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Early initiation of insulin therapy often remains contentious due to various patient and physician-related barriers. Insulin is delayed by several years despite high A1c and is the foremost reason for costly future complications. In addition, the problem of early aggressive use of insulin depleting drugs causes β-cell fatigue leading to "brittle diabetes" and higher insulin dose requirements. In this observational cohort study, a comparison has been made between early insulin initiators (EII) (within 7-8 years of diabetes onset) and late insulin initiators (LII) (>8 years of onset), in terms of progression of CKD (eGFR decline), if any. A total of 200 subjects in each arm were matched at baseline for T2DM duration (16.78±4.32 year), BP, BMI, HbA1c and presence of co-morbid illnesses. Both groups were closely followed-up through our Diabetes Tele Management System based health care model that have previously shown to be successful in safely achieving glycemic targets compared to conventional models of care. A paired t test was done for analyzing the eGFR decline within each arm. EII arm required a significantly lower total daily dose of insulin (TDD) (average of 9 units/day) to maintain glycemic control throughout than the LII arm (average of 30 units/day). The decline in eGFR was significant in the LII arm, whereas in the EII arm, eGFR was maintained throughout. Change in A1c was also significant. Disclosure J. Kesavadev: None. R. Warrier: None. L. Ramachandran: None. A. Shankar: None. A. David: None. N.A. Ajai: None. G. Sanal: None. K. Thampiraj: None. G. Krishnan: None. S. Jothydev: None.

Background and Aims: We considered if deep learning (DL) models trained to predict diabetic retinopathy (DR) are also useful for prediction of renal disease in people with type 1 diabetes. Materials and Methods: We used 35000 retinal images and associated ground truth DR grades from the online Kaggle dataset. These were used to train a Resnet convolutional neural network (CNN) to predict the ground truth DR grades. The CNN was then applied to retinal images for each patient in the SDRNT1BIO available from the national screening program generating 10 DL outputs corresponding to DR gradings for both eyes. Longitudinal eGFR readings and risk factor data were available for the SDRNT1BIO through linkage to clinical records. Univariate associations of DL outputs with final eGFR at follow-up was tested via linear regression models. A penalised Bayesian approach using 10-fold cross-validation was used to select the most predictive DL features and assess prediction performance. Results: We found 7 DL outputs had a significant univariate association with follow-up eGFR adjusting for age, sex, duration of diabetes, baseline eGFR, and length of follow-up at p Conclusion: This small study demonstrates that retinal images contain information for predicting eGFR decline and that deep learning can extract this information. Future work on a larger dataset using DL to predict renal disease progression directly is therefore warranted. Disclosure J.C. Mellor: None. A.J. Storkey: None. H. Colhoun: Advisory Panel; Self; Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Regeneron Pharmaceuticals, Sanofi. Stock/Shareholder; Self; Bayer AG, Roche Pharma. P.M. McKeigue: Advisory Panel; Spouse/Partner; Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Sanofi. Research Support; Spouse/Partner; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis. Stock/Shareholder; Spouse/Partner; Bayer AG, Roche Pharma.

Background We investigated the combined effects of chronic PM2.5 exposure and habitual exercise on the decline of renal function and the incidence of chronic kidney disease (CKD) in a large cohort in Taiwan. Methods The present data analysis included a total of 108,615 participants aged 18 years or above who were recruited between 2001 and 2016. All participants underwent at least two medical examinations. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The incident of eGFR decline ≥30% was defined as a decline in eGFR of ≥30% during the study period, while the incident CKD was defined as an eGFR Results Higher habitual exercise was associated with lower risks of renal function decline and CKD development, whereas higher PM2.5 exposure was associated with higher risks of renal function decline and CKD development. We found no significant interaction effect between PM2.5 and habitual exercise, with an HR (95% CI) of 1.02 (0.97, 1.07) for incident eGFR decline ≥30% and 1.00 (0.95, 1.05) for CKD development. Compared to participants with inactive-exercise and high-PM2.5, participants with high-exercise and low-PM2.5 had 74% and 61% lower risks of renal function decline and CKD development, respectively. Conclusion Increased habitual exercise and reduced PM2.5 exposures are associated with lower risks of renal function decline and CKD development. Habitual exercise reduces risks of renal function decline and CKD development regardless of the levels of chronic PM2.5 exposure. Our study suggests that habitual exercise is a safe approach for kidney health improvement even for people residing in relatively polluted areas and should be promoted.

