Glomerular Filtration Rate In Type Research Articles

Angiopoietin-like 4 is a potential biomarker for diabetic kidney disease in type 2 diabetes patients.

The association between serum angiopoietin-like 4 (ANGPTL4) levels and the severity of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus remains unclear. A total of 1,115 type 2 diabetes mellitus patients were analyzed in this cross-sectional study. DKD index included DKD stages defined by estimated glomerular filtration rate, the albuminuria grades and DKD risk management grades. Serum levels of ANGPTL4 and other biomarkers were detected. Multivariable-adjusted linear and logistic analyses were used to study the association between ANGPTL4 and DKD. The protein levels of ANGPTL4 were assessed in the kidney. Renal tubular cells were stimulated with glucose to study ANGPTL4 expression. Compared with the participants in the third or fourth quantile of ANGPTL4, those in the first or second quantile of ANGPTL4 were younger, with lower glycated hemoglobin, triglycerides and urinary albumin creatinine ratio (all P < 0.05). There was a negative nonlinear relationship between ANGPTL4 and estimated glomerular filtration rate in type 2 diabetes mellitus patients. One standard deviation increased serum ANGPTL4 levels, the odds ratio of having DKD was 1.40 (95% confidence interval 1.08-1.80). The mediation analysis showed that triglycerides did not mediate the association between ANGPTL4 and DKD. Furthermore, ANGPTL4 could be the strongest among multiple panels of biomarkers in its association of DKD. Compared with mice at 8 weeks-of-age, db/db mice at 18 weeks-of-age had increased ANGPTL4 expression in glomeruli and tubular segments. In vitro, glucose could stimulate ANGPTL4 expression in tubular cells in a dose-dependent manner. ANGPTL4 could be a potential marker and therapeutic target for DKD treatment.

Interpretable machine learning identifies metabolites associated with glomerular filtration rate in type 2 diabetes patients.

The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients. We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model. For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR. Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.

Serum Uric Acid to Creatinine Ratio with Estimated Glomerular Filtration Rate in Type 2 Diabetes Patients.

Diabetes mellitus is a metabolic disorder associated with cardiovascular and renal complications. The serum uric acid to creatinine ratio and estimated glomerular filtration rate are important markers used to assess kidney function in patients with type 2 diabetes. This study aimed to find the correlation between serum uric acid to creatinine ratio and estimated glomerular filtration rate to various parameters among the diabetes patients. It is an observational hospital-based, cross-sectional study. Patients with a diagnosis of diabetes for three years or more duration were selected. This study designed to serum uric acid to creatinine ratio with estimated glomerular filtration rate and its relationship with other biochemical parameters. The Modification of Diet in Renal Disease formula was used to calculate estimated glomerular filtration rate (eGFR). eGFR (mL/min∙1.73 m2) = 186 × (Scr) -1.154 × (age) - 0.203 × (0.742 female). Low eGFR was defined as eGFR<60 mL/min∙1.73 m2. The data were analyzed by SPSS version 20. Mean values of different variables, standard deviations and p-values were calculated. Mean serum uric acid to creatinine ratio was 6.09±1.71 and elevated among 49.1%. Mean blood urea and serum creatinine levels were 28.0±10.72 and 1.01±0.18, respectively. There was a significant positive correlation between eGFR and serum uric acid : serum creatinine ( r = 0.246, p = 0.007) in this study. The serum uric acid to creatinine ratio can serve as an early marker for renal injury, showing a positive correlation with estimated glomerular filtration rate (eGFR). Monitoring serum uric acid to creatinine ratio levels alongside eGFR can assistance in the identification and management of kidney damage in its early stages.

