Characteristics and clinical outcomes of patients with kidney failure of unknown aetiology from ANZDATA registry.

INTRODUCTION: Kidney failure of unknown aetiology (uESKD) is also heavily location dependent varying between 27% in Egypt to 54% in Aguacalientes, Mexico. There is limited information about the characteristics of people with uESKD in Australia and New Zealand, as well as their clinical outcomes on kidney replacement therapy. METHODS: Data on people commencing kidney replacement therapy 1989-2021 were received from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Primary exposure was cause of kidney failure-uESKD or non-uESKD (known-ESKD). Primary outcome was mortality. Secondary outcome was kidney transplantation. Dialysis and transplant cohorts were analysed separately. Cox Proportional Hazards Regression models were used to evaluate correlations between cause of kidney failure and mortality risk. Subgroup analyses were completed to compare mortality risk in people with uESKD to those with diabetic nephropathy, autosomal dominant polycystic kidney disease (ADPKD), glomerular disease and other kidney diseases. RESULTS: This study included 60,448 people on dialysis and 20,859 transplant recipients. 1-year, 3-year and 5-year mortality rates in people with uESKD on dialysis were 31.6%, 58.7% and 77.2%, respectively. 1-year, 3-year and 5-year mortality rates in transplant recipients with uESKD were 2.8%, 13.8% and 24.0%, respectively. People with uESKD on dialysis had a higher mortality risk compared to those without uESKD on univariable and multivariable analyses (adjusted hazard ratio [AHR] 1.10, 95% CI 1.06-1.16, p<0.001). Transplant recipients with uESKD have a higher mortality risk compared to those without uESKD on univariable and multivariable analyses (AHR 1.17, 95% CI 1.01-1.35, p<0.05). People with uESKD had similar likelihood of kidney transplantation compared to people with known-ESKD. CONCLUSION: People with uESKD on kidney replacement therapy have higher mortality risk compared to people with other kidney diseases. Further studies are required to identify contributing factors to these findings.

Foot and Ankle Care by Podiatrists and Amputations in Patients With Diabetes and Kidney Failure.

Importance: Patients with kidney failure have an increased risk of diabetes-related foot complications. The benefit of regular foot and ankle care in this at-risk population is unknown. Objective: To investigate foot and ankle care by podiatrists and the outcomes of diabetic foot ulcers (DFUs) in patients with kidney failure. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries with type 2 diabetes receiving dialysis who had a new DFU diagnosis. The analysis of the calendar year 2016 to 2019 data from the United States Renal Data System was performed on June 15, 2023, with subsequent updates on December 11, 2023. Exposures: Foot and ankle care by podiatrists during 3 months prior to DFU diagnosis. Main Outcomes and Measures: The outcomes were a composite of death and/or major amputation, as well as major amputation alone. Kaplan-Meier analysis was used to estimate 2 to 3 years of amputation-free survival. Foot and ankle care by podiatrists and the composite outcome was examined using inverse probability-weighted Cox regression, while competing risk regression models were used for the analysis of amputation alone. Results: Among the 14 935 adult patients with kidney failure and a new DFU (mean [SD] age, 59.3 [12.7] years; 35.4% aged ≥65 years; 8284 men [55.4%]; Asian, 2.7%; Black/African American, 35.0%; Hispanic, 17.7%; White, 58.5%), 18.4% (n = 2736) received care by podiatrists in the 3 months before index DFU diagnosis. These patients were older, more likely to be male, and have more comorbidities than those without prior podiatrist visits. Over a mean (SD) 13.5 (12.0)-month follow-up, 70% of those with podiatric care experienced death and/or major amputation, compared with 74% in the nonpodiatric group. Survival probabilities at 36 months were 26.3% vs 22.8% (P < .001, unadjusted Kaplan-Meier survival analysis). In multivariate regression analysis, foot and ankle care was associated with an 11% lower likelihood of death and/or amputation (hazard ratio [HR], 0.89 95% CI, 0.84-0.93) and a 9% lower likelihood of major amputation (above or below knee) (HR, 0.91; 95% CI, 0.84-0.99) than those who did not. Conclusions and Relevance: The findings of this study suggest that patients with kidney failure at risk for DFUs who receive foot and ankle care from podiatrists may be associated with a reduced likelihood of diabetes-related amputations.

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Multicentre external validation of the prognostic model kidney failure risk equation in patients with CKD stages 3 and 4 in Peru: a retrospective cohort study.