SOURCE CITATION Heerspink HJ, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-46. 32970396.

It is difficult to distinguish the onset of renal function decline from the typical variation in estimated glomerular filtration rate (eGFR) measurements in clinical practice. In this study, we used data analysis incorporating smoothing techniques to identify significant trends despite large amounts of noise. We identified the starting points of meaningful eGFR decline based on eGFR trajectories. This was a retrospective observational study of 2533 type 2 diabetes patients. We calculated 1-year eGFR decline rates from the difference between each eGFR value and that of the previous year. We examined the prediction capacity of 1-year eGFR decline rate for renal prognosis. When we performed receiver operating characteristic analysis, the area under the curve of 1-year eGFR decline rate was 0.963 (95% confidence interval: 0.953–0.973). With a cut-off value of more than 7.5% eGFR decline during a 1-year period, the sensitivity was 98.8% and specificity was 82.3%. The predictive accuracy of 1-year eGFR decline rate for renal prognosis was high.

Aim: Early intervention before the progression of chronic kidney disease (CKD) is essential to prevent end-stage renal disease (ESRD) and cardiovascular complications. This study evaluated the correlation between metabolic and lifestyle-related factors and the decline of estimated glomerular filtration rate (eGFR) over 1 year in a Japanese population without CKD. Methods: Subjects who received two consecutive annual health checkups from 2013 to 2015 were involved. Factors associated with eGFR decline were identified using multiple regression models. Results: A total of 2531 subjects aged 58.9 ± 11.7 years old were included in this study. Baseline levels of HDL-C and ApoA1 correlated with the eGFR decline over 1 year defined as eGFR reduction rate of 15% or more and/or eGFR at the next year < 60 ml/min/m2 (odds ratio (OR) 0.87 (per 10 mg/dl); 95% CI, 0.80–0.94; p = 0.0012, 0.90 (per 10 mg/dl); 0.86–0.96; p = 0.0004, respectively). A U-shaped relationship between the eGFR decline and HDL-C or ApoA1 levels was not observed in non-CKD population of this study. Metabolic syndrome was significantly associated with eGFR decline (OR 1.32; 1.04–1.67; p = 0.0205), although obesity-related factors did not show a significant correlation with eGFR decline over 1 year. Conclusion: Low HDL-C and ApoA1 levels significantly correlated with eGFR decline in a short period of 1 year. Metabolic syndrome also showed a significant association with eGFR decline. This study suggests the importance of hypertension and low HDL-C in the metabolic syndrome effect on eGFR decline rather than obesity in non-CKD population.

Retinal arteriolar narrowing and high pulse pressure (PP) are associated with macrovascular complications and microvascular renal disease. Few studies addressed whether in seniors (⩾60 years) estimated glomerular filtration rate (eGFR) is independently related to central retinal arteriolar equivalent (CRAE) and PP. In 292 randomly recruited seniors (49.3% women; mean, 68.2 years), we measured PP by standard sphygmomanometry, CRAE (IVAN software), eGFR (Chronic Kidney Disease Epidemiology Collaboration equation) and stage of chronic kidney disease (CKD (Kidney Disease Outcomes Quality Initiative guideline)). Statistical methods included linear and logistic regression. PP, CRAE and eGFR averaged 59.2 mm Hg, 146.3 μm and 79.9 ml min(-1) per 1.73 m(2). Decline in eGFR (-2.27 ml min(-1) per 1.73 m(2) per 15 μm; P=0.011) occurred in parallel with CRAE narrowing. CRAE (effect size per 1-s.d. increment, -1.85 μm; P=0.032) and eGFR (-2.68 ml min(-1) per 1.73 m(2); P=0.003) both declined with higher PP. With PP increasing from 63 to 73 mm Hg (threshold for macrovascular complications), CRAE dropped by -4.70 μm (P⩽0.037). A 70-mm Hg PP threshold corresponded with a 150-μm CRAE cutoff. The risk of CKD (stage ⩾2 vs. 1; n=203 vs. 89) rose with CRAE

