The Use of Telemedicine by US Nephrologists for In-Center Hemodialysis Care During the Pandemic: An Analysis of National Medicare Claims.

Rationale & Objective: Because of coronavirus disease 2019 (COVID-19), the US government issued emergency waivers in March 2020 that removed regulatory barriers around the use of telemedicine. For the first time, nephrologists were reimbursed for telemedicine care delivered during in-center hemodialysis. We examined the use of telemedicine for in-center hemodialysis during the first 16 months of the pandemic. Study Design: We ascertained telemedicine modifiers on nephrologist claims. We used multivariable regression to examine time trends and patient, dialysis facility, and geographic correlates of telemedicine use. We also examined whether the estimated effects of predictors of telemedicine use changed over time. Setting & Participants: US Medicare beneficiaries receiving in-center hemodialysis between March 1, 2020, and June 30, 2021. Exposures: Patient, geographic, and dialysis facility characteristics. Outcomes: The use of telehealth for in-center hemodialysis care. Analytic Approach: Retrospective cohort analysis. Results: Among 267,434 Medicare beneficiaries identified, the reported use of telemedicine peaked at 9% of patient-months in April 2020 and declined to 2% of patient-months by June 2021. Telemedicine use varied geographically and was more common in areas that were remote and socioeconomically disadvantaged. Patients were more likely to receive care by telemedicine in areas with higher incidence of COVID-19, although the predictive value of COVID-19 diminished later in the pandemic. Patients were more likely to receive care using telemedicine if they were at facilities with more staff, and the use of telemedicine varied by facility ownership type. Limitations: Limited reporting of telemedicine on claims could lead to underestimation of its use. Reported telemedicine use was higher in an analysis designed to address this limitation by focusing on patients whose physicians used telemedicine at least once during the pandemic. Conclusions: Some US nephrologists continued to use telemedicine for in-center hemodialysis throughout the pandemic, even as the association between COVID-19 incidence and telemedicine use diminished over time. These findings highlight unique challenges and opportunities to the future use of telemedicine in dialysis care.

Emergency waivers issued during the coronavirus disease 2019 pandemic enabled reimbursement to US nephrologists for telemedicine care delivered during in-center hemodialysis. Using modifiers from Medicare claims, we examined telemedicine use in the first 16 months of the pandemic. Reported telemedicine use peaked early in the pandemic and declined subsequently. Telemedicine use was more common in areas that were remote and socioeconomically disadvantaged and at facilities with more staff. Telemedicine use also varied by facility ownership type. Some nephrologists continued to use telemedicine for in-center hemodialysis throughout the pandemic, even as the association between coronavirus disease 2019 incidence and telemedicine use diminished over time. These findings highlight unique challenges and opportunities to the future use of telemedicine in dialysis care.

Hemodialysis Versus Peritoneal Dialysis Drug Expenditures: A Comparison Within the Private Insurance Market.

Rationale and Objective: Recent initiatives aim to improve patient satisfaction and autonomy by increasing the use of peritoneal dialysis (PD) in the United States. However, limited knowledge is available about the costs of different dialysis modalities, particularly those incurred by private insurers. In this study, we compared the costs of injectable dialysis drugs (and their oral equivalents) paid by insurers between privately insured patients receiving hemodialysis and PD. Study Design: A retrospective cohort study. Setting and Participants: From a private insurance claims database, we identified patients who started receiving PD or in-center hemodialysis between January 1, 2017, and December 31, 2020. Exposure: Patients started receiving PD. Outcomes: Average annual injectable drug and aggregate expenditures and expenditure subcategories. Analytical Approach: Patients who started receiving PD were propensity matched to similar patients who started receiving hemodialysis based on the year of dialysis initiation, patient demographics, health, geography, and comorbidities. Cost ratios (CRs) were estimated from generalized linear models. Results: We matched 284 privately insured patients who started receiving PD 1:1 with patients started receiving in-center hemodialysis. The average annual injectable drug expenditures for hemodialysis were 2-fold higher (CR: 1.99; 95% CI, 1.62-2.44) than that for PD. Compared those receiving PD, patients receiving hemodialysis incurred significantly lower nondrug dialysis-related expenditures (0.85; 95% CI, 0.76-0.94). The average annual expenditures for non-dialysis-dependent outpatient services were significantly higher among patients who underwent in-center hemodialysis (CR: 1.44; 95% CI, 1.10-1.90). Although aggregate and inpatient hospitalization expenditures were higher for in-center hemodialysis, these differences did not reach statistical significance. Limitations: Small sample sizes may have restricted our ability to identify differences in some cost categories. Conclusions: Compared with privately insured patients who started receiving PD, patients starting in-center hemodialysis incurred higher expenditures for injectable dialysis drugs, whereas differences in other expenditure categories varied. Recent increases in the use of PD may lead to reductions in injectable dialysis drug costs among privately insured patients. Plain Language Summary: Recent initiatives aim to improve patient satisfaction and autonomy by increasing the use of peritoneal dialysis (PD) in the United States. However, limited knowledge is available about the costs of different dialysis modalities, particularly those incurred by private insurers. In this study, we compared the costs of injectable dialysis drugs (and their oral equivalents) provided by insurers between privately insured patients receiving hemodialysis and PD. We found that the average annual injectable drug expenditures for hemodialysis were 2.0-fold higher compared with those for PD. These findings suggest that the recent increase in the use of PD may lead to reductions in injectable dialysis drug costs among privately insured patients.