OBJECTIVES: To externally validate the four-variable kidney failure risk equation (KFRE) in the Peruvian population for predicting kidney failure at 2 and 5 years. DESIGN: A retrospective cohort study. SETTING: 17 primary care centres from the Health's Social Security of Peru. PARTICIPANTS: Patients older than 18 years, diagnosed with chronic kidney disease stage 3a-3b-4 and 3b-4, between January 2013 and December 2017. Patients were followed until they developed kidney failure, died, were lost, or ended the study (31 December 2019), whichever came first. PRIMARY AND SECONDARY OUTCOME MEASURES: Performance of the KFRE model was assessed based on discrimination and calibration measures considering the competing risk of death. RESULTS: We included 7519 patients in stages 3a-4 and 2798 patients in stages 3b-4. The estimated cumulative incidence of kidney failure, accounting for competing event of death, at 2 years and 5 years, was 1.52% and 3.37% in stages 3a-4 and 3.15% and 6.86% in stages 3b-4. KFRE discrimination at 2 and 5 years was high, with time-dependent area under the curve and C-index >0.8 for all populations. Regarding calibration in-the-large, the observed to expected ratio and the calibration intercept indicated that KFRE underestimates the overall risk at 2 years and overestimates it at 5 years in all populations. CONCLUSIONS: The four-variable KFRE models have good discrimination but poor calibration in the Peruvian population. The model underestimates the risk of kidney failure in the short term and overestimates it in the long term. Further research should focus on updating or recalibrating the KFRE model to better predict kidney failure in the Peruvian context before recommending its use in clinical practice.

Effects of Low-Osmolar Contrast Media on Long-Term Renal Impairment After Coronary Angiography: Iohexol Versus Iopromide.

To investigate the long-term effects of 2 commonly used low-osmolar contrast media, iohexol and iopromide, on renal function and survival in patients who underwent coronary angiography. A total of 14,141 cardiology patients from 2006 to 2013 were recruited, of whom 1,793 patients (679 patients on iohexol and 1,114 on iopromide) were evaluated for long-term renal impairment and 5,410 patients (1,679 patients on iohexol and 3,731 on iopromide) were admitted for survival analyses spanning as long as 15 years. Univariate and multivariate logistic regression were used to explore the risk factors for long-term renal impairment. Cox proportional hazard regression was used to investigate the risk factors affecting survival. Propensity score matching and inverse probability of treatment weighting were applied to balance the baseline clinical characteristics. Patients receiving iohexol demonstrated a greater occurrence of renal impairment compared with those who received iopromide. Such difference remained consistent both before and after propensity score matching or inverse probability of treatment weighting, with a statistical significance of p <0.05. Among clinical variables, receiving contrast-enhanced contrast tomography/magnetic resonance imaging during follow-up, antihypertensive medication usage, presence of proteinuria, and anemia were identified as risk factors for long-term renal impairment (p = 0.041, 0.049, 0.006, and 0.029, respectively). During survival analyses, the difference was insignificant after propensity score matching and inverse probability of treatment weighting. In conclusion, administration of iohexol was more likely to induce long-term renal impairment than iopromide, particularly among patients diagnosed with anemia and proteinuria and those taking antihypertensive medication and with additional contrast exposure. The all-cause mortality, however, showed no significant difference between iohexol and iopromide administration.

Association of mild kidney dysfunction with diastolic dysfunction and heart failure with preserved ejection fraction.

AIMS: We aim to investigate the association between kidney dysfunction and left ventricular diastolic dysfunction parameters and heart failure with preserved ejection fraction (HFpEF) and whether this is sex-specific. METHODS AND RESULTS: We included participants from the HELPFul observational study. Outpatient clinical care data, including echocardiography, and an expert panel judgement on HFpEF was collected. Estimated glomerular filtration rate (eGFR) was calculated by creatinine and cystatin C without race. The association between eGFR with E/e', left ventricular mass index, relative wall thickness, and stage C/D heart failure was tested by multivariable adjusted regression models, stratified by sex, reporting odds ratios and 95% confidence intervals (95% confidence interval). We analysed 880 participants, mean age 62.9 (standard deviation: 9.3) years, 69% female. Four hundred six participants had mild (37.6%) kidney dysfunction (eGFR: 60-89 mL/min/1.73 m2 ) or moderate (8.5%) kidney dysfunction (eGFR: 30-59 mL/min/1.73 m2 ). HFpEF was significantly more prevalent in participants with mild and moderate kidney dysfunction (10.3% and 16.0%, respectively) than participants with normal kidney function (3.4%). A lower kidney function was associated with higher E/e' and higher relative wall thickness values. Participants with moderate kidney dysfunction had a higher likelihood of American College of Cardiology/American Heart Association stage C/D HF (odds ratio: 2.07, 95% confidence interval: 1.23, 3.49) than participants with normal kidney functions. CONCLUSIONS: Both mild and moderate kidney dysfunction are independently associated with left ventricular diastolic dysfunction parameters and HFpEF. This association is independent of sex and strongest for moderate kidney dysfunction. Considering mild-to-moderate kidney dysfunction as risk factor for HFpEF may help identify high-risk groups benefiting most from early intervention.

