Incident End-stage Kidney Disease Research Articles

Medicare Enrollment and Spending Among Patients Initiating Dialysis After the Affordable Care Act

Medicare finances health care for most US patients with end-stage kidney disease (ESKD), regardless of age. Medicare enrollment may have slowed for patients with incident ESKD who gained access to new private insurance options with the 2014 passage of the Affordable Care Act (ACA) and introduction of the ACA Marketplace. To describe trends in public and private insurance coverage and dialysis spending among patients with incident ESKD from 2012 to 2017. This serial cross-sectional study included patients 18 to 64 years old in Colorado who were not enrolled in Medicare at dialysis initiation. Data analysis was conducted from May to August 2023. Introduction of the ACA Marketplace in 2014. Medicare, Medicaid, or private insurance enrollment in the first year after dialysis initiation, and dialysis spending by insurance type. Of 2005 patients included in the sample, 1416 (70.6%) were 45 to 64 years old, and 1259 (62.8%) were male. A lower proportion of patients with incident ESKD starting dialysis were newly enrolled in Medicare in the years following the ACA (361 of 713 [50.6%]) compared to 2 years prior (420 of 595 [70.6%]). Unadjusted rates of switching from Medicaid to Medicare 1 year after dialysis initiation decreased 14.3 percentage points over time (68.9% in 2012-2013 vs 58.3% and 54.6% in 2014-2015 and 2016-2017, respectively). Unadjusted rates of switching from private insurance to Medicare 1 year after dialysis initiation decreased by 22.3 percentage points (68.1% in 2012-2013 vs 52.2% and 45.8% in 2014-2015 and 2016-2017, respectively). Over the entire 2012 to 2017 period, quarterly dialysis spending in the first year of dialysis among patients with private insurance was higher than among those with Medicare coverage ($26 351-$29 781 vs $10 039-$12 741). This cross-sectional study demonstrates that lower Medicare enrollment rates over time among those initiating dialysis may be inducing higher social spending. This finding raises concerns about the effectiveness of Medicare policies and federal leverage to improve access, outcomes, and value of dialysis care.

Incremental hemodialysis transition in veterans and nonveterans with kidney failure.

Initiation of hemodialysis treatment with a thrice-weekly prescription is currently the standard of care irrespective of patients' residual kidney function (RKF), comorbidities, and preferences. Each year ∼12 000 Veterans with advanced kidney disease progress to end-stage kidney disease (ESKD) requiring dialysis and comprise greater than 10% of the US incident ESKD population. Dialysis is costly and is associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first year of treatment. Evidence suggests an incremental dialysis transition using twice-weekly hemodialysis provides various benefits, including more dialysis-free time, longer RKF preservation, less vascular access damage, and lower patient burden. Pragmatic studies are needed to inform the efficacy and safety of incremental hemodialysis as a personalized dialysis regimen, and could inform its consideration as a conservation strategy during times of supply shortages. Broadly implementing twice-weekly hemodialysis could also potentially allow more Veterans to receive care within VA-based dialysis units. The VA IncHVets Trial is a pragmatic, multicenter, randomized controlled trial comparing the efficacy and safety of twice-weekly incremental vs. thrice-weekly hemodialysis among Veterans transitioning to ESKD. Further research is needed to determine whether incremental hemodialysis is well tolerated, effective, and facilitates a more favorable transition to dialysis.

Elevated risk of end-stage kidney disease in stroke patients: A population-based observational study.

Estimating the incidence of end-stage kidney disease (ESKD) in stroke survivors is important to assess and predict clinical course, improve post-stroke quality of life, and ultimately reduce health burden. Our objective was to assess the risk of ESKD in patients compared to a matched stroke-free control cohort. A nationwide retrospective cohort study was conducted in 315,326 stroke subjects and 390,781 matched stroke-free control subjects. Health examination results and claims data were collected from the Korean National Health Insurance Service during 2010-2018. Cox proportional hazard models were used to assess the risk of ESKD in the stroke cohort. During a mean follow-up period of 4.3 years, the incidence of ESKD was 1.83 per 100,000 person-years in the stroke cohort versus 0.57 per 100,000 person-years in the control cohort. The stroke cohort exhibited a significantly higher risk of developing ESKD compared to the matched control, with an adjusted hazard ratio (aHR) of 1.79 (95% confidence interval (CI) = 1.67-1.93). Stroke survivors were associated with a higher risk of developing ESKD, regardless of the severity of disability (aHRs of 1.93, 95% CI = 1.69-2.21 for severe disability; 1.71, 95% CI = 1.41-2.07 for mild disability; and 1.78, 95% CI = 1.65-1.92 for no disability), compared to the matching control cohort. The elevated risk was observed in both hemorrhagic stroke (aHR = 1.96, 95% CI = 1.73-2.23) and ischemic stroke (aHR = 1.75, 95% CI = 1.62-1.89). This study demonstrates that stroke patients have a significantly higher risk of incident ESKD. This highlights the need for heightened clinical awareness and improved monitoring of kidney function in this population.

