Rurality of patient residence and access to transplantation among children with kidney failure in the United States.

BACKGROUND: Residence in rural areas is often a barrier to health care access. To date, differences in access to kidney transplantation among children who reside in rural and micropolitan areas of the US have not been explored. METHODS: A retrospective cohort study of children < 18 years who developed kidney failure between 2000 and 2019 according to the United States Renal Data System (USRDS). We examined the association between rurality of patient residence and time to living and/or deceased donor kidney transplantation (primary outcomes) and waitlist registration (secondary outcome) using Fine-Gray models. RESULTS: We included 18,530 children, of whom 14,175 (76.5%) received a kidney transplant (39.8% from a living and 60.2% from a deceased donor). Residence in micropolitan (subhazard ratio (SHR) 1.16; 95% CI 1.06-1.27) and rural (SHR 1.18; 95% CI 1.06-1.3) areas was associated with better access to living donor transplantation compared with residence in metropolitan areas. There was no statistically significant association between residence in micropolitan (SHR, 0.95; 95%CI 0.88-1.03) and rural (SHR, 0.94; 95%CI 0.86-1.03) areas compared with metropolitan areas in the access of children to deceased donor transplantation. There was also no difference in the time to waitlist registration comparing micropolitan (SHR 1.04; 95%CI 0.98-1.10) and rural (SHR 1.05; 95% CI 0.98-1.13) versus metropolitan areas. CONCLUSIONS: In children with kidney failure, residence in rural and micropolitan areas was associated with better access to living donor transplantation and similar access to deceased donor transplantation compared with residence in metropolitan areas.

Association Between Dialysis Facility Ownership and Mortality Risk in Children With Kidney Failure.

Importance: In adults, treatment at profit dialysis facilities has been associated with a higher risk of death. Objective: To determine whether profit status of dialysis facilities is associated with the risk of death in children with kidney failure treated with dialysis and whether any such association is mediated by differences in access to transplant. Design, Setting, and Participants: This retrospective cohort study reviewed US Renal Data System records of 15 359 children who began receiving dialysis for kidney failure between January 1, 2000, and December 31, 2019, in US dialysis facilities. The data analysis was performed between May 2, 2022, and June 15, 2023. Exposure: Time-updated profit status of dialysis facilities. Main Outcomes and Measures: Adjusted Fine-Gray models were used to determine the association of time-updated profit status of dialysis facilities with risk of death, treating kidney transplant as a competing risk. Cox proportional hazards regression models were also used to determine time-updated profit status with risk of death regardless of transplant status. Results: The final cohort included 8465 boys (55.3%) and 6832 girls (44.7%) (median [IQR] age, 12 [3-15] years). During a median follow-up of 1.4 (IQR, 0.6-2.7) years, with censoring at transplant, the incidence of death was higher at profit vs nonprofit facilities (7.03 vs 4.06 per 100 person-years, respectively). Children treated at profit facilities had a 2.07-fold (95% CI, 1.83-2.35) higher risk of death compared with children at nonprofit facilities in adjusted analyses accounting for the competing risk of transplant. When follow-up was extended regardless of transplant status, the risk of death remained higher for children treated in profit facilities (hazard ratio, 1.47; 95% CI, 1.35-1.61). Lower access to transplant in profit facilities mediated 67% of the association between facility profit status and risk of death (95% CI, 45%-100%). Conclusions and Relevance: Given the higher risk of death associated with profit dialysis facilities that is partially mediated by lower access to transplant, the study's findings indicate a need to identify root causes and targeted interventions that can improve mortality outcomes for children treated in these facilities.

Intensive BP Control in Patients with CKD and Risk for Adverse Outcomes.

