Influence of Incomplete Death Information on Cumulative Risk Estimates in United States Claims Data.

Administrative claims databases often do not capture date or fact of death, so studies using these data may inappropriately treat death as a censoring event-equivalent to other withdrawal reasons-rather than a competing event. We examined 1-, 3-, and 5-year inverse-probability-of-treatment-weighted cumulative risks of a composite cardiovascular outcome among 34,527 initiators of telmisartan (exposure) and ramipril (referent) ages ≥55 in Optum claims from 2003 to 2020. Differences in cumulative risks of the cardiovascular endpoint due to censoring of death (cause-specific), as compared to treating death as a competing event (sub-distribution), increased with greater follow-up time and older age, where event and mortality risks were higher. Among ramipril users (selected results), 5-year cause-specific and sub-distribution cumulative risk estimates per 100, respectively, were 16.4 (95% CI 15.3, 17.5) and 16.2 (95% CI 15.1, 17.3) among ages 55-64 (difference=0.2) and were 43.2 (95% CI 41.3, 45.2) and 39.7 (95% CI 37.9, 41.4) among ages ≥75 (difference=3.6). Plasmode simulation results demonstrated the differences in cause-specific versus sub-distribution cumulative risks to increase with increasing mortality rate. We suggest researchers consider the cohort's baseline mortality risk when deciding whether real-world data with incomplete death information can be used without concern.

The Associations Between Opioid Use Disorder and Healthcare-Related Outcomes in Vaso-occlusive Crisis.

BACKGROUND: In patients who experience frequent vaso-occlusive crises (VOC), opioid dependence may be due to a need for pain control as opposed to addiction; the implications of opioid use disorder (OUD) in this population are unclear. OBJECTIVE: To compare outcomes in hospitalizations for VOC in those with a history of OUD to those without a history of OUD. DESIGN: A retrospective assessment of hospitalizations for adults in the USA with a primary discharge diagnosis of VOC using the National Inpatient Sample database from 2016 to 2019. We also compared VOC hospitalizations to hospitalizations for all other reasons to assess differences in OUD-associated clinical factors. PARTICIPANTS: In total, 273,460 hospitalizations for VOC; 23,120 (8.5%) of these hospital stays involved a secondary diagnosis of OUD. MAIN MEASURES: Primary outcomes were length of hospital stay and cost. Mortality was a secondary outcome. KEY RESULTS: Hospital length of stay was increased (mean 6.2 vs 4.9 days) in patients with OUD (adjusted rate ratio = 1.24, 95% CI 1.20-1.29, p < 0.001). Mean cost was also higher in those with OUD ($9076) than those without OUD ($8020, p < 0.001). Mortality was decreased in VOC hospitalizations in those with OUD, but the difference was not statistically significant (adjusted OR = 0.64, 95% CI 0.028-1.48, p = 0.30). CONCLUSIONS: OUD is associated with increased length of stay and costs in patients with VOC. While there are many possible explanations, providers should consider undertreatment of pain due to addiction concerns as a potential factor; individualized pain plans to mitigate this challenge could be explored.

Staging and clean room: Constructs designed to facilitate transparency and reduce bias in comparative analyses of real-world data.

PURPOSE: We describe constructs designed to protect the integrity of the results from comparative analyses using real-world data (RWD): staging and clean room. METHODS: Staging involves performing sequential preliminary analyses and evaluating the population size available and potential bias before conducting comparative analyses. A clean room involves restricted access to data and preliminary results, policies governing exploratory analyses and protocol deviations, and audit trail. These constructs are intended to allow decisions about protocol deviations, such as changes to design or model specification, to be made without knowledge of how they might affect subsequent analyses. We describe an example for implementing staging with a clean room. RESULTS: Stage 1 may involve selecting a data source, developing and registering a protocol, establishing a clean room, and applying inclusion/exclusion criteria. Stage 2 may involve attempting to achieve covariate balance, often through propensity score models. Stage 3 may involve evaluating the presence of residual confounding using negative control outcomes. After each stage, check points may be implemented when a team of statisticians, epidemiologists and clinicians masked to how their decisions may affect study outcomes, reviews the results. This review team may be tasked with making recommendations for protocol deviations to address study precision or bias. They may recommend proceeding to the next stage, conducting additional analyses to address bias, or terminating the study. Stage 4 may involve conducting the comparative analyses. CONCLUSIONS: The staging and clean room constructs are intended to protect the integrity and enhance confidence in the results of analyses of RWD.