Clinical biomarker-based biological ageing and the risk of adverse outcomes in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) show features of premature ageing. We aimed to evaluate the association between biological ageing and adverse outcomes, including end-stage kidney disease (ESKD), cardiovascular diseases (CVD) and all-cause mortality, in patients with CKD. 23435 participants with CKD and free of related adverse outcomes at baseline from the UK Biobank were included. Leukocyte telomere length (LTL) was measured by quantitative polymerase chain reaction assay. Clinical biomarker-based biological ages were quantified using Klemera-Doubal method biological age (KDM-BA) and PhenoAge algorithms. During a median follow-up of 12years, 3417 incident CVD, 383 incident ESKD and 3195 all-cause mortality were recorded. Per SD increment of KDM-BA acceleration was associated with a 56% [95% confidence interval (CI): 41%-73%], 26% (95% CI: 21%-31%) and 39% (95% CI: 34%-44%) increase in the risk of incident ESKD, incident CVD and all-cause mortality, respectively. Similar results were found for PhenoAge acceleration. LTL (per SD increment) was inversely associated with the risk of incident CVD [hazard ratio (HR): 0.96, 95% CI: 0.92-0.99] and all-cause mortality (HR: 0.94, 95% CI: 0.91-0.98) and was not significantly associated with the risk of incident ESKD (HR: 0.96, 95% CI: 0.86-1.06). Adding KDM-BA acceleration or PhenoAge acceleration, but not LTL, to the traditional validated clinical prediction models significantly improved the predictive performance for incident ESKD, all-cause mortality and CVD. In patients with CKD, both KDM-BA acceleration and PhenoAge acceleration were associated with an increased risk of ESKD, CVD and all-cause mortality, and KDM-BA or PhenoAge may be a better predictor on adverse outcomes than LTL.

An increasing trend of overweight and obesity in the Japanese incident end-stage kidney disease population.

The global prevalence of overweight/obesity has been rising, and this trend is apparent in US and European incident end-stage kidney disease (ESKD) populations. We aimed to examine temporal trends in the prevalence of overweight/obesity and underweight among adult incident ESKD patients in Japan by year of dialysis initiation between 2006 and 2019 in comparison with those observed in the Japanese adult population during the same period. Using data from the Japanese Society of Dialysis Therapy Renal Data Registry and the National Health and Nutrition Survey, the sex-specific prevalence of overweight/obesity and that of underweight (BMI ≥ 25 kg/m2 and <18.5 kg/m2, respectively) were calculated, adjusted for age according to the 2019 Population Census via the direct method. Average annual percentage changes (AAPCs) and corresponding 95% confidence intervals (CIs) were calculated to examine trends. From 2006 to 2019, the age-adjusted prevalence of overweight/obesity in the incident ESKD population increased for males (AAPC 3.36 [95% CI, 2.70 to 4.09]) and females (AAPC 2.86 [95% CI, 1.65 to 4.19]). The age-adjusted prevalence of overweight/obesity in the general population increased for males (AAPC 0.87 [95% CI, 0.26 to 1.42]) but not for females (AAPC 0.01 [95% CI, -0.55 to 0.57]). The age-adjusted prevalence of underweight in the incident ESKD population significantly decreased but was higher than that in the general population for both sexes. An increasing trend of overweight/obesity was observed in the incident ESKD population in Japan. There is a pressing need to address both underweight and overweight/obesity in the incident ESKD population.