SIGNIFICANCE STATEMENT: Although most guidelines recommend tightly controlling BP in patients with CKD, individuals with advanced kidney disease or severe albuminuria were not well-represented in trials examining the effect of this intervention on kidney outcomes. To examine the effect of intensive BP control on the risk of kidney outcomes in patients with CKD, the authors pooled individual-level data from seven trials. They found that overall, intensive BP control was associated with a 13% lower, but not significant, risk of a kidney outcome. However, the intervention's effect on the kidney outcome differed depending on baseline eGFR. Data from this pooled analysis suggested a benefit of intensive BP control in delaying KRT onset in patients with stages 4-5 CKD, but not necessarily in those with stage 3 CKD. BACKGROUND: The effect of intensive BP lowering (to systolic BP of <120 mm Hg) on the risk of kidney failure requiring KRT remains unclear in patients with advanced CKD. Such patients were not well represented in trials evaluating intensive BP control. METHODS: To examine the effect of intensive BP lowering on KRT risk-or when not possible, trial-defined kidney outcomes-we pooled individual-level data from seven trials that included patients with eGFR<60 ml/min per 1.73 m 2 . We performed prespecified subgroup analyses to evaluate the effect of intensive BP control by baseline albuminuria and eGFR (CKD stages 4-5 versus stage 3). RESULTS: Of 5823 trial participants, 526 developed the kidney outcome and 382 died. Overall, intensive (versus usual) BP control was associated with a lower risk of kidney outcome and death in unadjusted analyses but these findings did not achieve statistical significance. However, the intervention's effect on the kidney outcome differed depending on baseline eGFR ( P interaction=0.05). By intention-to-treat analysis, intensive (versus usual) BP control was associated with a 20% lower risk of the primary kidney outcome in those with CKD GFR stages 4-5, but not in CKD GFR stage 3. There was no interaction between intensive BP control and the severity of albuminuria for kidney outcomes. CONCLUSIONS: Data from this pooled analysis of seven trials suggest a benefit of intensive BP control in delaying KRT onset in patients with stages 4-5 CKD but not necessarily with stage 3 CKD. These findings suggest no evidence of harm from intensive BP control, but also point to the need for future trials of BP targets focused on populations with advanced kidney disease. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.

Association Between Dialysis Facility Ownership and Access to the Waiting List and Transplant in Pediatric Patients With End-stage Kidney Disease in the US.

Importance: Care of adults at profit vs nonprofit dialysis facilities has been associated with lower access to transplant. Whether profit status is associated with transplant access for pediatric patients with end-stage kidney disease is unknown. Objective: To determine whether profit status of dialysis facilities is associated with placement on the kidney transplant waiting list or receipt of kidney transplant among pediatric patients receiving maintenance dialysis. Design, Setting, and Participants: This retrospective cohort study reviewed the US Renal Data System records of 13 333 patients younger than 18 years who started dialysis from 2000 through 2018 in US dialysis facilities (followed up through June 30, 2019). Exposures: Time-updated profit status of dialysis facilities. Main Outcomes and Measures: Cox models, adjusted for clinical and demographic factors, were used to examine time to wait-listing and receipt of kidney transplant by profit status of dialysis facilities. Results: A total of 13 333 pediatric patients who started receiving maintenance dialysis were included in the analysis (median age, 12 years [IQR, 3-15 years]; 6054 females [45%]; 3321 non-Hispanic Black patients [25%]; 3695 Hispanic patients [28%]). During a median follow-up of 0.87 years (IQR, 0.39-1.85 years), the incidence of wait-listing was lower at profit facilities than at nonprofit facilities, 36.2 vs 49.8 per 100 person-years, respectively (absolute risk difference, -13.6 (95% CI, -15.4 to -11.8 per 100 person-years; adjusted hazard ratio [HR] for wait-listing at profit vs nonprofit facilities, 0.79; 95% CI, 0.75-0.83). During a median follow-up of 1.52 years (IQR, 0.75-2.87 years), the incidence of kidney transplant (living or deceased donor) was also lower at profit facilities than at nonprofit facilities, 21.5 vs 31.3 per 100 person-years, respectively; absolute risk difference, -9.8 (95% CI, -10.9 to -8.6 per 100 person-years) adjusted HR for kidney transplant at profit vs nonprofit facilities, 0.71 (95% CI, 0.67-0.74). Conclusions and Relevance: Among a cohort of pediatric patients receiving dialysis in the US from 2000 through 2018, profit facility status was associated with longer time to wait-listing and longer time to kidney transplant.