Using Relative Survival to Estimate the Burden of Kidney Failure.

RATIONALE & OBJECTIVE: Estimates of mortality from kidney failure are misleading because the mortality from kidney failure is inseparable from the mortality attributed to comorbid conditions. We sought to develop an alternative method to reduce the bias in estimating mortality due to kidney failure using life table methods. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: Using data from the US Renal Data System and the Medicare 5% sample, we identified an incident cohort of patients, age 66+, who first had kidney failure in 2009 and a similar general population cohort without kidney failure. EXPOSURE: Kidney failure. OUTCOME: Death. ANALYTICAL APPROACH: We created comorbidity, age, sex, race, and year-specific life tables to estimate relative survival of patients with incident kidney failure and to attain an estimate of excess kidney failure-related deaths. Estimates were compared with those based on standard life tables (not adjusted for comorbidity). RESULTS: The analysis included 31,944 adults with kidney failure with a mean age of 77±7 years. The 5-year relative survival was 31% using standard life tables (adjusted for age, sex, race, and year) versus 36% using life tables also adjusted for comorbidities. Compared with other chronic diseases, patients with kidney failure have among the lowest relative survival. Patients with incident kidney failure ages 66-70 and 76-80 have a survival comparable to adults without kidney failure roughly 86-90 and 91-95 years old, respectively. LIMITATIONS: Relative survival estimates can be improved by narrowing the specificity of the covariates collected (eg, disease severity and ethnicity). CONCLUSIONS: Estimates of survival relative to a matched general population partition the mortality due to kidney failure from other causes of death. Results highlight the immense burden of kidney failure on mortality and the importance of disease prevention efforts among older adults. PLAIN-LANGUAGE SUMMARY: Estimates of death due to kidney failure can be misleading because death information from kidney failure is intertwined with death due to aging and other chronic diseases. Life tables are an old method, commonly used by actuaries and demographers to describe the life expectancy of a population. We developed life tables specific to a patient's age, sex, year, race, and comorbidity. Survival is derived from the life tables as the percentage of patients who are still alive in a specified period. By comparing survival of patients with kidney failure to the survival of people from the general population, we estimate that patients with kidney failure have one-third the chance of survival in 5 years compared with people with similar demographics and comorbidity but without kidney failure. The importance of this measure is that it provides a quantifiable estimate of the immense mortality burden of kidney failure.

Risk of kidney failure in patients with systemic sclerosis: a nationwide population-based study.

OBJECTIVE: Data from a decade ago have shown that patients with systemic sclerosis (SSc) have a higher risk of kidney failure than the general population. However, as the incidence of kidney failure due to SSc has been declining, the comparative risk of kidney failure between patients with SSc and the general population could have changed over time. We investigated the risk of kidney failure in patients with SSc compared with the general population, up to more recent years. METHODS: This was a nationwide population-based study using the Korean National Health Insurance Service database. Patients with claims data for SSc between 2010 and 2017 (n=2591) and 1:5 age-matched and sex-matched controls (n=12 955) were selected. The index date was the earliest date of claim for SSc between 2010 and 2017. The follow-up duration was from the index date to 2019. The adjusted HRs (aHRs) and 95% CI for kidney failure were estimated using multivariable Cox proportional hazard models. RESULTS: Over 5.2±2.6 years, the incidence rates of kidney failure in patients with SSc and controls were 2.88 and 0.35 per 1000 person-years, respectively. Patients with SSc had a significantly higher risk of kidney failure than controls (aHR=7.244, 95% CI=4.256 to 12.329). The effect size was larger in patients diagnosed with SSc between 2014 and 2017 (aHR=9.754, 95% CI=3.254 to 29.235) than in those diagnosed before 2010 (aHR=6.568, 95% CI=2.711 to 15.571) or between 2010 and 2013 (aHR=6.553, 95% CI=2.721 to 15.781). CONCLUSION: The risk of kidney failure remains higher in patients with SSc than in the general population.

