Obesogenic Medication Use in End-Stage Kidney Disease and Association With Transplant Listing.

OBJECTIVES: Obesogenic medications are a putative contributor to the obesity epidemic. While 20% of adults take ≥1 obesogenic medication, the proportion in the end-stage kidney disease (ESKD) population-a group enriched for cardiometabolic complications-is unknown. Obesogenic medications may contribute to obesity and hamper weight loss efforts to achieve transplant listing. METHODS: Using 2017-2020 USRDS and Medicare claims, patients were identified as taking obesogenic medications if prescribed anticonvulsants, antidepressants, antidiabetics, anti-inflammatories, antipsychotics, and/or antihypertensives known to cause weight gain for ≥30 days in their first hemodialysis year. Ordinal logistic and Cox regression with inverse probability of treatment weighting were used to quantify obesogenic medications' association with body mass index (BMI) and listing, respectively. RESULTS: Among 271 401 hemodialysis initiates, 63.5% took ≥1 obesogenic medication. For those in underweight, normal weight, overweight, and class I, II, and III categories, 54.3%, 58.4%, 63.1%, 66.5%, 68.6%, and 68.8% took ≥1, respectively. Number of obesogenic medications was associated with increased BMI; use of one was associated with 13% increased odds of higher BMI (aOR [adjusted odds ratio] 1.14; 95%CI: 1.13-1.16; p < 0.001), use of three was associated with a 55% increase (aOR 1.55; 95%CI: 1.53-1.57; p < 0.001). Any use was associated with 6% lower odds of transplant listing (aHR [adjusted hazard ratio] 0.94; 95%CI: 0.92-0.96; p < 0.001). Within each BMI category, obesogenic medication use was associated with lower listing likelihood. CONCLUSIONS: Obesogenic medication use is common in ESKD patients-particularly those with obesity-and is associated with lower listing likelihood. Whenever possible, non-obesogenic alternatives should be chosen for ESKD patients attempting weight loss to achieve transplant listing.

Parathyroidectomy and Cinacalcet Use in Medicare-Insured Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Posttransplant hyperparathyroidism is common, and treatment practices are poorly characterized. The goal of this study was to examine the incidence, associations, and outcomes of posttransplant parathyroidectomy and calcimimetic use in a cohort of Medicare-insured US kidney transplant recipients. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: We used the US Renal Data System to extract demographic, clinical, and prescription data from Medicare Parts A, B, and D-insured patients who received their first kidney transplant in 2007-2013. We excluded patients with pretransplant parathyroidectomy. PREDICTORS: Calendar year of transplantation and pretransplant patient characteristics. OUTCOME: (1) Incidence of and secular trends in parathyroidectomy and cinacalcet use in the 3 years after transplant; (2) 90-day outcomes after posttransplant parathyroidectomy and cinacalcet initiation. ANALYTICAL APPROACH: Temporal trends and pretransplant correlates of parathyroidectomy and cinacalcet use were assessed using proportional hazards models and multivariable Poisson regression, respectively. RESULTS: The inclusion criteria were met by 30,127 patients, of whom 10,707 used cinacalcet before transplant, 551 underwent posttransplant parathyroidectomy, and 5,413 filled≥1 prescription for cinacalcet. The rate of posttransplant parathyroidectomy was stable over time. By contrast, cinacalcet use increased during the period studied. Long dialysis vintage and pretransplant cinacalcet use were strongly associated with posttransplant parathyroidectomy and cinacalcet use. Roughly 1 in 4 patients were hospitalized within 90 days of posttransplant parathyroidectomy, with hypocalcemia-related diagnoses being the most common complication. Parathyroidectomy (vs cinacalcet initiation) was not associated with an increase in acute kidney injury. LIMITATIONS: We lacked access to laboratory data to help assess the severity of secondary/tertiary hyperparathyroidism. The cohort was limited to Medicare beneficiaries. CONCLUSIONS: Almost one-fifth of our study cohort was treated with parathyroidectomy and/or cinacalcet. Further studies are needed to establish the optimal treatment for posttransplant hyperparathyroidism.

Hurricanes and Mortality among Patients Receiving Dialysis.