Bariatric surgery prior to transplantation and risk of early hospital re-admission, graft failure, or death following kidney transplantation.

Bariatric surgery has been shown to be safe in the dialysis population. Whether bariatric surgery before kidney transplantation influences posttransplant outcomes has not been examined nationally. We included severely obese (BMI >35) dialysis patients between 18 and 70 years who received a kidney transplant according to the US Renal Data System. We determined the association between history of bariatric surgery and risk of 30-day readmission, graft failure, or death after transplantation using multivariable logistic, Fine-Gray, and Cox models. We included 12 573 patients, of whom 503 (4%) received bariatric surgery before transplantation. Median age at transplant was 53 years; 42% were women. Overall, history of bariatric surgery was not statistically significantly associated with graft failure (HR 1.02; 95% CI 0.77-1.35) or death (HR 1.10; 95% CI 0.84-1.45). However, sleeve gastrectomy (vs. no bariatric surgery) was associated with lower risk of graft failure (HR 0.39; 95% CI 0.16-0.95). In conclusion, history of bariatric surgery prior to kidney transplantation was not associated with allograft or patient survival, but findings varied by surgery type. Sleeve gastrectomy was associated with better graft survival and should be considered in severely obese transplant candidates receiving dialysis.

Recovery of kidney function after dialysis initiation in children and adults in the US: A retrospective study of United States Renal Data System data.

BACKGROUND: Little is known about factors associated with recovery of kidney function-and return to dialysis independence-or temporal trends in recovery after starting outpatient dialysis in the United States. Understanding the characteristics of individuals who may have the potential to recover kidney function may promote better recognition of such events. The goal of this study was to determine factors associated with recovery of kidney function in children compared with adults starting dialysis in the US. METHODS AND FINDINGS: We determined factors associated with recovery of kidney function-defined as survival and discontinuation of dialysis for ≥90-day period-in children versus adults who started maintenance dialysis between 1996 and 2015 according to the United States Renal Data System (USRDS) followed through 2016 in a retrospective cohort study. We also examined temporal trends in recovery rates over the last 2 decades in this cohort. Among 1,968,253 individuals included for study, the mean age was 62.6 ± 15.8 years, and 44% were female. Overall, 4% of adults (83,302/1,953,881) and 4% of children (547/14,372) starting dialysis in the outpatient setting recovered kidney function within 1 year. Among those who recovered, the median time to recovery was 73 days (interquartile range [IQR] 43-131) in adults and 100 days (IQR 56-189) in children. Accounting for the competing risk of death, children were less likely to recover kidney function compared with adults (sub-hazard ratio [sub-HR] 0.81; 95% CI 0.74-0.89, p-value <0.001; point estimates <1 indicating increased risk for a negative outcome). Non-Hispanic black (NHB) adults were less likely to recover compared with non-Hispanic white (NHW) adults, but these racial differences were not observed in children. Of note, a steady increase in the incidence of recovery of kidney function was noted initially in adults and children between 1996 and 2010, but this trend declined thereafter. The diagnoses associated with the highest recovery rates of recovery were acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) in both adults and children, where 25%-40% of patients recovered kidney function depending on the calendar year of dialysis initiation. Limitations to our study include the potential for residual confounding to be present given the observational nature of our data. CONCLUSIONS: In this study, we observed that discontinuation of outpatient dialysis due to recovery occurred in 4% of patients with end-stage kidney disease (ESKD) and was more common among those with ATN or AIN as the cause of their kidney disease. While recovery rates rose initially, they declined starting in 2010. Additional studies are needed to understand how to best recognize and promote recovery in patients whose potential to discontinue dialysis is high in the outpatient setting.

Sex Disparity in Deceased-Donor Kidney Transplant Access by Cause of Kidney Disease.