Social deprivation and kidney failure due to an undiagnosed nephropathy.

BACKGROUND: In France, kidney diseases of undetermined origin account for 5%-20% of all causes of end-stage kidney disease. We investigated the impact of social disadvantage on the lack of aetiological diagnosis of nephropathies. METHODS: Data from patients who started dialysis in France between 1 January 2017 and 30 June 2018 were extracted from the French Renal Epidemiology and Information Network registry. The social deprivation of each individual was estimated by the European Deprivation Index (EDI) defined by the patient's address. Logistic regression was used to perform mediation analysis to study the potential association between social deprivation and unknown nephropathy. RESULTS: Of the 7218 patients included, 1263 (17.5%) had unknown kidney disease. A total of 394 (31.4%) patients in the unknown kidney disease belonged to the most deprived quintile of the EDI [fifth quintile (Q5)], vs 1636 (27.5%) patients in the known kidney disease group. In the multivariate analysis, unknown kidney disease was associated with Q5 (odds ratio 1.40, 95% confidence interval 1.12-1.74, P = .003). Mediation analysis did not identify any variables (e.g. obesity, initiation of dialysis in emergency, number of visits to the general practitioner and nephrologist before initiation of dialysis, date of first nephrology consultation) that mediated the association between social deprivation and nephropathy of unknown origin. CONCLUSIONS: Our results show that, compared with nondeprived subjects, individuals experiencing social deprivation have a higher risk of unknown nephropathy at dialysis initiation. However, mediation analysis did not identify any variables that explained the association between social deprivation and nephropathy of unknown origin.

Prevalence and Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease with Renal Insufficiency in Overweight/Obese Adults.

INTRODUCTION: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) with renal insufficiency in recent years and the association between MAFLD and renal insufficiency are not entirely clear, especially in overweight/obesity. The aim of this study was to analyze the prevalence and risk factors of MAFLD with renal insufficiency in overweight/obese adults. METHODS: Individuals who attended checkup at the Second Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2021 were included. The prevalence of MAFLD with renal insufficiency (estimated glomerular filtration rate ≤90 mL/min/1.73 m2) in overweight/obesity was estimated. Propensity score-matched analysis, univariate and multivariate analyses were used to determine the risk factors for MAFLD with renal insufficiency. RESULTS: From 2016 to 2021, the prevalence of MAFLD in overweight/obesity reached its highest of 44.7% in 2017 and its lowest of 36.9% in 2018; and 33.9% in 2021 and 21.8% in 2019 is the highest and lowest prevalence of MAFLD with renal insufficiency, respectively. MAFLD was more common in men, old individuals, and persons with a higher body mass index (BMI) and was characterized by significant renal insufficiency. MAFLD with renal insufficiency was more common in women, old individuals, and persons with a higher BMI and was characterized by significant metabolic dysfunction and liver fibrosis. Multivariable analysis showed that BMI, uric acid, and fibrosis (evaluated with noninvasive liver fibrosis score [fibrosis-4]) were independent risk factors for MAFLD with renal insufficiency. CONCLUSION: The prevalence of MAFLD with renal insufficiency in overweight/obese adults is quite high in the last 5 years. BMI, uric acid, and fibrosis are independent risk factors for MAFLD with renal insufficiency.

Cardiac Troponin, Kidney Function, Heart Failure and Mortality After Myocardial Infarction in Patients With and Without Kidney Impairment.