Pragmatic considerations for negative control outcome studies to guide non-randomized comparative analyses: A narrative review.

PURPOSE: This narrative review describes the application of negative control outcome (NCO) methods to assess potential bias due to unmeasured or mismeasured confounders in non-randomized comparisons of drug effectiveness and safety. An NCO is assumed to have no causal relationship with a treatment under study while subject to the same confounding structure as the treatment and outcome of interest; an association between treatment and NCO then reflects the potential for uncontrolled confounding between treatment and outcome. METHODS: We focus on two recently completed NCO studies that assessed the comparability of outcome risk for patients initiating different osteoporosis medications and lipid-lowering therapies, illustrating several ways in which confounding may result. In these studies, NCO methods were implemented in claims-based data sources, with the results used to guide the decision to proceed with comparative effectiveness or safety analyses. RESULTS: Based on this research, we provide recommendations for future NCO studies, including considerations for the identification of confounding mechanisms in the target patient population, the selection of NCOs expected to satisfy required assumptions, the interpretation of NCO effect estimates, and the mitigation of uncontrolled confounding detected in NCO analyses. We propose the use of NCO studies prior to initiating comparative effectiveness or safety research, providing information on the potential presence of uncontrolled confounding in those comparative analyses. CONCLUSIONS: Given the increasing use of non-randomized designs for regulatory decision-making, the application of NCO methods will strengthen study design, analysis, and interpretation of real-world data and the credibility of the resulting real-world evidence.

A Collaborative Pilot to Support Patients With Diabetes Through Tailored Food Box Home Delivery.

We conducted a randomized, controlled prospective pilot study to determine feasibility and impact of food bank and health system collaboration to home-delivered food to adults with type 2 diabetes mellitus experiencing food insecurity. Treatment group received biweekly, ethnically tailored, home-delivered food for 24 weeks. Analysis included intervention feasibility and impact on healthcare utilization, HbA1c, and other health-related measures. Intervention was feasible and successful with high levels of participant satisfaction. At baseline, participants with highest HbA1c reported poorer health, lower medication adherence and self-care, and higher diabetes distress and medicine for food tradeoffs. At 24 weeks, treatment group reported improved food security and health status. There were no differences in HbA1c or healthcare utilization measures between the two groups. It is feasible for a community food bank and nearby hospital to successfully collaborate and provide supplemental food staples to food insecure adults with type 2 diabetes and improve food insecurity and health status. Public policy efforts should utilize and expand this strategy with the goal of improving health and reducing health disparities. Future work could include more comprehensive food support focused on those with poorest glycemic control, and expanded, coordinated interventions directed at other social determinants of health. Future programming and policies should be cocreated with community input to ensure greatest success.

Kidney-Metabolic Factors Associated with Cognitive Impairment in Chronic Kidney Disease: A Pilot Study.

INTRODUCTION: The associations of kidney-metabolic biomarkers with cognitive impairment (CI) beyond the estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) and albuminuria levels are not well understood. In exploratory analysis, our objective was to determine the extent that three kidney-metabolic factors, previously proposed as mechanisms of CI and commonly abnormal in chronic kidney disease (CKD), were associated with prevalent CI in CKD participants, adjusted for kidney function measures. METHODS: The study cohort included community-dwelling individuals aged ≥45 years with CKD (eGFR <60), not requiring dialysis, recruited from four health systems. We examined the serum biomarkers bicarbonate (CO2), TNFαR1, and cholesterol as primary exposures. A structured neuropsychological battery conducted by trained staff measured global and domain-specific cognitive performance. Logistic regression analyses estimated the cross-sectional associations between kidney-metabolic measures and global and cognitive domain-specific moderate/severe (Mod/Sev) CI, adjusted for the eGFR, urinary albumin-creatinine ratio (UACR, mg/g), demographics, comorbid conditions, and other kidney-metabolic biomarkers commonly abnormal in CKD. RESULTS: Among 436 CKD participants with mean age 70 years, 16% were Black, the mean eGFR was 34, and the median [IQR] UACR was 49 [0.0, 378] mg/g. In adjusted models, increased TNFαR1 was associated with global Mod/Sev CI (odds ratio [95% confidence interval] = 1.40 [1.02, 1.93]; p = 0.04); low bicarbonate (CO2 <20 mEq/L) with Mod/Sev memory impairment (3.04 [1.09, 8.47]; p = 0.03), and each 10-mg/dL lower cholesterol was associated with Mod/Sev executive function/processing speed impairment (1.12 [1.02, 1.23]; p = 0.02). However, after adjustment for multiple comparisons, these associations were no longer significant nor were any other kidney-metabolic factors significant for any CI classification. CONCLUSION: In exploratory analyses in a CKD population, three kidney-metabolic factors were associated with CI, but after adjustment for multiple comparisons, were no longer significant. Future studies in larger CKD populations are needed to assess these potential risk factors for CI.