BACKGROUND: Hurricanes are severe weather events that can disrupt power, water, and transportation systems. These disruptions may be deadly for patients requiring maintenance dialysis. We hypothesized that the mortality risk among patients requiring maintenance dialysis would be increased in the 30 days after a hurricane. METHODS: Patients registered as requiring maintenance dialysis in the United States Renal Data System who initiated treatment between January 1, 1997 and December 31, 2017 in one of 108 hurricane-afflicted counties were followed from dialysis initiation until transplantation, dialysis discontinuation, a move to a nonafflicted county, or death. Hurricane exposure was determined as a tropical cyclone event with peak local wind speeds ≥64 knots in the county of a patient's residence. The risk of death after the hurricane was estimated using time-varying Cox proportional hazards models. RESULTS: The median age of the 187,388 patients was 65 years (IQR, 53-75) and 43.7% were female. There were 27 hurricanes and 105,398 deaths in 529,339 person-years of follow-up on dialysis. In total, 29,849 patients were exposed to at least one hurricane. Hurricane exposure was associated with a significantly higher mortality after adjusting for demographic and socioeconomic covariates (hazard ratio, 1.13; 95% confidence interval, 1.05 to 1.22). The association persisted when adjusting for seasonality. CONCLUSIONS: Patients requiring maintenance dialysis have a higher mortality risk in the 30 days after a hurricane.

Azithromycin use increases the risk of sudden cardiac death in patients with hemodialysis-dependent kidney failure.

Azithromycin is an antibiotic with QT-prolonging potential commonly prescribed to individuals receiving hemodialysis. Hemodialysis patients have a high prevalence of clinical conditions, such as structural heart disease, that can enhance the pro-arrhythmic effects azithromycin, but were excluded from prior investigations evaluating the cardiac safety of azithromycin. Using data from the United States Renal Data System (2007-2017), we conducted two cohort studies to examine the cardiac safety of azithromycin relative to amoxicillin-based antibiotics (amoxicillin, amoxicillin/clavulanic acid) and levofloxacin (a fluoroquinolone antibiotic known to prolong the QT-interval) in the hemodialysis population. The primary outcome was five-day sudden cardiac death. Using inverse probability of treatment weighted survival models, we estimated hazard ratios, risk differences, and 95% confidence intervals. The azithromycin vs. amoxicillin-based antibiotic cohort included 282,899 patients and 725,431 treatment episodes (381,306 azithromycin and 344,125 amoxicillin-based episodes). Azithromycin vs. amoxicillin-based antibiotic treatment was associated with higher relative and absolute risks of sudden cardiac death, weighted hazard ratio of 1.70 (95% Confidence Interval, 1.36 to 2.11) and weighted risk difference per 100,000 treatment episodes of 25.0 (15.5 to 36.5). The azithromycin vs. levofloxacin cohort included 245,143 patients and 554,557 treatment episodes (387,382 azithromycin and 167,175 levofloxacin episodes). Azithromycin vs. levofloxacin treatment was associated with lower relative and absolute risks of sudden cardiac death, weighted hazard ratio of 0.79 (0.64 to 0.96) and weighted risk difference per 100,000 treatment episodes of -18.9 (-35.5 to -3.8). Thus, when selecting among azithromycin, levofloxacin, and amoxicillin-based antibiotics, clinicians should weigh the relative antimicrobial benefits of these drugs against their potential cardiac risks.

Patient Frailty and Functional Use of Hemodialysis Vascular Access: A Retrospective Study of the US Renal Data System.

RATIONALE & OBJECTIVE: Despite the high prevalence of frailty among dialysis patients, it is unknown whether frailty is associated with dialysis vascular access failure. This study examined the association between frailty and functional use of vascular access. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Patients who initiated hemodialysis through a tunneled catheter in the US Renal Data System database from 2012 through 2017 and underwent subsequent creation of an arteriovenous fistula or graft. PREDICTORS: The "claims-based frailty indicator" (CFI) was calculated using a validated claims-based disability status model anchored to a well-described frailty phenotype. OUTCOMES: Time to functional use for fistulas and grafts defined as the time from initiation of hemodialysis to treatments using the index vascular access with 2 needles. ANALYTICAL APPROACH: Fine and Gray competing risk models separately examining fistula and graft outcomes. Patient survival was modeled for the entire cohort using Cox proportional hazards regression. RESULTS: A total of 41,471 patients met inclusion criteria, including 33,212 who underwent fistula creation and 8,259 who underwent graft placement. Higher CFI quartiles were associated with a greater rate of mortality. Patients in the highest CFI quartile had more than 2 times the rate of mortality compared with patients in the lowest CFI quartile (hazard ratio [HR], 2.49 [95% CI, 2.41-2.58]). In multivariable analyses, the highest CFI quartile was significantly associated with longer time to functional use of fistulas (HR, 0.65 [95% CI, 0.62-0.69]) and grafts (HR, 0.88 [95% CI, 0.79-0.98]). LIMITATIONS: Generalizability may be limited by the requirement of 12 months of Medicare claims availability before initiation of dialysis. There were no data on patient anatomic characteristics or surgeon characteristics and limited patient-specific sociodemographic data. CONCLUSIONS: Higher degrees of frailty are associated with longer times to vascular access functional use. Frailty may be useful for informing clinical decision-making regarding choice of vascular access.