Cardiac troponins (cTn) are routinely measured for the diagnosis and prognosis of myocardial infarction (MI). The relation between troponin levels, estimated glomerular filtration rate (eGFR), postinfarction heart failure (HF), and mortality is unclear in patients with kidney impairment. This is a retrospective, cross-sectional study of patients presenting to the Emergency Department at a single tertiary center. Participants presenting with confirmed type I MI from January 1, 2019, to December 31, 2021, were analyzed from the Myocardial Ischemia National Audit Project database. Main outcomes were acute HF, measured using Killip class, and inpatient mortality. Peak cardiac troponin T (cTnT) level was a secondary outcome. Data on 2,815 patients (67±14 years, 28% female) were analyzed. Ordinal logistic regression analysis was used to test for predictors of increasing Killip class. Binary logistic regression was used to test for predictors of inpatient mortality. Analysis of a sub-sample matched for age and diabetes mellitus status showed increased mortality in patients with eGFR <60 ml/min/1.73 m2 (12.2% vs 4.4%, p <0.001). Multivariate predictors of acute HF included log-transformed peak cTnT, eGFR, body mass index (BMI), and diabetes mellitus status. Multivariate predictors of inpatient mortality included log-transformed peak cTnT, eGFR, age, BMI, and Killip class 3/4. On multivariate analysis, eGFR, ST-elevation MI diagnosis, BMI, male gender, diabetes mellitus status, and hypertension were all predictive of peak cTnT after MI. In conclusion, peak cTnT level and eGFR at presentation after MI are independent predictors of acute HF severity and death in patients with and without kidney impairment.

A Predictive Model for Kidney Failure After Nephrectomy for Localized Kidney Cancer: The Kidney Cancer Risk Equation.

RATIONALE & OBJECTIVE: Nephrectomy is the mainstay of treatment for individuals with localized kidney cancer. However, surgery can potentially result in the loss of kidney function or in kidney failure requiring dialysis/kidney transplantation. There are currently no clinical tools available to preoperatively identify which patients are at risk of kidney failure over the long term. Our study developed and validated a prediction equation for kidney failure after nephrectomy for localized kidney cancer. STUDY DESIGN: Population-level cohort study. SETTING & PARTICIPANTS: Adults (n=1,026) from Manitoba, Canada, with non-metastatic kidney cancer diagnosed between January 1, 2004, and December 31, 2016, who were treated with either a partial or radical nephrectomy and had at least 1 estimated glomerular filtration rate (eGFR) measurement before and after nephrectomy. A validation cohort included individuals in Ontario (n=12,043) with a diagnosis of localized kidney cancer between October 1, 2008, and September 30, 2018, who received a partial or radical nephrectomy and had at least 1 eGFR measurement before and after surgery. NEW PREDICTORS & ESTABLISHED PREDICTORS: Age, sex, eGFR, urinary albumin-creatinine ratio, history of diabetes mellitus, and nephrectomy type (partial/radical). OUTCOME: The primary outcome was a composite of dialysis, transplantation, or an eGFR<15mL/min/1.73m2 during the follow-up period. ANALYTICAL APPROACH: Cox proportional hazards regression models evaluated for accuracy using area under the receiver operating characteristic curve (AUC), Brier scores, calibration plots, and continuous net reclassification improvement. We also implemented decision curve analysis. Models developed in the Manitoba cohort were validated in the Ontario cohort. RESULTS: In the development cohort, 10.3% reached kidney failure after nephrectomy. The final model resulted in a 5-year area under the curve of 0.85 (95% CI, 0.78-0.92) in the development cohort and 0.86 (95% CI, 0.84-0.88) in the validation cohort. LIMITATIONS: Further external validation needed in diverse cohorts. CONCLUSIONS: Our externally validated model can be easily applied in clinical practice to inform preoperative discussions about kidney failure risk in patients facing surgical options for localized kidney cancer. PLAIN-LANGUAGE SUMMARY: Patients with localized kidney cancer often experience a lot of worry about whether their kidney function will remain stable or will decline if they choose to undergo surgery for treatment. To help patients make an informed treatment decision, we developed a simple equation that incorporates 6 easily accessible pieces of patient information to predict the risk of reaching kidney failure 5 years after kidney cancer surgery. We expect that this tool has the potential to inform patient-centered discussions tailored around individualized risk, helping ensure that patients receive the most appropriate risk-based care.

Outcome of COVID-19 and tolerance of Remdesivir in patients with renal failure: a single center experience from Pakistan.