Systolic inter-arm blood pressure difference and estimated glomerular filtration rate in type 2 diabetic patients in Palestine: a cross-sectional study

Objectives This study aimed to investigate the association between systolic inter-arm blood pressure difference (IABPD) and the estimated glomerular filtration rate (eGFR), as well as chronic kidney disease (CKD), in patients with type 2 diabetes mellitus (T2DM). Patients and methods This cross-sectional study included 189 Palestinians diagnosed with T2DM. Data were collected through personal interviews, medical records and three separate blood pressure measurements from both arms. Patients were stratified in two ways: based on systolic IABPD ≥15 mmHg and the presence of CKD, indicated by an eGFR of <60 mL/min/1.73 m2 over a three months period. We used simple and multiple linear regression analyses to clarify the association between systolic IABPD (mmHg) and eGFR and to identify independent predictors for eGFR. Results The mean age was 61.3 years, with a female percentage of 57.7%. The prevalence of systolic IABPD ≥15 mmHg and CKD was 27.5% and 30.2%, respectively. Among patients with eGFR <60 mL/min/1.73 m2, the median systolic IABPD was 12.5 mmHg (interquartile range (IQR), 13.5 mmHg), whereas in patients with eGFR ≥60 mL/min/1.73 m2, it was 7.5 mmHg (IQR, 9.8 mmHg) with a significant difference (p = .021). The results of the multiple linear regression model did not reveal an independent association between systolic IABPD and eGFR, with an unstandardized coefficient (B) of −0.257 (95% confidence interval (CI), −0.623 to 0.109; p = .167). However, older age (B, −0.886; 95% CI, −1.281 to −0.49; p < .001), hypertension (B, −12.715; 95% CI, −22.553 to −2.878; p = .012) and a longer duration of DM (B, −0.642; 95% CI, −1.10 to −0.174; p = .007) were significantly and negatively associated with eGFR. Conclusions Systolic IABPD did not exhibit an independent association with eGFR in T2DM patients. However, older age, a previous history of hypertension, and a longer duration of DM were all significantly associated with lower eGFR.

Accuracy evaluation of 2021 Chronic Kidney Disease Epidemiology Collaboration, Full Age Spectrum and European Kidney Function Consortium equations for estimating glomerular filtration rate in type 2 diabetes mellitus and healthy adults

Background and aimsEstimated glomerular filtration rate (eGFR) equations accuracy has been questioned in diabetes mellitus (DM). We aimed to evaluate the performance of three equations – European Kidney Function Consortium (EKFC), Full Age Spectrum (FAS), and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) – in healthy and type 2 DM participants. Material and methodsThis cross-sectional studycompared eGFR equations withareference method: measured GFR (mGFR) by 51Cr-EDTA. The equations performance was assessed usingBland-Altman plot,concordance correlation coefficient (CCC), bias,P30 andP15 accuracy. ResultsIn the 100 healthy adults included (aged 39 ± 15 years, 67% women, mean mGFR 107 ± 15, 2021 CKD-EPI 109 ± 14, FAS 107 ± 18 and EKFC 101 ± 12 mL/min/1.73 m2), all equations reached P30 accuracy above the desirable benchmark of 90%. In the 122 patients with type 2 DM (aged 61 ± 10 years, 55% women, mGFR97 ± 22, 2021 CKD-EPI 86 ± 20, FAS 83 ± 25 and EKFC 79 ± 18 mL/min/1.73 m2), the equations presented larger biases, worst agreement with mGFR and inferior accuracy, with 2021 CKD-EPI (83%) and EKFC (82%) presenting greater P30 than FAS (77%). ConclusionIn healthy Brazilian adults, 2021 CKD-EPI, FAS and EKFC are suitable to estimate GFR. However, all equations underperform in people with type 2 DM.

T184 HbA1c and serum uric acid to creatinine ratio: A predictor of kidney diseases in association with estimated glomerular filtration rate in type 2 diabetes patients

T184 HbA1c and serum uric acid to creatinine ratio: A predictor of kidney diseases in association with estimated glomerular filtration rate in type 2 diabetes patients

Glomerular filtration rate in type 1 diabetic adolescent by using single plasma sample and gamma camera methods

Glomerular filtration rate in type 1 diabetic adolescent by using single plasma sample and gamma camera methods

Relationship between plasma growth differentiation factor-15 level and estimated glomerular filtration rate in type 2 diabetes patients with and without albuminuria.

