s low-TyG group, P = 0.019). In addition, the high-TyG index was associated with a greater risk of CKD progression (HR 1.794, 95% CI 1.026-3.137, P = 0.040). And reclassification analyses confirmed the final adjusted model improved NRI (61.90% v.s model 2, 43.80% v.s model 1). The further RCS curves presented an inverted S-shaped relationship between the TyG index and the risk of CKD progression. Internal validation verified that a higher TyG index was associated with 2.10-fold increased odds of 2-year ESKD risk >10% (95% CI 1.82-8.21). Moreover, subgroup analysis suggested that the association was more pronounced in those at relatively early CKD stages (higher than stage 2) and with no medication history of oral hypoglycemic agents. An elevated TyG index was associated with a higher risk of CKD progression in T2DM patients. Our findings suggested that timely targeting insulin sensitivity at the early stages of T2DM might be associated with declined future risk of CKD development.

Association between lower phase angle and chronic kidney disease progression in type 2 diabetes patients.

Phase angle (PhA), derived from bioelectrical impedance analysis (BIA), is the angle of vector determined by the body's resistance and reactance. It indicates cellular integrity and hydration status. Though extracellular volume excess was associated with chronic kidney disease (CKD) progression, the association between PhA and CKD progression is unknown. Matrix metalloproteinase-2 (MMP-2) is a member of zinc-dependent endopeptidase family and promotes renal interstitial fibrosis. We investigated association between PhA and CKD progression, and whether the association was through MMP-2 in patients with type 2 diabetes mellitus (T2DM). We conducted a prospective study on 1,078 patients with T2DM (mean age 58.9±9.1 years). PhA was measured using BIA. CKD progression was defined as ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline with deterioration across eGFR categories. Multiplex immunoassay was used to quantitate MMP-2. We examined association between PhA and CKD progression using Cox proportional hazards model, adjusting for demographics, clinical parameters and medications. Over 8.6 years of follow-up, 43.7% of participants had CKD progression. Compared to tertile 3 PhA (higher level), tertiles 1 and 2 PhA were associated with higher hazards of CKD progression, with corresponding unadjusted hazard ratios (HRs) of 2.27 (95% confidence interval [CI] 1.80-2.87, P<0.001) and 1.57 (95% CI 1.24-2.01, P<0.001). The positive association between tertiles 1 and 2 PhA with CKD progression persisted in the fully adjusted model with corresponding HRs of 1.71 (95% CI 1.30-2.26, P<0.001) and 1.46 (95% CI 1.13-1.88, P=0.004). MMP-2 accounted for 14.7% of association between tertile 1 PhA and CKD progression. Our findings revealed a previously unobserved association between BIA-derived lower PhA and CKD progression through MMP-2 in patients with T2DM.

Linking adiponectin expression and kidney dysfunction among Indian patients with and without diabetic nephropathy.

Diabetic kidney disease is a common cause of end stage renal disease has a high incidence rate in population with type 2 diabetes mellitus patients. Adiponectin is an adipocytokine shown to strive anti-diabetic, anti-oxidative as well as anti-inflammatory. The present study aimed to determine the serum adiponectin levels in type 2 diabetes mellitus and explore its association with nephropathy. This cross sectional study recruited 90 type 2 diabetes mellitus patients with (n = 60) and without nephropathy (n = 30). Additionally 30 age, gender, and body mass index matched healthy controls were included. Enzyme linked immunosorbent assay method were used to determine adiponectin concentration. Blood sugars, glycated hemoglobin, body mass index all sounded to be brawny risk factors for nephropathy and microalbumin, e GFR showed a significant association with kidney disease progression in type 2 diabetes mellitus with nephropathy. Both the groups of type 2 diabetes mellitus patients had elevated adiponectin concentrations than controls. Serum adiponectin concentrations were significantly higher in type 2 diabetes mellitus without nephropathy and there was a significant association with nephropathy activity (P<0.0001**). The receiver operating characteristics curve analysis was used to examine the diagnostic performance of adiponectin for nephropathy shown a significant area under the curve 0.998 with sensitivity 100% and specificity 93.33% (P<0.0001**). Hence our study findings concluded that serum adiponectin concentrations considered for the early predictable and prognostic marker for nephropathy.

Impaired Amino Acid Metabolism and Its Correlation with Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus.