INTRODUCTION: Coronavirus disease-19 (COVID-19) is known to cause severe disease in chronic kidney disease and maintenance dialysis patients. We aim to report the outcome of COVID-19 and the adverse effects of Remdesivir (RDV) in patients with renal failure. METHODOLOGY: A retrospective observational study included all admitted patients with COVID-19 who received Remdesivir. Clinical characteristics and outcomes were compared in patients with renal failure (RF) and non-renal failure (NRF). We also evaluated RDV-associated nephrotoxicity and observed renal functions during antiviral treatment. RESULTS: A total of 142 patients received RDV, 38 (26.76%) in RF and 104 (73.23%) in the non-RF group. The median absolute lymphocyte count was low while C-reactive protein, ferritin, and D-dimer were significantly high on admission in the RF group. A significant number of patients in the RF group required ICU admission (58% vs. 35% p = 0.01) and expired (29% vs. 12.5 p = 0.02). Among survivors and non-survivors in the RF group, raised inflammatory markers and low platelet count on presentation were significantly associated with high mortality. Median serum creatinine (mg/dL) was 0.88 on admission, remained at 0.85 in the NRF group, and improved from 4.59 to 3.87 (mg/dL) after receiving five days of RDV in the RF group. CONCLUSIONS: COVID-19 in renal failure has a high risk for ICU admissions leading to increased mortality. Multiple comorbidities and raised inflammatory markers are predictors of poor outcomes. We observed no significant drug-related adverse effects, and none of our patients required discontinuation of RDV due to worsening renal function.

Adverse Clinical Outcomes and Associated Predictors in Rivaroxaban-Treated Atrial Fibrillation Patients With Renal Impairment.

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.

Structural Racism, Historical Redlining, and Incidence of Kidney Failure in US Cities, 2012-2019.

SIGNIFICANCE STATEMENT: Residing in neighborhoods designated as grade D (hazardous) by the Home Owners' Loan Corporation (HOLC) under historical redlining-a discriminatory housing policy beginning in the 1930s-has been associated with present-day adverse health outcomes such as diabetes mortality. Historical redlining might underlie conditions in present-day neighborhoods that contribute to inequitable rates of kidney failure incidence, particularly for Black individuals, but its association with kidney disease is unknown. The authors found that among adults with incident kidney failure living in 141 metropolitan areas, residence in a historically redlined neighborhood rated grade D was associated with significantly higher kidney failure incidence rates compared with residence in a redlined grade A (best) neighborhood. These findings suggest that historical racist policies continue to affect current-day racial inequities in kidney health. BACKGROUND: Historical redlining was a 1930s federally sponsored housing policy that permitted the Home Owners' Loan Corporation (HOLC) to develop color-coded maps and grade neighborhoods' mortgage lending risk on the basis of characteristics that included racial makeup. This practice has been associated with present-day health disparities. Racial inequities in kidney disease-particularly for Black individuals-have been linked to residential segregation and other structural inequities. METHODS: Using a registry of people with incident kidney failure and digitized HOLC maps, we examined the association between residence in a historically redlined US census tract (CT) with a historical HOLC grade of D or hazardous) and present-day annual CT-level incidence of kidney failure incidence among adults in 141 US metropolitan areas, in 2012 through 2019. RESULTS: Age-adjusted and sex-adjusted kidney failure incidence rates were significantly higher in CTs with a historical HOLC grade D compared with CTs with a historical HOLC grade of A or best (mean, 740.7 per million versus 326.5 per million, respectively, a difference of 414.1 per million). Compared with national averages of all adults in our sample, rates of kidney failure incidence were higher for Black adults in our study sample, irrespective of CT HOLC grade. Age-adjusted and sex-adjusted incidence rates for Black persons in CTs with a HOLC grade D were significantly higher than for Black persons residing in HOLC grade A CTs (mean, 1227.1 per million versus 1030.5 per million, respectively [a difference of 196.6 per million]). CONCLUSIONS: Historical redlining is associated with present-day disparities in kidney failure incidence, demonstrating the legacy of historical racist policies on contemporary racial inequities in kidney health. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_08_24_JASN0000000000000165.mp3.

Long-term social and professional outcomes in adults after pediatric kidney failure.

BACKGROUND: Little is known about the long-term social and professional outcomes in adults after pediatric kidney replacement therapy (KRT). In this study, we described social and professional outcomes of adults after kidney failure during childhood and compared these outcomes with the general population. METHODS: We sent a questionnaire to 143 individuals registered in the Swiss Pediatric Renal Registry (SPRR) with KRT starting before the age of 18 years. In the questionnaire, we assessed social (partner relationship, living situation, having children) and professional (education, employment) outcomes. Logistic regression models adjusted for age at study and sex were used to compare outcomes with a representative sample of the Swiss general population and to identify socio-demographic and clinical characteristics associated with adverse outcomes. RESULTS: Our study included 80 patients (response rate 56%) with a mean age of 39 years (range 19-63). Compared to the general population, study participants were more likely to not have a partner (OR = 3.7, 95%CI 2.3-5.9), live alone (OR = 2.5, 95%CI 1.5-4.1), not have children (OR = 6.8, 95%CI 3.3-14.0), and be unemployed (OR = 3.9, 95%CI 1.8-8.6). No differences were found for educational achievement (p = 0.876). Participants on dialysis at time of study were more often unemployed compared to transplanted participants (OR = 5.0, 95%CI 1.2-21.4) and participants with > 1 kidney transplantation more often had a lower education (OR = 3.2, 95%CI 1.0-10.2). CONCLUSIONS: Adults after pediatric kidney failure are at risk to experience adverse social and professional outcomes. Increased awareness among healthcare professionals and additional psycho-social support could contribute to mitigate those risks. A higher resolution version of the Graphical abstract is available as Supplementary information.