To assess the relationship between growth differentiation factor-15 (GDF-15) levels and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus (DM) patients with and without albuminuria. We examined 324 patients with type 2 DM in a cross-sectional study. eGFR was determined using equations from creatinine (eGFRcr) and the combination of creatinine and cystatin C (eGFRcr-cys). The patients were classified into two groups based on urinary albumin: creatinine ratio (ACR): the normoalbuminuria group (urinary ACR < 30 mg/g) and the albuminuria group (urinary ACR ≥ 30 mg/g). In individuals both with and without albuminuria, higher GDF-15 levels were associated with lower eGFRcr and eGFRcr-cys. Plasma GDF-15 levels were inversely correlated with eGFRcr in individuals both with and without albuminuria (γ = -0.624, p < 0.001 and γ = -0.509, p < 0.001, respectively). A multiple regression analysis showed that GDF-15 levels were significantly associated with eGFRcr after adjusting for age, sex and other confounders, including urinary ACR as a continuous or categorical variable (β = -0.309, p < 0.001 and β = -0.318, p < 0.001, respectively). Similarly, these results were replicated when eGFRcr-cys was considered instead of eGFRcr in correlation and regression analyses. GDF-15 levels were inversely associated with eGFR in patients with type 2 DM. This relationship was independent of albuminuria status.

Stronger Association of Albuminuria with the Risk of Vascular Complications than Estimated Glomerular Filtration Rate in Type 2 Diabetes

Introduction: Albuminuria is a risk factor for macro- and microvascular complications of type 2 diabetes (T2D).With an increasing trend of normoalbuminuria, however, of the 2 predictors – estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) – which one is a better predictor of vascular complications of T2D is not clear. Objective: This study aimed to compare the impacts of albuminuria and eGFR on patients with T2D associated with micro- and macrovascular complications. Methods: This retrospective study recruited 4,715 patients with T2D and grouped them based on the values of UACR (high UACR: ≥30 mg/g, low UACR: <30 mg/g) and eGFR (mL/[min × 1.73 m²]) (G1: eGFR ≥ 90; G2: eGFR = 60–89; G3–5: eGFR < 60) from April 2008 to November 2018. Logistic regression analysis was carried out for risk factors in patients with diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD), left ventricular remodeling, diastolic disorders, and carotid atherosclerotic plaque in 6 different groups: low UACR + G1 (control group), low UACR + G2, low UACR + G3–5, high UACR + G1, high UACR + G2, and high UACR + G3–5. Patients were grouped according to the change in the UACR value (UACR-decreased group: ≤−30%, UACR-stable group: −30 to 30%, and UACR-increased group ≥30%), eGFR value (eGFR-decreased group: >3%, and eGFR-stable group: ≤3%) and followed up. Results: Compared with the control group, patients with higher albuminuria and lower eGFR had higher adjusted odds ratio (OR) trends of complications, especially in the high UACR + G3–5 group. The OR of 2.010, 3.444, 1.633, 2.742, and 3.014 were obtained for DR, DPN, PAD, left ventricular remodeling, and diastolic disorders, respectively. No statistically significant difference was found in the risk of complications within each one of 2 phenotypes, regardless of the change in the eGFR. After grouping by eGFR, the regression analysis of the urinary protein level in each stage revealed that a majority of complications had a statistically significant difference, except for DR and PAD in the high UACR + G3–5 group. DR in the follow-up study had a higher risk in the UACR-stable/increased group than the UACR-decreased group (UACR stable: OR = 2.568; 95% confidence interval (CI): 1.128–5.849; p = 0.025; UACR increased: OR = 2.489; 95% CI: 1.140–5.433; p = 0.022). Conclusion: UACR is a more predictive risk factor for diabetic complications compared with a reduced eGFR.