BACKGROUND: Random assignment to the intensive systolic blood pressure (SBP) arm (

Cynthia J Janmaat,1 Merel van Diepen,1 Cheyenne CE van Hagen,1 Joris I Rotmans,2 Friedo W Dekker,1 Olaf M Dekkers1,2 1Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands, 2Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands Purpose: Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3–5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3–5 patients, in these two different study types. Patients and methods: We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline(mL/min/1.73 m2) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. Results: We included 60 studies (43 CKD 3–5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m2 in CKD 3–5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). Conclusion: To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3–5 cohorts. Thus, eGFR decline data from CKD 3–5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome. Keywords: meta-analysis, systematic review, kidney function decline, dialysis, chronic kidney disease, pre-dialysis, CKD progression

BACKGROUND: The Systolic BP Intervention Trial (SPRINT) found that intensive versus standard systolic BP control (targeting

Rationale & Objective: Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine. Study Design: Pooled analysis of 4 Italian observational cohort studies. Setting & Participants: 1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 followed up in renal clinics. Predictor: Sex. Outcomes: End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes. Analytical Approach: Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline. Results: Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6 ± 10.2 in men and 26.0 ± 10.6 mL/min/1.73 m2 in women (P < 0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P < 0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of ∼0.5 g/d or greater. The slope of decline in eGFR was steeper in men (−2.09; 95% CI, −2.21 to −1.97 mL/min/1.73 m2 per year) than in women (−1.79; 95% CI, −1.92 to −1.66 mL/min/1.73 m2 per year; P < 0.001). Although sex differences in eGFR decline were not different across CKD stages (P = 0.3), the difference in slopes between men and women was progressively larger with proteinuria > 0.5 g/d (P = 0.04). Limitations: Residual confounding; only whites were included. Conclusions: Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women.

Rationale & objectiveRandom assignment to intensive blood pressure (BP) lowering (systolic BP

Body weight (BW) changes may affect muscle mass and thus creatinine (Cr) levels. Estimating glomerular filtration rate (eGFR) by Cr-based equations may not accurately reflect changes in kidney function when BW changes. Dulaglutide (DU) treatment was associated with BW loss and lesser eGFR (Cr-CKD-EPI) decline in people with T2D and moderate to severe CKD compared to insulin glargine (IG) (Table). The aim was to evaluate if the lesser eGFR decline observed with DU is related to BW loss. eGFR was evaluated with Cr-based equations (MDRD, CKD-EPI) compared to cystatin C-CKD-EPI equation. Cystatin C is not affected by muscle mass changes. CrCL was evaluated with the Cockcroft-Gault equation. BL characteristics were similar between treatments ([mean±SD] eGFR (Cr-CKD-EPI): 38.3±12.8 mL/min/1.73m2, A1c: 8.6±1.0%, age: 64.6±8.6 y, T2D duration: 18.1±8.7 y). All equations consistently show that eGFR remained stable with DU, but significantly decreased with IG regardless of BW loss in DU or gain in IG (Table). Since BW is a factor in CrCL calculations, compared to eGFR equations, BW loss in DU led to bias toward greater reductions in CrCL. This bias disappeared when using lean BW (Table). In conclusion, compared to IG, DU was associated with lesser eGFR decline in people with T2D and moderate to severe CKD regardless of BW changes. Disclosure K.R. Tuttle: Consultant; Self; Eli Lilly and Company, Boehringer Ingelheim GmbH, AstraZeneca, Gilead Sciences, Inc. M. Lakshmanan: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. B.L. Rayner: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Novartis AG, Servier. Advisory Panel; Self; AstraZeneca. R.S. Busch: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. A.G. Zimmermann: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. B. Woodward: Employee; Self; Eli Lilly and Company. F.T. Botros: Employee; Self; Eli Lilly and Company.

