Incident End-stage Kidney Disease Research Articles

#2491 Survival outcome of tunneled and non-tunneled hemodialysis catheters in incident hemodialysis requiring patients: a short term study

Abstract Background and Aims For long term hemodialysis, tunnel catheters are preferred over non –tunneled as vascular access. High cost and expertise in its catheterization are major limitations. It is unclear about the advantage of low cost non- tunneled catheter preference over costly tunnel catheters as short term access while awaiting AVF maturation. Method All consented incident End Stage Kidney Disease (ESKD) patients requiring hemodialysis from March’ 2021 to October’ 2023 were included. Less than 18 years of age, opting for peritoneal dialysis and patients initiating hemodialysis with AVF or AV Graft were excluded from the study. Subjects were randomized in two catheter groups (Tunneled and Non-tunneled). Under aseptic precautions, all catheters were inserted by ultrasound and C-arm guided following standard protocol. Mechanical, infective and catheter survival outcomes were recorded during dialysis initiation, at 2nd, 6th and 12th weeks. Blood culture samples were sent for those patients who were having fever with chills during dialysis. If the blood culture comes out to be positive for organism, all were treated for one week intravenous antibiotic depending upon the sensitivity or as per standard protocol. Catheter salvage in both the groups was tried till 6 weeks or till AVF maturation. If in any case, AVF is not matured, we continued dialysis with the same catheter. New catheter was inserted if patient do not respond antibiotics after one week of therapy, mechanical complications or due to inadequate flow. Adequacy of the dialysis and overall outcome of patients were monitored in both the groups of catheter. All demography data and survival analysis were analyzed. Results A total 133 patients were randomized into Tunneled-65 (48.87%) and non-tunneled-68 (51.12%). Average patient's age of tunneled and non-tunneled was 45.15 ± 15.89 and 40.39 ± 12.21 respectively. A total of 50 (37.3%) were males in tunneled and 54 (40.3%) males in non tunneled groups. A total 65 (54.2%) patients were complained fever with chills during dialysis, of them 31 (25.8%) in tunneled and 34 (28.3%) in non-tunneled group. Among the CRBSI group a total 3 catheters were removed in non-tunneled group whereas all patients in tunneled group were responded to antibiotic. There were total of 24 (18.2%) infections were reported and labelled as CRBSI. Of them 9 (6.7%) in tunneled and 15 (11.2%) in non-tunneled. Most common organism was Klebsiella and Coagulase negative Staphylococcus (Cons) in both the groups. There was only one mechanical complication in case of non- tunneled catheter. The estimated days for catheter survival is 66 for tunneled and 57 for non tunneled (p-0.001). However, in case of non tunneled catheter, 15 cases were reported in which two times catheter were inserted. A total of 14 (10.5%) patients were lost to follow up 8 (6%) in tunneled and 6 (4.5%) in non- tunneled. A total of 9 (5.8%) patients died, 5 (3.8%) in tunneled and 4 (3%) in non- tunneled within 12 weeks. Conclusion Although tunneled catheter showed longer catheter survival period, low cost and easy cannulation procedure in non-tunneled hemodialysis catheter is a better viable option for all incident ESKD patients while waiting for AVF maturation.

Kidney and Cardiovascular Effectiveness of Empagliflozin Compared With Dipeptidyl Peptidase-4 Inhibitors in Patients With Type 2 Diabetes