306-OR: A Metabolic Mismatch between Renal Oxygenation and Glomerular Filtration Rate in Type 1 Diabetes

Glomerular filtration rate (GFR) is a major determinant of renal energy expenditure. Animal models support a mismatch between renal oxygenation (RO2) and energy expenditure in diabetic kidney disease (DKD). The objective of this study was to compare the ratio of RO2 to GFR (RO2:GFR) in adolescents with and without type 1 diabetes (T1D) and correlate the ratio with albuminuria, effective renal plasma flow (ERPF), blood pressure, trunk mass and renal oxygen consumption. RO2 was measured by blood oxygenation level dependent (BOLD) MRI before and after 20 mg of I.V. furosemide, trunk mass by DXA, GFR by iohexol clearance, ERPF by p-aminohippurate clearance and albuminuria by urine albumin-to-creatinine ratio (UACR) in 50 adolescents with T1D (mean age 16.1±3.0 yrs, trunk mass 44.8±2.2%, HbA1c 8.6±1.2%, GFR 189±40 ml/min) and 20 non-obese controls (mean age 16.1±2.9 yrs, trunk mass 44.9±2.2%, HbA1c 5.2±0.2%, GFR 136±22 ml/min). The RO2:GFR (s/ml/min*1000) was calculated as renal oxygenation (T2*, s) divided by GFR (ml/min), and furosemide-suppressible oxygenation (FSOC) as change in RO2 in responses to furosemide. Relationships were evaluated by correlation and multivariable generalized linear regression models. RO2:GFR was 25% lower in adolescents with T1D vs. controls (mean±SD: 0.24±0.04 vs. 0.32±0.04, p&amp;lt;0.0001). In adolescents with T1D, lower RO2:GFR was associated with higher UACR (r=-0.31, p=0.03), diastolic blood pressure (r=-0.33, p=0.02), ERPF (r=-0.52, p=0.0009) and trunk mass (r=-0.39, p=0.006). Lower RO2:GFR was also associated with elevated FSOC after adjustments for age, sex and HbA1c (β±SE: -10.5±3.2, p=0.002). For the first time, we demonstrate an imbalance between RO2 and GFR in adolescents with T1D compared with healthy non-obese controls. Additionally, low RO2:GFR independently associated with albuminuria, central adiposity and elevated renal oxygen consumption. These data suggest a potential role of relative renal hypoxia in the development of early DKD. Disclosure C.L. Vinovskis: None. K.J. Nadeau: None. K.L. Tommerdahl: None. P.V. Prasad: None. L. Li: None. L. Pyle: None. M. Rewers: None. M. Pragnell: None. F.H. Mahmud: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation. D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck &amp; Co., Inc., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck &amp; Co., Inc., Sanofi. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk. R. Nelson: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc. Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Novo Nordisk Foundation. Research Support; Self; Horizon Pharma. Funding JDRF (2-SRA-2018-627-M-B); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK116720)

Correlation between Proteinuria and Glomerular Filtration Rate in Type 2 Diabetes Mellitus