The modifying effect of the serum-to-dialysate potassium gradient on the cardiovascular safety of SSRIs in the hemodialysis population: a pharmacoepidemiologic study.

BACKGROUND: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs). METHODS: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus <4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study. RESULTS: The study included 25 099 patients: 11 107 (44.3%) higher QT-prolonging potential SSRI new users and 13 992 (55.7%) lower QT-prolonging potential SSRI new users. Overall, higher versus lower QT-prolonging potential SSRI use was not associated with SCD [weighted HR 1.03 (95% CI 0.86-1.24)]. However, a greater risk of SCD was associated with higher versus lower QT-prolonging potential SSRI use among patients with baseline potassium gradients ≥4 mEq/l but not among those with gradients <4 mEq/l [weighted HR 2.17 (95% CI 1.16-4.03) versus 0.95 (0.78-1.16)]. Nested case-control analyses yielded analogous results. CONCLUSIONS: The serum-to-dialysate potassium gradient may modify the association between higher versus lower QT-prolonging SSRI use and SCD among people receiving HD. Minimizing the potassium gradient in the setting of QT-prolonging medication use may be warranted.

Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis.

PURPOSE: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug-drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT-prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions. METHODS: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007-2017) and a new-user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1-year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11-1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06-1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85-1.26]). CONCLUSIONS: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients.

Changes in Treatment of Patients with Incident ESKD during the Novel Coronavirus Disease 2019 Pandemic.

BACKGROUND: The COVID-19 pandemic caused major disruptions to care for patients with advanced CKD. METHODS: We investigated the incidence of documented ESKD, ESKD treatment modalities, changes in eGFR at dialysis initiation, and use of incident central venous catheters (CVCs) by epidemiologic week during the first half of 2020 compared with 2017-2019 historical trends, using Centers for Medicare and Medicaid Services data. We used Poisson and logistic regression for analyses of incidence and binary outcomes, respectively. RESULTS: Incidence of documented ESKD dropped dramatically in 2020 compared with the expected incidence, particularly during epidemiologic weeks 15-18 (April, incidence rate ratio [IRR], 0.75; 95% CI, 0.73 to 0.78). The decrease was most pronounced for individuals aged ≥75 years (IRR, 0.69; 95% CI, 0.66 to 0.73). Pre-emptive kidney transplantation decreased markedly during weeks 15-18 (IRR, 0.56; 95% CI, 0.46 to 0.67). Mean eGFR at dialysis initiation decreased by 0.33 ml/min per 1.73 m2 in weeks 19-22; non-Hispanic Black patients exhibited the largest decrease, at 0.61 ml/min per 1.73 m2. The odds of initiating dialysis with eGFR <10 ml/min per 1.73 m2 were highest during weeks 19-22 (May, OR, 1.14; 95% CI, 1.05 to 1.17), corresponding to an absolute increase of 2.9%. The odds of initiating peritoneal dialysis (versus hemodialysis) were 24% higher (OR, 1.24; 95% CI, 1.14 to 1.34) in weeks 11-14, an absolute increase of 2.3%. Initiation with a CVC increased by 3.3% (OR, 1.30; 95% CI, 1.20 to 1.41). CONCLUSIONS: During the first wave of the COVID-19 pandemic, the number of patients starting treatment for ESKD fell to a level not observed since 2011. Changes in documented ESKD incidence and other aspects of ESKD-related care may reflect differential access to care early in the pandemic.

Arteriovenous Vascular Access-Related Procedural Burden Among Incident Hemodialysis Patients in the United States.