Aims: To investigate the association between estimated baseline glomerular filtration rate (GFR) and renal function decline in Chinese patients with type 2 diabetes with normoalbuminuria. Main Methods: A longitudinal study was performed on 368 Chinese patients with type 2 diabetes whose estimated GFR (eGFR) was determined at baseline with a 3.12-year follow-up. The patients were divided into three groups according to baseline eGFR (mL/min/1.73 m2): G1 (eGFR ≥ 120), G2 (90 ≤ eGFR < 120), G3 (60 ≤ eGFR < 90). The association between baseline eGFR and the renal function decline rate was assessed using binary logistic regression. Decliners were defined as a negative change ≥ −3.3% per year. Key Findings: Among G1 patients, the decliners were younger, had a higher baseline eGFR, shorter duration of diabetes, and lower diastolic blood pressure, compared with non-decliners. The G1 eGFR decline slope (% per year) was significantly higher than that in G2 and G3 patients. The percentage of decliners among G1 patients was significantly higher than that among G2 and G3 patients. Baseline eGFR group, HbA1c, hypertension history, and diastolic blood pressure were independent risk factors for progressive renal decline. Patients in the decliners group were more likely to progress to microalbuminuria and macroalbuminuria compared with those in the non-decliners group; however, the albuminruria progression percentage was not significantly different among G1, G2, and G3 decliners. Significance: Patients with baseline eGFR ≥ 120 mL/min/1.73 m2 had a higher risk for more rapid eGFR decline among Chinese patients with type 2 diabetes with nomalbuminuria. Disclosure J. Wan: None. H. Chen: None.

Background: EXSCEL was a multinational, randomized, blinded, placebo-controlled, pragmatic CV outcome trial of once-weekly exenatide on the background of usual care. We report exenatide’s impact on estimated glomerular filtration rate (eGFR), new macroalbuminuria and 2 renal composites from a prespecified analysis plan. Methods: Opportunistic local laboratory data were collected. Overall least squares mean difference (LSMD) eGFR (95% confidence interval [95% CI]) was calculated for 13844 patients with baseline and ≥1 follow-up value. Effect on new macroalbuminuria was estimated with a Cox regression model. Effects on renal composites were estimated with interval censored time to event models, with and without covariate adjustment (demographics and disease characteristics). Results: Intention-to-treat analyses showed no significant difference in eGFR levels with exenatide (LSMD +0.21 [-0.27, 0.70] mL/min.1.73m2, p=0.39). New macroalbuminuria occurred in 2.2% and 2.5% of the exenatide and placebo groups (p=0.19). There was a 15% lower renal composite 2 adjusted risk with exenatide (p=0.027) (Table). Conclusions: A composite of 40% eGFR decline, renal replacement, renal death or new macroalbuminuria was significantly reduced in an adjusted analysis by the addition of exenatide in a broad range of people with type 2 diabetes. Other renal outcomes were numerically but not statistically improved with exenatide. Disclosure M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. R.J. Mentz: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. P. Merrill: None. J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck & Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp & Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. N. Iqbal: Employee; Self; AstraZeneca. N. Jakuboniene: None. B.G. Katona: Employee; Self; AstraZeneca. Y. Lokhnygina: None. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc.. A.P. Maggioni: None. P.K. Ohman: Employee; Self; AstraZeneca. N.R. Poulter: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc.. Research Support; Self; Servier. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Amgen Inc., Servier. Other Relationship; Self; International Society of Hypertension. A. Ramachandran: None. T. Tankova: None. B. Zinman: Consultant; Self; Novo Nordisk A/S, Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi, Merck & Co., Inc., Abbott. A.F. Hernandez: Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca.