Cinacalcet and gastrointestinal bleeding risk in patients receiving hemodialysis.

PURPOSE: Secondary hyperparathyroidism (SHPT) is common among dialysis patients, and calcimimetics are a mainstay of treatment. This study assessed whether cinacalcet use is associated with gastrointestinal bleeding in a large hemodialysis cohort. METHODS: A linked database of clinical records and medical claims for patients receiving hemodialysis in a large dialysis organization, 2007-2010, was used. A nested case-control study was performed among patients aged ≥18 years who had received hemodialysis for ≥90 days, had Medicare Parts A, B, and D coverage for ≥1 year, and had clinical evidence of SHPT (parathyroid hormone >300 pg/mL). Cases were those who experienced death or hospitalization caused by gastrointestinal bleeding. Each case was matched to up to four controls. Exposure was measured by any cinacalcet use, current use, past use, cumulative exposure days, and cumulative dosage. Conditional logistic models were used to assess the association. RESULTS: Of 48 437 patients included, 2570 experienced gastrointestinal bleeding events (2498 non-fatal, 72 fatal), and 2465 (2397 non-fatal, 68 fatal) were matched to 9500 controls; 17.2% of cases and 15.8% of controls had cinacalcet exposure and 11.1% of both cases and controls had current use. The adjusted odds ratios (95% CI) of gastrointestinal bleeding for any use, current use, and past use of cinacalcet were 1.04 (0.91-1.19), 0.97 (0.83-1.13), and 1.22 (0.99-1.50), respectively, with no use as the reference. CONCLUSION: The results do not suggest an elevated risk of gastrointestinal bleeding resulting in hospitalization or death for hemodialysis patients exposed to cinacalcet.

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.

Initial Effects of COVID-19 on Patients with ESKD.

BACKGROUND: Reports from around the world have indicated a fatality rate of patients with coronavirus disease 2019 (COVID-19) in the range of 20%-30% among patients with ESKD. Population-level effects of COVID-19 on patients with ESKD in the United States are uncertain. METHODS: We identified patients with ESKD from Centers for Medicare and Medicaid Services data during epidemiologic weeks 3-27 of 2017-2020 and corresponding weeks of 2017-2019, stratifying them by kidney replacement therapy. Outcomes comprised hospitalization for COVID-19, all-cause death, and hospitalization for reasons other than COVID-19. We estimated adjusted relative rates (ARRs) of death and non-COVID-19 hospitalization during epidemiologic weeks 13-27 of 2020 (March 22 to July 4) versus corresponding weeks in 2017-2019. RESULTS: Among patients on dialysis, the rate of COVID-19 hospitalization peaked between March 22 and April 25 2020. Non-Hispanic Black race and Hispanic ethnicity associated with higher rates of COVID-19 hospitalization, whereas peritoneal dialysis was associated with lower rates. During weeks 13-27, ARRs of death in 2020 versus 2017-2019 were 1.17 (95% confidence interval [95% CI], 1.16 to 1.19) and 1.30 (95% CI, 1.24 to 1.36) among patients undergoing dialysis or with a functioning transplant, respectively. Excess mortality was higher among non-Hispanic Black, Hispanic, and Asian patients. Among patients on dialysis, the rate of non-COVID-19 hospitalization during weeks 13-27 in 2020 was 17% lower versus hospitalization rates for corresponding weeks in 2017-2019. CONCLUSIONS: During the first half of 2020, the clinical outcomes of patients with ESKD were greatly affected by COVID-19, and racial and ethnic disparities were apparent. These findings should be considered in prioritizing administration of COVID-19 vaccination.