Indonesia faces a double burden of communicable and non-communicable diseases, including metabolic and degenerative problems. Delay in the detection of diabetic nephropathy (DN) as one of the chronic microvascular complications is often seen, leading to the need for hemodialysis due to the end-stage renal disease (ESRD). An assessment of diabetes mellitus (DM) control target achievement, based on the guideline from the Indonesian Society of Endocrinology (Perkumpulan Endokrinologi Indonesia, PERKENI), and nephropathy early detection was performed in 54 Type-2 DM patients from 5 private hospitals in Pekanbaru Riau, Indonesia, from November 2018 to September 2019. Results showed poor achievement of DM control with 61.1% had abnormal body mass index, 57.5% had HbA1c>7%, and 77.7% had LDL serum >100 mg/dL. Nevertheless, most patients achieved good blood pressure control (74%). A high percentage of nephropathy-proteinuria was seen (40.7%) with 40.9% of them revealed renal insufficiency classified as chronic kidney disease (CKD) stage 3 and 4. There was a significant correlation between proteinuria and declined GFR (p=0.016), onset of DM (p=0.02), and diastolic blood pressure (p=0.03). No correlation was found between HbA1c and declined GFR, which may be due to the cross-sectional nature of the study. It will be interesting to perform a prospective study on proteinuria modification as a predictor of nephropathy early detection in DM patients since kidney biopsy and urine albumin creatinine ratio assessment are not available in primary health care services in remote areas. Korelasi antara Proteinuria dan Laju Filtrasi Glomerulus pada Diabetes Melitus Tipe 2 Indonesia menghadapi beban ganda penyakit menular dan tidak menular, termasuk masalah metabolisme dan degeneratif. Keterlambatan dalam deteksi nefropati diabetik sebagai salah satu komplikasi mikrovaskular kronis sering terlihat, mengarah pada kebutuhan untuk hemodialisis karena penyakit ginjal stadium akhir (ESRD). Dari 54 pasien diabetes melitus (DM) tipe-2 tanpa keluhan edema, sesak, dan lemas dari 5 rumah sakit swasta di Pekanbaru, Riau, Indonesia, dari November 2018 hingga September 2019, dilakukan penilaian kontrol DM sesuai panduan Perkumpulan Endokrinologi Indonesia (PERKENI). Didapatkan hasil bahwa pencapaian kontrol DM masih buruk dengan 61,1% memiliki indeks massa tubuh abnormal 57,5% memiliki HbA1c >7%, dan 77,7% memiliki serum LDL >100 mg/dL. Namun demikian, sebagian besar pasien mencapai kontrol tekanan darah yang baik (74%). Pasien terdeteksi proteinuria >25 mg/dL mencapai 40,7% dengan 40,9% diantaranya mengalami gangguan filtrasi ginjal yang didefinisikan sebagai GFR <60 diklasifikasikan penyakit ginjal kronis tahap 3 dan 4. Walaupun secara statistik tidak ditemukan hubungan bermakna antara kontrol glikemik dengan insufisiensi renal, namun ditemukan hubungan yang bermakna antara nefropati dengan penurunan laju filtrasi glomerulus (GFR) (p=0.016), awitan DM (p=0,02), dan tekanan darah diastolik (p=0,03). Tidak ada hubungan bermakna antara HbA1c dan penurunan GFR yang mungkin disebabkan observasi sesaat. Akan menarik untuk melakukan studi prospektif pada modifikasi proteinuria sebagai prediktor deteksi dini nefropati pada pasien DM karena biopsi ginjal dan penilaian rasio albumin kreatinin urin tidak tersedia di layanan perawatan kesehatan primer di daerah terpencil.

Lower serum 25-hydroxyvitamin D levels are associated with impaired glomerular filtration rate in type 2 diabetes patients.

Background:25-Hydroxyvitamin D [25(OH)D] deficiency has been implicated as a possible risk factor for the onset and progression of diabetes kidney disease (DKD). The aim of this study was to evaluate the interaction between levels of 25(OH)D and DKD in type 2 diabetes mellitus (DM) patients.Methods:Cross-sectional design, outpatient type 2 DM. Glomerular filtration rate (GFR) was measured by 51Cr-EDTA and estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), urinary albumin excretion (UAE) by immunoturbidimetry, and 25(OH)D by chemiluminescence. Receiver operating characteristic (ROC) curve analysis and generalized linear model (Poisson robust regression estimator) were used to assess the interaction between 25(OH)D levels and renal function.Results:A total of 114 type 2 DM patients aged 60 ± 10 years, 49 males (43%), DM duration 22 ± 10 years, with GFR > 60 ml/min/1.73 m2 were evaluated. Patients with GFRs 60–90 (n = 50) had significantly lower 25(OH)D levels than individuals with GFRs > 90 ml/min/1.73 m2 (n = 64), respectively 40 ± 20 versus 48 ± 20 nmol/l, p = 0.027. This difference was more pronounced for older individuals (39 ± 20 versus 54 ± 23 nmol/l, respectively), and Poisson robust regression disclosed that lower 25(OH)D [Poisson regression (PR) = 0.989, confidence interval (CI): 0.978–0.999, p = 0.034], and advanced age (PR = 1.050, CI: 1.007–1.096, p = 0.023) were significantly associated with the lower GFR category, adjusted for seasons. ROC curve analysis showed that the cutoff point of 25(OH)D of 41 nmol/l was associated with lower GFR [area under the curve (AUC) = 0.694, p = 0.009]. CKD-EPI estimated GFR (eGFR) was not associated with 25(OH)D in any analysis. There was no difference in 25(OH)D levels between patients with elevated UAE as compared with normoalbuminuric ones (44 ± 21 versus 46 ± 19 nmol/l, p = 0.587).Conclusion:Lower levels of 25(OH)D are associated with decreased GFR in patients with type 2 DM, especially in older patients, with no evidence of interaction with UAE levels.