Associations of Serum and Dialysate Potassium Concentrations With Incident Atrial Fibrillation in a Cohort Study of Older US Persons Initiating Hemodialysis for Kidney Failure.

Introduction: Atrial fibrillation (AF) disproportionally affects persons on maintenance hemodialysis (HD). Associations of serum and dialysate potassium concentrations [K+] with AF incidence are poorly understood. Methods: We conducted a cohort study using Medicare claims merged with clinical data from a dialysis provider to determine whether serum-[K+] and/or dialysate-[K+] independently associated with AF incidence. Persons insured by fee-for-service Medicare aged ≥67 years at dialysis initiation and free from diagnosed AF prior to day 120 of dialysis were eligible. Serum-[K+] and dialysate-[K+] were assessed in 30-day intervals and patients were followed-up with for AF incidence in subsequent 30-day intervals. Results: During 2006 to 2011, 15,190 persons (mean age = 76.3 years) initiating HD had no prior AF diagnosis. Mean serum-[K+] was 4.5 mEq/l; dialysate-[K+] was 3 mEq/l in 34% and 2 mEq/l in 52% of patients. Followed-up over 21,907 person-years, 2869 persons had incident AF (incidence/100 person-years, 13.1 [95% confidence interval [CI], 12.6-13.6]). The multivariable-adjusted association of serum-[K+] with incident AF was J-shaped as follows: relative to a serum-[K+] of 4.5 mEq/l, lower serum-[K+] associated with increased AF risk, whereas confidence bands for higher serum-[K+] indicated no association. Dialysis against a dialysate-[K+] of 3 mEq/l versus 2 mEq/l independently associated with a 14% (95% CI, 5%-24%) lower incidence of AF. No effect modification between serum-[K+] and dialysate-[K+] was detected (P = 0.34). Conclusion: Lower serum-[K+] was independently associated with incident AF whereas elevated serum-[K+] was not. The findings support adoption of dialysate solutions with a dialysate-[K+] of 3 mEq/l, regardless of patients' serum-[K+], and elimination of lower dialysate-[K+] solutions from practice. Clinical trials randomizing patients to different dialysate-[K+] are warranted to establish causality.

Hydroxychloroquine Dose and Risk for Incident Retinopathy : A Cohort Study.

BACKGROUND: Hydroxychloroquine is recommended for all patients with systemic lupus erythematosus and is often used for other inflammatory conditions, but a critical long-term adverse effect is vision-threatening retinopathy. OBJECTIVE: To characterize the long-term risk for incident hydroxychloroquine retinopathy and examine the degree to which average hydroxychloroquine dose within the first 5 years of treatment predicts this risk. DESIGN: Cohort study. SETTING: U.S. integrated health network. PARTICIPANTS: All patients aged 18 years or older who received hydroxychloroquine for 5 or more years between 2004 and 2020 and had guideline-recommended serial retinopathy screening. MEASUREMENTS: Hydroxychloroquine dose was assessed from pharmacy dispensing records. Incident hydroxychloroquine retinopathy was assessed by central adjudication of spectral domain optical coherence tomography with severity assessment (mild, moderate, or severe). Risk for hydroxychloroquine retinopathy was estimated over 15 years of use according to hydroxychloroquine weight-based dose (>6, 5 to 6, or ≤5 mg/kg per day) using the Kaplan-Meier estimator. RESULTS: Among 3325 patients in the primary study population, 81 developed hydroxychloroquine retinopathy (56 mild, 17 moderate, and 8 severe), with overall cumulative incidences of 2.5% and 8.6% at 10 and 15 years, respectively. The cumulative incidences of retinopathy at 15 years were 21.6% for higher than 6 mg/kg per day, 11.4% for 5 to 6 mg/kg per day, and 2.7% for 5 mg/kg per day or lower. The corresponding risks for moderate to severe retinopathy at 15 years were 5.9%, 2.4%, and 1.1%, respectively. LIMITATION: Possible misclassifications of dose due to nonadherence to filled prescriptions. CONCLUSION: In this large, contemporary cohort with active surveillance retinopathy screening, the overall risk for hydroxychloroquine retinopathy was 8.6% after 15 years, and most cases were mild. Higher hydroxychloroquine dose was associated with progressively greater risk for incident retinopathy. PRIMARY FUNDING SOURCE: National Institutes of Health.