BACKGROUND AND OBJECTIVES: Women with kidney failure have lower access to kidney transplantation compared with men, but the magnitude of this disparity may not be uniform across all kidney diseases. We hypothesized that the attributed cause of kidney failure may modify the magnitude of the disparities in transplant access by sex. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective cohort study of adults who developed kidney failure between 2005 and 2017 according to the United States Renal Data System. We used adjusted Cox models to examine the association between sex and either access to waitlist registration or deceased-donor kidney transplantation, and tested for interaction between sex and the attributed cause of kidney failure using adjusted models. RESULTS: Among a total of 1,478,037 patients, 271,111 were registered on the waitlist and 89,574 underwent deceased-donor transplantation. The rate of waitlisting was 6.5 per 100 person-years in women and 8.3 per 100 person-years for men. In adjusted analysis, women had lower access to the waitlist (hazard ratio, 0.89; 95% confidence interval, 0.89 to 0.90) and to deceased-donor transplantation after waitlisting (hazard ratio, 0.96; 95% confidence interval, 0.94 to 0.98). However, there was an interaction between sex and attributed cause of kidney disease in adjusted models (P<0.001). Women with kidney failure due to type 2 diabetes had 27% lower access to the kidney transplant waitlist (hazard ratio, 0.73; 95% confidence interval, 0.72 to 0.74) and 11% lower access to deceased-donor transplantation after waitlisting compared with men (hazard ratio, 0.89; 95% confidence interval, 0.86 to 0.92). In contrast, sex disparities in access to either the waitlist or transplantation were not observed in kidney failure secondary to cystic disease. CONCLUSIONS: The disparity in transplant access by sex is not consistent across all causes of kidney failure. Lower deceased-donor transplantation rates in women compared with men are especially notable among patients with kidney failure attributed to diabetes.

Weighing the waitlist: Weight changes and access to kidney transplantation among obese candidates.

High body mass index is a known barrier to access to kidney transplantation in patients with end-stage kidney disease. The extent to which weight and weight changes affect access to transplantation among obese candidates differentially by race/ethnicity has received little attention. We included 10 221 obese patients waitlisted for kidney transplantation prior to end-stage kidney disease onset between 1995-2015. We used multinomial logistic regression models to examine the association between race/ethnicity and annualized change in body mass index (defined as stable [-2 to 2 kg/m2/year], loss [>2 kg/m2/year] or gain [>2 kg/m2/year]). We then used Fine-Gray models to examine the association between weight changes and access to living or deceased donor transplantation by race/ethnicity, accounting for the competing risk of death. Overall, 29% of the cohort lost weight and 7% gained weight; 46% received a transplant. Non-Hispanic blacks had a 24% (95% CI 1.12-1.38) higher odds of weight loss and 22% lower odds of weight gain (95% CI 0.64-0.95) compared with non-Hispanic whites. Hispanics did not differ from whites in their odds of weight loss or weight gain. Overall, weight gain was associated with lower access to transplantation (HR 0.88 [95% CI 0.79-0.99]) compared with maintenance of stable weight, but weight loss was not associated with better access to transplantation (HR 0.96 [95% CI 0.90-1.02]), although this relation differed by baseline body mass index and for recipients of living versus deceased donor organs. For example, weight loss was associated with improved access to living donor transplantation (HR 1.24 [95% CI 1.07-1.44]) in whites but not in blacks or Hispanics. In a cohort of obese patients waitlisted before dialysis, blacks were more likely to lose weight and less likely to gain weight compared with whites. Weight loss was only associated with improved access to living donor transplantation among whites. Further studies are needed to understand the reasons for the observed associations.

Trends in Cardiovascular Mortality Among a Cohort of Children and Young Adults Starting Dialysis in 1995 to 2015.

