Incident End-stage Kidney Disease Research Articles

1308-P: Glutamic Acid Decarboxylase Autoantibodies (GADA) in Type 2 Diabetes Do Not Predict Long-Term Diabetes Complications

Some adults with type 2 diabetes (T2D) have islet autoantibodies that may explain clinical heterogeneity, yet limited long-term studies have examined their relationship with diabetes outcomes. We investigated the association between GADA, the most prevalent islet autoantibody, and diabetes complications and mortality in Look AHEAD (Action for Health in Diabetes), a trial that randomized adults with clinically-diagnosed T2D to intensive lifestyle intervention vs. control for 9.6 years, and then followed them observationally. GADA was measured by radioligand binding assay in 87% of the cohort at baseline and categorized as negative, low-level (35-199 U/mL) or high-level (≥200 U/mL). We used Cox proportional hazards regression adjusted for age, sex, race/ethnicity, and study arm to analyze the association between GADA category and time-to-event outcomes: CVD (MI, stroke, hospitalized angina, CVD death), incident eGFR <45 ml/min/1.73m2, incident end stage kidney disease, and all-cause mortality. Among 4,492 participants, the median age was 59 years and diabetes duration 5 years. GADA was low-level and high-level positive in 131 (2.9%) and 85 (1.9%), respectively. Over a median follow-up of 17 years, there was no significant association between GADA levels and outcomes (Table). Overall, the presence of GADA above 35 U/mL was not predictive of CVD, or renal outcomes or mortality. Disclosure S.J.Pilla: None. A.Ramelius: None. R.Bennet: None. Å.Lernmark: Advisory Panel; Diamyd Medical. N.N.Mathioudakis: None. J.Clark: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions. W.C.Knowler: None. A.Balasubramanyam: None. C.S.Hampe: Employee; Immusoft corp. S.Pietropaolo: None. A.M.Anderson: None. M.Li: None. N.Zhao: None. S.L.Zeger: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK126825, K23DK128572)

126-OR: Metformin Discontinuation and Clinical Outcomes in Patients with Diabetes and Advanced Chronic Kidney Disease—A Prospective Cohort Study

Introduction: Metformin can now be used in patients with chronic kidney disease (CKD) up to estimated glomerular filtration rate [eGFR] ≥30 ml/min/1.73m2. However, surveys suggested its continuing use in some patients with eGFR<30 ml/min/1.73m2 in real world practice although the risk-benefit ratios remain uncertain. Methods: This was a prospective, population-based cohort of 36,940 patients with diabetes in Hong Kong stratified by continuation of metformin within 6 months after reaching eGFR<30 ml/min/1.73m2 in 2002-2018, followed up until 2019. We used Cox model with time-dependent exposure and covariates to estimate the hazard ratio (HR) of death, major-adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD) in a propensity-score overlap-weighted cohort of continued versus discontinued-metformin users. Results: Of 36,940 metformin users with new-onset eGFR<30 ml/min/1.73m2, 8400 (22.7%) discontinued metformin within 6 months whereas 28,540 (77.3%) continued with metformin. The median metformin daily dose was 1000 [interquartile range, IQR: 1000, 1000] mg in continued-metformin users. During a median follow-up of 3.5 (IQR:1.8-5.8) years, 15.3%, 16.6%, and 28.1% had incident MACE, heart failure, and ESKD respectively, and 41.5% died. Compared to continued-metformin use, discontinuation was associated with higher risk of MACE (weighted and adjusted HR=1.42, 95% CI: 1.31-1.54), heart failure (HR=1.70, 1.58-1.83), ESKD (HR=1.73, 1.63-1.83), and death (HR=1.24, 1.19-1.29). Results were consistent in patients with and without established cardiovascular diseases (CVD). Conclusions: Discontinuation of metformin was associated with increased risk of cardiovascular-renal events, regardless CVD status. Continuation of metformin below eGFR 30ml/min/1.73m2 may be associated with cardio-renal and mortality benefits that needs to be weighed against the risks of lactic acidosis. Disclosure A.Yang: None. R.C.Ma: Advisory Panel; AstraZeneca, Merck & Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. M.Shi: None. H.Wu: None. E.S.H.Lau: None. J.T.K.Cheung: None. X.Zhang: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Speaker's Bureau; Abbott, AstraZeneca, Lilly, Bayer Inc., Boehringer Ingelheim Inc. A.Luk: Research Support; Novo Nordisk, Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; Eli Lilly and Company. Funding Chinese University of Hong Kong