Background: Metabolomics is useful in elucidating the progression of diabetes; however, the follow-up changes in metabolomics among health, diabetes mellitus, and diabetic kidney disease (DKD) have not been reported. This study was aimed to reveal metabolomic signatures in diabetes development and progression. Methods: In this cross-sectional study, we compared healthy (n = 30), type 2 diabetes mellitus (T2DM) (n = 30), and DKD (n = 30) subjects with the goal of identifying gradual altering metabolites. Then, a prospective study was performed in T2DM patients to evaluate these altered metabolites in the onset of DKD. Logistic regression was conducted to predict rapid eGFR decline in T2DM subjects using altered metabolites. The prospective association of metabolites with the risk of developing DKD was examined using logistic regression and restricted cubic spline regression models. Results: In this cross-sectional study, impaired amino acid metabolism was the main metabolic signature in the onset and development of diabetes, which was characterized by increased N-acetylaspartic acid, L-valine, isoleucine, asparagine, betaine, and L-methionine levels in both the T2DM and DKD groups. These candidate metabolites could distinguish the DKD group from the T2DM group. In the follow-up study, higher baseline levels of L-valine and isoleucine were significantly associated with an increased risk of rapid eGFR decline in T2DM patients. Of these, L-valine and isoleucine were independent risk factors for the development of DKD. Notably, nonlinear associations were also observed for higher baseline levels of L-valine and isoleucine, with an increased risk of DKD among patients with T2DM. Conclusion: Amino acid metabolism was disturbed in diabetes, and N-acetylaspartic acid, L-valine, isoleucine, asparagine, betaine, and L-methionine could be biomarkers for the onset and progression of diabetes. Furthermore, high levels of L-valine and isoleucine may be risk factors for DKD development.

Triglyceride-glucose index is prospectively associated with chronic kidney disease progression in Type 2 diabetes - mediation by pigment epithelium-derived factor.

BackgroundTriglyceride-glucose (TyG) index is a surrogate marker of insulin resistance. Its role in chronic kidney disease (CKD) progression in Type 2 Diabetes Mellitus (T2DM) is unclear. We investigated the association between TyG index and CKD progression, and possible mediation of the association by pigment epithelium-derived factor (PEDF).MethodsThis was a prospective study on 1571 patients with T2DM. CKD progression was defined as worsening across KDIGO estimated glomerular filtration rate (eGFR) categories with ≥25% reduction from baseline. PEDF was quantitated using enzyme-linked immunosorbent assay method. Cox proportional hazards regression model was used to assess the relationship between TyG index and CKD progression.ResultsOver a follow-up period of up to 8.6 years (median 4.6 years, IQR 3.0–3.6), 42.7% of subjects had CKD progression. Every unit increase in TyG was associated with hazards of 1.44 (95%CI 1.29–1.61; p < 0.001) in unadjusted analysis and 1.21 (1.06–1.37; p = 0.004) in fully adjusted model. Compared to tertile 1, tertiles 2 and 3 TyG index were positively associated with CKD progression with corresponding hazard ratios HRs 1.24 (1.01–1.52; p = 0.037) and 1.37 (1.11–1.68; p = 0.003) in fully adjusted models. PEDF accounted for 36.0% of relationship between TyG index and CKD progression.ConclusionsHigher TyG index independently predicted CKD progression in T2DM. PEDF mediated the association between TyG index and CKD progression.

Cardiac Autonomic Dysfunction Is Associated With Risk of Diabetic Kidney Disease Progression in Type 2 Diabetes Mellitus.