Development and outcomes of hyperkalemia in hospitalized patients: potential implications for care.

INTRODUCTION: While severe hyperkalemia is commonly encountered, its manifestation in hospitalized patients and related outcomes are unclear. We aimed to examine development of hyperkalemia in hospitalized patients and associated outcomes. METHODS: Data from a county hospital electronic health record were used to assess all inpatient admissions, 2012-2016, for non-dialysis-dependent patients with ≥1 K value for development of hyperkalemia. Unadjusted odds ratios (ORs) were calculated for associations of the maximum K value with in-hospital mortality and adjusted ORs were calculated for death associated with hyperkalemia. RESULTS: In 47,018 individual patient hospitalizations, 1.3% had a maximum K ≥6.0 mEq/L and 4.2% <3.5 mEq/L. Fifth and 95th percentiles for maximum K values were 3.5 and 5.3 mEq/L. For high-K patients with a prior K value, the mean (SD) of the immediate pre-maximum K value was 5.0 ± 1.0 mEq/L, and the mean difference in K values (immediate pre-maximum to maximum) was 1.5 ± 1.1 mEq/L; mean duration between these two K tests was 10.7 ± 14.9 hours. Compared with maximum K values 3.5 to 4.0 mEq/L, ORs for death were 37.1 (95% confidence intervals, 25.8-53.3) for K 6.0 to <6.5, 88.6 (56.8-138.2) for K ≥7.0, and 18.9 (4.3-82.2) for K <3.0 mEq/L. In adjusted models, the OR for death for K ≥6.0 mEq/L was 4.9 (3.7-6.4). DISCUSSION/CONCLUSIONS: Peak K values ≥6.0 mEq/L were associated with mortality. Values tended to increase rapidly, limiting opportunities for detection and treatment. Systems-based approaches to detect life-threatening hyperkalemia should be studied.

Risk of hyperkalemia from renin-angiotensin-aldosterone system inhibitors and factors associated with treatment discontinuities in a real-world population.

BACKGROUND: Hyperkalemia rates in renin-angiotensin-aldosterone system (RAAS) inhibitor users, and factors associated with treatment interruptions and cessations, have not been explored in a large, population-wide database. METHODS: RAAS inhibitor users were identified in the linked UK Clinical Practice Research Datalink-Hospital Episodes Statistics data set, 2009-15. Treatment interruptions (no active prescription followed by reappearance) and cessations were determined. Hyperkalemia (serum K+>5.5 mmol/L) rates were calculated and factors associated with interruptions and cessations modeled using time-varying Cox regression, including hyperkalemia (as a time-dependent variable). RESULTS: Among 434 027 RAAS inhibitor users, the hyperkalemia rate was 1.30 (95% confidence interval 1.28-1.32) per 100 patient-years. Of 73.7% of patients who experienced off-treatment periods, 57.6% experienced interruption only, 7.5% cessation only and 8.6% both. Within 1 year of initiating RAAS inhibitor treatment, approximately one-third of the patients experienced interruption or cessation. Hazard ratios for patients with severe hyperkalemia were 1.10 (10.5-1.16) for interruptions and 3.37 (3.25-3.50) for cessation. Compared with no chronic kidney disease (CKD), risk of interruption was 1.20 (1.16-1.25) and 1.57 (1.44-1.72) for Stages 4 and 5, respectively, and of cessation was 2.20 (2.07-2.33) and 2.87 (2.56-3.22). Risk of interruption increased for patients with heart failure or diabetes [1.04 (1.02-1.05); 1.13 (1.12-1.14), respectively] but the risk of cessation decreased [0.85 (0.82-0.87); 0.92 (0.90-0.94)]. CONCLUSIONS: Risk of RAAS inhibitor interruption and cessation increased as CKD stage progressed. Efforts targeting reasons for interruptions and, especially, cessations, such as hyperkalemia prevention, could decrease off-treatment periods for patients who would otherwise benefit, such as those with CKD, heart failure or diabetes.