28-LB: Diabetic Retinopathy Is an Additional Risk Factor for Hemodialysis Induction and Mortality in Type 2 Diabetic Patients

High urinary albumin excretion (UAE) and low glomerular filtration rate (GFR) are risk factors for progressive renal function loss in type 2 diabetic patients. In addition, diabetic retinopathy (DR) is also a risk factor for progressive renal function decline in microalbuminuric type 2 diabetic patients. We aimed to elucidate factors, including DR, associated with more severe situation, hemodialysis (HD) induction or mortality in 325 type 2 diabetic patients whose GFRs were measured by the iohexol injection in 1995-1997. Two-hundred and sixty were followed for &amp;gt;5 years (mean follow-up period, 16±6 years). The UAE levels were classified as normoalbuminuria (NA; n=130), microalbuminuria (MA, n=96), and macroalbuminuria (ON; n=34). Patients were also divided into the normofiltration (NF; n=213) and low filtration (LF; n=47) groups according to the age-appropriate GFR range. One hundred patients had DR and 119 had hypertension. During the study period, 25 patients received HD induction and 39 died. The HD induction and mortality rates in the LF, ON, and DR groups were significantly higher than those in the NF, NA and MA, and no-DR groups, respectively. A Kaplan-Meier analysis revealed LF (log rank p&amp;lt;0.001), ON (p&amp;lt;0.001) and DR (p&amp;lt;0.001) were associated with a significantly higher risk of HD induction than NF, NA and MA and no-DR, respectively. A Kaplan-Meier analysis revealed that LF (p&amp;lt;0.001), ON (p&amp;lt;0.001) and DR (p=0.008) were associated with a significantly higher risk of mortality than NF, NA and MA and no DR, respectively. A stepwise regression analysis revealed LF (F=28.0, p=0.000), ON (F=34.4, p=0.000) and DR (F=7.9, p=0.005) affected the HD induction, but hypertension did not (F=0.2, p=0.6). LF (F=13.2, p=0.000), ON (F=4.4, p=0.04) and DR (F=6.4, p=0.01) affected the mortality, but hypertension did not (F=1.6, p=0.2). DR should also be considered as a risk factor to no small extent for HD induction and mortality in addition to UAE and GFR in type 2 diabetic patients. Disclosure T. Moriya: None. M. Matsubara: None. M. Ouchi: None.

Association between circulating tumor necrosis factor-related biomarkers and estimated glomerular filtration rate in type 2 diabetes

Chronic inflammation plays a crucial role in the development/progression of diabetic kidney disease. The involvement of tumor necrosis factor (TNF)-related biomarkers [TNFα, progranulin (PGRN), TNF receptors (TNFR1 and TNFR2)] and uric acid (UA) in renal function decline was investigated in patients with type 2 diabetes (T2D). Serum TNF-related biomarkers and UA levels were measured in 594 Japanese patients with T2D and an eGFR ≥30 mL/min/1.73 m2. Four TNF-related biomarkers and UA were negatively associated with estimated glomerular filtration rate (eGFR). In a logistic multivariate model, each TNF-related biomarker and UA was associated with lower eGFR (eGFR <60mL /min/1.73 m2) after adjustment for relevant covariates (basic model). Furthermore, UA and TNF-related biomarkers other than PGRN added a significant benefit for the risk factors of lower eGFR when measured together with a basic model (UA, ΔAUC, 0.049, p < 0.001; TNFα, ΔAUC, 0.022, p = 0.007; TNFR1, ΔAUC, 0.064, p < 0.001; TNFR2, ΔAUC, 0.052, p < 0.001) in receiver operating characteristic curve analysis. TNFR ligands were associated with lower eGFR, but the associations were not as strong as those with TNFRs or UA in patients with T2D and an eGFR ≥30 mL/min/1.73 m2.