Defunctioning loop ileostomy in anterior resection for rectal cancer and subsequent renal failure: nationwide population-based study.

BACKGROUND: Electrolyte disturbances and dehydration are common after anterior resection for rectal cancer with a defunctioning loop ileostomy. High-quality population-based studies on the impact of a defunctioning loop ileostomy on renal failure are lacking. METHODS: This was a nationwide observational study, based on the Swedish Colorectal Cancer Registry of patients undergoing anterior resection for rectal cancer between 2008 and 2016, with follow-up until 2017. Patients with severe co-morbidity, with age greater than 80 years, and with pre-existing renal failure were excluded. Loop ileostomy at index surgery constituted exposure, while a diagnosis of renal failure was the outcome. Acute and chronic events were analysed separately. Inverse probability weighting with adjustment for confounding derived from a causal diagram was employed. Hazards ratios (HRs) with 95 per cent c.i. are reported. RESULTS: A total of 5355 patients were eligible for analysis. At 5-year follow-up, all renal failure events (acute and chronic) were 7.2 per cent and 3.3 per cent in the defunctioning stoma and no stoma groups respectively. In the weighted analysis, a HR of 11.59 (95 per cent c.i. 5.68 to 23.65) for renal failure in ostomates was detected at 1 year, with the largest effect from acute renal failure (HR 24.04 (95 per cent c.i. 8.38 to 68.93)). Later follow-up demonstrated a similar pattern, but with smaller effect sizes. CONCLUSION: Patients having a loop ileostomy in combination with anterior resection for rectal cancer are more likely to have renal failure, especially early after surgery. Strategies are needed, such as careful fluid management protocols, and further research into alternative stoma types or reduction in stoma formation.

Comparative Effectiveness of Rituximab- Versus Cyclophosphamide-Based Remission Induction Strategies in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis for the Risk of Kidney Failure and Mortality.

OBJECTIVE: To compare rituximab- versus cyclophosphamide-based remission induction strategies for the long-term risks of kidney failure and death in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in a real-world cohort. METHODS: We performed a cohort study using the Mass General Brigham AAV Cohort, which includes proteinase 3-ANCA+ and myeloperoxidase (MPO)-ANCA+ AAV patients diagnosed from January 1, 2002 to December 31, 2019. We included cases in which the initial remission induction strategy was based either on rituximab or cyclophosphamide. The primary outcome was the composite outcome of kidney failure or death. We used multivariable Cox proportional hazards models and propensity score-matched analyses to assess the association of rituximab- versus cyclophosphamide-based treatment strategies with the composite outcome of kidney failure or death. RESULTS: Of 595 included patients, 352 patients (~60%) received rituximab-based and 243 patients (~40%) received cyclophosphamide-based regimens. The mean age was 61 years, 58% of patients were female, 70% of patients were MPO-ANCA+, and 69% of patients had renal involvement (median estimated glomerular filtration rate 37.3 ml/minute/1.73 m2 ). There were 133 events at 5 years, and the incidence rates in rituximab- and cyclophosphamide-based regimens were 6.8 and 6.1 per 100 person-years, respectively. The risk of kidney failure or death was similar in both groups in multivariable-adjusted analyses (hazard ratio [HR] 1.03 [95% confidence interval (95% CI) 0.55-1.93]) and in propensity score-matched analyses (HR 1.05 [95% CI 0.55-1.99]) at 5 years. Our findings were similar when outcomes were assessed at 1 and 2 years as well as in subgroups stratified according to renal involvement and severity as well as major organ involvement. CONCLUSION: Rituximab- and cyclophosphamide-based remission induction strategies for AAV are associated with similar risks of kidney failure and death.