Placebo-controlled trials of sodium-glucose cotransporter-2 inhibitors (SGLT2i) demonstrate kidney and cardiovascular benefits for people with type 2 diabetes (T2D) and chronic kidney disease (CKD). We used real-world data to compare the kidney and cardiovascular effectiveness of empagliflozin to dipeptidyl peptidase-4 inhibitors (DPP4i), a commonly prescribed antiglycemic medication, in a diverse population with and without CKD. Using electronic health record data from 20 large US health systems, we leveraged propensity overlap weighting to compare outcomes for empagliflozin and DPP4i initiators with T2D between 2016 and 2020. The primary composite kidney outcome included 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease (ESKD), or all-cause mortality through 2 years or censoring. We also assessed cardiovascular and safety outcomes. Among 62,197 new users, 20,279 initiated empagliflozin, and 41,918 initiated DPP4i. Over a median follow-up of 1.1 years, empagliflozin prescription was associated with a lower risk of the primary outcome (HR 0.75, 95% CI 0.65-0.87) compared with DPP4i. Risks for mortality (HR 0.76, 95% CI 0.62-0.92) and a cardiovascular composite of stroke, myocardial infarction, or all-cause mortality (HR 0.81, 95% CI 0.70-0.95) were also lower for empagliflozin initiators. No difference in heart failure hospitalization risk between groups was observed. Genital mycotic infections were more common in patients prescribed empagliflozin (HR 1.72, 95% CI 1.58 - 1.88). Empagliflozin was associated with a lower risk of the primary outcome in patients with CKD (HR 0.68, 95% CI 0.53-0.88) and those without CKD (HR 0.79, 95% CI 0.67 - 0.94). In conclusion, initiation of empagliflozin was associated with a significantly lower risk of kidney and cardiovascular outcomes compared with DPP4i over a median of just over 1 year. The association with a lower risk for clinical outcomes was apparent even for people without known CKD at baseline.

Association of Urinary Dickkopf-3 Levels with Cardiovascular Events and Kidney Disease Progression in Systolic Blood Pressure Intervention Trial.

Urinary Dickkopf-3 (uDKK3) is a tubular epithelial-derived profibrotic protein secreted into the urine under tubular stress. It is associated with kidney disease progression in persons with chronic kidney disease (CKD) and diabetes, and post-operative and contrast-associated acute kidney injury (AKI). We explored associations of uDKK3 with cardiovascular disease (CVD), kidney and mortality outcomes within the subset of Systolic Blood Pressure Intervention Trial (SPRINT) participants with non-diabetic CKD. We included 2,344 participants with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at baseline. We used Cox proportional hazards models to evaluate associations of uDKK3 with CVD (acute decompensated heart failure, myocardial infarction, acute coronary syndrome, stroke or CVD death), kidney outcomes (incident end stage kidney disease [ESKD], incident AKI, and eGFR decline ≥30%), and all-cause mortality. We used linear mixed models to examine the association of uDKK3 with annual percentage change in eGFR. Models were adjusted for demographic and clinical characteristics, eGFR and albuminuria. Over a median follow up of 3.5 years, there were 292 CVD, 73 ESKD, 183 AKI, 471 eGFR decline, and 228 mortality events. In multivariable models without adjustment for eGFR and albuminuria, uDKK3 was strongly associated with CVD, ESKD, AKI, eGFR decline ≥30%, and mortality. However, after further adjustment for eGFR and albuminuria, uDKK3 was no longer associated with risks for composite CVD (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.92-1.23), ESKD (0.80; 0.62-1.02), AKI (1.01; 0.85-1.21), eGFR decline >30% (0.88; 0.79-0.99) or mortality (1.02; 0.87-1.20). For the linear eGFR change outcome, higher uDKK3 also had no association in the fully adjusted model (-0.03; -0.41-0.36). Among individuals with hypertension and non-diabetic CKD, higher uDKK3 appeared to have associations with a greater risk of CVD events, incident ESKD, incident AKI, eGFR decline ≥30%, and mortality, but was not independent of eGFR and albuminuria.