A Comparison of US Medicare Expenditures for Hemodialysis and Peritoneal Dialysis.

BACKGROUND: Observations that peritoneal dialysis (PD) may be an effective, lower-cost alternative to hemodialysis for the treatment of ESKD have led to policies encouraging PD and subsequent increases in its use in the United States. METHODS: In a retrospective cohort analysis of Medicare beneficiaries who started dialysis between 2008 and 2015, we ascertained average annual expenditures (for up to 3 years after initiation of dialysis) for patients ≥67 years receiving in-center hemodialysis or PD. We also determined whether differences in Medicare expenditures across dialysis modalities persisted as more patients were placed on PD. We used propensity scores to match 8305 patients initiating PD with 8305 similar patients initiating hemodialysis. RESULTS: Overall average expenditures were US$108,656 (2017) for hemodialysis and US$91,716 for PD (proportionate difference, 1.11; 95% confidence interval [CI], 1.09 to 1.13). This difference did not change over time (P for time interaction term=0.14). Hemodialysis had higher estimated intravenous (iv) dialysis drug costs (1.69; 95% CI, 1.64 to 1.73), rehabilitation expenditures (1.35; 95% CI, 1.26 to 1.45), and other nondialysis expenditures (1.34; 95% CI, 1.30 to 1.37). Over time, initial differences in total dialysis expenditures disappeared and differences in iv dialysis drug utilization narrowed as nondialysis expenditures diverged. Estimated iv drug costs declined by US$2900 per patient-year in hemodialysis between 2008 and 2014 versus US$900 per patient-year in PD. CONCLUSIONS: From the perspective of the Medicare program, savings associated with PD in patients ≥67 years have remained unchanged, despite rapid growth in the use of this dialysis modality. Total dialysis expenditures for the two modalities converged over time, whereas nondialysis expenditures diverged.

Potential Mechanisms Involved in Chronic Kidney Disease of Unclear Etiology.

BACKGROUND AND OBJECTIVES: The etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for Mesoamerican nephropathy in an immigrant dialysis population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Migrants with Mesoamerican nephropathy kidney failure (n=52) were identified by exclusion of known causes of kidney disease and compared using a cross-sectional survey with demographically similar patients with kidney failure from other causes (n=63) and age/sex/place of origin-matched healthy participants (n=16). Survey results were extended to the bench; C57BL/6 mice (n=73) received 10-15 weekly intraperitoneal injections of paraquat (a reactive oxygen species-generating herbicide) or vehicle. Kidney function, histology, and expression of organic cation transporter-2 (proximal tubule entry for paraquat) and multidrug and toxin extrusion 1 (extrusion pathway) were examined. Kidney biopsies from Nicaraguan patients with acute Mesoamerican nephropathy were stained for the above transporters and compared with patients with tubulointerstitial nephritis and without Mesoamerican nephropathy. RESULTS: Patients with Mesoamerican nephropathy and kidney failure were young agricultural workers, almost exclusively men; the majority were from Mexico and El Salvador; and they had prior exposures to agrochemicals, including paraquat (27%). After adjustment for age/sex, exposure to any agrochemical or paraquat was associated with Mesoamerican nephropathy kidney failure (odds ratio, 4.86; 95% confidence interval, 1.82 to 12.96; P=0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; P=0.02, respectively). Adjusted for age/sex and other covariates, 1 year of agrochemical exposure was associated with Mesoamerican nephropathy kidney failure (odds ratio, 1.23; 95% confidence interval, 1.04 to 1.44; P=0.02). Compared with 16 matched healthy controls, Mesoamerican nephropathy kidney failure was significantly associated with exposure to paraquat and agrochemicals. Paraquat-treated male mice developed kidney failure and tubulointerstitial nephritis consistent with Mesoamerican nephropathy. Organic cation transporter-2 expression was higher in male kidneys versus female kidneys. Paraquat treatment increased organic cation transporter-2 expression and decreased multidrug and toxin extrusion 1 expression in male kidneys; similar results were observed in the kidneys of Nicaraguan patients with Mesoamerican nephropathy. CONCLUSIONS: Exposure to agrochemicals is associated with Mesoamerican nephropathy, and chronic exposure of mice to paraquat, a prototypical oxidant, induced kidney failure similar to Mesoamerican nephropathy.

Allopurinol Initiation and All-Cause Mortality Among Patients With Gout and Concurrent Chronic Kidney Disease : A Population-Based Cohort Study.

BACKGROUND: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown. OBJECTIVE: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD. DESIGN: Cohort study. SETTING: The Health Improvement Network U.K. primary care database (2000 to 2019). PARTICIPANTS: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD. MEASUREMENTS: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators. RESULTS: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07). LIMITATION: Residual confounding cannot be ruled out. CONCLUSION: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD. PRIMARY FUNDING SOURCE: Project Program of National Clinical Research Center for Geriatric Disorders.

Patient Health Outcomes following Dialysis Facility Closures in the United States.