Importance: Survival of patients receiving dialysis has improved during the last 2 decades. However, few studies have examined temporal trends in the attributed causes of death (especially cardiovascular-related) in young populations. Objective: To determine temporal trends and risk of cause-specific mortality (ie, cardiovascular and infectious) for children and young adults receiving dialysis. Design, Setting, and Participants: This retrospective cohort study examined the records of children and young adults (aged <30 years) starting dialysis between 1995 and 2015 according to the United States Renal Data System database. Analyses were performed between June 2019 and June 2020. Fine-Gray models were used to examine trends in risk of different cardiovascular-related deaths. Models were adjusted for age, sex, race, neighborhood income, cause of end-stage kidney disease, insurance type, and comorbidities. Analyses were performed separately for children (ie, age <18 years) and young adults (between ages 18 and 30 years). Follow-up was censored at death or administratively, and transplantation was treated as a competing event. Exposures: Calendar year. Main Outcomes and Measures: Cardiovascular cause-specific mortality. Results: A total of 80 189 individuals (median [interquartile range] age, 24 [19-28] years; 36 259 [45.2%] female, 29 508 [36.8%] Black, and 15 516 [19.3%] Hispanic white) started dialysis and 16 179 experienced death during a median (interquartile range) of 14.3 (14.0-14.7) years of follow-up. Overall, 40.2% of deaths were from cardiovascular-related causes (6505 of 16 179 patients). In adjusted analysis, risk of cardiovascular-related death was stable initially but became statistically significantly lower after 2006 (vs 1995) in those starting dialysis as either children (subhazard ratio [SHR], 0.74; 95% CI, 0.55-1.00) or adults (SHR, 0.90; 95% CI, 0.83-0.98). Risk of sudden cardiac death improved steadily for all age groups, but to a greater degree in children (SHR, 0.31; 95% CI, 0.20-0.47) vs young adults (SHR, 0.64; 95% CI, 0.56-0.73) comparing 2015 vs 1995. Risk of stroke became statistically significantly lower around 2010 (vs 1995) for children (SHR, 0.40; 95% CI, 0.18-0.88) and young adults (SHR, 0.76; 95% CI, 0.59-0.99). Conclusions and Relevance: In this study, the risk of cardiovascular-related death declined for children and young adults starting dialysis during the last 2 decades, but trends differed depending on age at dialysis initiation and the specific cause of death. Additional studies are needed to improve risk of cardiovascular disease in young populations.

Prognostic Value of Ambulatory Blood Pressure Load in Pediatric CKD.

BACKGROUND AND OBJECTIVES: Elevated BP load is part of the criteria for ambulatory hypertension in pediatric but not adult guidelines. Our objectives were to determine the prevalence of isolated BP load elevation and associated risk with adverse outcomes in children with CKD, and to ascertain whether BP load offers risk discrimination independently or in conjunction with mean ambulatory BPs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 533 children in the CKD in Children (CKiD) Study to determine the prevalence of normotension, isolated BP load elevation (≥25% of all readings elevated but mean BP normal), and ambulatory hypertension. We examined the association between these categories of BP control and adverse outcomes (left ventricular hypertrophy [LVH] or ESKD). We used c-statistics to determine risk discrimination for outcomes by BP load used either independently or in conjunction with other BP parameters. RESULTS: Overall, 23% of the cohort had isolated BP load elevation, but isolated BP load elevation was not statistically significantly associated with LVH in cross-section (odds ratio, 1.8; 95% CI, 0.8 to 4.2) or time to ESKD (hazard ratio, 1.2; 95% CI, 0.7 to 2.0). In unadjusted cross-sectional analysis, every 10% higher systolic BP load was associated with 1.1-times higher odds of LVH (95% CI, 1.0 to 1.3), but discrimination for LVH was poor (c=0.61). In unadjusted longitudinal analysis, every 10% higher systolic BP load was associated with a 1.2-times higher risk of ESKD (95% CI, 1.1 to 1.2), but discrimination for ESKD was also poor (c=0.60). After accounting for mean systolic BP, systolic BP load was not statistically significantly associated with either LVH or ESKD. Findings were similar with diastolic BP load. CONCLUSIONS: BP load does not provide additive value in discriminating outcomes when used independently or in conjunction with mean systolic BP in children with CKD. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_03_11_CPOD10130819.mp3.

Association between BMI changes and mortality risk in children with end-stage renal disease.