Predictive Value of Serum Hepcidin Levels for the Risk of Incident End-Stage Kidney Disease in Patients with Chronic Kidney Disease: The KNOW-CKD

Introduction: Despite the pivotal role of hepcidin in the development of anemia among the patients with chronic kidney disease (CKD), the association between serum hepcidin levels and CKD progression has been never investigated. We here hypothesized that elevation in serum hepcidin levels might be associated with the risk of incident end-stage kidney disease (ESKD) among the patients with pre-dialysis CKD. Methods: A total of 2,109 patients with pre-dialysis CKD at stages 1 to pre-dialysis 5 were categorized into the quartiles by serum hepcidin levels. The study outcome was incident ESKD. The median duration of follow-up was 7.9 years. Results: The analysis of the baseline characteristics revealed that unfavorable clinical features were in general associated with higher serum hepcidin levels. The cumulative incidence of ESKD was significantly differed by serum hepcidin levels, with the highest incidence in the 4th quartile (p < 0.001, by log-rank test). Cox regression analysis demonstrated that, compared to the 1st quartile, the risk of incident ESKD is significantly increased in the 4th quartile (adjusted hazard ratio 1.372, 95% confidence interval 1.070–1.759). Penalized spline curve analysis illustrated a linear, positive correlation between serum hepcidin levels and the risk of incident ESKD. Subgroup analyses revealed that the association is significantly more prominent in the patients with advanced CKD (i.e., estimated glomerular filtration rate <45 mL/min/1.73 m2). Conclusion: Elevation in serum hepcidin levels is significantly associated with the risk of incident ESKD among the patients with pre-dialysis CKD.

GLP1R Gene Expression and Kidney Disease Progression

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control. To investigate the association of genetically proxied GLP-1RAs with kidney disease progression. This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024. Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project. The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression. Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status. In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.

Association of pulse pressure with incident end-stage kidney disease according to histopathological kidney findings in patients with diabetic nephropathy.

Diabetic patients as well as the elderly are known to have high pulse pressure (PP), but there are few studies on how microangiopathy and macroangiopathy are involved in its mechanism. In this study, we examined the association between PP and atherosclerotic lesions by vessel size in kidney biopsy tissue and examined how PP is associated with kidney prognosis. This retrospective observational study included 408 patients with biopsy-proven diabetic nephropathy at Nara Medical University Hospital. Exposure of interest was PP measured at kidney biopsy. Outcome variable was kidney failure with replacement therapy (KFRT). Cox proportional hazards and competing risk regression models with all-cause mortality as a competing event were used to examine these associations. A total of 408 patients were divided into tertiles based on PP (mmHg): Tertile 1 (reference), <51; Tertile 2, 51-64; and Tertile 3, >64. Among the 408 patients, 99 developed KFRT during a median follow-up period of 6.7 years. Higher PP was independently associated with higher incidences of KFRT (hazard ratio [95% confidence interval] for Tertile 3 vs. Tertile 1; 2.07 [1.05-4.09]. In histological lesions, PP was strongly associated with glomerular lesions, tubulointerstitial lesions, and arteriolar hyalinosis (all ps for trend <0.001), but not with intimal thickening (p for trend = 0.714). PP was significantly associated with diabetic glomerular/tubulointerstitial lesions and arteriolar hyalinosis but not with intimal thickening at the time of kidney biopsy and was also significantly associated with subsequent KFRT in patients with diabetic nephropathy.

Setting reasonable goals for kidney transplant referral among dialysis facilities

BackgroundDetermining whether a patient is eligible for kidney transplantation is complex. In this study, we estimate what proportion of patients with end-stage kidney disease (ESKD) might have been suitable candidates for kidney transplantation but were not referred.MethodsWe identified 43,952 people initiating dialysis for kidney failure between 2012 and 2017 in the states of Georgia, North Carolina, or South Carolina from the United States Renal Data System and linked to the Early-Steps to Transplant Access Registry to obtain data on referral and waitlisting up until December 2020. We identified ‘good transplant candidates’ as those who were waitlisted within 2-years of referral, among all patients referred within 1-year of dialysis initiation. Using propensity score cut-offs, logistic regression, and area under the curve (AUC), we then estimated the proportion of individuals who may have been good transplant candidates, but were not referred.ResultsOverall, 42.6% of incident dialysis patients were referred within one year and among them, 32.9% were waitlisted within 2 years of referral. Our model had reasonably good discrimination for identifying good transplant candidates with an AUC of 0.70 (95%CI 0.69–0.71), sensitivity of 0.68 and specificity of 0.61. Overall, 25% of individuals not referred for transplant may have been ‘good’ transplant candidates. Adding these patients to the existing 18,725 referred patients would increase the proportion of incident ESKD patients being referred within one year from 42.6% to 57.2% (a ~ 14.6% increase).ConclusionsIn this study, we show that a significant proportion of potentially good transplant candidates are not being referred for transplant. A ~ 14% increase in the proportion of patients being referred from dialysis facilities is both a meaningful and realistic goal and could lead to more qualified patients being referred and subsequently waitlisted for a lifesaving transplant.