#4834 THE PROPORTION OF UNAFFECTED GLOMERULI IS A ROBUST PROGNOSTIC FACTOR OF KIDNEY OUTCOME IN PATIENTS WITH ANCA-ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN), the most common form of secondary GN in elderly (>60 years), requires immunosuppressive treatment that may increase risk of opportunistic infections. This study evaluated the prognostic value of clinical factors and histopathologic findings affecting kidney outcome in ANCA-associated GN patients. Method From 2000 to 2018, we identified 106 adults (≥18 years old) who were pathologically confirmed as ANCA-associated GN. The number of normal, crescent, and sclerotic glomeruli was recorded for each biopsy by slide review. The primary outcome was incident end stage kidney disease (ESKD). Results The age was 67 (57-73) years, the estimated glomerular filtration rate (eGFR) was 19 (11-36) mL/min/1.73 m2, and % of normal glomeruli in kidney specimen was 25 (11-47) %. Overall kidney survival was 85% and 76% at 1 and 5 years, respectively. Among clinical variables, lower eGFR (adjusted hazard ratio [aHR], 0.339; 95% confidence interval [CI], 0.180-0.638; p<0.001) was independently associated with increased risk of incident of ESKD. Multivariate Cox proportional hazard model including both clinical and histological variables demonstrated that % of normal glomeruli (aHR, 0.960; 95% CI, 0.935-0.986; p<0.001) was a sole risk factor of incident ESKD, independently of eGFR and other pathological findings. When the % of normal glomeruli was divided by quartiles, the risk of incident ESKD in the lowest quartile was significantly increased compared to the highest quartile (<11%; HR, 5.986; 95% CI, 2.114-16.950 vs. >46%; p<0.001). Conclusion The proportion of unaffected glomeruli was independent predictor of kidney outcome in patients with ANCA-associated GN.

#4292 PATIENT-REPORTED MENTAL HEALTH PROBLEMS, SUICIDE IDEATION, AND CLINICAL OUTCOMES IN ADULTS WITH NON-DIALYSIS CKD: RESULTS OF THE KNOW-CKD STUDY

Abstract Background and Aims Mental health is important for health and well-being at every stage of life and disease. Mental health problems are common and bothersome in chronic kidney disease (CKD). Mental health problems of CKD are poorly understood and evaluated. To address the importance of mental health in CKD, we analyzed a prospective cohort database from prospective CKD cohort. Method We analyzed 1897 participants from the KNOW-CKD cohort. We evaluated 4 items as indicators of patient-reported mental health: sleep duration, perceived stress, depressive symptoms, and suicidal ideation. To facilitate interpretation of the mental health problems in CKD, we measure a scaled effect size (ES) for the Kidney Disease Quality of Life Short Form (KDQOL-SF) differences among the groups of mental health problems. We investigated the association between patient-reported mental health problems and clinical outcomes of incident end-stage kidney disease (ESKD) all-cause death in non-dialysis CKD. Results The mean age was 53 ± 12 years and 62% were male. The participants had mental health problems of inadequate sleep duration (17.4%), subject distress (27.3%), experience of depression (13.2%), and suicide ideation (16.8%), but had not well taken care (psychiatric counselling 1.9%, antidepressant therapy 2.8%). The 4 item indicators of mental health showed large effect size between-groups KDQOL mental component summary (ES = 1.67). In the fully adjusted Cox proportional model, poor mental health (≥2 mental health problems) was associated with high risk of ESKD [HR = 1.46; 95% CI (1.18∼1.08)] and death [HR = 1.55; 95% CI (1.04∼2.32)] compared to good mental health (no mental health problems). Among 4 item indicators of patient-reported mental health, suicide ideation was the most predictive indicator of clinical outcomes. Conclusion Mental health problem is common and undertreated in CKD. Poor mental health is associated with high risk of ESKD and death in non-dialysis CKD and the single question of suicide ideation is significantly associated with high risk of ESKD and death. It suggests that the evaluation and management of mental health problem is important to the clinical outcomes in CKD.

