Associations of COVID-19 Outcomes with Dialysis Modalities and Settings.

How maintenance dialysis modality, dialysis setting, and residence in a nursing facility have jointly associated with coronavirus disease 2019 (COVID-19)-related outcomes in the United States is relevant to future viral outbreaks. Using Medicare claims, we determined the incidence of COVID-19-related infection, hospitalization, and death between March 15, 2020 and June 5, 2021. The exposure was one of five combinations of dialysis modality and care setting: in-facility hemodialysis without a recent history of skilled nursing facility care, in-facility hemodialysis with a recent history of skilled nursing facility care, hemodialysis in a skilled nursing facility, home hemodialysis, and (home) peritoneal dialysis. Patient-weeks were pooled to estimate the adjusted associations of event incidence with each dialysis modality/setting during four intervals in 2020-2021. Relative to in-facility hemodialysis without a recent history of skilled nursing facility care, home dialysis was associated with 36%-60% lower odds of all events during weeks 12-23 of 2020; 24%-37% lower odds of all events during weeks 24-37 of 2020; 20%-33% lower odds of infection and hospitalization during the winter of 2020-2021; and similar odds of all events thereafter. In contrast, exposure to skilled nursing facilities was associated with 570%-1140% higher odds of all events during spring of 2020, although excess risk attenuated as the pandemic transpired, especially among patients who received hemodialysis in skilled nursing facilities. In conclusion, home dialysis was associated with lower risks of COVID-19 diagnosis, hospitalization, and death until vaccines were available, whereas care in skilled nursing facilities was associated with higher risks.

Challenges of Conducting Clinical Trials during the SARS-CoV-2 Pandemic: The ASCEND Global Program Experience.

The coronavirus disease 2019 pandemic has had an unprecedented effect on health and health care and posed challenges to the conduct of clinical trials.Targeted mitigating strategies, on the basis of early and continued data collection from site surveys, limited disruption to the ASCEND trials.Flexibly allowing hemoglobin assessment at local laboratories to inform randomized treatment dosing was key to limiting the discontinuation of treatment.

Catheter-Associated Bloodstream Infections among Patients on Hemodialysis: Progress before and during the COVID-19 Pandemic.

Measures implemented to prevent transmission of severe acute respiratory syndrome coronavirus 2 in outpatient dialysis facilities may also help to prevent catheter-associated bloodstream infections in patients receiving hemodialysis. We used United States Renal Data System data to examine rates of antibiotic administration within dialysis facilities and rates of hospital admission for catheter-associated bloodstream infection from March 2018 through November 2020, and rates of hospitalization for sepsis, to address overall changes in hospitalization during the coronavirus disease 2019 (COVID-19) pandemic. Using logistic regression, we estimated year-over-year adjusted odds ratios of these events in 3-month intervals. During the first 6 months of the pandemic, rates of antibiotic administration were between 20% and 21% lower, and rates of hospitalization for catheter-associated bloodstream infection were between 17% and 24% lower than during corresponding periods in 2019, without significant changes in rates of hospitalization for sepsis. However, rates of catheter-associated events also decreased between 2018 and 2019, driven by reductions in facilities operated by a large dialysis provider. These data suggest that significant reductions in catheter-associated infections occurred during the pandemic, superimposed on nonpandemic-related reductions in some facilities before the pandemic. Even after the pandemic, it may be prudent to continue some COVID-19 mitigation measures to prevent catheter-associated bloodstream infections.

Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis.

BACKGROUND: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels. METHODS: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25. RESULTS: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.).

Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis.

BACKGROUND: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown. METHODS: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).

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.

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time.

BACKGROUND: Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. METHODS: We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m2. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. RESULTS: By eGFRcr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m2 and ESKD was 32% shorter for Blacks versus Whites. By eGFRcys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFRcr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24-25 ml/min per 1.73 m2 might improve racial equity in accruable wait time before ESKD onset. CONCLUSIONS: Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.

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.