Background: NHANES data (2009-2014) suggests that 25% of U.S. adults with diabetes have CKD (eGFR < 60 ml/min/1.73m2 or ACR ≥ 30 mg/g). However, prevalence may be different among patients evaluated in clinical practice or in adults with T1D compared to T2D. Methods: We utilized a clinical laboratory database maintained by LabCorp® to assess CKD prevalence and classified risk (low, moderate, high or very high) based on KDIGO criteria. The population included 48,036 adults with T1D and 1,461,915 with T2D who had both an ACR and a CKD-EPI eGFR between August 2014 and August 2017. Rates of eGFR decline were calculated for patients with ≥ 3 eGFR results over at least a 1 year period. Results: CKD prevalence was 40% higher in T2D than T1D (44.3% vs. 31.6%, p 300, was uncommon (T1D: 7.8%, T2D: 8.3%); the majority with MA had an eGFR ≥ 60 (T1D: 60%, T2D: 53%). Median eGFR decline (ml/min/year) was low in the entire population (T1D: -0.6, T2D: -0.8), and in patients with ACR < 30 (T1D: -0.34, T2D: -0.47) or ACR 30-300 (T1D: -0.97, T2D: - 1.06). However, median annual rates of decline in patients with MA were -3.80 in T1D and -3.58 in T2D. Conclusions: These findings suggest that CKD prevalence and risk are higher in T2D than T1D among adult patients recently evaluated in U.S. clinical practices. Although MA is uncommon and most frequently observed in patients with normal or only mildly reduced eGFR, it was a potent predictor of eGFR decline in both T1D and T2D. Availability of a large clinical laboratory database may add value when eligibility criteria, enrichment strategies, study endpoints or feasibility are assessed in clinical trials of patients with diabetes and CKD. Disclosure M. Cressman: Employee; Self; Covance Inc. J.L. Ennis: Employee; Self; LabCorp. Stock/Shareholder; Self; LabCorp. B.J. Goldstein: Employee; Self; Covance Inc.. L. Gourgiotis: None. D. Luo: None. M. Puri: Employee; Self; Covance Inc.. B. Gillespie: None.

Low-protein diet (LPD) together with supplementation with ketoanalogs (KA) is associated with slower decline of estimated glomerular filtration rate (eGFR) in chronic kidney disease (CKD). We compared potential clinical and economic outcomes of KA supplement initiation at eGFR 15 - 29 mL/min/1.73 m2 vs. eGFR15 mL/min/1.73 m2 in CKD patients on LPD from the healthcare payer's perspective.Markov model was designed to simulate outcomes of adult patients with eGFR 15 - 29 mL/min/1.73 m2 on two strategies LPD with KA supplementation; watchfulwaiting on LPD alone and KA initiation when eGFR declined to15 mL/min/1.73 m2. Medical cost and quality-adjusted life-years (QALYs) were calculated over 10 years. Results The early-initiation group gained higher QALYs (3.926 QALYs vs. 3.787 QALYs) with lower cost (USD 564,637 vs. USD 914,236) (USD 1 = NTD 30) when compared with the watchful-waiting group in base-case analysis. Sensitivity analysis indicated that early KA initiation at eGFR at 17 - 29 mL/min/1.73 m2 would be the preferred cost-effective option, if relative reduction of eGFR decline associated with LPD plus KA was4%. 10,000 Monte Carlo simulations showed the early-initiation group to be less costly with higher QALYs gained than the watchful-waiting group by USD 343,665 (95% CI 342,139 - 345,191) and 0.160 QALYs (95% CI 0.140 - 0.180), respectively.Early KA supplementation with LPD in CKD patients appeared to be cost-saving and gained higher QALYs in Taiwan. Acceptance of early supplemented LPD as cost-effective depended upon the reduction of eGFR decline associated with KA plus LPD and eGFR level to initiate KA supplementation.