#3011 INCIDENT CHRONIC KIDNEY DISEASE IN NEWLY DIAGNOSED DIABETES MELLITUS

Abstract Background and Aims Singapore has the world's 3rd highest rate of incident end-stage kidney disease (ESKD) on dialysis. Diabetes mellitus (DM) was the cause of ESKD in 68% of patients initiating dialysis in 2020. We explored the rate of incident CKD in newly diagnosed DM, and risk factors associated with the development of incident CKD. Method This is a retrospective cohort of patients newly diagnosed with DM in 2014-2020, in primary care and specialist clinics across Singapore's largest health system. Patients were excluded if they had known CKD, were not screened for CKD, or were diagnosed with CKD at the first screening (which may reflect pre-existing CKD). CKD was defined as a CKD-EPI glomerular filtration rate (GFR) <60 ml/min/1.73 m2, and/or urine albumin-creatinine ratio (UACR) >3 mg/mmol. Two readings ≥3 months apart were required for diagnosis. Demographic and laboratory data was retrieved from electronic records, and analysed using Pearson's Chi-square, Wilcoxon rank-sum test, and Cox regression evaluating time to onset of incident CKD. Results Of 25714 patients with newly-diagnosed DM and no known CKD, 3963 (15.4%) were not screened for CKD, and 2019 (7.9%) were diagnosed with CKD at the first screening; both groups were excluded. The remainder 19732 patients (76.7%) formed the study cohort. This included 14175 Chinese (71.8%), 3085 Malay (15.6%), 1658 Indian (8.4%), and 814 patients of other ethnicities (4.1%). Baseline mean (SD) GFR was 90.7 (17.6) ml/min/1.73 m2. Over a mean follow up of 2.28 (1.98) years, 5929 patients (30.0%) developed incident CKD after a mean of 1.35 (1.09) years. Of patients who developed CKD, 869 (14.7%) met the GFR criteria, 4847 (81.8%) developed albuminuria, and 213 (3.6%) met both criteria. GFR declined more rapidly in patients who developed CKD (−2.8 (4.4) ml/min/1.73 m2/year), than in patients who did not (−1.7 (5.7) ml/min/1.73 m2/year, p<0.001). GFR decline began in the first year. Baseline characteristics associated with incident CKD on bivariate analysis (Table 1) included older age (61 (11) vs 59 (12) years, p<0.001), female gender (p<0.001), lower GFR (89 (19) vs 91 (17) ml/min/1.73 m2, p<0.001), higher systolic blood pressure (136 (17) vs 135 (17) mmHg, p<0.001), and ischemic heart disease (p<0.001). On multivariate Cox regression exploring characteristics associated with time to incident CKD, independent risk factors include female gender (HR 1.30, 95%CI 1.23-1.39), lower GFR (per 10ml/min/1.73 m2 lower GFR, HR 1.10, 95%CI 1.08-1.11), higher systolic blood pressure (per 10mmHg rise, HR 1.06, 95%CI 1.04-1.08), higher HbA1c (per 1% rise, HR 1.06, 95%CI 1.05-1.08), cerebrovascular accident (HR 1.16, 95%CI 1.02-1.31) and gout (HR 1.16, 95%CI 1.01-1.32). Despite a prevalence of hypertension of 85%, only 5440 (28%) of the cohort with incident CKD received an angiotensin converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB) (as at 6 months after diagnosis of DM). 498 patients (2.5%) received a sodium-glucose cotransporter-2 inhibitor, which was not widely available during the period of this study. Conclusion Incident CKD was frequent in early DM; the risk factors above may identify higher-risk patients who benefit from enhanced screening. The relatively low rate of ACE/ARB prescription may require further review.

Prognostic significance of albuminuria in elderly of various ages with diabetes

It remains uncertain whether albuminuria can identify elderly patients with diabetes at a high risk of incident end-stage kidney disease (ESKD) or mortality. 3065 patients (aged ≥ 65 years) with type 2 diabetes were included. We examined the association between albuminuria stages (normoalbuminuria, A1; microalbuminuria, A2; and macroalbuminuria, A3) and the risk of incident ESKD and all-cause mortality for each age group (65–69, 70–74, and ≥ 75 years). A2 and A3 were observed in 25.5% and 9.4% of the subjects, respectively. For A1, A2, and A3, the probabilities of ESKD at 8 years were 1.0%, 6.3%, and 29.7% (P < 0.001 for all), and the all-cause mortality was 13.1%, 27.4%, and 31.7% (P < 0.001 for A1 vs A2, P < 0.001 for A1 vs A3), respectively. Albuminuria stages were independently associated with an increased risk of ESKD [fully adjusted hazard ratios (HR): 3.650 (1.987–6.702) for A2, 10.404 (5.706–18.972) for A3 vs. A1]. The HRs of all-cause mortality were 1.742 (1.411–2.153) for A2 and 1.810 (1.344–2.441) for A3. The associations between albuminuria stages and the risk of ESKD and all-cause mortality were consistent across all age groups. Even microalbuminuria is also a risk factor for incident ESKD and mortality in elderly patients with diabetes.

Estimated 24-h urinary sodium excretion and risk of end-stage kidney disease

The association between sodium intake and long-term kidney disease endpoints is debated and yet to be proven. We aimed to investigate the associations of estimated 24-h urinary sodium excretion, reflecting daily sodium intake, with the incidence of end-stage kidney disease (ESKD). In this prospective cohort study including 444,375UK Biobank participant, 865 (0.2%) ESKD events occurred after median follow-up of 12.7 years. For every 1g increment in estimated 24-h urinary sodium excretion, multivariable-adjusted hazard ratio for incident ESKD was 1.09 (95% confidence interval 0.94-1.26). Nonlinear associations were not detected with restricted cubic splines. The null findings were confirmed by a series of sensitivity analyses, which attenuated potential bias from measurement errors of the exposure, regression dilution, reverse causality, and competing risks. In conclusion, there is insufficient evidence that estimated 24-h urinary sodium excretion is associated with the incidence of ESKD.