BackgroundEvidence on the relationship between heart rate variability (HRV) and albumin-to-creatinine ratio (ACR) combined with estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM) is rare. Thus, this study aimed to investigate the relationship between heart rate variability and the risk of diabetic kidney disease (DKD) progression in diabetes patients.MethodOverall, 747 T2DM patients who were admitted to the Second Affiliated Hospital of Nanchang University underwent 24-hour dynamic electrocardiograms for HRV analysis. Time-domain HRV measures included mean heart rate, standard deviation of the R-R interval (SDNN), SDNN index, root mean squared difference of successive RR intervals (RMSSD), and percent of adjacent RR intervals with a difference greater than 50 ms (PNN50). Frequency-domain measures included low frequency (LF), very low frequency (VLF), high frequency (HF) components and LF-to-HF ratio. The risk of DKD progression was determined by combining ACR and eGFR and stratified as low risk (Group A), moderately increased risk (Group B), high risk (Group C), and very high risk (Group D) based on the Kidney Disease: Improving Global Outcomes guidelines.ResultThere were significant differences in HRV parameters among the four risk groups (SDNN: 113 ms vs 109 ms vs 101 ms vs 81 ms, P<0.01; LF: 240.2 ms2 vs 241.1 ms2 vs 155.2 ms2 vs 141.9 ms2, P<0.01; LF-to-HF ratio: 1.70 vs 1.24 vs 1.12 vs 0.93, P<0.01; VLF: 723.7 ms2 vs 601.1 ms2 vs 446.4 ms2 vs 356.3 ms2, P<0.01). A very high risk of DKD progression was significantly associated with a lower SDNN (β=-19.5, 95% CI: -30.0 to -10.0, P<0.01), and moderately increased, high, and very high risks were associated with lower LF-to-HF ratio and VLF (P<0.05). Logistic regression analysis showed that group D had a higher risk of reduced SDNN, LF-to-HF ratio, and VLF compared with group A after adjusting for systolic blood pressure, glycated haemoglobin, haemoglobin, high-density lipoprotein cholesterol, and age (odds ratio (95% CI): 0.989 (0. 983–0.996), 0.674 (0.498–0.913), and 0.999 (0.999–1.000), respectively).ConclusionCardiac autonomic dysfunction is associated with a risk of DKD progression in adults with T2DM, and reduced heart rate variability increased such risk. Thus, HRV screening may be necessary in patients with T2DM, especially those with high proteinuria.

Higher extracellular water to total body water ratio was associated with chronic kidney disease progression in type 2 diabetes.

We studied the association between extracellular volume status and chronic kidney disease (CKD) progression; and the role of extracellular volume excess as a potential mediator in the relationship between matrix metalloproteinases (MMP)-2 and CKD progression in Type 2 diabetes mellitus (T2DM). We conducted a prospective cohort study of 1079 T2DM patients. Bioelectrical impedance analysis (BIA) was performed to assess body fluid status. After up to 8.6 years of follow-up, 471 (43.7%) patients experienced CKD progression. In the fully adjusted model, extracellular water (ECW)/ total body water (TBW)ratios 0.39-0.40 and > 0.40 were associated with 45% and 78% higher risk of CKD progression respectively. Patients with an increase in ECW/TBW ratio had 40% higher risk of CKD progression compared to those with no change or reduction of ECW/TBW ratio. Higher ECW/TBW ratio accounted for 17.4% of the relationship between MMP-2 and CKD progression in T2DM (p = 0.026). Extracellular volume excess was independently associated with CKD progression in T2DM. Higher ECW/TBW ratio mediated the positive association between MMP-2 and CKD progression. Further studies are needed to elucidate the role of extracellular volume excess in deterioration of renal function.

The role of pulse pressure in navigating the paradigm of chronic kidney disease progression in type 2 diabetes mellitus.

Arterial stiffness is a risk factor for chronic kidney disease progression (CKD). Pulse pressure is a surrogate marker of arterial stiffness. It is unclear if pulse pressure predicts CKD progression in type 2 diabetes mellitus. This was prospective study involving 1494 patients with estimated glomerular filtration rate (eGFR) ≥ 15ml/min/1.73 m2. Carotid-femoral pulse wave velocity was measured using applanation tonometry. Pulse pressure was calculated as difference between systolic and diastolic blood pressures. CKD progression was defined as worsening of eGFR categories (stage 1, ≥ 90ml/min/1.73m2; stage 2, 60-89ml/min/1.73m2; stage 3a, 45-59ml/min/1.73m2; stage 3b, 30-44ml/min/1.73m2; stage 4; 15-29ml/min/1.73m2; and stage 5, < 15ml/min/1.73m2) with ≥ 25% decrease in eGFR from baseline. After follow-up of up to 6years, CKD progression occurred in 33.5% of subjects. Subjects in 2nd, 3rd and 4th quartiles of peripheral pulse pressure experienced higher risk of CKD progression with unadjusted hazard ratios (HRs) 1.55 [95% confidence interval (CI) 1.13-2.11; p = 0.006], 2.58 (1.93-3.45; p < 0.001) and 3.41 (2.58-4.52; p < 0.001). In the fully adjusted model, the association for 2nd, 3rd and 4th quartiles remained with HRs 1.40 (1.02-1.93; p = 0.038), 1.87 (1.37-2.56; p < 0.001) and 1.75 (1.25-2.44; p = 0.001) respectively. Similarly, 2nd, 3rd and 4th quartiles of aortic pulse pressure were associated with higher hazards of CKD progression with HRs 1.73 (1.25-2.40; p = 0.001), 1.65 (1.18-2.29; p = 0.003) and 1.81 (1.26-2.60; p = 0.001). Increasing urinary albumin-to-creatinine ratio accounted for 44.0% of the association between peripheral pulse pressure and CKD progression. Individuals with high pulse pressure were more susceptible to deterioration of renal function. Pulse pressure could potentially be incorporated in clinical practice as an inexpensive and readily available biomarker of renal decline in type 2 diabetes mellitus. Graphic abstract.

