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Purpose: Patients treated with radical cystectomy experience a high rate of postoperative complications and frequent hospital readmissions. We sought to explore the utility of the Care Assessment Need (CAN) score, derived from electronic health data, to estimate the risk of these adverse clinical outcomes, thereby aiding patient counseling and informed treatment decision-making. Materials and Methods: We retrospectively examined data from 982 patients with bladder cancer who underwent radical cystectomy between 2013 and 2018 within the national Veterans Health Administration system. We tested for associations between the preoperative CAN score and length of stay, discharge location, and readmission rates. Results: We observed a correlation between higher CAN scores and longer hospital stays (adjusted relative risk = 1.03 [95% CI: 1.02-1.05]). An increased CAN score was also linked to greater odds of discharge to a skilled nursing facility or death (adjusted odds ratio = 1.16 [95% CI: 1.06-1.26]). Furthermore, the score was associated with hospital readmission at both 30 and 90 days postdischarge (adjusted HR = 1.03 [95% CI: 1.00-1.07] and 1.04 [95% CI: 1.00-1.07], respectively). Conclusions: The CAN score is associated with length of hospital stay, discharge to a skilled nursing facility, and readmission within 30 and 90 days after radical cystectomy. These findings highlight the potential of health care systems leveraging electronic health records for automatically calculating multidimensional tools, such as the CAN score, to identify patients at risk of adverse clinical outcomes after radical cystectomy. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is the most common cancer among men in the United States, yet modifiable risk factors remain elusive. In this study, the authors investigated the potential role of agricultural pesticide exposure in prostate cancer incidence and mortality. Methods: For this environment‐wide association study (EWAS), linear regression was used to analyze county‐level associations between the annual use of 295 distinct pesticides (measured in kg per county) and prostate cancer incidence and mortality rates in the contiguous United States. Data were analyzed in two cohorts: 1997–2001 pesticide use with 2011–2015 outcomes (discovery) and 2002–2006 use with 2016–2020 outcomes (replication). The reported effect sizes highlight how a 1‐standard‐deviation increase in log‐transformed pesticide use (kg per county) corresponds to changes in incidence. Analyses were adjusted for county‐level demographics, agricultural data, and multiple testing. Results: Twenty‐two pesticides showed consistent, direct associations with prostate cancer incidence across both cohorts. Of these, four pesticides were also associated with prostate cancer mortality. In the replication cohort, each 1‐standard‐deviation increase in log‐transformed pesticide use corresponded to incidence increases per 100,000 individuals (trifluralin, 6.56 [95% confidence interval (CI), 5.04–8.07]; cloransulam‐methyl, 6.18 [95% CI, 4.06–8.31]; diflufenzopyr, 3.20 [95% CI, 1.09–5.31]; and thiamethoxam, 2.82 [95% CI, 1.14–4.50]). Limitations included ecological study design, potential unmeasured confounding, and lack of individual‐level exposure data. Conclusions: The results of this study suggest a potential link between certain pesticides and increased prostate cancer incidence and mortality. These findings warrant further investigation of these specific pesticides to confirm their role in prostate cancer risk and to develop potential public health interventions. For this environment‐wide association study, the authors assessed potential associations between pesticide exposure and prostate cancer outcomes in US counties, identifying 22 pesticides associated with increased prostate cancer incidence and mortality. These findings underline the significance of exploring these associations further to inform public health interventions. [ABSTRACT FROM AUTHOR]

Patients with kidney failure have the option of starting dialysis or continuing medical management. This observational cohort study used a target trial emulation approach to determine the mean survival and number of days at home for adults who start dialysis within 30 days of an eGFR below 12 mL/min/1.73 m 2 compared with those who continue medical management. Visual Abstract. Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure: Patients with kidney failure have the option of starting dialysis or continuing medical management. This observational cohort study used a target trial emulation approach to determine the mean survival and number of days at home for adults who start dialysis within 30 days of an eGFR below 12 mL/min/1.73 m 2 compared with those who continue medical management. Background: For older adults with kidney failure who are not referred for transplant, medical management is an alternative to dialysis. Objective: To compare survival and home time between older adults who started dialysis at an estimated glomerular filtration rate (eGFR) less than 12 mL/min/1.73 m 2 and those who continued medical management. Design: Observational cohort study using target trial emulation. Setting: U.S. Department of Veterans Affairs, 2010 to 2018. Participants: Adults aged 65 years or older with chronic kidney failure and eGFR below 12 mL/min/1.73 m 2 who were not referred for transplant. Intervention: Starting dialysis within 30 days versus continuing medical management. Measurements: Mean survival and number of days at home. Results: Among 20 440 adults (mean age, 77.9 years [SD, 8.8]), the median time to dialysis start was 8.0 days in the group starting dialysis and 3.0 years in the group continuing medical management. Over a 3-year horizon, the group starting dialysis survived 770 days and the group continuing medical management survived 761 days (difference, 9.3 days [95% CI, −17.4 to 30.1 days]). Compared with the group continuing medical management, the group starting dialysis had 13.6 fewer days at home (CI, 7.7 to 20.5 fewer days at home). Compared with the group continuing medical management and forgoing dialysis completely, the group starting dialysis had longer survival by 77.6 days (CI, 62.8 to 91.1 days) and 14.7 fewer days at home (CI, 11.2 to 16.5 fewer days at home). Limitation: Potential for unmeasured confounding due to lack of symptom assessments at eligibility; limited generalizability to women and nonveterans. Conclusion: Older adults starting dialysis when their eGFR fell below 12 mL/min/1.73 m 2 who were not referred for transplant had modest gains in life expectancy and less time at home. Primary Funding Source: U.S. Department of Veterans Affairs and National Institutes of Health. [ABSTRACT FROM AUTHOR]

Aim: To determine the comparative effectiveness regarding major cardiovascular events of glucagon‐like peptide‐1 (GLP‐1) receptor agonists and sodium‐glucose cotransporter‐2 (SGLT‐2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Materials and Methods: We assembled a cohort of commercially insured adult patients with T2DM in the United States (derived from Optum Clinformatics DataMart 2003‐2021) who were new users of GLP‐1 receptor agonists or SGLT‐2 inhibitors. We compared risks of non‐fatal myocardial infarction or stroke in patients with and without CKD, and further categorized by CKD stage: stages G1 or G2 [estimated glomerular filtration rate (eGFR) ≥60 ml/min] and A2 (urine albumin to creatinine ratio 30 to <300 mg/g) or A3 (urine albumin to creatinine ratio ≥300 mg/g), stage G3a (eGFR 45 to <60 ml/min/1.73 m2) and stage G3b (eGFR 30 to <45 ml/min/1.73 m2). We used proportional hazards regression after inverse probability of treatment weighting to compute hazard ratios and 95% confidence intervals. Results: After accounting for the probability of treatment, patients with T2DM and CKD treated with SGLT‐2 inhibitors experienced a 14% lower risk of non‐fatal myocardial infarction or stroke (hazard ratio 0.86, 95% confidence interval 0.78‐0.94) relative to those treated with GLP‐1 receptor agonists. Conclusions: Recognizing the potential for residual confounding, selection bias and immortal time bias, commercially insured patients in the United States with T2DM and CKD treated with SGLT‐2 inhibitors experienced significantly lower risks of non‐fatal myocardial infarction or stroke relative to those treated with GLP‐1 receptor agonists. [ABSTRACT FROM AUTHOR]

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its subtypes, granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (EGPA), frequently present with acute kidney injury and can often lead to kidney failure, even with successful induction therapy. Few contemporary, nationally representative studies have described hospital complications of AAV. Methods: Using data from the 2016–2020 National Inpatient Sample, a nationally representative database, we identified hospitalizations from adults with a new diagnosis of AAV (subtype or unspecified) and an inpatient kidney biopsy during the index hospitalization. We described baseline characteristics, associated inpatient procedures and complications, and compared lengths of stay and costs by geographic region, hospital characteristics, and AAV subtype. Results: We identified an average of 1,329 cases of hospitalized AAV with a concurrent kidney biopsy per year over the 5-year period. More than 50% were not designated as having a specific subtype, likely owing to delays in documentation of histopathology. Kidney involvement was severe as the majority of patients developed acute kidney injury, and the proportion of patients who required inpatient dialysis was approximately 24%. Approximately 20% of patients developed hypoxia. Inpatient