RATIONALE & OBJECTIVE: As the proportion of arteriovenous fistulas (AVFs) compared with arteriovenous grafts (AVGs) in the United States has increased, there has been a concurrent increase in interventions. We explored AVF and AVG maturation and maintenance procedural burden in the first year of hemodialysis. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Patients initiating hemodialysis from July 1, 2012, to December 31, 2014, and having a first-time AVF or AVG placement between dialysis initiation and 1 year (N = 73,027), identified using the US Renal Data System (USRDS). PREDICTORS: Patient characteristics. OUTCOME: Successful AVF/AVG use and intervention procedure burden. ANALYTICAL APPROACH: For each group, we analyzed interventional procedure rates during maturation maintenance phases using Poisson regression. We used proportional rate modeling for covariate-adjusted analysis of interventional procedure rates during the maintenance phase. RESULTS: During the maturation phase, 13,989 of 57,275 patients (24.4%) in the AVF group required intervention, with therapeutic interventional requirements of 0.36 per person. In the AVG group 2,904 of 15,572 patients (18.4%) required intervention during maturation, with therapeutic interventional requirements of 0.28 per person. During the maintenance phase, in the AVF group 12,732 of 32,115 patients (39.6%) required intervention, with a therapeutic intervention rate of 0.93 per person-year. During maintenance phase, in the AVG group 5,928 of 10,271 patients (57.7%) required intervention, with a therapeutic intervention rate of 1.87 per person-year. For both phases, the intervention rates for AVF tended to be higher on the East Coast while those for AVG were more uniform geographically. LIMITATIONS: This study relies on administrative data, with monthly recording of access use. CONCLUSIONS: During maturation, interventions for both AVFs and AVGs were relatively common. Once successfully matured, AVFs had lower maintenance interventional requirements. During the maturation and maintenance phases, there were geographic variations in AVF intervention rates that warrant additional study.

Selective Serotonin Reuptake Inhibitor Use and Hip Fracture Risk Among Patients on Hemodialysis.

RATIONALE & OBJECTIVE: Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with hip fracture risk in the general population. This study examined this relationship among patients with kidney failure treated by hemodialysis, a unique high-risk subpopulation, within which the impact of SSRIs on hip fracture risk remains unexplored. STUDY DESIGN: Case-control study. SETTINGS & PARTICIPANTS: Eligible cases of hip fracture among maintenance hemodialysis patients between January 1, 2009, and September 30, 2015, were identified using the US Renal Data System. Each case was matched on index date with 10 eligible controls. To be eligible, study participants needed to have more than 1 year of Medicare Parts A and B coverage and more than 3 years of Part D coverage. For a separate examination of new short-term SSRI exposure, we selected cases and controls with more than 18 months of Part D coverage and no prior antidepressant use for 1 year. EXPOSURE: During the 3-year Part D coverage period, use of SSRIs characterized as any (≥1 prescription filled), low, moderate, and high use (<20%, 20%-<80%, and≥80% of days covered by filled prescriptions, respectively). OUTCOME: We selected cases using International Classification of Diseases, Ninth Revision codes 820.xx and 821.xx. In addition to 1 of these codes tied to a hospitalization, we required a corresponding surgical procedural code within 7 days of diagnosis. ANALYTIC APPROACH: Conditional logistic regression to estimate unadjusted and multivariable-adjusted ORs and 95% CIs. RESULTS: We identified 4,912 cases and 49,120 controls. SSRI use was associated with increased hip fracture risk (adjusted OR, 1.25; 95% CI, 1.17-1.35). Risk for fracture was estimated for any, low, moderate, and high SSRI use: adjusted conditional ORs were 1.25 (95% CI, 1.17-1.35), 1.20 (95% CI, 1.08-1.32), 1.31 (95% CI, 1.18-1.43), and 1.26 (95% CI, 1.12-1.41), respectively. The association between hip fracture events and SSRI use was also seen in the examination of new short-term use (adjusted OR, 1.43; 95% CI, 1.23-1.67). LIMITATIONS: Biomarkers of mineral bone disorder were not captured and accounted for in this analysis. CONCLUSIONS: We demonstrated an association between increased hip fracture risk and both long- and new short-term SSRI use. The stronger association with new short-term use may suggest an acute mechanism potentially related to falls.

Obstetric Deliveries in US Women With ESKD: 2002-2015.