Birth cohort effects in incident renal replacement therapy in Japan, 1982-2021.

This study aimed to investigate the long-term trends of incident end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) in Japan using age-period-cohort analysis and evaluated birth cohort effects for incident ESKD requiring RRT. The number of incident RRT patients aged between 20 and 84years by sex from 1982 to 2021 was extracted from the Japanese Society of Dialysis Therapy registry data. Annual incidence rates of RRT were calculated using census population as denominators, and changes in the incidence rates were evaluated using an age-period-cohort model. The age and survey year period categories generated 20 birth cohorts with 5-year intervals (from 1902-1907 to 1997-2001). The incidence rates of RRT in both sexes initially rose in the birth cohorts born in the early 1900s, and then decelerated and peaked during 1940-1960s in men and 1930-1940s in women, following a steady decline in both sexes. Compared with the reference 1947-1951 birth cohort, the highest cohort rate ratio was 1.14 (95% CI, 1.04-1.25) in the 1967-1971 birth cohort in men and 1.04 (95% CI, 0.98-1.10) in the 1937-1941 birth cohort in women. Significant cohort effects were identified in both sexes, but the peak of RRT was different for each sex. Our findings suggest that men born between 1940 and 1960s and women born between 1930 and 40s may be important target populations to consider when decreasing incidence rates of RRT among the general Japanese population.

A prediction model on incident ESKD among individuals with T2D and CKD

BackgroundDiabetes is the leading cause of end-stage kidney disease (ESKD). This study aimed to predict incident ESKD among individuals with T2D and CKD. MethodThe Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial data were split into a training set and a validation set by a ratio of 7:3. A dynamic time-varying Cox model was fit to predict the development of incident ESKD. Significant predictors were identified from a list of candidate variables, including demographic characteristics, physical exam results, laboratory results, medical history, drug information, and healthcare utilization. Model performance was evaluated by Brier score and C statistics. Decomposition analysis was conducted to assess the variable importance. Patient-level data from Harmony Outcome clinical trial and CRIC study were used for external validation. ResultsA total of 6982 diabetes patients with CKD were used for model development, with a median follow-up of four years and 312 ESKD events. The significant predictors for the final model were female sex, race, smoking status, age at T2D diagnosis, SBP, HR, HbA1c, estimated glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR), retinopathy event occurring in last year, antihypertensive drug use, and an interaction term between SBP and female. The model demonstrated good performance in discrimination (C-statistic 0.764 [95 % CI 0.763–0.811]) and calibration (Brier Score 0.0083 [95 % CI 0.0063–0.0108]). The top 3 most important predictors in the prediction model were eGFR, retinopathy event, and UACR. Acceptable discrimination (C-statistic: 0.701 [95 % CI 0.665–0.716]; 0.86 [95 % CI 0.847–0.872]) and calibration (Brier Score: 0.0794 [95 % CI 0.0733–0.1022]; 0.0476 [95 % CI 0.0440, 0.0506]) were demonstrated in the Harmony Outcome and CRIC data, respectively. ConclusionThe dynamic risk prediction of incident ESKD among individuals with T2D can be a useful tool to support better disease management to lower the risk of developing ESKD.

Association of MAFLD with end-stage kidney disease: a prospective study of 337,783 UK Biobank participants.

Metabolic dysfunction-associated fatty liver (MAFLD) has been found to be associated with the prevalence of chronic kidney disease (CKD). However, it is unknown whether MAFLD is associated with CKD development and the incidence of end-stage kidney disease (ESKD). We aimed to clarify the association between MAFLD and incident ESKD in the prospective UK Biobank cohort. We analyzed the data of 337,783 UK Biobank participants and relative risks for the ESKD were calculated by using the Cox regression analysis. Among 337,783 participants over a median duration of 12.8years follow-up, a total of 618 ESKD cases were diagnosed. Participants with MAFLD were twice likely to develop ESKD (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.68-2.46, p < 0.001). The association of MAFLD with ESKD risk remained significant in both non-CKD and CKD participants. Our results also showed that there were graded associations between liver fibrosis scores and the risk of ESKD in MAFLD cases. Compared to non-MAFLD individuals, the adjusted HRs for incident ESKD in MAFLD patients with increasing levels of NAFLD fibrosis score were 1.23 (95% CI 0.96-1.58), 2.45 (1.98-3.03) and 7.67 (5.48-10.73), respectively. Furthermore, the risking alleles of PNPLA3 rs738409, TM6SF2 rs58542926, GCKR rs1260326 and MBOAT7 rs641738 amplified the MAFLD effect on ESKD risk. In conclusion, MAFLD is associated with incident ESKD. MAFLD may help identify the subjects at high risk of ESKD development and MAFLD interventions should be encouraged to slow down CKD progression.