Greater H+retention in animal models of chronic kidney disease (CKD) mediates faster glomerular filtration rate (GFR) decline and dietary H+reduction slows eGFR decline in CKD patients with reduced eGFR and H+retention due to the high acid (H+) diets of developed societies. We examined if H+retention in CKD is inversely associated with estimated GFR (eGFR) using cross-sectional and longitudinal analysis of individuals with CKD stage 1 (>90 ml·min− 1·1.73 m−2), CKD stage 2 (60–89 ml/min per 1.73 m2), and CKD stage 3 (30–59 ml·min− 1·1.73 m−2) eGFR. H+retention was assessed using the difference between observed and expected plasma total CO22 h after 0.5 meq/kg body wt oral NaHCO3. H+retention was higher in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.02) at baseline and 5 yr, and was higher in CKD 2 vs. CKD 1 ( P < 0.01) at 10 yr. All groups had lower eGFR at subsequent time points ( P < 0.01) but H+retention was not different among the three time points for CKD 1. By contrast, eGFR decrease was associated with higher H+retention in CKD 2 at 5 yr ( P = 0.04) and 10 yr ( P < 0.01) and with higher H+retention in CKD 3 at 5 yr ( P < 0.01). Yearly eGFR decline rate was faster in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.01). The data show that H+retention is inversely associated with eGFR, with faster eGFR decline, and support the need for greater dietary H+reduction therapy for CKD individuals with lower eGFR.

BACKGROUND: The impact of treating OSA on renal function decline is controversial. Previous studies usually included small samples and did not consider specific effects of different CPAP modalities. The aim of this study was to evaluate the respective influence of fixed and autoadjusting CPAP modes on estimated glomerular filtration rate (eGFR) in a large sample of patients derived from the prospective European Sleep Apnea Database cohort. METHODS: In patients of the European Sleep Apnea Database, eGFR prior to and after follow-up was calculated by using the Chronic Kidney Disease-Epidemiology Collaboration equation. Three study groups were investigated: untreated patients (n = 144), patients receiving fixed CPAP (fCPAP) (n = 1,178), and patients on autoadjusting CPAP (APAP) (n = 485). RESULTS: In the whole sample, eGFR decreased over time. The rate of eGFR decline was significantly higher in the subgroup with eGFR above median (91.42 mL/min/1.73 m(2)) at baseline (P < .0001 for effect of baseline eGFR). This decline was attenuated or absent (P < .0001 for effect of treatment) in the subgroup of patients with OSA treated by using fCPAP. A follow-up duration exceeding the median (541 days) was associated with eGFR decline in the untreated and APAP groups but not in the fCPAP group (P < .0001 by two-way ANOVA for interaction between treatment and follow-up length). In multiple regression analysis, eGFR decline was accentuated by advanced age, female sex, cardiac failure, higher baseline eGFR, and longer follow-up duration, whereas there was a protective effect of fCPAP. CONCLUSIONS: fCPAP but not APAP may prevent eGFR decline in OSA.

To retard progression of chronic kidney disease (CKD) and reduce end-stage kidney disease, it is important to detect acute kidney function worsening on CKD (AW-CKD) immediately and bring back their kidney functions to baselines by appropriate treatment. However, in general outpatient practice, it is difficult to detect the change in the slope of estimated glomerular filtration rate (eGFR). We made automatic calculation system for the rate of eGFR decline (ΔeGFR), and retrospectively observed the situation of AW-CKD among outpatients, who had visited all clinical departments of Steel Memorial Hirohata Hospital between May and August 2016, using the system. The patients with ΔeGFR over 20 mL/min/1.73 m2/year were classified into “Detected cases”, who were immediately detected AW-CKD by the attending physicians, and “Not detected cases”. For each stratum of ΔeGFR, subsequent eGFR recovery rates between two groups were compared. Among 6719 outpatients, 865 had CKD stages G3–5 and of which 196 had ΔeGFR over 20 mL/min/1.73 m2/year. We revealed that, in cases of ΔeGFR over 30 mL/min/1.73 m2/year, eGFR recovery rates in “Detected cases” were significantly higher than those in “Not detected cases” (103.2 vs 43.9%, p