RATIONALE & OBJECTIVE: Women with end-stage kidney disease (ESKD) have decreased fertility and are at increased risk for pregnancy complications. This study examined secular trends and outcomes of obstetric deliveries in a US cohort of women with ESKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Women aged 18 to 44 years with ESKD and registered in the US Renal Data System from 2002 to 2015. EXPOSURE: ESKD modality (hemodialysis [HD], peritoneal dialysis, transplantation). OUTCOMES: Infant delivery, preterm delivery, cesarean delivery. ANALYTICAL APPROACH: Unadjusted delivery rates were expressed as number of delivering women per 1,000 patient-years among women aged 18 to 44 years within each year during the study period, stratified by ESKD modality. Logistic regression models were used to evaluate associations of delivery, preterm delivery, and cesarean delivery with patient characteristics. RESULTS: The delivery rate in women undergoing HD and women with a kidney transplant increased from 2.1 to 3.6 and 3.1 to 4.6 per 1,000 patient-years, respectively (P<0.001 for each). The delivery rate in patients undergoing peritoneal dialysis was lower and did not increase significantly (P=0.9). Women with a transplant were less likely to deliver preterm compared with women undergoing HD (OR, 0.92; 95% CI, 0.84-1.00), though more likely have a cesarean delivery (OR, 1.18; 95% CI, 1.06-1.31). For deliveries occurring in the 2012 to 2015 period, 75% of women treated with HD were prescribed 4 or fewer outpatient HD treatments per week and 25% were prescribed 5-plus treatments per week in the 30 days before delivery. LIMITATIONS: Ascertainment of outcomes and comorbid conditions using administrative claims data. CONCLUSIONS: The delivery rate in women of reproductive age with ESKD increased from 2002 to 2015 among those treated with transplantation or HD. Women with a functioning transplant were less likely to deliver preterm, but more likely to have a cesarean delivery. Prescriptions for outpatient intensified HD for pregnant women with ESKD were infrequent in 2012 to 2015.

Dialysis Modality and Incident Atrial Fibrillation in Older Patients With ESRD.

RATIONALE & OBJECTIVE: Atrial fibrillation (AF) is common in patients with kidney failure treated by maintenance dialysis. Whether the incidence of AF differs between patients receiving hemodialysis and peritoneal dialysis is uncertain. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using the US Renal Data System, we identified older patients (≥67 years) with Medicare Parts A and B who initiated dialysis therapy (1996-2011) without a diagnosis of AF during the prior 2 years. EXPOSURE: Dialysis modality at incident end-stage renal disease (ESRD) and maintained for at least 90 days. OUTCOME: Patients were followed up for 36 months or less for a new diagnosis of AF. ANALYTICAL APPROACH: Time-to-event analysis using multivariable Cox proportional hazards regression to estimate cause-specific HRs while censoring at modality switch, kidney transplantation, or death. RESULTS: Overall, 271,722 older patients were eligible; 17,487 (6.9%) were treated with peritoneal dialysis, and 254,235 (93.1%), with hemodialysis, at the onset of ESRD. During 406,225 person-years of follow-up, 69,705 patients had AF newly diagnosed. Because the proportionality assumption was violated, we introduced an interaction term between time (first 90 days vs thereafter) and modality. The AF incidence during the first 90 days was 187/1,000 person-years on peritoneal dialysis therapy and 372/1,000 person-years on hemodialysis therapy. Patients on peritoneal dialysis therapy had an adjusted 39% (95% CI, 34%-43%) lower incidence of AF than those on hemodialysis therapy. From day 91 onward, AF incidence was ∼140/1,000 person-years with no major difference between modalities. LIMITATIONS: Residual confounding from unobserved differences between exposure groups; ascertainment of AF from billing claims; study of first modality may not generalize to patients switching modalities; uncertain generalizability to younger patients. CONCLUSIONS: Although patients initiating dialysis therapy using peritoneal dialysis had a lower AF incidence during the first 90 days of ESRD, there was no major difference in AF incidence thereafter. The value of interventions to reduce the early excess AF risk in patients receiving hemodialysis may warrant further study.

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.