Clinical outcomes following discontinuation of renin-angiotensin-system inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: A prospective cohort study.

Renin-angiotensin-system inhibitors (RASi), that include angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) reduce proteinuria, delay chronic kidney disease (CKD) progression, protect against cardiovascular events and heart failure hospitalizations. We examined the associations of discontinuation of ACEi/ARBs with risk of clinical outcomes in Chinese patients with type 2 diabetes (T2D) and advanced-CKD (estimated-glomerular filtration rate [eGFR] <30ml/min/1.73m2). We conducted a prospective, population-based cohort study including 10,400 patients with T2D in Hong Kong stratified by continuation of ACEi/ARBs within 6 months after reaching eGFR <30ml/min/1.73m2 from January 01, 2002 to December 31, 2018 and observed until December 31, 2019. The primary outcomes were death, major-adverse cardiovascular events (MACE), heart failure, end-stage kidney disease (ESKD), and all-cause mortality. Cox-model with time-dependent exposure and covariates was used to estimate the hazard ratio (HR) of outcomes in a propensity-score overlap-weighted cohort. The risk of occurrence of hyperkalemia (plasma potassium >5.5mmol/L) in discontinued-ACEi/ARBs versus continued-ACEi/ARBs users was assessed in a register-based cohort. In the population-based cohort of 10,400 ACEi/ARBs users with new-onset eGFR<30ml/min/1.73m2, 1766 (17.0%) discontinued ACEi/ARBs and 8634 (83.0%) persisted with treatment. During a median follow-up of 3.6 (interquartile range, IQR: 2.11-5.8) years (41,623 person-years), 13.5%, 12.9%, and 27.6% had incident MACE, heart failure and ESKD respectively, and 35.8% died. Discontinued-ACEi/ARBs use was associated with higher risk of MACE (HR=1.27, 95% CI: 1.08-1.49), heart failure (HR=1.85, 95% CI: 1.53-2.25) and ESKD (HR=1.30, 95% CI: 1.17-1.43), and neutral risk of all-cause mortality (HR=0.93, 95% CI: 0.86-1.01) compared to counterparts with continued use. In the register-based cohort (583 discontinued-ACEi/ARBs users and 3817 continued-ACEi/ARBs users), discontinued-ACEi/ARBs had neutral risk of hyperkalemia (HR=0.95, 95% CI: 0.84-1.08). Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events supporting their continued use in patients with T2D and advanced-CKD. CUHK Impact Research Fellowship Scheme.

Urine Leucine-Rich α-2 Glycoprotein 1 (LRG1) Predicts the Risk of Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes.

Leucine-rich α-2 glycoprotein 1 (LRG1) was recently identified as an amplifier of transforming growth factor-β (TGF-β)-induced kidney fibrosis in animal models. We aimed to study whether urine LRG1 is associated with risk of progression to end-stage kidney disease (ESKD) in individuals with type 2 diabetes. A total of 1,837 participants with type 2 diabetes and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were recruited from a regional hospital and a primary care facility. Association of urine LRG1 with risk of ESKD (progression to sustained eGFR <15 mL/min/1.73 m2, dialysis, or death resulting from renal causes) was assessed by survival analyses. During a median follow-up of 8.6 (interquartile range 5.8-9.6) years, 134 incident ESKD events were identified. Compared with those in the lowest tertile, participants with baseline urine LRG1 in the highest tertile had a 1.91-fold (95% CI 1.04-3.50) increased risk of progression to ESKD, after adjustment for cardiorenal risk factors, including eGFR and albuminuria. As a continuous variable, 1 SD increment in urine LRG1 was associated with a 1.53-fold (95% CI 1.19-1.98) adjusted risk of ESKD. Of note, the association of urine LRG1 with ESKD was independent of plasma LRG1. Moreover, urine LRG1 was associated with rapid kidney function decline and progression to macroalbuminuria, two common pathways leading to ESKD. Urine LRG1, a TGF-β signaling modulator, predicts risk of progression to ESKD independently of clinical risk factors in patients with type 2 diabetes, suggesting that it may be a novel factor involved in the pathophysiological pathway leading to kidney disease progression.