plasmapheresis was delivered to 20.4% and 20.6% of patients with GPA and MPA, respectively. There were no clinically meaningful or statistically significant differences in adjusted length of stay or inpatient costs among AAV subtypes. Admission in the Midwest region was associated with shorter hospital stays and lower costs than that in the Northeast, South, or West regions of the USA (adjusted p = 0.007 and <0.001, respectively). Conclusion: AAV with acute kidney involvement remains a challenging, high-risk condition. Maintaining a high index of suspicion and a low threshold for kidney biopsy should help ameliorate short- and long-term complications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypertension frequently accompanies chronic kidney disease (CKD) as etiology and sequela. We examined contemporary trends in hypertension treatment and control in a national sample of adults with CKD. METHODS: We evaluated 5% cross-sectional samples of adults with CKD between 2011 and 2019 in the Veterans Health Administration. We defined CKD as a sustained estimated glomerular filtration rate value <60 mL/min per 1.73 m2 or a urine albumin-to-creatinine ratio =30 mg/g. The main outcomes were blood pressure (BP) control, defined as a systolic BP <140 mmHg and a diastolic BP <90 mmHg based on the mean of monthly BP measurements, and prescriptions for antihypertensive medications. RESULTS: The annual samples ranged between n=22 110 and n=33 039 individuals, with a mean age of 72 years, 96% of whom were men. Between 2011 and 2014, the age-adjusted proportion of adults with controlled BP declined from 78.0% to 72.2% (P value for linear trend, <0.001), reached a nadir of 71.0% in 2015, and then increased to 72.9% by 2019 (P value for linear trend, <0.001). Among adults with BP above goal, the age-adjusted proportion who did not receive antihypertensive treatment increased throughout the decade from 18.8% to 21.6%, and the age-adjusted proportion who received =3 antihypertensive medications decreased from 41.8% to 36.3%. Prescriptions for first-line antihypertensive agents also decreased. CONCLUSIONS: Among adults with CKD treated in the Veterans Health Administration, the proportion with controlled BP declined between 2011 and 2015 followed by a modest increase, coinciding with fewer prescriptions for antihypertensive medications. [ABSTRACT FROM AUTHOR]

Background: Kidney cancer incidence demonstrates significant geographic variation suggesting a role for environmental risk factors. This study sought to evaluate associations between groundwater exposures and kidney cancer incidence. Methods: The authors identified constituents from 18,506 public groundwater wells in all 58 California counties measured in 1996–2010, and obtained county‐level kidney cancer incidence data from the California Cancer Registry for 2003–2017. The authors developed a water‐wide association study (WWAS) platform using XWAS methodology. Three cohorts were created with 5 years of groundwater measurements and 5‐year kidney cancer incidence data. The authors fit Poisson regression models in each cohort to estimate the association between county‐level average constituent concentrations and kidney cancer, adjusting for known risk factors: sex, obesity, smoking prevalence, and socioeconomic status at the county level. Results: Thirteen groundwater constituents met stringent WWAS criteria (a false discovery rate <0.10 in the first cohort, followed by p values <.05 in subsequent cohorts) and were associated with kidney cancer incidence. The seven constituents directly related to kidney cancer incidence (and corresponding standardized incidence ratios) were chlordane (1.06; 95% confidence interval [CI], 1.02–1.10), dieldrin (1.04; 95% CI, 1.01–1.07), 1,2‐dichloropropane (1.04; 95% CI, 1.02–1.05), 2,4,5‐TP (1.03; 95% CI, 1.01–1.05), glyphosate (1.02; 95% CI, 1.01–1.04), endothall (1.02; 95% CI, 1.01–1.03), and carbaryl (1.02; 95% CI, 1.01–1.03). Among the six constituents inversely related to kidney cancer incidence, the standardized incidence ratio furthest from the null was for bromide (0.97; 95% CI, 0.94–0.99). Conclusions: This study identified several groundwater constituents associated with kidney cancer. Public health efforts to reduce the burden of kidney cancer should consider groundwater constituents as environmental exposures that may be associated with the incidence of kidney cancer. This study analyzed 180 groundwater exposures in California and used a water‐wide association study (WWAS) platform, based on XWAS methodology, to identify associations between groundwater exposures and kidney cancer incidence. Results revealed 13 groundwater constituents meeting stringent WWAS criteria, with seven directly linked to increased kidney cancer incidence, suggesting that public health efforts should consider environmental exposures that may be associated with the incidence of kidney cancer. [ABSTRACT FROM AUTHOR]