Revisiting racial differences in ESRD due to ADPKD in the United States.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) affects all races. Whether the progression of ADPKD varies by race remains unclear. METHODS: In this retrospective cohort study from 2004 to 2013 non-Hispanic blacks and non-Hispanic whites of all ages classified in the US Renal Data System (USRDS) with incident ESRD from ADPKD (n = 23,647), hypertension/large vessel disease (n = 296,352), or diabetes mellitus (n = 451,760) were stratified into five-year age categories ranging from < 40 to > 75 (e.g., < 40, 40-44, 45-49, …, 75+). The Cochran-Mantel-Haenszel test was used to determine the association of race and incidence of ESRD from ADPKD, diabetes, or hypertension. The difference in the proportions of ESRD in non-Hispanic black and non-Hispanic white patients at each age categorical bin was compared by two-sample proportion test. The age of ESRD onset between non-Hispanic black and non-Hispanic white patients at each year was compared using two-sample t-test with unequal variance. RESULTS: 1.068% of non-Hispanic blacks and 2.778% of non-Hispanic whites had ESRD attributed to ADPKD. Non-Hispanic blacks were less likely than non-Hispanic whites to have ESRD attributed to ADPKD (odds ratio (OR) (95% CI) = 0.38 (0.36-0.39), p <  0.0001). Using US Census data as the denominator to adjust for population differences non-Hispanic blacks were still slightly under-represented (OR (95% CI) 0.94 (0.91-0.96), p = 0.004). However, non-Hispanic blacks with ADPKD had a younger age of ESRD (54.4 years ±13) than non-Hispanic whites (55.9 years ±12.8) (p <  0.0001). For those < 40 years old, more non-Hispanic blacks had incident ESRD from ADPKD than non-Hispanic whites (9.49% vs. 7.68%, difference (95% CI) = 1.81% (0.87-2.84%), p <  0.001) for the combined years examined. CONCLUSIONS: As previously shown, we find the incidence of ESRD from ADPKD in non-Hispanic blacks is lower than in non-Hispanic whites. Among the younger ADPKD population (age < 40), however, more non-Hispanic blacks initiated dialysis than non-Hispanic whites. Non-Hispanic blacks with ADPKD initiated dialysis younger than non-Hispanic whites. A potential implication of these findings may be that black race should be considered an additional risk factor for progression in ADPKD.

De Novo Heart Failure After Kidney Transplantation: Trends in Incidence and Outcomes.

BACKGROUND: Heart failure is an important cause of morbidity and mortality following kidney transplantation. Some studies in the general population have shown that the incidence of heart failure has decreased during the past 20 years. However, it is not currently known whether such a trend exists in the kidney transplantation population. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Adult patients included in the US Renal Data System who underwent their first kidney transplantation in the United States between 1998 and 2010 with at least 6 months of continuous Medicare parts A and B coverage before transplantation and no prior evidence for a diagnosis of heart failure before kidney transplantation. PREDICTORS: Calendar year of transplantation and calendar year of posttransplantation heart failure diagnosis. OUTCOMES: De novo posttransplantation heart failure defined using International Classification of Diseases, Ninth Revision diagnosis codes and mortality following de novo posttransplantation heart failure diagnosis. Secular trends in de novo post-kidney transplantation heart failure were examined using Cox proportional hazards analysis. RESULTS: Within a study cohort of 48,771 patients, 7,269 developed de novo heart failure within 3 years of kidney transplantation, with a median time to heart failure of 0.76 years. The adjusted HR for heart failure with death as competing risk comparing patients who underwent transplantation in 2010 with those who underwent transplantation in 1998 was 0.69 (95% CI, 0.60-0.79). No temporal trend in mortality following a diagnosis of post-kidney transplantation heart failure was observed. LIMITATIONS: Potential residual confounding from either incorrectly ascertained or unavailable confounders. The cohort was limited to Medicare beneficiaries. CONCLUSIONS: Adjusted for demographic and clinical characteristics, the risk for developing de novo post-kidney transplantation heart failure has declined significantly between 1998 and 2010, with no apparent change in subsequent mortality.

Mortality and Allograft Loss Trends Among US Pediatric Kidney Transplant Recipients With and Without Focal Segmental Glomerulosclerosis.