Abstract 11706: Association of Left Atrial Function With Incident Chronic Kidney Disease: Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Echocardiographic measures of left ventricular (LV) structure and function are associated with incident chronic kidney disease (CKD). Reduced left atrial (LA) function is an emerging novel risk factor for cardiovascular disease but its association with incident CKD is unknown. Hypothesis: Lower LA function is independently associated with incident CKD in older adults in the ARIC study, a prospective community-based cohort. Methods: We included ARIC participants without prevalent CKD (as defined by eGFR&lt;60ml/min/1.73m 2 ) who underwent echocardiographic exam at visit 5 (2011-13). LA function measures included LA reservoir strain, contractile strain, and conduit strain. Incident CKD was defined as a composite outcome of &gt;25% decline to eGFR &lt;60 mL/min/1.73m 2 , hospitalization with CKD diagnosis, or incident end-stage kidney disease through 2017. Cox proportional hazards model was used. Results: Among the 3,970 participants (mean [SD] age, 75 [5] years; 58% women; 20.9% Black individuals), 382 cases of incident CKD were ascertained over a median follow-up of 5.5 years. Lower LA reservoir and contractile strain were significantly associated with higher risk of CKD (HR [95% CI] lowest vs highest quintile: 2.76 [1.91-3.98], and 2.56 [1.79-3.65], respectively) (Table). The associations remained significant after accounting for other major echocardiographic parameters (model 2) including left atrial volume index (model 3). LA conduit strain was not significantly associated with CKD. Conclusions: Lower LA function is significantly associated with incident CKD, independent of CKD risk factors, LV size and function, and LA size. These findings indicate that impaired LA function is a novel predictor marker for CKD.

GCKR and GCK polymorphisms are associated with increased risk of end-stage kidney disease in Chinese patients with type 2 diabetes: The Hong Kong Diabetes Register (1995–2019)

AimsGlucokinase (GCK) and glucokinase regulatory protein (GKRP) regulate glucose and lipid metabolism. We investigated the associations of GCKR and GCK polymorphisms with kidney outcomes. MethodsAnalyses were performed in a prospective cohort who were enrolled in the Hong Kong Diabetes Register between 1995 and 2017. The associations of GCKR rs1260326 and GCK rs1799884 polymorphisms with incident end-stage kidney disease (ESKD), albuminuria and rapid eGFR decline were analysed by Cox regression or logistic regression with adjustment. Results6072 patients (baseline mean age 57.4 years; median diabetes duration 6.0 years; 54.5 % female) were included, with a median follow-up of 15.5 years. The GCKR rs1260326 [HR (95 %CI) 1.23 (1.05–1.44) for CT; HR 1.23 (1.02–1.48) for TT] and GCK rs1799884 T alleles [HR 1.73 (1.24–2.40) for TT] were independently associated with increased risk of ESKD versus their respective CC genotypes. GCKR rs1260326 T allele was also associated with albuminuria [OR 1.18 (1.05–1.33) for CT; OR 1.34 (1.16–1.55) for TT] and rapid eGFR decline. ConclusionsIn Chinese patients with type 2 diabetes, T allele carriers of GCKR rs1260326 and GCK rs1799884 were at high risk for ESKD. These genetic markers may be used to identify high risk patients for early intensive management for renoprotection.

Renin: Measurements, Correlates, and Associations With Long-Term Adverse Kidney Outcomes.

The association of renin with adverse kidney outcomes is largely unknown, and renin measurement strategies vary. We aimed to measure the clinical correlates of different renin measurements and the association between renin and incident chronic kidney disease (CKD), end-stage kidney disease (ESKD), and mortality. We performed a prospective cohort analysis of 9,420 participants in the Atherosclerosis Risk in Communities study followed from 1996 to 1998 through 2019. We estimated longitudinal associations of renin measured using SomaScan modified nucleotide aptamer assay with incident CKD, ESKD, and death using Cox proportional hazards models. Using samples from a subsequent study visit, we compared SomaScan renin with plasma renin activity (PRA) and renin level from Olink, and estimated associations with covariates using univariate and multivariable regression. Higher SomaScan renin levels were associated with a higher risk of incident CKD (hazard ratio per two-fold higher [HR], 1.14; 95% confidence interval [CI], 1.09 to 1.20), ESKD (HR, 1.20; 95% CI, 1.03 to 1.41), and mortality (HR, 1.08; 95% CI, 1.04 to 1.13) in analyses adjusted for demographic, clinical, and socioeconomic covariates. SomaScan renin was moderately correlated with PRA (r = 0.61) and highly correlated with Olink renin (r = 0.94). SomaScan renin and PRA had similar clinical correlates except for divergent associations with age and beta-blocker use, both of which correlated positively with SomaScan renin but negatively with PRA. SomaScan aptamer-based renin level was associated with a higher risk of CKD, ESKD, and mortality. It was moderately correlated with PRA, sharing generally similar clinical covariate associations.