BACKGROUND: Ongoing changes to reimbursement of United States dialysis care may increase the risk of dialysis facility closures. Closures may be particularly detrimental to the health of patients receiving dialysis, who are medically complex and clinically tenuous. METHODS: We used two separate analytic strategies-one using facility-based matching and the other using propensity score matching-to compare health outcomes of patients receiving in-center hemodialysis at United States facilities that closed with outcomes of similar patients who were unaffected. We used negative binomial and Cox regression models to estimate associations of facility closure with hospitalization and mortality in the subsequent 180 days. RESULTS: We identified 8386 patients affected by 521 facility closures from January 2001 through April 2014. In the facility-matched model, closures were associated with 9% higher rates of hospitalization (relative rate ratio [RR], 1.09; 95% confidence interval [95% CI], 1.03 to 1.16), yielding an absolute annual rate difference of 1.69 hospital days per patient-year (95% CI, 0.45 to 2.93). Similarly, in a propensity-matched model, closures were associated with 7% higher rates of hospitalization (RR, 1.07; 95% CI, 1.00 to 1.13; P=0.04), yielding an absolute rate difference of 1.08 hospital days per year (95% CI, 0.04 to 2.12). Closures were associated with nonsignificant increases in mortality (hazard ratio [HR], 1.08; 95% CI, 1.00 to 1.18; P=0.05 for the facility-matched comparison; HR, 1.08; 95% CI, 0.99 to 1.17; P=0.08 for the propensity-matched comparison). CONCLUSIONS: Patients affected by dialysis facility closures experienced increased rates of hospitalization in the subsequent 180 days and may be at increased risk of death. This highlights the need for effective policies that continue to mitigate risk of facility closures.

Estimation of total mediation effect for high-dimensional omics mediators.

BACKGROUND: Environmental exposures can regulate intermediate molecular phenotypes, such as gene expression, by different mechanisms and thereby lead to various health outcomes. It is of significant scientific interest to unravel the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposure and traits. Mediation analysis is an important tool for investigating such relationships. However, it has mainly focused on low-dimensional settings, and there is a lack of a good measure of the total mediation effect. Here, we extend an R-squared (R[Formula: see text]) effect size measure, originally proposed in the single-mediator setting, to the moderate- and high-dimensional mediator settings in the mixed model framework. RESULTS: Based on extensive simulations, we compare our measure and estimation procedure with several frequently used mediation measures, including product, proportion, and ratio measures. Our R[Formula: see text]-based second-moment measure has small bias and variance under the correctly specified model. To mitigate potential bias induced by non-mediators, we examine two variable selection procedures, i.e., iterative sure independence screening and false discovery rate control, to exclude the non-mediators. We establish the consistency of the proposed estimation procedures and introduce a resampling-based confidence interval. By applying the proposed estimation procedure, we found that 38% of the age-related variations in systolic blood pressure can be explained by gene expression profiles in the Framingham Heart Study of 1711 individuals. An R package "RsqMed" is available on CRAN. CONCLUSION: R-squared (R[Formula: see text]) is an effective and efficient measure for total mediation effect especially under high-dimensional setting.

Mortality, Kidney Failure, and Hospitalization Among Medicare Beneficiaries With CKD and Pulmonary Hypertension.

RATIONALE & OBJECTIVE: Pulmonary hypertension (PH) is highly prevalent among patients with chronic kidney disease (CKD) not requiring kidney replacement therapy. We studied the associations of PH with mortality, kidney failure, as well as cardiovascular (CV) and non-CV hospitalization among Medicare beneficiaries with a CKD diagnosis. STUDY DESIGN: Retrospective, observational study using a matched cohort design. SETTING & PARTICIPANTS: Patients with PH (based on 2 claims within 2 years) and patients without PH matched on CKD stage from the Medicare 5% CKD sample (1996-2016). PREDICTOR: Presence of pulmonary hypertension. OUTCOME: Mortality, kidney failure, and all-cause, CV, and non-CV hospitalization. ANALYTICAL APPROACH: Cox proportional hazards models to assess the association between PH and mortality, adjusting for age, sex, race, and comorbidities. Death was considered as a competing event in Fine-Gray models to assess the association between PH and kidney failure. Negative binomial model was used to evaluate the relationship between PH and all-cause, CV, and non-CV hospitalizations. RESULTS: 30,052 patients with PH and CKD and 150,260 CKD stage-matched patients without diagnosed PH were studied. The median age of the study population was 80.7 years, 57.8% were women, and 10.3% were African Americans. The presence of PH was associated with an increased risk of mortality after 1 (HR, 2.87 [95% CI, 2.79-2.95]), 2-3 (HR, 1.56 [95% CI, 1.51-1.61]), and 4-5 (HR, 1.47 [95% CI, 1.40-1.53]) years of follow-up, and a higher risk of all-cause, CV, and non-CV hospitalization during the same period. PH was also associated with kidney failure in after 1 and 2-3 years but not after 4-5 years of follow-up evaluation. Patients with PH also experienced higher rates of acute kidney injury (AKI), and AKI requiring dialysis support within 30 and 90 days of AKI. LIMITATIONS: Reliance on billing codes and lack of echocardiogram or right heart catheterization data CONCLUSIONS: Among older Medicare beneficiaries with a CKD diagnosis not requiring kidney replacement therapy, the presence of PH was associated with an increased risk of mortality, kidney failure, and hospitalization. Understanding of the mechanism of these associations, especially the increased risk of kidney failure, requires further study.

Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and Gabapentinoids.

BACKGROUND: Despite opioids' known association with hip fracture risk in the general population, they are commonly prescribed to patients with ESKD. Whether use of opioids or gabapentinoids (also used to treat pain in patients with ESKD) contributes to hip fracture risk in patients with ESKD on hemodialysis remains unknown. METHODS: In a case-control study nested within the US Renal Data System, we identified all hip fracture events recorded among patients dependent on hemodialysis from January 2009 through September 2015. Eligible cases were risk-set matched on index date with ten eligible controls. We required >1 year of Medicare Parts A and B coverage and >3 years of part D coverage to study cumulative longer-term exposure. To examine new, short-term exposure, we selected individuals with >18 months of Part D coverage and no prior opioid or gabapentinoid use between 18 and 7 months before index. We used conditional logistic regression to estimate unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: For the longer-term analyses, we identified 4912 first-time hip fracture cases and 49,120 controls. Opioid use was associated with increased hip fracture risk (adjusted OR, 1.39; 95% CI, 1.26 to 1.53). Subgroups of low, moderate, and high use yielded adjusted ORs of 1.33 (95% CI, 1.20 to 1.47), 1.53 (95% CI, 1.36 to 1.72), and 1.66 (95% CI, 1.45 to 1.90), respectively. The association with hip fractures was also elevated with new, short-term use (adjusted OR, 1.38; 95% CI, 1.25 to 1.52). There were no associations between gabapentinoid use and hip fracture. CONCLUSIONS: Among patients dependent on hemodialysis in the United States, both short-term and longer-term use of opioid analgesics were associated with hip fracture events.

[Hospitalization and Critical Illness in Chronic Kidney Disease].

BACKGROUND: Patients with chronic kidney disease (CKD) who are hospitalized with a critical illness are at increased risk for adverse outcomes. We studied the predictors of hospitalization with critical illness among patients with non-dialysis-dependent CKD stages 3 and 4 in a safety-net healthcare setting. METHODS: A retrospective cohort study was conducted among patients ≥18 years of age with CKD stages 3 and 4 using a CKD registry from a safety-net healthcare system. Hospitalizations with critical illness were identified among patients requiring nonelective admission or transfer to the intermediate or intensive care unit during a 3-year period after the diagnosis of CKD. Poisson regression was used to determine associations between baseline characteristics and hospitalization requiring intermediate or intensive care among all CKD patients and in those with different stages of CKD. Outcomes of these hospitalizations were also tabulated. RESULTS: Among 8,302 patients with CKD stages 3 and 4, 1,298 were hospitalized and 495 required intermediate or intensive care during a 3-year follow-up period. In the adjusted analysis, advanced CKD, Hispanics (incident rate ratio [IRR]: 1.88), non-Hispanic Blacks (IRR: 1.48), presence of congestive heart failure (IRR: 2.09), cardiovascular disease (IRR: 1.57), chronic pulmonary disease (IRR: 1.60), liver disease, malignancy, and anemia were associated with higher risk of hospitalization requiring intermediate or intensive care. The association of age, gender, race/ethnicity, congestive heart failure, anemia, and body mass index with hospitalization requiring intermediate or intensive care differed significantly by CKD stage (p value for interaction term <0.05). Congestive heart failure and severity of anemia were associated with a higher risk of hospitalization requiring intermediate or intensive care among patients with mild CKD, and the magnitude of association attenuated among patients with advanced CKD. CONCLUSIONS: The burden of hospitalization with critical illness among patients with non-dialysis-dependent CKD stages 3 and 4 remains high and was associated with demographic factors and comorbid medical conditions, especially among those with congestive heart failure and cardiovascular disease. Targeted, effective interventions to reduce the burden of hospitalization and critical illness in CKD patients within safety-net healthcare systems are needed.

Patterns of Change Over Time in Knee Bone Shape Are Associated with Sex.