BACKGROUND: Few studies have examined how changes in BMI [body mass index] over time associate with risk of adverse outcomes in children receiving renal replacement therapy [RRT]. The objective of this study was to examine the association between annualized changes in BMI and the risk of death in children treated with RRT. METHODS: We performed a retrospective cohort study of 1182 pediatric dialysis and transplant patients in the Pediatric Growth and Development Special Study of the United States Renal Data System. Quintiles of annualized change in BMI z-score (with cutoffs of - 0.50, - 0.13, 0.09, 0.57) were used as the primary predictor, with the middle quintile (- 0.13 to 0.09) serving as the reference category. Cox models were used to examine the association between exposure and death, with time of analysis starting from the second BMI measurement. RESULTS: Median follow-up time to death or censoring was 6 years. Median age was 14.6 years, and 61% of children had a functional graft at cohort entry. There was a U-shaped association between BMI change and mortality risk: a large decline in annualized BMI z-score change (> - 0.50) was associated with an increased risk of death (adjusted hazard ratio [aHR] 1.54 (95% CI 1.17-2.03), p = 0.002). A large increase in annualized BMI z-score change (> 0.57) was also associated with an increased risk of death (aHR 1.44 (95% CI 1.07-1.92), p = 0.02). No interaction was noted between annualized BMI change and initial treatment modality (dialysis or transplant, p = 0.15). CONCLUSIONS: Maintenance of a stable BMI in pediatric patients receiving RRT may be associated with improved survival.

Magnitude of the Difference Between Clinic and Ambulatory Blood Pressures and Risk of Adverse Outcomes in Patients With Chronic Kidney Disease.

Background Obtaining 24-hour ambulatory blood pressure ( BP ) is recommended for the detection of masked or white-coat hypertension. Our objective was to determine whether the magnitude of the difference between ambulatory and clinic BP s has prognostic implications. Methods and Results We included 610 participants of the AASK (African American Study of Kidney Disease and Hypertension) Cohort Study who had clinic and ambulatory BPs performed in close proximity in time. We used Cox models to determine the association between the absolute systolic BP ( SBP ) difference between clinic and awake ambulatory BPs (primary predictor) and death and end-stage renal disease. Of 610 AASK Cohort Study participants, 200 (32.8%) died during a median follow-up of 9.9 years; 178 (29.2%) developed end-stage renal disease. There was a U-shaped association between the clinic and ambulatory SBP difference with risk of death, but not end-stage renal disease. A 5- to <10-mm Hg higher clinic versus awake SBP (white-coat effect) was associated with a trend toward higher (adjusted) mortality risk (adjusted hazard ratio, 1.84; 95% CI, 0.94-3.56) compared with a 0- to <5-mm Hg clinic-awake SBP difference (reference group). A ≥10-mm Hg clinic-awake SBP difference was associated with even higher mortality risk (adjusted hazard ratio, 2.31; 95% CI, 1.27-4.22). A ≥-5-mm Hg clinic-awake SBP difference was also associated with higher mortality (adjusted hazard ratio, 1.82; 95% CI, 1.05-3.15) compared with the reference group. Conclusions A U-shaped association exists between the magnitude of the difference between clinic and ambulatory SBP and mortality. Higher clinic versus ambulatory BPs (as in white-coat effect) may be associated with higher risk of death in black patients with chronic kidney disease.

Psychoactive Medications and Adverse Outcomes among Older Adults Receiving Hemodialysis.