Echocardiography-Based Cardiac Structure Parameters for the Long-term Risk of End-Stage Kidney Disease in Black Individuals: The Atherosclerosis Risk in Communities Study

ObjectiveTo assess whether echocardiographic parameters of left ventricular (LV) structure and function relate to the long-term risk of incident end-stage kidney disease (ESKD). Patients and MethodsWe conducted a prospective cohort study analyzing 2137 Black participants from the Jackson site of the Atherosclerosis Risk in Communities Study from January 1, 1993, through July 31, 2017. Echocardiographic parameters of LV structure and function were obtained from 1993 to 1995. The primary outcome incident ESKD was identified through the linkage to the United States Renal Data System. Cox proportional hazards models were used to estimate the hazard ratios (HRs) according to each echocardiographic parameter. ResultsThere were 117 incident ESKD cases during a median follow-up of 22.2 (interquartile range, 15.0-23.3) years. Multivariable Cox models revealed that a higher LV mass index was significantly associated with the risk of ESKD (HR, 2.38; 95% CI, 1.21 to 4.68 for highest vs lowest quartile, P = 0.012). The HRs were significant and even higher for LV posterior wall thickness, with slightly higher HRs when their measures in end-systole (HR for highest vs lowest quartile, 4.38; 95% CI, 1.94 to 9.92, P < 0.001) vs end-diastole (HR, 3.50; 95% CI, 1.53 to 8.01, P = 0.003) were used. The associations were not significant for LV function parameters. ConclusionIn Black individuals residing in the community, echocardiographic parameters of LV structure, including LV wall thickness, were robustly associated with the risk of subsequently incident ESKD. These results have potential implications for novel prevention and management strategies for persons with abnormal LV structure.

Rates of Medicare Enrollment Among Dialysis Patients After Implementation of Medicare Payment Reform and the Affordable Care Act Marketplace

Medicare finances health care for most US patients with end-stage kidney disease (ESKD), regardless of age. The 2011 Medicare prospective payment system (PPS) for dialysis reduced reimbursement for hemodialysis, and the 2014 Patient Protection and Affordable Care Act (ACA) Marketplace increased patient access to new private insurance options, potentially influencing organizations that provide health care, such as hospitals, nursing homes, and dialysis facilities, to adjust their payer mix away from Medicare sources. To describe Medicare enrollment trends among patients with incident ESKD in 2006 to 2016. This retrospective cohort study involved US patients aged 18 to 64 years who were not enrolled in Medicare at dialysis initiation in 2006 to 2016, with 1-year follow-up through 2017. Data analysis was conducted April 2021 to June 2022. The exposure of interest was a 3-category indicator of time, whether patients initiated dialysis before policies were enacted (2006-2010), in the first years of the Medicare ESKD PPS (2011-2013), or during the Medicare ESKD PPS and implementation of the ACA Marketplace (2014-2016). Patient-level Medicare enrollment through the first year of dialysis. Logistic regression and Cox models were used to examine associations of time, patient characteristics, and Medicare enrollment, adjusting for patient demographic, clinical, and market-level characteristics. Of 335 157 patients aged 18 to 64 years with ESKD not actively enrolled in Medicare when they initiated dialysis in 2006 to 2016, the mean (SD) age was 49.9 (10.8) years, 198 164 (59.1%) were men, 188 290 (56.2%) were White, and 313 622 (93.6%) received in-center hemodialysis. New Medicare enrollment was higher in 2006 to 2010 (110 582 patients [73.1%]) than after the Medicare ESKD PPS and ACA Marketplace in 2014 to 2016 (55 382 patients [58.5%]). In adjusted analyses, declining Medicare enrollment was associated with implementation of 2011 Medicare ESKD PPS and 2014 ACA policies and was disproportionately lower among younger, racially minoritized, and ethnically Hispanic patients. There was declining Medicare enrollment among new dialysis patients associated with the 2011 Medicare ESKD PPS and 2014 ACA Marketplace that raise concerns about benefits and harms to patients and payers and continued disparities in kidney care. As the dialysis payer mix moves toward higher proportions of patients not covered by Medicare, it will be important to understand the implications for health care system and patient outcomes.

Perpetuating Disparity: Failure of the Kidney Transplant System to Provide the Most Kidney Transplants to Communities With the Greatest Need.