Clinical trials in kidney transplantation suffer from several major issues including: 1) Unfeasibility due to low short-term event rates of hard outcomes and 2) Reliance on a composite outcome that consists of unequal endpoints that may generate misleading results. This thesis attempts to explore and apply methods to solve these issues and ultimately, improve kidney transplantation trials. We present a secondary analysis of the ACE trial in kidney transplant using composites with alternative graft function surrogate endpoints. Typically, kidney transplant trials—including the ACE trial— use a time-to-event composite of death, end-stage renal disease (ESRD), and doubling of serum creatinine. Instead of doubling of serum creatinine, we investigated the use of percentage declines of estimate glomerular filtration rate (eGFR) within a time-to-event composite of death and ESRD. Additionally, we present an application of an innovative analysis method, the win ratio approach, to the ACE trial as a way of lessening concerns associated with unequal composite endpoints. Composites of death, ESRD, and either a 40%, 30% or 20% decline in eGFR did not alter original ACE trial results, interpretations, or conclusions. The win ratio approach, and the presentation of a win ratio, generated very comparable results to a standard time-to-event analysis while lessening the impact of unequal composite endpoints and making fewer statistical assumptions. This research provides a novel, trial-level application of alternative endpoints and analysis techniques within a kidney transplant trial setting.

Background: Hyperuricemia is associated with the progression of chronic kidney disease (CKD), but it is not known whether the relationship is causal. We examined the association of hyperuricemia and uric acid lowering therapy (UALT) with progression of CKD in patients with CKD 3 and 4 in the Cleveland Clinic CKD registry. Methods: We included 1,676 patients with CKD stages 3 and 4 from Ohio, who had measured their uric acid (UA) levels a year prior to the recording of the second eGFR 2, and follow-up eGFR, between 2005 and 2009. Our primary composite outcome included a 50% drop in eGFR or progression to ESRD. Secondary outcomes included the rate of decline in eGFR, all-cause mortality, progression to ESRD, and a composite measure of progression to ESRD or death. We assessed the association between UA, UALT, and outcomes using Cox models and competing risks regression models. Results: In multivariable models, higher UA was associated with the composite endpoint, but it reached statistical significance only in the 4th quartile (≥8.9 mg/dL). Receipt of UALT was significantly associated with increased risk of the composite outcome. Neither UA nor UALT (considered a time-dependent covariate) was significantly associated with mortality. The inference was similar for UA as high vs. low, quartiles, or continuous. Similarly, neither high UA nor UALT were significantly associated with ESRD, the composite of ESRD and mortality, or eGFR decline. Conclusions: Hyperuricemia is associated with increased risk of progression to ESRD in patients with CKD stages 3 and 4, but UALT does not ameliorate the risk, suggesting that the relationship is not causal.

Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs, n = 49 each). We analyzed the time &times, group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time &times, group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers, however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.

Background and Aim: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. Methods: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. Results: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (β = -5.77, p = 0.001), baseline renal function (β = -0.12, p < 0.001) and level of proteinuria (β = -2.36, p = 0.015) were independently associated with the rate of renal function decline. Conclusions: Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline.

Approximately 7% to 9% of patients with donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) fail within 1 year post-DSA onset. However, little is known as to how this DSA-associated failure temporally progresses. This longitudinal study investigates DSA's temporal relationship to allograft dysfunction and identifies predictors of allograft function's progressive deterioration post-DSA.A cohort of 175 non-HLA identical patients receiving their first transplant between March 1999 and March 2006 were analyzed. Protocol testing for DSA via single antigen beads was done before transplantation and at 1, 3, 6, 9, and 12 months after transplantation then annually. Estimated glomerular filtration rate (eGFR) was analyzed before and after DSA onset.Forty-two patients developed DSA and had adequate eGFR information for analysis. Before DSA onset, the 42 patients had stable eGFR. By 1 year post-DSA, the cohort's eGFR was significantly lower (P0.001); however, 30 of 42 had stable function. Twelve patients had failure or early allograft dysfunction (eGFR decline25% from DSA onset). Those who failed early (by 1 year post-DSA) had more antibody-mediated rejection than stable patients (P=0.03). Late failures (after 1 year post-DSA) were predictable with evidence of early allograft dysfunction (eGFR decline25% by 1 year post-DSA; P0.001). Early allograft dysfunction preceded late failure by nearly 1 year.DSA is temporally related to allograft function deterioration. However, in many cases, late allograft failures are preceded by early allograft dysfunction. Therefore, monitoring for early allograft dysfunction provides treating physicians with a window of opportunity for treatment or continued monitoring.