BACKGROUND: Guidelines recommend avoidance of several psychoactive medications such as hypnotics in older adults due to their adverse effects. Older patients on hemodialysis may be particularly vulnerable to complications related to use of these agents, but only limited data are available about the risks in this population. OBJECTIVES: To evaluate the association between the use of psychoactive medications and time to first emergency department visit or hospitalization for altered mental status, fall, and fracture among older patients receiving hemodialysis. DESIGN: Observational cohort study. SETTING: National registry of patients receiving hemodialysis (US Renal Data System). PARTICIPANTS: A total of 60 007 adults 65 years or older receiving hemodialysis with Medicare Part D coverage in 2011. MEASUREMENTS: The predictors were use of sedative-hypnotics and anticholinergic antidepressants (modeled as separate time-varying exposures). The outcomes were time to first emergency department visit or hospitalization for altered mental status, fall, and fracture (modeled separately). RESULTS: Overall, 17% and 6% used sedative-hypnotics and anticholinergic antidepressants, respectively, in 2011. In multivariable-adjusted Cox regression, anticholinergic antidepressant use was associated with a 25%, 27%, and 39% higher hazard of altered mental status, fall, and fracture, respectively, compared with no use. Use of sedative-hypnotics was not associated with adverse outcomes. CONCLUSION: Anticholinergic antidepressants were associated with adverse outcomes in older hemodialysis patients, and alternative treatments should be considered. Sedative-hypnotics were not associated with the risks evaluated in this study, but further investigation of the harms of this class of agents is warranted before their recommendation as a treatment option for insomnia in this population. J Am Geriatr Soc 67:449-454, 2019.

Muscle Relaxant Use Among Hemodialysis Patients: Prevalence, Clinical Indications, and Adverse Outcomes.

RATIONALE & OBJECTIVE: Muscle relaxants are often used to treat musculoskeletal pain or cramping, which are commonly experienced by hemodialysis patients. However, the extent to which muscle relaxants are prescribed in this population and the risks associated with their use have not been characterized. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 140,899 Medicare-covered adults receiving hemodialysis in 2011, identified in the US Renal Data System. EXPOSURE: Time-varying muscle relaxant exposure. OUTCOMES: Primary outcomes were time to first emergency department visit or hospitalization for altered mental status, fall, or fracture. Secondary outcomes were death and composites of death with each of the primary outcomes. ANALYTICAL APPROACH: Multivariable Cox regression analysis. RESULTS: 10% of patients received muscle relaxants in 2011. 11%, 6%, 3%, and 13% had an episode of altered mental status, fall, fracture, and death, respectively. Muscle relaxant use was associated with higher risk for altered mental status (HR, 1.39; 95% CI, 1.29-1.51) and fall (HR, 1.18; 95% CI, 1.05-1.33) compared to no use. Muscle relaxant use was not statistically significantly associated with higher risk for fracture (HR, 1.17; 95% CI, 0.98-1.39). Muscle relaxant use was associated with lower hazard of death (HR, 0.85; 95% CI, 0.76-0.94). However, hazards were higher for altered mental status or death (HR, 1.17; 95% CI, 1.10-1.25), fall or death (HR, 1.14; 95% CI, 1.06-1.22), and fracture or death (HR, 1.10; 95% CI, 1.01-1.20). LIMITATIONS: A causal association between muscle relaxant use and outcomes cannot be inferred, and residual confounding cannot be excluded. Exposure and outcomes were ascertained using administrative claims. CONCLUSIONS: Muscle relaxant use was common in hemodialysis patients and associated with altered mental status and falls. We could not rule out a clinically meaningful association between muscle relaxant use and fracture. The lower risk for death with muscle relaxants may have been the result of residual confounding. Future research to define the appropriate use of muscle relaxants in this population is warranted.

Sex Disparities in Risk of Mortality Among Children With ESRD.

RATIONALE & OBJECTIVE: In the general population, girls have lower mortality risk compared with boys. However, few studies have focused on sex differences in survival and in access to kidney transplantation among children with end-stage kidney disease. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Children aged 2 to 19 years registered in the US Renal Data System who started renal replacement therapy (RRT) between 1995 and 2011. PREDICTOR: Study participant sex. OUTCOME: Time to death and time to kidney transplantation. ANALYTICAL APPROACH: We used adjusted Cox models to examine the association between sex and all-cause mortality. We used Fine-Gray models to examine the association between sex and kidney transplantation accounting for the competing risk for death. RESULTS: We included 14,024 children, of whom 1,880 died during a median 7.1 years of follow-up. In adjusted analyses, the HR for death was higher for girls (HR, 1.36; 95% CI, 1.25-1.50) than boys. When we further adjusted our survival models for transplantation as a time-dependent covariate, the hazard rate of death in girls was partially attenuated but remained statistically significantly higher than that for boys (HR, 1.28; 95% CI, 1.17-1.41). Girls were also less likely to receive a kidney transplant than boys (adjusted subdistribution HR, 0.91; 95% CI, 0.88-0.95) in analyses treating death as a competing risk. LIMITATIONS: Lack of data for disease course before the onset of RRT and observational study data. CONCLUSIONS: The mortality rate was substantially higher for girls than for boys treated with RRT. Access to transplantation was lower for girls than boys, but differences in transplantation access accounted for only a small proportion of the survival differences by sex.