The burden of end-stage kidney disease (ESKD) and kidney transplant rates vary significantly across the United States. This study aims to examine the mismatch between ESKD burden and kidney transplant rates from a perspective of spatial epidemiology. US Renal Data System data from 2015 to 2017 on incident ESKD and kidney transplants per 1000 incident ESKD cases was analyzed. Clustering of ESKD burden and kidney transplant rates at the county level was determined using local Moran's I and correlated to county health scores. Higher percentile county health scores indicated worse overall community health. Significant clusters of high-ESKD burden tended to coincide with clusters of low kidney transplant rates, and vice versa. The most common cluster type had high incident ESKD with low transplant rates (377 counties). Counties in these clusters had the lowest overall mean transplant rate (61.1), highest overall mean ESKD incidence (61.3), and highest mean county health scores percentile (80.9%, P <0.001 vs all other cluster types). By comparison, counties in clusters with low ESKD incidence and high transplant rates (n=359) had the highest mean transplant rate (110.6), the lowest mean ESKD incidence (28.9), and the lowest county health scores (20.2%). All comparisons to high-ESKD/low-transplant clusters were significant at P value <0.001. There was a significant mismatch between kidney transplant rates and ESKD burden, where areas with the greatest need had the lowest transplant rates. This pattern exacerbates pre-existing disparities, as disadvantaged high-ESKD regions already suffer from worse access to care and overall community health, as evidenced by the highest county health scores in the study.

An algorithm for identifying chronic kidney disease in the French national health insurance claims database

BackgroundPublished algorithms for identifying chronic kidney disease in healthcare claims databases have poor performance except in patients with renal replacement therapy. We propose and describe an algorithm to identify all stage chronic kidney disease in a French healthcare claims databases and assessed its performance by using data from the Renal Epidemiology and Information Network registry and the French Childhood Cancer Survivor Study cohort. MethodsA group of experts met several times to define a list of items and combinations of items that could be related to chronic kidney disease. For the French Childhood Cancer Survivor Study cohort, information on confirmed chronic kidney disease cases extracted from medical records was considered the gold standard (KDIGO definition). Sensitivity, specificity, and positive and negative predictive value and kappa coefficients were estimated. The contribution of each component of the algorithm was assessed for 1 and 2 years before the start of renal replacement therapy for confirmed end-stage kidney disease in the Renal Epidemiology and Information Network registry. ResultsThe algorithm's sensitivity was 78%, specificity 97.4%, negative predictive value 98.4% and positive predictive value 68.7% in French Childhood Cancer Survivor Study cohort and the kappa coefficient was 0.79 for agreement with the gold standard. The algorithm 93.6% and 55.1% of confirmed incident end-stage kidney disease cases from the Renal Epidemiology and Information Network registry when considering 1 year and 2 years, respectively, before renal replacement therapy start. ConclusionsThe algorithm showed good performance among younger patients and those with end-stage kidney disease in the twol last years prior to renal replacement therapy. Future research will address the ability of the algorithm to detect early chronic kidney disease stages and to classify the severity of chronic kidney disease.

12-LB: A Prediction Model on Incident End-Stage Kidney Disease (ESKD) among Individuals with Type 2 Diabetes (T2D) and Chronic Kidney Disease (CKD)

Diabetes is the leading cause of ESKD, a costly and disabling condition that often results in premature death. This study aimed to predict incident ESKD among individuals with T2D comorbid with CKD. The ACCORD clinical trial data were split into a training set and a validation set by a ratio of 7:3. A dynamic time-varying Cox model was fit to predict the development of incident ESKD. Significant predictors were identified from a list of candidate variables, including demographic characteristics, physical exam results, laboratory results, medical history, drug information, and healthcare utilization. Model performance was evaluated by Brier score and C statistics. Confidence intervals (CI) were calculated using a bootstrap method. Decomposition analysis was conducted to assess the variable importance. Patient-level data of HARMONY Outcome clinical trial was used for external validation. A total of 6,982 diabetes patients with CKD at baseline were used for model development, with a median follow-up of 4 years and 312 ESKD events. The significant predictors for the ESKD risk model were female, race, smoking status, age at T2D diagnosis, SBP, HR, HbA1c, estimated glomerular filtration rate (eGFR) , urine albumin-creatinine ratio (UACR) , retinopathy event happened in last year, antihypertensive drug use, and an interaction term between SBP and female. The model demonstrated good performance in discrimination (C-statistics 0.764 [95% CI 0.763-0.811]) and calibration (Brier Score 0.0083 [95% CI 0.0063-0.0108]) . The top 3 most important predictors in the prediction model were eGFR, retinopathy event, and UACR. There were 2,954 patients with CKD extracted from HARMONY Outcome with 545 ESKD events and a median follow-up of 2 years. Acceptable discrimination (C-statistics: 0.701 [95% CI 0.665-0.716]) and calibration (Brier Score: 0.0794 [95% CI 0.0733-0.1022]) were demonstrated in the external data. The dynamic risk prediction of incident ESKD among individuals with T2D can be used to support better disease management to lower the risk of developing ESKD. Disclosure Y. Lin: None. H. Shao: Board Member; BRAVO4HEALTH, LLC. A. H. Anderson: None. V. Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. V. Batuman: None. L. Shi: None.