RESULTS: 153 patients [23.5% (36 with >25% decline)/ 76.5% (117 with 25% decline); median follow up 48 months] were analyzed. More female (63.9% vs. 28.2%, p1⁄40.0001) and diabetic (41.7% vs. 26.2%, p1⁄40.021) patients had decrease of eGFR>25%. Median tumor size was significantly higher in the >25% eGFR decrease (2.8 vs. 2.4 cm, p1⁄40.005) as was median RENAL score (7 vs. 5, p 25% eGFR decline group. MVA demonstrated decreasing PPP (OR 1.4, p 25%. CONCLUSIONS: Absence of global renal ischemic insult does not protect the kidney from renal functional decline and a significant proportion of patients may yet go on to suffer significant decreases in GFR. Increasing tumor complexity and decreasing percentage parenchyma spared and female sex were independently associated with significant renal functional decline. Development of predictive computer modeling to aid in optimal patient selection and procedure planning may aid in optimizing renal functional outcomes.

Introduction. There is no report about risk factors for renal deterioration according to the clinical stage, divided by the estimated glomerular filtration rate (eGFR) in type 2 diabetes.Materials and Methods. We evaluated the factors correlated with the annual eGFR decline in 1303 subjects with type 2 diabetes whose eGFR was ≥30 mL/min/1.73 m2. eGFR strata were defined by baseline eGFR value as follows: stratum 1: ≥90, stratum 2: ≥60, Results. The annual eGFR decline was2.3±5.4 mL/min/1.73 m2in overall subjects. Multiple linear regression analysis demonstrated that age, male sex, systolic blood pressure, logarithmically transformed albumin excretion rate (AER), eGFR strata, and hemoglobin concentration were significantly correlated with the annual eGFR decline. When stratified by eGFR, the factors that showed a significant correlation were different among eGFR strata. AER was significantly correlated with annual eGFR decline in all eGFR strata. Hemoglobin concentration showed a significant correlation only in the advanced eGFR stratum.Conclusion. The factors correlated with the annual eGFR decline were different among eGFR strata in type 2 diabetes mellitus, and hemoglobin concentration and AER were important factors for renal deterioration, especially in the advanced eGFR stratum.

Summary Background and objectives Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. Design, setting, participants, & measurements This study identified 3318 women participating in the Nurses’ Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included 1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and 2/d. Microalbuminuria (MA) was considered a urinary albumin-tocreatinine ratio of 25 to 355 g/mg. For kidney function change, the primary outcome was a 30% decline in eGFR over 11 years; rapid eGFR decline defined as 3 ml/min per 1.73 m 2 per year was also examined. Results Consumption of 2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline 30% (OR 2.02, 95% CI 1.36 to 3.01) and 3 ml/min per 1.73 m 2 per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for 2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Conclusions Consumption of 2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women. Clin J Am Soc Nephrol 6: 160–166, 2011. doi: 10.2215/CJN.03260410

Many heart transplant recipients experience declining kidney function following transplantation. We aimed to quantify change in kidney function in heart transplant recipients stratified by pre-transplant kidney function. A total of 230 adult heart transplant recipients between May 1, 2008, and December 31, 2014, were evaluated for up to 5 years post-transplant (median 1 year). Using 19 398 total estimated glomerular filtration rate (eGFR) assessments, we evaluated trends in eGFR in recipients with normal/near-normal (eGFR ≥45 mL/min/1.73 m2 ) vs impaired (eGFR