BACKGROUND: Knee osteoarthritis (OA) is more common in females than in males; however, the biological mechanisms for the difference in sex in patients with knee OA are not well understood. Knee shape is associated with OA and with sex, but the patterns of change in the bone's shape over time and their relation to sex and OA are unknown and may help inform how sex is associated with shape and OA and whether the effect is exerted early or later in life.Questions/purposes (1) Does knee shape segregate stably into different groups of trajectories of change (groups of knees that share similar patterns of changes in bone shape over time)? (2) Do females and males have different trajectories of bone shape changes? (3) Is radiographic OA at baseline associated with trajectories of bone shape changes? METHODS: We used data collected from the NIH-funded Osteoarthritis Initiative (OAI) to evaluate a cohort of people aged 45 to 79 years at baseline who had either symptomatic knee OA or were at high risk of having it. The OAI cohort included 4796 participants (58% females; n = 2804) at baseline who either had symptomatic knee OA (defined as having radiographic tibiofemoral knee OA and answering positively to the question "have you had pain, aching or stiffness around the knee on most days for at least one month during the past 12 months") or were at high risk of symptomatic knee OA (defined as having knee symptoms during the prior 12 months along with any of the following: overweight; knee injury; knee surgery other than replacement; family history of total knee replacement for OA; presence of Heberden's nodes; daily knee bending activity) or were part of a small nonexposed subcohort. From these participants, we limited the eligible group to those with radiographs available and read at baseline, 2 years, and 4 years, and randomly selected participants from each OAI subcohort in a manner to enrich representation in the study of the progression and nonexposed subcohorts, which were smaller in number than the OA incidence subcohort. From these patients, we randomly sampled 473 knees with radiographs available at baseline, 2 years, and 4 years. We outlined the shape of the distal femur and proximal tibia on radiographs at all three timepoints using statistical shape modelling. Five modes (each mode represents a particular type of knee bone shape variation) were derived for the proximal tibia and distal femur's shape, accounting for 78% of the total variance in shape. Group-based trajectory modelling (a statistical approach to identify the clusters of participants following a similar progression of change of bone shape over time, that is, trajectory group) was used to identify distinctive patterns of change in the bone shape for each mode. We examined the association of sex and radiographic OA at baseline with the trajectories of each bone shape mode using a multivariable polytomous regression model while adjusting for age, BMI, and race. RESULTS: Knee bone shape change trajectories segregated stably into different groups. In all modes, three distinct trajectory groups were derived, with the mean posterior probabilities (a measure of an individual's probability of being in a particular group and often used to characterize how well the trajectory model is working to describe the population) ranging from 84% to 99%, indicating excellent model fitting. For most of the modes of both the femur and tibia, the intercepts for the three trajectory groups were different; however, the rates of change were generally similar in each mode. Females and males had different trajectories of bone shape change. For Mode 1 in the femur, females were more likely to be in trajectory Groups 3 (odds ratio 30.2 [95% CI 12.2 to 75.0]; p < 0.001) and 2 than males (OR 4.1 [95% CI 2.3 to 7.1]; p < 0.001); thus, females had increased depth of the intercondylar fossa and broader shaft width relative to epicondylar width compared with males. For Mode 1 in the tibia, females were less likely to be in trajectory Group 2 (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.01) than males (that is, knees of females were less likely to display superior elevation of tibial plateau or decreased shaft width relative to head width). Radiographic OA at baseline was associated with specific shape-change trajectory groups. For Mode 1 in the femur, knees with OA were less likely to be in trajectory Groups 3 (OR 0.4 [95% CI 0.2 to 0.8]; p = 0.008) and 2 (OR 0.6 [95% CI 0.3 to 1.0]; p = 0.03) than knees without OA; thus, knees with OA had decreased depth of the intercondylar fossa and narrower shaft width relative to epicondylar width compared with knees without OA. For Mode 1 in the tibia, knees with OA were not associated with trajectory. CONCLUSIONS: The shapes of the distal femur and proximal tibia did not change much over time. Sex and baseline knee radiographic OA status are associated with the trajectory of change in the bone's shape, suggesting that both may contribute earlier in life to the associations among trajectories observed in older individuals. Future studies might explore sex-related bone shape change earlier in life to help determine when the sex-specific shapes arise and also the degree to which these sex-related shapes are alterable by injury or other events. LEVEL OF EVIDENCE: Level III, prognostic study.

Readmissions after Acute Kidney Injury during Left Ventricular Assist Device Implantation Hospitalization.

BACKGROUND: Acute kidney injury (AKI) frequently complicates hospitalizations for left ventricular assist device (LVAD) implantation. Little is known about the relationship of AKI with subsequent readmissions, and we investigated the relationship of AKI during LVAD implantation hospitalization with all-cause and cause-specific 30-day readmissions. METHODS: We used a United States (US) nationwide all-payer administrative database, identifying patients who underwent implantable LVAD placement 2010-2015. Patients were classified into 3 mutually exclusive groups based on presence and severity of AKI during the LVAD placement hospitalization: no AKI, AKI, and AKI requiring dialysis (AKI-D). Outcomes were all-cause and cause-specific 30-day readmissions. RESULTS: Within 30 days after discharge 25.4% of patients were readmitted. Of those without AKI, 23.9% were readmitted, compared to 25.5% of those with AKI and 42.2% of those with AKI-D. Compared to no AKI (adjusted for demographics, index hospitalization and chronic comorbidity factors, and year), odds of 30-day readmission were 2.18 (95% CI 1.37-3.49) times higher for those with AKI-D, whereas those with AKI not requiring dialysis had similar 30-day readmission risk (OR 1.03 [95% CI 0.89-1.20]). Those with AKI-D had higher risk of 30-day readmission for infection (OR 2.02 [95% CI 1.13-3.61]), gastrointestinal (GI) bleed (2.32 [95% CI 1.24-4.34]), and kidney disease (13.9 [95% CI 4.0-48]). There was no increased risk for stroke readmission with AKI or AKI-D. CONCLUSION: AKI-D was associated with highest -30-day readmission risk, possibly related to negatively synergistic effects of LVAD, kidney dysfunction, and dialysis related factors on infection and GI bleeding risks. AKI alone was not associated with increased readmission risk.