Mitochondrial genetic variation and risk of chronic kidney disease and acute kidney injury in UK Biobank participants

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function. We used linear and logistic regression models to evaluate associations of these mtDNA haplotypes with estimated glomerular filtration rate by serum creatinine and cystatin C (eGFRCr-CysC, N = 362,802), prevalent (N = 416 cases) and incident (N = 405 cases) end-stage kidney disease (ESKD), AKI defined by diagnostic codes (N = 14,170 cases), and urine albumin/creatinine ratio (ACR, N = 114,662). The mean age was 57 ± 8 years and the mean eGFR was 90 ± 14 ml/min/1.73 m2. MtDNA haplotype was significantly associated with eGFR (p = 2.8E−12), but not with prevalent ESKD (p = 5.9E−2), incident ESKD (p = 0.93), AKI (p = 0.26), or urine ACR (p = 0.54). The association of mtDNA haplotype with eGFR remained significant after adjustment for diabetes mellitus and hypertension (p = 1.2E−10). When compared to the reference haplotype, mtDNA haplotypes I (β = 0.402, standard error (SE) = 0.111; p = 2.7E−4), IV (β = 0.430, SE = 0.073; p = 4.2E−9), and V (β = 0.233, SE = 0.050; p = 2.7E−6) were each associated with higher eGFR. Among self-identified white UK Biobank participants, mtDNA haplotype was associated with eGFR, but not with ESKD, AKI or albuminuria.

Characteristics and Outcomes of Patients With Pregnancy-Related End-Stage Kidney Disease

ImportanceThe incidence of pregnancy-related acute kidney injury is increasing and is associated with significant maternal morbidity including progression to end-stage kidney disease (ESKD). Little is known about characteristics and long-term outcomes of patients who develop pregnancy-related ESKD.ObjectivesTo examine the characteristics and clinical outcomes of patients with pregnancy-related ESKD and to investigate associations between pre-ESKD nephrology care and outcomes.Design, Setting, and ParticipantsThis was a cohort study of 183 640 reproductive-aged women with incident ESKD between January 1, 2000, and November 20, 2020, from the US Renal Data System and maternal data from births captured in the US Centers for Disease Control and Prevention publicly available natality data. Data were analyzed from December 2022 to June 2023.ExposurePregnancy-related primary cause of ESKD, per International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes reported at ESKD onset by the primary nephrologist on Centers for Medicare and Medicaid Services form 2728.Main Outcomes MeasuresMultivariable Cox proportional hazards and competing risk models were constructed to examine time to (1) mortality, (2) access to kidney transplant (joining the waiting list or receiving a live donor transplant), and (3) receipt of transplant after joining the waitlist.ResultsA total of 341 patients with a pregnancy-related primary cause of ESKD were identified (mean [SD] age 30.2 [7.3]). Compared with the general US birthing population, Black patients were overrepresented among those with pregnancy-related ESKD (109 patients [31.9%] vs 585 268 patients [16.2%]). In adjusted analyses, patients with pregnancy-related ESKD had similar or lower hazards of mortality compared with those with glomerulonephritis or cystic kidney disease (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.76-1.19), diabetes or hypertension (aHR, 0.49; 95% CI, 0.39-0.61), or other or unknown primary causes of ESKD (aHR, 0.60; 95% CI, 0.48-0.75). Despite this, patients with pregnancy-related ESKD had significantly lower access to kidney transplant compared with those with other causes of ESKD, including (1) glomerulonephritis or cystic kidney disease (adjusted subhazard ratio [aSHR], 0.51; 95% CI, 0.43-0.66), (2) diabetes or hypertension (aSHR, 0.81; 95% CI, 0.67-0.98), and (3) other or unkown cause (aSHR, 0.82; 95% CI, 0.67-0.99). Those with pregnancy-related ESKD were less likely to have nephrology care or have a graft or arteriovenous fistula placed before ESKD onset (nephrology care: adjusted relative risk [aRR], 0.47; 95% CI, 0.40-0.56; graft or arteriovenous fistula placed: aRR, 0.31; 95% CI, 0.17-0.57).Conclusion and RelevanceIn this study, those with pregnancy-related ESKD had reduced access to transplant and nephrology care, which could exacerbate existing disparities in a disproportionately Black population. Increased access to care could improve quality of life and health outcomes among these young adults with high potential for long-term survival.