Frailty Among Patients Receiving Hemodialysis: Evolution of Components and Associations With Mortality.

BACKGROUND: Understanding how components of frailty change over time and how they can be modeled as time-dependent predictors of mortality could lead to better risk prediction in the dialysis population. METHODS: We measured frailty at baseline, 12 months, and 24 months among 727 patients receiving hemodialysis in Northern California and Atlanta. We examined the likelihood of meeting frailty components (weight loss, exhaustion, low physical activity, weak grip strength, and slow gait speed) as a function of time in logistic regression analysis and association of frailty components with mortality in time-updated multivariable Cox models. RESULTS: Physical activity and gait speed declined, exhaustion and grip strength did not change, and the odds of meeting the weight loss criterion declined with time. All five components were associated with higher mortality in multivariable analyses, but gait speed was the strongest individual predictor. All frailty components except physical inactivity were independently associated with mortality when all five components were included in the same model. The number of frailty components met was associated with mortality in a gradient that ranged from a hazard ratio of 2.73 for one component to 10.07 for five components met; the model including all five components was the best model based on Akaike information criterion. CONCLUSIONS: Measurement of all frailty components was necessary for optimal mortality prediction, and the number of components met was strongly associated with mortality in this cohort.

Childhood Seizures After Phototherapy.

: media-1vid110.1542/5804915133001PEDS-VA_2018-0648Video Abstract BACKGROUND AND OBJECTIVES: In a recent Danish study, researchers found an increased risk of childhood epilepsy after phototherapy but only in boys. We investigated this association in a Kaiser Permanente Northern California cohort. METHODS: From 499 642 infants born at ≥35 weeks' gestation in 1995-2011 followed for ≥60 days, we excluded 1773 that exceeded exchange transfusion thresholds and 1237 with seizure diagnoses at <60 days. We ascertained phototherapy, covariates, and outcomes from electronic records and existing databases. Our primary outcome was ≥1 encounter with a seizure diagnosis plus ≥1 prescription for an antiepileptic drug. We used Cox and Poisson models to adjust for bilirubin levels and other confounding variables. RESULTS: A total of 37 683 (7.6%) infants received any phototherapy. The mean (SD) follow-up time was 8.1 (5.2) years. The crude incidence rate per 1000 person-years of the primary outcome was 1.24 among phototherapy-exposed children and 0.76 among those unexposed (rate ratio: 1.63; 95% confidence interval [CI]: 1.44 to 1.85). The adjusted hazard ratio (aHR) was 1.22 (95% CI: 1.05 to 1.42; P = .009). Boys were at higher risk of seizures overall (aHR = 1.18; 95% CI: 1.10 to 1.27) and had a higher aHR for phototherapy (1.33; 95% CI: 1.10 to 1.61) than girls (1.07; 95% CI: 0.84 to 1.37), although effect modification by sex was not statistically significant (P = .17). The adjusted 10-year excess risks per 1000 were 2.4 (95% CI: 0.6 to 4.1) overall, 3.7 (95% CI: 1.2 to 6.1) in boys, and 0.8 (95% CI: -1.7 to 3.2) in girls. CONCLUSIONS: Phototherapy in newborns is associated with a small increased risk of childhood seizures, even after adjusting for bilirubin values, and the risk is more significant in boys.

Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis Patients.

Background Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking.Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0-100, >100-200, >200-300, and >300 mg) and pregabalin (>0-100 and >100 mg).Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%-41%) and fall (26%-30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively.Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.