Association of Serum Angiopoietin-Like Protein 8 With Albuminuria in Type 2 Diabetic Patients: Results From the GDMD Study in China.

Background: Hyperglycemia, insulin resistance and hypertriglyceridesmia are risk factors for albuminuria in type 2 diabetes. Angiopoietin-like Protein 8(ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the relationship between ANGPTL8 and albuminuria in type 2 diabetes.Methods: Serum ANGPTL8 levels were determined in groups of control (n = 50) and type 2 diabetic patients with normoalbuminuria (A1, n = 100), microalbuminuria (A2, n = 45), and macroalbuminuria (A3, n = 33).Results: Serum levels of ANGPTL8 and triglycerides were significantly increased in type 2 diabetic patients with albuminuria as compared with controls (P < 0.001). ANGPTL8 levels were positively correlated with triglycerides, duration of diabetes, and urine albumin-to-creatinine ratio (ACR) and negatively correlated with estimated glomerular filtration rate in type 2 diabetic patients with A2 and A3 (all P < 0.05). Logistic regression analysis indicated that ANGPTL8 had higher odds of having A2 (OR = 2.52, 95% CI 1.16–5.48, P = 0.019) and A3 (OR = 4.89, 95% CI 2.10–11.39, P < 0.001) in type 2 diabetes. Mediation analysis indicated that triglycerides might act as a partial mediator in the relationship between ANGPTL8 and ACR.Conclusions: Triglycerides might partially mediate the correlation between ANGPTL8 and ACR. Our data provide the evidence for a strong link between ANGPTL8 and albuminuria, indicating that ANGPTL8 may be a new biomarker for diabetic kidney disease in type 2 diabetes.Trial Registration Number: ChiCTR-EPC-14005273

Serum Adipocyte Fatty Acid-Binding Protein 4 Levels Are Independently Associated with Radioisotope Glomerular Filtration Rate in Type 2 Diabetic Patients with Early Diabetic Nephropathy.

Serum fatty acid-binding protein 4 (FABP4) has been linked to renal dysfunction. This study evaluated the association between serum FABP4 and the radioisotope glomerular filtration rate (rGFR) in type 2 diabetic patients (T2DM) with early diabetic nephropathy. Twenty healthy controls and 172 patients with T2DM were enrolled. Serum FABP4 and renal impairment biomarkers including urinary albumin-to-creatinine ratio (UACR), serum retinal-binding protein 4 (RBP4), urinary cystatin C-to-creatinine ratio (CysC/Cr), and neutrophil gelatinase-associated lipocalin-to-creatinine ratio (NGAL/Cr) were measured. Diethylenetriaminepentaacetic acid (99mTc-DTPA) was used to test rGFR. Serum FABP4 levels were higher in T2DM patients compared with the controls. There was no significant correlation between serum FABP4 and UACR in patients with T2DM. Multivariate stepwise regression analysis showed that, in patients with T2DM, FABP4 was significantly associated with rGFR while CysC/Cr and RBP4 were significantly associated with UACR independently. But UACR had no independent association with rGFR. NGAL/Cr had no significant correlation with either rGFR or UACR. FABP4 might be an early biomarker for diabetic nephropathy if combined with UACR.