Outcomes Following Ischemic Stroke in Older Patients With CKD Stages 4 and 5: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: The associations between ischemic stroke and time to dialysis initiation and/or death in adults with late-stage chronic kidney disease (CKD) have not been explored. We sought to measure the rate and factors associated with stroke in CKD stages 4 and 5 (CKD4-5) and assess the association of stroke with initiation of dialysis and death. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: Patients with CKD4-5 in Medicare 2007 to 2014. EXPOSURE OR PREDICTOR: Ischemic stroke in CKD4-5. OUTCOMES: Initiation of maintenance dialysis or death. ANALYTICAL APPROACH: Cox proportional hazard modeling assessed factors associated with ischemic stroke. A matched analysis (stroke/no stroke) estimated the cumulative incidence of incident kidney failure and death, treated as competing events. Simulations using a state transition model determined differences in expected time to kidney failure or death and death alone for patients with and without stroke with CKD5. RESULTS: 123,251 patients with CKD4 and 22,054 with CKD5 were identified. Mean ages were 81.0 and 79.2 years, respectively. Female sex (HRs of 1.21 [95% CI, 1.12-1.31] and 1.39 [95% CI, 1.04-1.86] for CKD4 and CKD5, respectively) and black race (HRs of 1.25 [95% CI, 1.12-1.39] and 1.12 [95% CI, 0.80-1.58] for CKD4 and CKD5, respectively) were factors associated with ischemic stroke. Rates for 30-day mortality were 13.3% and 18.8%, and for 1-year mortality, 40.0% and 38.2%. For patients with CKD5, kidney failure or death occurred an average of 3.6 months sooner for patients with an ischemic stroke, and death (irrespective of kidney failure), a mean of 24.3 months sooner. LIMITATIONS: Study design cannot determine causality; lack of data for stroke severity. CONCLUSIONS: Female sex and black race were associated with increased risk for stroke in CKD4 and CKD5. In CKD5, stroke was associated with a shorter time to kidney failure or death by nearly 4 months, and to death, by more than 2 years.

Factors Associated with Elective Withdrawal of Maintenance Hemodialysis: A Case-Control Analysis.

BACKGROUND: Associations of demographic factors with elective dialysis withdrawal and setting of death, patterns of illness trajectories preceding death, and how illness trajectories, particularly worsening putative disability, are associated with elective withdrawal are poorly understood. METHODS: Using United States Renal Data System data, we performed a case-control analysis of hemodialysis patients who died in 2010-2015. A disability proxy score characterized disability; logistic regression identified characteristics associated with death from withdrawal and with death setting; and group-based trajectory models characterized the trajectory of disability in the months preceding death. RESULTS: We identified 14,571 (9.2%) patients who withdrew and 144,305 (90.8%) who died of a non-withdrawal cause. Women were more likely than men to withdraw (OR 1.19, 95% CI 1.15-1.24). The most rural patients were more likely to withdraw than the most urban (OR 1.37, 95% CI 1.25-1.50). Medicaid coverage (a marker for impoverishment) was associated with less withdrawal (OR 0.90, 95% CI 0.86-0.94). Disability proxy score was strongly related to withdrawal: the OR for patients in the highest score category was 31.16 (95% CI 28.40-34.20) versus those with a score of 0. Women and whites (vs. blacks) were overrepresented in the worst, versus better, proxy disability score trajectory. In-hospital death and death in the intensive care unit were more common in women and minorities than in men and whites, but less common in the most rural patients. CONCLUSIONS: Important differences separate patients who electively withdraw from those who die of non-withdrawal causes. Worsening disability, in particular, may be a marker for withdrawal.

Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population.