It has been well established that randomized clinical trials have poor external validity, resulting in findings that may not apply to relevant—or target—populations. When the trial is sampled from the target population, generalizability methods have been proposed to address the applicability of trial findings to target populations. When the trial sample and target populations are distinct, transportability methods may be applied for this purpose. However, generalizability and transportability studies present challenges, particularly around the strength of their conclusions. We review and summarize state-of-the-art methods for translating trial findings to target populations. We additionally provide a novel step-by-step guide to address these challenges, illustrating principles through a published case study. When conducted with rigor, generalizability and transportability studies can play an integral role in regulatory decisions by providing key real-world evidence. [ABSTRACT FROM AUTHOR]

Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24‐hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24‐hour urine citrate excretion (<200, 200–400, and >400 mg/d) and the time to osteoporosis or fracture according to 24‐hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24‐hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03–1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98–1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) vaccination is indicated for all end stage kidney disease patients, including all solid organ transplant candidates. Maintenance of adequate immunity is especially important for immunosuppressed solid organ recipients who are at increased risk for donor or community acquired HBV. The impact of age and immunosuppression on long‐term maintenance of HBV immunity postvaccination has not been fully investigated. Methods: We performed a single‐center retrospective study of 96 kidney transplant recipients, transplanted between July 2012 and December 2020, who had Hepatitis B surface antibody (HBsAb) levels measured pretransplantation and 1‐year posttransplantation. We compared the change in HBsAb levels stratified by patient's age (<45, 45–60, and >60) and by whether or not the patient received lymphocyte depleting induction therapy. Results: Our results demonstrate that HBsAb IgG levels vary by age group, decreased significantly at 1‐year posttransplant (p <.0001) and were significantly lower in the older cohort (p =.03). Among recipients who received rabbit anti‐thymocyte globulin induction (rATG), the log HbsAb levels were significantly lower in the older age group (2.15 in age <45, 1.75 in age 45–60 and 1.47 in age >60, p =.01). Age group (p =.004), recipient HBcAb status (p =.002), and rATG (p =.048) were independently associated with >20% reduction in log HBsAb levels posttransplant. Conclusion: Significant declines in HBsAb levels occur postkidney transplantation, especially in older individuals, thus placing exposed older kidney transplant recipients at greater risk of HBV infection and associated complications. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) is associated with a higher risk for chronic kidney disease. This retrospective cohort study used a target trial emulation approach to evaluate whether parathyroidectomy was associated with a lower incidence of sustained decline in kidney function among adults with PHPT. Visual Abstract. Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism: Primary hyperparathyroidism (PHPT) is associated with a higher risk for chronic kidney disease. This retrospective cohort study used a target trial emulation approach to evaluate whether parathyroidectomy was associated with a lower incidence of sustained decline in kidney function among adults with PHPT. Background: Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m 2. Limited data address the effect of parathyroidectomy on long-term kidney function. Objective: To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management. Design: Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting. Setting: Veterans Health Administration. Patients: Patients with a new biochemical diagnosis of PHPT in 2000 to 2019. Measurements: Sustained decline of at least 50% from pretreatment eGFR. Results: Among 43 697 patients with PHPT (mean age, 66.8 years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9 years. The weighted cumulative incidence of eGFR decline was 5.1% at 5 years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60 years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60 years or older (HR, 1.08 [CI, 0.87 to 1.34]). Limitation: Analyses were done in a predominantly male cohort using observational data. Conclusion: Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions. Primary Funding Source: National Institute on Aging. [ABSTRACT FROM AUTHOR]