The sodium-glucose cotransporter 2 inhibitor tofogliflozin prevents diabetic kidney disease progression in type 2 diabetic mice.

Trials on cardiovascular and renal outcomes in patients with type 2 diabetes have consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of diabetic kidney disease (DKD) progression. However, their renal protective mechanisms have yet to be completely understood and the effect on albuminuria reduction in animal models is controversial. We investigated these issues using KK and KK-Ay mice as a control (CTRL) and as a model for type 2 diabetes (DKD), respectively. KK-Ay mice were treated with 0.015% tofogliflozin, which is an SGLT2 inhibitor, starting at seven weeks of age for eight weeks. Compared with the CTRL mice, the DKD mice had higher HbA1c levels and albuminuria. Although tofogliflozin treatment significantly lowered HbA1c levels, it did not reverse albuminuria. Tofogliflozin treatment enhanced damage in both the glomerular (i.e., enlarged mesangial area, increased foot process effacement rate, and decreased number of WT-1-positive cells) and tubulointerstitial (increased protein levels of KIM-1 and MCP-1, increased number of macrophages, and abnormal mitochondrial morphology) areas. Our results suggest that tofogliflozin may prevent glomerular and tubulointerstitial damage, partly by ameliorating hyperglycemia, renal inflammation, and abnormalmitochondrial morphology.

SGLT2 Inhibitors: Slowing of Chronic Kidney Disease Progression in Type 2 Diabetes.

Diabetic kidney disease (DKD) is a topic of increasing concern among clinicians involved in the management of type 2 diabetes mellitus (T2DM). It is a progressive and costly complication associated with increased risk of adverse cardiovascular (CV) and renal outcomes and mortality. Ongoing monitoring of the estimated glomerular filtration (eGFR) rate alongside the urine albumin:creatinine ratio (ACR) is recommended during regular T2DM reviews to enable a prompt DKD diagnosis or to assess disease progression, providing an understanding of adverse risk for each individual. Many people with DKD will progress to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT), typically haemodialysis or kidney transplantation. A range of lifestyle and pharmacological interventions is recommended to help lower CV risk, slow the advancement of DKD and prevent or delay the need for RRT. Emerging evidence concerning sodium-glucose co-transporter-2 inhibitor (SGLT2i) agents suggests a role for these medicines in slowing eGFR decline, enabling regression of albuminuria and reducing progression to ESKD. Improvements in renal end points observed in SGLT2i CV outcome trials (CVOTs) highlighted the possible impact of these agents in the management of DKD. Data from the canagliflozin CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) have since demonstrated the effectiveness of this medicine in reducing the risk of kidney failure and CV events in a population comprising individuals with T2DM and renal disease. CREDENCE was the first SGLT2i study to examine renal outcomes as the primary end point. Real-world studies have reaffirmed these outcomes in routine clinical practice. This article summarises the evidence regarding the use of SGLT2i medicines in slowing the progression of DKD and examines the possible mechanisms underpinning the renoprotective effects of these agents. The relevant national and international guidance for monitoring and treatment of DKD is also highlighted to help clinicians working to support this vulnerable group.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00930-x) contains supplementary material, which is available to authorized users.