BACKGROUND: Pediatric patients with focal segmental glomerulosclerosis (FSGS) have high rates of disease recurrence and allograft failure after kidney transplantation, but there are few data for long-term survival posttransplantation. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 12,303 pediatric patients (aged <18 years), including 1,408 (11%) patients with FSGS, who received a first kidney transplant in 1990 through 2009 and were followed up through June 2015 were identified from the US Renal Data System database. PREDICTORS: Primary cause of end-stage renal disease, FSGS or other. OUTCOMES: All-cause patient mortality and allograft loss. RESULTS: All-cause mortality significantly improved for patients with FSGS who underwent transplantation in the 2000s versus the 1990s (6.72 vs 12.24 deaths/1,000 patient-years; HR, 0.55; 95% CI, 0.39-0.78; P<0.001). Reductions in allograft loss were less dramatic (75.91 vs 89.05 events/1,000 patient-years; HR, 0.85; 95% CI, 0.74-0.98; P=0.02). After adjusting for baseline characteristics at the time of transplantation, patients with FSGS had similar rates of death compared with patients without FSGS (HRs of 0.81 [P=0.6] and 1.06 [P=0.2] among those who underwent transplantation in the 2000s and 1990s, respectively) despite higher rates of allograft loss (HRs of 1.17 [P=0.03] and 1.27 [P<0.001], respectively). Among patients who underwent transplantation in the 2000s, further adjustment for allograft failure as a time-varying covariate demonstrated a lower rate of death among patients with FSGS compared with those without FSGS (HR, 0.70; P=0.02). LIMITATIONS: Lack of information about certain risk factors for mortality, including duration of chronic kidney disease; missing data; and potential primary disease misclassification. CONCLUSIONS: Survival of pediatric kidney transplant recipients with FSGS improved between the 1990s and 2000s and was similar to that of recipients without FSGS. Interestingly, adjustment for allograft failure showed greater survival for pediatric patients with FSGS who underwent transplantation in the 2000s as compared with others, suggesting that effective interventions to decrease allograft loss due to disease recurrence may improve patient survival.

The Role of Big Data in the Development and Evaluation of US Dialysis Care.

Rapid growth in electronic communications and digitalization, combined with advances in data management, analysis, and storage, have led to an era of "Big Data." The Social Security Amendments of 1972 turned end-stage renal disease (ESRD) care into a single-payer system for most patients requiring dialysis in the United States. As a result, there are few areas of medicine that have been as influenced by Big Data as dialysis care, for which Medicare's large administrative data sets have had a central role in the evaluation and development of public policy for several decades. In the 1970/1980s, Medicare data helped identify concerning trends in costs, access to dialysis care, and quality of care delivered. As the research community and policymakers made Medicare's administrative data increasingly accessible for investigation, analyses of Medicare claims have had a large role in facilitating policy synthesis and refinement. Efforts to address the skyrocketing cost of injectable drugs in the 1990s and 2000s exemplify this expanded role of Big Data. Although there are opportunities for large government and nongovernmental administrative data sets to continue serving a critical role in the evaluation and development of ESRD policies, it is important to understand challenges and limitations associated with their use.

Health Insurance and the Use of Peritoneal Dialysis in the United States.

BACKGROUND: Many patients in the United States have limited or no health insurance at the time they develop end-stage renal disease (ESRD). We examined whether health insurance limitations affected the likelihood of peritoneal dialysis (PD) use. STUDY DESIGN: Retrospective cohort analysis of patients from the US Renal Data System initiating dialysis therapy in 2006 through 2012. SETTING & PARTICIPANTS: We identified socioeconomically similar groups of patients to examine the association between health insurance and PD use. Patients aged 60 to 64 years with "limited insurance" (defined as having Medicaid or no insurance) at ESRD onset were compared with patients aged 66 to 70 years who were dually eligible for Medicare and Medicaid at ESRD onset. PREDICTOR: Type of insurance coverage at ESRD onset. OUTCOMES: The likelihoods of receiving PD before dialysis month 4, when all patients qualified for Medicare due to ESRD, and of switching to PD therapy following receipt of Medicare. RESULTS: After adjusting for observable patient and geographic differences, patients with limited insurance had an absolute 2.4% (95% CI, 1.1%-3.7%) lower probability of PD use by dialysis month 4 compared with patients with Medicare at ESRD onset. The association between insurance and PD use reversed when patients became Medicare eligible; patients with limited insurance had a 3-fold higher rate of switching to PD therapy between months 4 and 12 of dialysis (HR, 2.9; 95% CI, 1.8-4.6) compared with patients with Medicare at ESRD onset. LIMITATIONS: Because this study was observational, there is a potential for bias from unmeasured patient-level factors. CONCLUSIONS: Despite Medicare's policy of covering patients in the month that they initiate PD therapy, insurance limitations remain a barrier to PD use for many patients. Educating providers about Medicare reimbursement policy and expanding access to pre-ESRD education and training may help overcome these barriers.