A Novel Kidney Failure Prediction Model in Individuals with CKD: Impact of Serum Bilirubin Levels.

Predicting the progression of chronic kidney disease (CKD) to end-stage kidney disease (ESKD) is crucial for improving patient outcomes. To reveal the highly predictive activity of serum bilirubin levels for the progression of CKD to ESKD, and to develop and validate a novel ESKD prediction model incorporating serum bilirubin levels. We assessed the relative importance of 20 candidate predictors for ESKD, including serum bilirubin levels, in a CKD cohort (15< eGFR <60 mL/min/1.73 m2), and subsequently developed a prediction model using the selected variables. The development cohort comprised 4,103 individuals with CKD who underwent follow-up at Kyushu University Hospital, Japan, from 2008 to 2018. The primary outcome was incident ESKD, defined as an eGFR <15 mL/min/1.73 m2, chronic dialysis, or renal transplantation. The mean follow-up time was 7.0 ± 4.2 years, during which 489 individuals (11.9%) progressed to ESKD. The Cox proportional hazard model selected eGFR, serum bilirubin, proteinuria, age, diabetes, gender, hypertension, serum albumin, and hemoglobin in order of their importance. The predictive performance of the model was optimized by incorporating these 9 variables in discrimination evaluated by time-dependent area under the curve (AUC). This model also demonstrated excellent calibration. Additionally, this model exhibited excellent predictive performance in both discrimination (2-year AUC: 0.943, 5-year AUC: 0.935) and calibration in a validation cohort (n=2,799). Serum bilirubin levels were strong predictors for the progression of CKD to ESKD. Our novel model that incorporates serum bilirubin levels could accurately predict ESKD in individuals with CKD.

Incident heart failure and the subsequent risk of progression to end stage kidney disease in individuals with type 2 diabetes

BackgroundDiabetic kidney disease is an established risk factor for heart failure. However, the impact of incident heart failure on the subsequent risk of renal failure has not been systematically assessed in diabetic population. We sought to study the risk of progression to end stage kidney disease (ESKD) after incident heart failure in Asian patients with type 2 diabetes.MethodsIn this prospective cohort study, 1985 outpatients with type 2 diabetes from a regional hospital and a primary care facility in Singapore were followed for a median of 8.6 (interquartile range 6.2–9.6) years. ESKD was defined as a composite of progression to sustained eGFR below 15 ml/min/1.73m2, maintenance dialysis or renal death, whichever occurred first.Results180 incident heart failure events and 181 incident ESKD events were identified during follow-up. Of 181 ESKD events, 38 (21%) occurred after incident heart failure. Compared to those did not progress to ESKD after incident heart failure (n = 142), participants who progressed to ESKD after heart failure occurrence were younger, had higher HbA1c and higher urine albumin-to-creatinine ratio at baseline. The excess risk of ESKD manifested immediately after heart failure occurrence, persisted for two years and was moderated thereafter. Cox regression suggested that, compared to counterparts with no heart failure event, participants with heart failure occurrence had 9.6 (95% CI 5.0- 18.3) fold increased risk for incident ESKD after adjustment for baseline cardio-renal risk factors including eGFR and albuminuria. It appeared that heart failure with preserved ejection fraction had a higher risk for ESKD as compared to those with reduced ejection fraction (adjusted HR 13.7 [6.3–29.5] versus 6.5 [2.3–18.6]).ConclusionIncident heart failure impinges a high risk for progression to ESKD in individuals with type 2 diabetes. Our data highlight the need for intensive surveillance of kidney function after incident heart failure, especially within the first two years after heart failure diagnosis.

A prospective, randomized, multicenter, open‐label trial comparing survival in subjects receiving peritoneal dialysis or conventional in‐center hemodialysis

AbstractBackgroundPeritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear.MethodsWe conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25.ResultsA total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment.ConclusionsPD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality.Trial registrationRegistered at ClinicalTrials.gov (NCT01413074).

#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.

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

The 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. To examine the characteristics and clinical outcomes of patients with pregnancy-related ESKD and to investigate associations between pre-ESKD nephrology care and outcomes. This 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. Pregnancy-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. Multivariable 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. A 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). In 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.