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.

Acute Kidney Injury With Ventricular Assist Device Placement: National Estimates of Trends and Outcomes.

RATIONALE & OBJECTIVE: Ventricular assist devices (VADs) are used for end-stage heart failure not amenable to medical therapy. Acute kidney injury (AKI) in this setting is common due to heart failure decompensation, surgical stress, and other factors. Little is known about national trends in AKI diagnosis and AKI requiring dialysis (AKI-D) and associated outcomes with VAD implantation. We investigated national estimates and trends for diagnosed AKI, AKI-D, and associated patient and resource utilization outcomes in hospitalizations in which implantable VADs were placed. STUDY DESIGN: Cohort study of 20% stratified sample of US hospitalizations. SETTING & PARTICIPANTS: Patients who underwent implantable VAD placement in 2006 to 2015. EXPOSURE: No AKI diagnosis, AKI without dialysis, AKI-D. OUTCOMES: In-hospital mortality, length of stay, estimated hospitalization costs. ANALYTICAL APPROACH: Multivariate logistic and linear regression using survey design methods to account for stratification, clustering, and weighting. RESULTS: An estimated 24,140 implantable VADs were placed, increasing from 853 in 2006 to 3,945 in 2015. AKI was diagnosed in 56.1% of hospitalizations and AKI-D occurred in 6.5%. AKI diagnosis increased from 44.0% in 2006 to 2007 to 61.7% in 2014 to 2015; AKI-D declined from 9.3% in 2006 to 2007 to 5.2% in 2014 to 2015. Mortality declined in all AKI categories but this varied by category: those with AKI-D had the smallest decline. Adjusted hospitalization costs were 19.1% higher in those with diagnosed AKI and 39.6% higher in those with AKI-D, compared to no AKI. LIMITATIONS: Administrative data; timing of AKI with respect to VAD implantation cannot be determined; limited pre-existing chronic kidney disease ascertainment; discharge weights not derived for subpopulation of interest. CONCLUSIONS: A decreasing proportion of patients undergoing VAD implantation experience AKI-D, but mortality among these patients remains high. AKI diagnosis with VAD implantation is increasing, possibly reflecting changes in AKI surveillance, awareness, and coding.

Blood Pressure and Incident Atrial Fibrillation in Older Patients Initiating Hemodialysis.

BACKGROUND AND OBJECTIVES: We examined the association of predialysis systolic and diastolic BP and intradialytic hypotension with incident atrial fibrillation in older patients initiating hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the US Renal Data System linked to the records of a large dialysis provider to identify patients aged ≥67 years initiating hemodialysis between January 2006 and October 2011. We examined quarterly average predialysis systolic BP, diastolic BP, and proportion of sessions with intradialytic hypotension (i.e., nadir systolic BP <90 mm Hg). We applied an extended Cox model to compute adjusted hazard ratios (HRs) of each exposure with incident atrial fibrillation. RESULTS: Among 17,003 patients, 3785 developed atrial fibrillation. When comparing predialysis systolic BP to a fixed reference of 140 mm Hg, lower predialysis systolic BP was associated with a higher hazard of atrial fibrillation, whereas higher systolic BP was associated with a lower hazard of atrial fibrillation. When comparing across a range of systolic BP for two hypothetical patients with similar measured covariates, the association varied by mean systolic BP: at systolic BP 190 mm Hg, each 10 mm Hg lower systolic BP was associated with lower atrial fibrillation hazard (HR, 0.94; 95% confidence interval, 0.90 to 1.00), whereas at systolic BP 140 mm Hg, a 10 mm Hg lower systolic BP was associated with a higher atrial fibrillation hazard (HR, 1.12; 95% confidence interval, 1.10 to 1.14). Lower diastolic BP was associated with higher atrial fibrillation hazards. Intradialytic hypotension was weakly associated with atrial fibrillation. CONCLUSIONS: In this observational study of older patients initiating hemodialysis, lower predialysis systolic BP and diastolic BP were associated with higher incidence of atrial fibrillation.