BACKGROUND: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified. METHODS: We used data from the Centers for Disease Control and Prevention (CDC) Outpatient Influenza-like Illness Surveillance Network and Centers for Medicare and Medicaid Services ESRD death data from 2000 to 2013. After addressing the increasing trend in deaths due to the growing prevalent ESRD population, we calculated quarterly relative mortality compared with average third-quarter (summer) death counts. We used linear regression models to assess the relationship between ILI data and mortality, separately for quarters 4 and 1 for each influenza season, and model parameter estimates to predict seasonal mortality counts and calculate excess ILI-associated deaths. RESULTS: An estimated 1% absolute increase in quarterly ILI was associated with a 1.5% increase in relative mortality for quarter 4 and a 2.0% increase for quarter 1. The average number of annual deaths potentially attributable to ILI was substantial, about 1100 deaths per year. CONCLUSIONS: We found an association between community ILI activity and seasonal variation in all-cause mortality in patients with ESRD, with ILI likely contributing to >1000 deaths annually. Surveillance efforts, such as timely reporting to the CDC of ILI activity within dialysis units during influenza season, may help focus attention on high-risk periods for this vulnerable population.

Adherence to Kidney Disease: Improving Global Outcomes Mineral and Bone Guidelines for Monitoring Biochemical Parameters.

BACKGROUND: Mineral and bone disorder (MBD) is common in patients with chronic kidney disease (CKD), and is associated with risk of fractures, cardiovascular disease, and death. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend monitoring CKD-MBD biochemical markers, including parathyroid hormone (PTH), phosphorus, 25-hydroxyvitamin D (25D), calcium, and alkaline phosphatase (ALP), in patients with moderate-to-severe CKD. METHODS: To determine guideline adherence, we used administrative claims records from the 20% sample of Medicare beneficiaries with Parts A, B, and D coverage, 2007 to 2015, and identified cohorts of patients with nondialysis stage 3, 4, or 5 CKD. Testing for biochemical markers during follow-up was defined based on laboratory procedure codes. Baseline factors associated with laboratory testing were determined using logistic regression. All analyses were performed separately by CKD stage. RESULTS: A total of 640,946 stage 3, 136,278 stage 4, and 22,076 stage 5 CKD patients, 50.2-52.9% women, mean age 74.4-78.0 years, were followed for a mean of 2.5, 1.3, and 0.7 years respectively. The frequency of testing was low for PTH (35.2-48.2%), phosphorus (46.6-62.0%), and 25D (29.3-46.7%). Testing was somewhat higher for calcium (88.1-95.4%) and ALP (63.5-88.1%); most tests were features of larger panels (e.g., basic metabolic panel). Older age, most comorbid conditions, and lack of prior nephrology care were associated with lower likelihood of testing. CONCLUSIONS: In fee-for-service Medicare beneficiaries, laboratory testing for CKD-MBD biochemical markers appears to be suboptimal in relation to KDIGO guidelines. Competing priories, such as management of comorbid disease and preparation for renal replacement therapy, may distract from CKD-MBD monitoring.

Association of diabetes-related kidney disease with cardiovascular and non-cardiovascular outcomes: a retrospective cohort study.

BACKGROUND: Diabetes-related kidney disease is associated with end-stage renal disease and mortality, but opportunities remain to quantify its association with cardiovascular and non-cardiovascular morbidity outcomes. METHODS: We used the Truven Health MarketScan Commercial Claims and Encounters Database, 2010-2014, which includes specific health services records for employees and their dependents from a selection of large employers, health plans, and government and public organizations. We used administrative claims data to quantify the association between diabetes-related kidney disease and end-stage renal disease, myocardial infarction, congestive heart failure, stroke, and infections. Cox proportional hazard regression models were used to estimate adjusted hazard ratios of developing complications. RESULTS: Among 2.2 million patients with diabetes, 7.1% had diabetes-related kidney disease: 13.5%, stage 1-2; 33.8%, stage 3; 13.2% stages 4-5; 39.5%, unknown stage. In multivariable Cox proportional hazard models adjusted for demographic characteristics, baseline comorbid conditions, and total hospital days during the baseline period, hazard ratios for each outcome increased with greater diabetes-related kidney disease severity (stage 1-2 vs. stage 4-5) compared with no diabetes-related kidney disease: myocardial infarction, 1.2 (95% confidence interval 1.1-1.4) and 3.1 (2.9-3.4); congestive heart failure, 1.7 (1.6-1.9) and 5.6 (5.3-5.8); stroke, 1.3 (1.2-1.5) and 2.3 (2.1-2.5); infection, 1.4 (1.3-1.5) and 2.9 (2.8-3.0). Among patients with stage 4-5 disease, 36-month cumulative incidence was nearly 22.8% for congestive heart failure, and 25.8% for infections. CONCLUSIONS: Diabetes-related kidney disease appears to be formally diagnosed at a more advanced stage than might be expected, given clinical practice guidelines. Risks of cardiovascular and non-cardiovascular outcomes are high.