516-P: Urine Metabolite Biomarkers Predict Progression of Diabetic Nephropathy in 2,531 Individuals with Type 1 Diabetes

People living with type 1 diabetes have increased risk to develop diabetic nephropathy. No targeted cure exists, but the progression can be slowed down if detected early. We tested whether metabolic biomarkers measured in urine could predict progression of diabetic nephropathy (DN) in the Finnish nationwide FinnDiane Study. At baseline, 18 urine metabolites were measured with nuclear magnetic resonance metabolomics and scaled relative to urine creatinine. Individuals were followed for DN status for 9.0 years (± 5.1 years) until they progressed to their most severe DN status (334 events) or the latest known DN status for non-progressors. A Bonferroni-corrected P&amp;lt;0.003 was considered significant. Five out of 18 urine metabolites were robustly associated with risk for DN progression in Cox regression models adjusted for sex, year of diabetes diagnosis as well as baseline age, DN status, BMI and eGFR. Individuals with elevated urinary levels of alanine (Hazard Ratio (HR) = 1.49 [1.26, 1.77] per 1-SD creatinine-scaled metabolite concentration, , P=3×10-6), valine (HR = 1.34 [1.22, 1.48], P=4×10-9), 2–hydroxyisobutyrate (HR = 1.48 [1.30, 1.67], P=1×10-9), cis-Aconitate (HR = 1.17 [1.06, 1.28], P=9×10-4) and pseudouridine (HR = 1.45 [1.24, 1.69], P=4×10-6) showed higher DN progression rate. We conclude that urinary biomarkers are indicative of kidney disease progression in type 1 diabetes, independently of baseline microalbuminuria and eGFR. The urinary biomarkers span multiple metabolic pathways, including microbial metabolism, citric acid cycle, and amino acids reflecting adiposity and dietary quality. Disclosure S. Mutter: None. E.A. Valo: None. V. Aittomäki: Employee; Self; Nightingale Health Ltd. Other Relationship; Self; Nightingale Health Ltd. C. Forsblom: None. P. Groop: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Sanofi, Sanofi. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medscape, Merck Sharp &amp; Dohme Corp., Mundipharma International. P. Wurtz: Employee; Self; Nightingale Health Ltd. Stock/Shareholder; Self; Nightingale Health Ltd. Funding Folkhälsan Finland; Novo Nordisk Foundation; Academy of Finland

Zinc-α2-glycoprotein is associated with non-albuminuric chronic kidney disease progression in type 2 diabetes: a retrospective study with 4-year follow-up.

To investigate the association between baseline plasma zinc-α2-glycoprotein and non-albuminuric chronic kidney disease progression in type 2 diabetes. Adults with normoalbuminuria at entry (n=341; age 57±10 years, 52% men) were analysed. Chronic kidney disease progression was defined as a decrease in chronic kidney disease stage and a decline of ≥25% in estimated GFR from baseline. Baseline plasma zinc-α2-glycoprotein levels were quantified by immunoassay, and analysed either as a continuous variable or by tertiles in Cox proportional hazards models. Model discrimination was assessed using Harrell's C-index. A sensitivity analysis was performed on a subset of individuals who maintained normoalbuminuria during follow-up. Chronic kidney disease progression occurred in 54 participants (16%). Zinc-α2-glycoprotein levels were elevated in chronic kidney disease progressors (P = 0.011), and more progressors were assigned to the higher zinc-α2-glycoprotein tertile than non-progressors. In the unadjusted Cox model, zinc-α2-glycoprotein, both as a continuous variable (hazard ratio 1.72, 95% CI 1.08-2.75) and tertile 3 (vs tertile 1; hazard ratio 2.14, 95% CI 1.10-4.17), predicted chronic kidney disease progression. The association persisted after multivariable adjustment. The C-index of the Cox model increased significantly after incorporation of zinc-α2-glycoprotein into a base model comprising renin-angiotensin system antagonist usage. Sensitivity analysis showed that zinc-α2-glycoprotein independently predicted chronic kidney disease progression among individuals who maintained normoalbuminuria during follow-up. Plasma zinc-α2-glycoprotein is associated with chronic kidney disease progression, and may serve as a useful early biomarker for predicting non-albuminuric chronic kidney disease progression in type 2 diabetes.

Impact of haemoglobin A1c trajectories on chronic kidney disease progression in type 2 diabetes.