Serum Uric Acid to Creatinine Ratio as a Marker of Estimated Glomerular Filtration Rate in Type 2 Diabetes Patients

Serum Uric Acid to Creatinine Ratio as a Marker of Estimated Glomerular Filtration Rate in Type 2 Diabetes Patients

Postmeal triglyceridemia and variability of HbA1c and postmeal glycemia were predictors of annual decline in estimated glomerular filtration rate in type 2 diabetic patients with different stages of nephropathy

BackgroundThis study examined associations of annual glycemic variability and postprandial dysmetabolism with annual decline in estimated glomerular filtration rate (eGFR) in type 2 diabetic patients with different stages of nephropathy.MethodsIntrapersonal mean and coefficient of variation (CV) of HbA1c, fasting and postmeal concentrations of plasma glucose (FPG and PMPG, respectively) and serum triglycerides (FTG and PMTG, respectively) during the first 12 months after enrollment were calculated in a cohort of 168 type 2 diabetic patients: 53 with optimal albumin/creatinine ratio (ACR < 10 mg/g), 62 with high normal ACR (10–29 mg/g) and 53 with elevated ACR (≧30 mg/g). Annual changes in eGFR were computed using 52 (median) creatinine measurements obtained over a median follow-up of 6.0 years. Multivariate linear regressions assessed the independent correlates of changes in eGFR.ResultsKidney function declined faster in patients with high normal and elevated ACR (−1.47 and −2.01 ml/min/1.73 m2/year, respectively) compared to patients with optimal ACR (0.08 ml/min/1.73 m2/year, p < 0.05). In patients with high normal ACR, age (standardized β、-0.30、p = 0.01), CV-HbA1c (standardized β、-0.66、p < 0.001) and CV-PMPG (standardized β、-0.27、p = 0.01) was associated with annual eGFR decline independently of mean HbA1c and PMPG, sex, BMI, waist circumference, diabetes duration and therapy, means and CVs of FPG and systolic blood pressure, baseline eGFR, log ACR and uses of anti-hypertensive medications (R2 = 0.47). In patients with elevated ACR, PMTG (standardized β、-0.408, p = 0.007) was associated with annual eGFR decline (R2 = 0.15).ConclusionsConsistency of glycemic control and management of postprandial glycemia and lipidemia are important to preserve kidney function in type 2 diabetic patients.

Association of –1082A>G Polymorphism in the Interleukin-10 Gene with Estimated Glomerular Filtration Rate in Type 2 Diabetes

Background/Aims: The -1082A>G polymorphism (rs1800896) in the interleukin-10 (IL10) gene has been associated with type 2 diabetes and diabetic retinopathy, but its relationship with diabetic kidney disease (DKD) is uncertain. The aim of this case-control study was to investigate whether the -1082A>G polymorphism is associated with DKD in white Brazilians with type 2 diabetes mellitus. Methods: Genotyping was done by real-time polymerase chain reaction for 597 type 2 diabetic outpatients. The definition of DKD was based on estimated glomerular filtration rate (eGFR) and albuminuria, and the patients were grouped in three categories: no DKD (n=249), mild to moderate DKD (n=222), and severe DKD (n=126). Results: The frequency of the minor (G) allele in subjects without DKD did not differ from that observed in subjects with DKD (0.35 vs 0.39, respectively; P = 0.192). Genotype frequencies in subjects without DKD were not significantly different from those observed among patients with mild to moderate DKD or severe DKD. However, considering only the eGFR categories as an indicator of renal function, the AG genotype was independently associated with an increased risk of mildly to moderately decreased eGFR (G3a category) and GG genotype was independently associated with increased risk of kidney failure (G5 category) as compared with AA genotype. Conclusion: Our findings support the hypothesis that the -1082A>G polymorphism in the IL10 gene might be associated with DKD in white Brazilians with type 2 diabetes.

Intensive glycemic control and the risk of end-stage renal disease: an ADVANCE in the management of diabetes?

Posttrial follow-up of participants randomized to intensive versus standard glycemic control in the ADVANCE trial has demonstrated a significant benefit of intensive glycemic control on the risk of end-stage renal disease. In a more detailed analysis, intensive glycemic control appears to be of benefit only before the development of clinically evident kidney disease or in patients with documented early-stage chronic kidney disease.