Factors Associated With Withdrawal From Maintenance Dialysis: A Case-Control Analysis.

BACKGROUND: Little is known about differences in the clinical course between patients receiving maintenance dialysis who do and do not withdraw from dialysis therapy. STUDY DESIGN: Case-control analysis. SETTING & PARTICIPANTS: US patients with Medicare coverage who received maintenance hemodialysis for 1 year or longer in 2008 through 2011. PREDICTORS: Comorbid conditions, hospitalizations, skilled nursing facility stays, and a morbidity score based on durable medical equipment claims. OUTCOME: Withdrawal from dialysis therapy. MEASUREMENTS: Rates of medical events, hospitalizations, skilled nursing facility stays, and a morbidity score. RESULTS: The analysis included 18,367 (7.7%) patients who withdrew and 220,443 (92.3%) who did not. Patients who withdrew were older (mean age, 75.3±11.5 [SD] vs 66.2±14.1 years) and more likely to be women and of white race, and had higher comorbid condition burdens. The odds of withdrawal among women were 7% (95% CI, 4%-11%) higher than among men. Compared to age 65 to 74 years, age 85 years or older was associated with higher adjusted odds of withdrawal (adjusted OR, 1.61; 95% CI, 1.54-1.68), and age 18 to 44 years with lower adjusted odds (adjusted OR, 0.36; 95% CI, 0.32-0.40). Blacks, Asians, and Hispanics were less likely to withdraw than whites (adjusted ORs of 0.36 [95% CI, 0.35-0.38], 0.47 [95% CI, 0.42-0.53], and 0.46 [95% CI, 0.44-0.49], respectively). A higher durable medical equipment claims-based morbidity score was associated with withdrawal, even after adjustment for traditional comorbid conditions and hospitalization; compared to a score of 0 (lowest presumed morbidity), adjusted ORs of withdrawal were 3.48 (95% CI, 3.29-3.67) for a score of 3 to 4 and 12.10 (95% CI, 11.37-12.87) for a score ≥7. Rates of medical events and institutionalization tended to increase in the months preceding withdrawal, as did morbidity score. LIMITATIONS: Results may not be generalizable beyond US Medicare patients; people who withdrew less than 1 year after dialysis therapy initiation were not studied. CONCLUSIONS: Women, older patients, and those of white race were more likely to withdraw from dialysis therapy. The period before withdrawal was characterized by higher rates of medical events and higher levels of morbidity.

Insights From the 2016 Peer Kidney Care Initiative Report: Still a Ways to Go to Improve Care for Dialysis Patients.

Although outcomes improved during the past decade for patients receiving maintenance dialysis, gains were few in certain key areas, as highlighted in the 2016 Peer Kidney Care Initiative Report. Overall incidence rates of dialysis therapy initiation in adults remained relatively stable (∼42 per 100,000 US population, 2009-2013), but rates varied more than 2-fold, from 26 to 54, across US geographic regions. Hospitalization rates in incident patients decreased from 261 hospitalizations per 100 patient-years in 2003 to 207 in 2012, but observation stay rates increased from 40 to 67, attenuating the decline in hospitalizations by half. Decreases in prevalent patient hospitalizations for heart failure, from 15.6 per 100 patient-years in 2004 to 9.5 in 2013, were partially offset by increases in hospitalizations for volume overload, from 3.0 in 2004 to 6.1 in 2013. Prevalent patient rates of hospitalizations for arrhythmias (∼4.6 per 100 patient-years) did not improve during the past decade, whereas sudden cardiac death as a proportion of total cardiovascular deaths increased from 53% to 73%. Hospitalization rates for pneumonia/influenza, at about 8.3 per 100 patient-years in prevalent patients, did not decrease during this period, while hospitalization rates for bacteremia/sepsis increased from 8.6 to 12.0. If decreases in mortality rates are to be sustained, novel approaches to these challenges will be required.