To characterize haemoglobin A1c (HbA1c) trajectories and examine their associations with chronic kidney disease (CKD) progression. This was a prospective cohort study on 770 patients with type 2 diabetes mellitus (T2DM) attending a diabetes centre in 2002-2017. Group-based trajectory modelling was used to identify HbA1c trajectories. Cox proportional hazards models were used to examine association between the trajectories and CKD progression which was defined as deterioration across the Kidney Disease: Improving Global Outcomes estimated glomerular filtration rate categories with ≥25% drop from baseline. We identified four HbA1c trajectories: 'near-optimal stable' (49.1%), 'moderate stable' (37.9%), 'moderate-increasing' (6.0%) and 'high-decreasing' (7.0%). Over a median follow-up period of 4.6 years (interquartile range 2.5-5.6), CKD progression occurred in 35.6% of patients. The risk of CKD progression was significantly higher in the moderate-increasing with adjusted hazard ratios (HR) 2.23 (95% confidence interval (CI) 1.09-4.57). After additional adjustment for mean HbA1c, the association between the moderate-increasing subgroup and CKD progression remained significant at HR 3.07 (95% CI 1.08-8.77). Moderate-increasing HbA1c trajectory is associated with renal disease progression in patients with T2DM, independent of mean HbA1c. The deleterious effects of deteriorating HbA1c trajectory highlight the importance of achieving sustained good glycaemic control in diabetes management.

Development and validation of a predictive model for Chronic Kidney Disease progression in Type 2 Diabetes Mellitus based on a 13-year study in Singapore.

This study aims to develop and validate a predictive model for Chronic Kidney Disease (CKD) progression in Type 2 Diabetes Mellitus (T2DM). We conducted a prospective study on 1582 patients with T2DM from a Diabetes Centre in regional hospital in 2002-2014. CKD progression was defined as deterioration across eGFR categories with ⩾25% drop from baseline. The dataset was randomly split into development (70%) and validation (30%) datasets. Stepwise multivariable logistic regression was used to identify baseline predictors for model development. Model performance in the two datasets was assessed. During median follow-up of 5.5years, 679 (42.9%) had CKD progression. Progression occurred in 467 (42.2%) and 212 patients (44.6%) in development and validation datasets respectively. Systolic blood pressure, HbA1c, estimated glomerular filtration rate and urinary albumin-to-creatinine ratio were associated with progression. Areas under receiving-operating-characteristics curve for the training and test datasets were 0.80 (95%CI, 0.77-0.83) and 0.83 (95%CI, 0.79-0.87). Observed and predicted probabilities by quintiles were not statistically different with Hosmer-Lemeshow χ2 0.65 (p=0.986) and 1.36 (p=0.928) in the two datasets. Sensitivity and specificity were 71.4% and 72.2% in development dataset, and 75.6% and 72.3% in the validation dataset. A model using routinely available clinical measurements can accurately predict CKD progression in T2DM.

Biomarkers of rapid chronic kidney disease progression in type 2 diabetes

Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.

Serum cystatin C in early prediction of risk of chronic kidney disease progression in type 2 diabetes (LB727)

Serum cystatin C (CysC) is superior to serum creatinine (SCr) in diagnosing mild diabetic nephropathy. We hypothesized that, CysC can predict the risk of CKD progression at an early stage in T2DM. Our objective was to compare levels of CysC, SCr and eGFR in T2DM patients in no/low risk with moderate risk of CKD progression according to Kidney Disease Initiative Global Outcomes (KDIGO) guideline’s CKD risk stratification. Sixty one non‐obese, T2DM patients aged 30‐60 years, suspected of mild to moderate CKD were recruited. Creatinine was measured using Jaffe method in serum and urine. Serum CysC and urine albumin were measured using immunoturbidimetry. eGFRs were calculated using Modification of Diet in Renal Disease equation (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equations. Moreover, Albumin to Creatinine Ratio (ACR) was calculated. Patients were categorized, to CKD risks categories using eGFR CKD‐EPI based on SCr and ACR. Our results demonstrate that patients in the moderately increased risk group had significantly higher CysC than those in the no/low risk group. However, SCr, eGFR based on CKD EPI and MDRD equations were not significantly different between the two groups. Thus, CysC is valuable in detecting moderately increased risk in CKD progression in T2DM patients than SCr and SCr based eGFR. These observations may be useful for early prediction of CKD progression and clinical management of patients with early diabetic nephropathy.Grant Funding Source: Research award from the University of Sri Jayewardenepura (Grant number : ASP/06/R/MED/2011/21), and Texas Tech University

3: Group versus individual appointments and their impact on kidney disease progression in type 2 diabetes patients who attend the Cleveland Clinic Florida

3: Group versus individual appointments and their impact on kidney disease progression in type 2 diabetes patients who attend the Cleveland Clinic Florida