Plasma Tryptophan-Kynurenine Pathway Metabolites and Risk for Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes.

We sought to study the associations between plasma metabolites in the tryptophan-kynurenine pathway and the risk of progression to end-stage kidney disease (ESKD) in patients with type 2 diabetes. Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, and xanthurenic acid concentrations were measured in discovery (n = 1,915) and replication (n = 346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (n = 1,312). The primary outcome was a composite of incident ESKD (progression to estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, sustained dialysis, or renal death). The secondary outcome was annual eGFR decline. In the discovery cohort, tryptophan was inversely associated with risk for ESKD, and kynurenine-to-tryptophan ratio (KTR) was positively associated with risk for ESKD after adjustment for clinical risk factors, including baseline eGFR and albuminuria (adjusted hazard ratios [HRs] 0.62 [95% CI 0.51, 0.75] and 1.48 [1.20, 1.84] per 1 SD). High levels of kynurenic acid and xanthurenic acid were associated with low risks of ESKD (0.74 [0.60, 0.91] and 0.74 [0.60, 0.91]). Consistently, high levels of tryptophan, kynurenic acid, and xanthurenic acid were independently associated with a slower eGFR decline, while a high KTR was predictive of a faster eGFR decline. Similar outcomes were obtained in the replication cohort. Furthermore, the inverse association between kynurenic acid and risk of ESKD was externally validated in CRIC participants with diabetes (adjusted HR 0.78 [0.65, 0.93]). Accelerated catabolism of tryptophan in the kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward the kynurenic acid branch may potentially slow renal progression.

Kidney Biopsy Findings and Clinical Outcomes of US Veterans with Inflammatory Bowel Disease

Introduction: Patients with inflammatory bowel disease (IBD; ulcerative colitis [UC] and Crohn’s disease [CD]) may have unique patterns of kidney injury related to their underlying or coexisting disease or to medications. We present the kidney biopsy findings and clinical outcomes of veterans with UC or CD from the US Department of Veteran’s Affairs (VA) health system. Methods: Histopathologic and clinical data were extracted by retrospective review of the VA electronic health record of patients with IBD and a kidney biopsy between 2000 and 2018. Incident end-stage kidney disease (ESKD) was defined as requirement of kidney replacement therapy. Statistical analyses were performed using SAS. Results: A total of 140 patients (UC: 91 and CD: 49) underwent kidney biopsy. The three most common diagnoses were IgA nephropathy (17.1%), diabetic nephropathy (14.3%), and acute interstitial nephritis (9.3%). Significant interstitial fibrosis, tubular atrophy, and arteriosclerosis were present in 45% of biopsies. Twenty-six percent of patients with UC and 20% of those with CD progressed to ESKD, with a mean time from kidney biopsy of 3.1 and 1.9 years, respectively. Forty-five percent of patients with UC and 34% of those with CD died, with a mean time from kidney biopsy of 4.3 and 4.6 years, respectively. Conclusion: Among US veterans with IBD who underwent a kidney biopsy, IgA nephropathy, diabetic nephropathy, and interstitial nephritis were among the most common findings. Additionally, features of advanced kidney disease with rapid clinical progression to ESKD or death were observed. These findings suggest a delay and possibly a low rate of diagnosis.

Racial Disparities in End-Stage Kidney Disease Outcomes among Asians and Native Hawaiians and Other Pacific Islanders across Geographic Residence