Association of Hospitalization and Mortality Among Patients Initiating Dialysis With Hemodialysis Facility Ownership and Acquisitions.

Importance: Mergers and acquisitions among health care institutions are increasingly common, and dialysis markets have undergone several decades of mergers and acquisitions. Objective: To examine the outcomes of hemodialysis facility acquisitions independent of associated changes in market competition resulting from acquisitions. Design, Setting, and Participants: Cohort study using difference-in-differences (DID) analyses to compare changes in health outcomes over time among in-center US dialysis facilities that were acquired by a hemodialysis chain with facilities located nearby but not acquired. Multivariable Cox proportional hazards regression models and negative binomial models with predicted marginal effects were developed to examine health outcomes, controlling for patient, facility, and geographic characteristics. All facility ownership types were examined together and stratified analyses were conducted of facilities that were independently owned and chain owned prior to acquisitions. The study was conducted from January 2001 to September 2015; 174 905 patients starting in-center dialysis in the 3 years before and following dialysis facility acquisitions were included. Data were analyzed from March 2017 to December 2018. Exposures: Acquisition by a hemodialysis chain. Main Outcomes and Measures: Twelve-month hazard of death and hospital days per patient-year were the primary outcomes. Results: Of the 174 905 patients included in the study, 79 705 were women (45.6%), 24 409 (14.0%) were of Hispanic ethnicity, 61 815 (35.3%) were black, 105 272 (60.2%) were white, and 1247 (0.7%) were Native American. Mean (SD) age was 65 (15) years. Before acquisitions, adjusted mortality and hospitalization rates were 10% (95% CI, -16% to -5%) and 2.9 days per patient-year (95% CI, -3.8 to -2.0) lower, respectively, at independently owned facilities that were acquired compared with those that were not acquired, while hospitalization rates were 0.7 days (95% CI, -1.2 to -2.0) lower at chain-owned facilities that were acquired compared with those that were not acquired. In stratified analyses of independently owned facilities, mortality decreases were smaller at acquired (-8.4%; 95% CI, -14% to -25%) vs nonacquired (-20.3%; 95% CI, -25.8% to -14.3%) facilities (DID P < .001). Similarly, hospitalization rates did not change at acquired facilities and decreased by 2.6 days per patient-year (95% CI, -3.6 to -1.7 days) at nonacquired facilities (DID P < .001). Acquisitions were not associated with changes in health outcomes at chain-owned facilities. Slower reductions in mortality and hospitalization rates at independently owned facilities contributed to significant differences in hospitalizations (-2.0 days; 95% CI, -2.5 to -1.6, at nonacquired vs 0.9 days; 95% CI, -1.3 to -0.5, at acquired facilities; DID, P < .001) across all ownership types but not mortality (DID, P = .28) with regard to acquisitions. Conclusions and Relevance: Acquisition of independently owned dialysis facilities by larger dialysis organizations was associated with slower decreases in mortality and hospitalization rates, as nonacquired facilities appeared to experience more rapid improvements in outcomes over time.

Predialysis Nephrology Care and Incident Atrial Fibrillation in Older Patients With ESKD Initiating Dialysis.

BACKGROUND: Atrial fibrillation (AF) is common in patients with end-stage kidney disease (ESKD) on dialysis. Whether pre-ESKD nephrology care associates with AF is uncertain. METHODS: We conducted a retrospective cohort study of older US patients (≥67 years) with Medicare A&B who initiated dialysis (1996-2013) without a prior diagnosis of AF. Patients were categorized by the duration and number of predialysis nephrology outpatient visits. Patients were followed for 1 year for a new diagnosis of AF. We used multivariable Cox proportional hazards regression while accounting for the competing risks of kidney transplantation and death. RESULTS: We identified 316,067 patients with ESKD initiating dialysis between 1996 and 2013 who had no prior AF diagnosis. In this cohort, 66.9% had any pre-ESKD outpatient nephrology care, with the first outpatient nephrology visit before dialysis initiation occurring at ≤6 months in 17.9%, 7 to 12 months in 9.4%, and >12 months in 39.6%. Outpatient pre-ESKD nephrology care for ≤6, 7 to 12, and >12 months versus none yielded adjusted cause-specific hazard ratios (HRs) of 0.87 (95% CI: 0.84-0.89), 0.83 (95% CI: 0.81-0.86), and 0.85 (95% CI: 0.83-0.87) for incident AF, respectively. Further, having 1 to 4 pre-ESKD outpatient nephrology visits, 5 to 9 visits, and ≥10 visits versus none yielded adjusted cause-specific HRs of 0.89 (95% CI: 0.86-0.91), 0.86 (95% CI: 0.83-0.88), and 0.81 (95% CI: 0.79-0.83), respectively. CONCLUSIONS: Having any predialysis nephrology care before initiation of dialysis was associated with slightly lower adjusted rates of incident AF over the first year of dialysis. The optimal timing and intensity of nephrology care to reduce the incidence of AF and other adverse health events requires further study.