Arteriovenous Fistula Maturation in Prevalent Hemodialysis Patients in the United States: A National Study.

BACKGROUND: Arteriovenous fistulas (AVFs) are the preferred form of hemodialysis vascular access, but maturation failures occur frequently, often resulting in prolonged catheter use. We sought to characterize AVF maturation in a national sample of prevalent hemodialysis patients in the United States. STUDY DESIGN: Nonconcurrent observational cohort study. SETTING & PARTICIPANTS: Prevalent hemodialysis patients having had at least 1 new AVF placed during 2013, as identified using Medicare claims data in the US Renal Data System. PREDICTORS: Demographics, geographic location, dialysis vintage, comorbid conditions. OUTCOMES: Successful maturation following placement defined by subsequent use identified using monthly CROWNWeb data. MEASUREMENTS: AVF maturation rates were compared across strata of predictors. Patients were followed up until the earliest evidence of death, AVF maturation, or the end of 2014. RESULTS: In the study period, 45,087 new AVFs were placed in 39,820 prevalent hemodialysis patients. No evidence of use was identified for 36.2% of AVFs. Only 54.7% of AVFs were used within 4 months of placement, with maturation rates varying considerably across end-stage renal disease (ESRD) networks. Older age was associated with lower AVF maturation rates. Female sex, black race, some comorbid conditions (cardiovascular disease, peripheral artery disease, diabetes, needing assistance, or institutionalized status), dialysis vintage longer than 1 year, and catheter or arteriovenous graft use at ESRD incidence were also associated with lower rates of successful AVF maturation. In contrast, hypertension and prior AVF placement at ESRD incidence were associated with higher rates of successful AVF maturation. LIMITATIONS: This study relies on administrative data, with monthly recording of access use. CONCLUSIONS: We identified numerous associations between AVF maturation and patient-level factors in a recent national sample of US hemodialysis patients. After accounting for these patient factors, we observed substantial differences in AVF maturation across some ESRD networks, indicating a need for additional study of the provider, practice, and regional factors that explain AVF maturation.

Association of Medicare's Bundled Payment Reform With Changes in Use of Vitamin D Among Patients Receiving Maintenance Hemodialysis: An Interrupted Time-Series Analysis.

BACKGROUND & RATIONALE: Medicare's 2011 prospective payment system (PPS) was introduced to curb overuse of separately billable injectable drugs. After epoietin, intravenous (IV) vitamin D analogues are the biggest drug cost drivers in hemodialysis (HD) patients, but the association between PPS introduction and vitamin D therapy has been scarcely investigated. STUDY DESIGN: Interrupted time-series analyses. SETTING & PARTICIPANTS: Adult US HD patients represented in the US Renal Data System between 2008 and 2013. EXPOSURES: PPS implementation. OUTCOMES: The cumulative dose of IV vitamin D analogues (paricalcitol equivalents) per patient per calendar quarter in prevalent HD patients. The average starting dose of IV vitamin D analogues and quarterly rates of new vitamin D use (initiations/100 person-months) in incident HD patients within 90 days of beginning HD therapy. ANALYTICAL APPROACH: Segmented linear regression models of the immediate change and slope change over time of vitamin D use after PPS implementation. RESULTS: Among 359,600 prevalent HD patients, IV vitamin D analogues accounted for 99% of the total use, and this trend was unchanged over time. PPS resulted in an immediate 7% decline in the average dose of IV vitamin D analogues (average baseline dose = 186.5 µg per quarter; immediate change = -13.5 µg [P < 0.001]; slope change = 0.43 per quarter [P = 0.3]) and in the starting dose of IV vitamin D analogues in incident HD patients (average baseline starting dose = 5.22 µg; immediate change = -0.40 µg [P < 0.001]; slope change = -0.03 per quarter [P = 0.03]). The baseline rate of vitamin D therapy initiation among 99,970 incident HD patients was 44.9/100 person-months and decreased over time, even before PPS implementation (pre-PPS ß = -0.46/100 person-months [P < 0.001]; slope change = -0.19/100 person-months [P = 0.2]). PPS implementation was associated with an immediate change in initiation levels (by -4.5/100 person-months; P < 0.001). LIMITATIONS: Incident HD patients were restricted to those 65 years or older. CONCLUSION: PPS implementation was associated with a 7% reduction in the average dose and starting dose of IV vitamin D analogues and a 10% reduction in the rate of vitamin D therapy initiation.