Introduction: While Asian and Native Hawaiian and other Pacific Islander (NHOPI) patients have a high prevalence of kidney disease risk factors, there are sparse data examining their end-stage kidney disease (ESKD) outcomes. As Hawaii has high representation of Asian and NHOPI individuals, we compared their ESKD outcomes based on residence in the mainland USA versus Hawaii/Pacific Islands (PIs). Materials and Methods: Using United States Renal Data System data, we examined the impact of geographic residence in the mainland versus Hawaii/PIs on race-mortality associations among incident ESKD patients transitioning to dialysis over January 1, 2000–December 31, 2016 using Cox regression. We examined likelihood of post-dialysis kidney transplantation using Cox models and cumulative incidence curves. Results: Compared with White patients in the mainland, Asian and NHOPI patients in the mainland had lower mortality: adjusted HRs (95% CIs) 0.67 (0.66–0.67) and 0.72 (0.70–0.73), respectively. When examining Asian and NHOPI patients in Hawaii/PIs, survival benefit was attenuated in Asian and diminished to the null in NHOPI patients (ref: mainland White patients). Cumulative incidence curves comparing Asian, NHOPI, and White patients showed Asian and NHOPI patients in the mainland had the highest likelihood of transplantation, whereas NHOPI and Asian patients in Hawaii/PIs had the lowest likelihood. Conclusion: In the mainland, Asian and NHOPI patients had lower mortality versus White patients, whereas in Hawaii/PIs, this survival benefit was diminished in Asian and mitigated in NHOPI patients. NHOPI and Asian patients in Hawaii/PIs had less transplantation versus those in the mainland. Further research is needed to uncover factors contributing to differential ESKD outcomes among Asian and NHOPI patients across geographic residence.

Association between long-term exposure to low level air pollutants and incident end-stage kidney disease in the UK Biobank: A prospective cohort

BackgroundPrevious studies suggest that air pollution can increase the risk of incident chronic kidney disease (CKD). However, the association between end-stage kidney disease (ESKD) and co-exposure to relatively low-level air pollutants remains unclear. MethodsA prospective cohort was designed based on UK Biobank. From 1 January 2010 to 12 November 2021, 453,347 participants were followed up over a median of 11.87 years. Principal component analysis was used to identify major patterns of five air pollutants, including PM2.5, PM2.5-10, PM10, NO2, and NOx. Sub-distribution hazards models were used to estimate the associations between air pollution, individually or jointly, and incident ESKD, CKD, and all-cause death, respectively. ResultsPrincipal component analysis identified two principal components, namely RC1 (PM2.5, NO2, and NOx) and RC2 (PM2.5-10 and PM10). An elevated risk of incident ESKD was associated with an interquartile range (IQR) increase in PM2.5 (hazard ratio: 1.11, 95% confidence interval: 1.02–1.22), NO2 (1.16, 1.04–1.30), NOx (1.08, 1.00–1.17), and RC1 (1.12, 1.02–1.23). An elevated risk of incident CKD was associated with an IQR increase in PM2.5 (1.05, 1.03–1.07), NO2 (1.04, 1.02–1.06), NOx (1.03, 1.02–1.05), and RC1 (1.04, 1.02–1.06). An increased risk of all-cause mortality was associated with an IQR increase in PM2.5 (1.02, 1.00–1.04). Restricted cubic spline analyses indicated a monotonic elevating association of PM2.5, NO2, NOx, and RC1 with ESKD incidence. ConclusionsLong-term exposure to PM2.5, NO2, NOx, and their complex was associated with elevated ESKD incidence, even at relatively lower levels of air pollution.

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 &amp;lt;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&amp;lt;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&amp;lt;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&amp;lt;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 &amp; 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 (&amp;gt;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&amp;lt;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&amp;lt;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 (&amp;lt;11%; HR, 5.986; 95% CI, 2.114-16.950 vs. &amp;gt;46%; p&amp;lt;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) &amp;lt;60 ml/min/1.73 m2, and/or urine albumin-creatinine ratio (UACR) &amp;gt;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&amp;lt;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&amp;lt;0.001), female gender (p&amp;lt;0.001), lower GFR (89 (19) vs 91 (17) ml/min/1.73 m2, p&amp;lt;0.001), higher systolic blood pressure (136 (17) vs 135 (17) mmHg, p&amp;lt;0.001), and ischemic heart disease (p&amp;lt;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.