Kidney Function and Physical Performance Decline: The Brain in Kidney Disease (BRINK) Cohort Study.

Rationale & Objective: Patients with kidney failure have poor physical performance, but its trajectory is less clear. We examined physical function over the course of kidney disease, including the transition to dialysis. Study Design: Observational cohort. Setting & Participants: Community-dwelling adults aged ≥45 years in the Brain in Kidney Disease (BRINK) cohort study. Predictors: Estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR). Outcomes: Change in physical performance using the Short Physical Performance Battery (SPPB) (primary) and gait speed (secondary). Analytical Approach: Linear mixed effects regression models. Results: The analytical cohort included 562 participants with mean age of 69.3 (SD, 9.8) years followed for up to 63 months. In total, 49.8% were women. In addition, 79.9% self-identified as White, and 15.3% self-identified as Black. In total, 48.8% had diabetes. Mean eGFR at baseline was 48.1 (SD, 24.3) mL/min/1.73 m2. In unadjusted analysis, lower eGFR was associated with greater decline in SPPB score (P trend < 0.001). The decline in SPPB score was larger among participants with lower eGFR, with a gradient from -0.15 (95% CI, -0.23 to -0.07) points per year for participants with eGFR ≥60 mL/min/1.73 m2 to -0.56 (95% CI, -0.84 to -0.27) for participants with eGFR <15 mL/min/1.73 m2 and -0.61 (95% CI, -0.90 to -0.33) after dialysis initiation. In covariate-adjusted models, SPPB did not continue to decline after dialysis initiation. In secondary analyses evaluating change in gait speed, gait speed continued to decline after dialysis initiation. Higher UACR was also associated with a greater decline in SPPB score and gait speed in unadjusted and adjusted models. Limitations: Small number of participants started dialysis. Conclusions: We found a graded association of chronic kidney disease stage and albuminuria with decline in physical performance. The decline in SPPB was not accelerated after dialysis initiation in covariate-adjusted models, whereas gait speed continued to decline.

Physical function is an important patient-centered outcome in chronic kidney disease (CKD), but whether physical performance changes as kidney disease progresses or when patients start dialysis is not well understood. We found that measures of physical performance, like strength and walking speed, worsened as kidney disease worsened. However, 1 combination of physical performance tests appeared stable (rather than getting worse) after starting dialysis compared to those with very advanced CKD who had not yet started dialysis, while gait speed continued to get worse. This information may help counsel patients who are learning about CKD and considering treatment options. It may also help guide research on interventions to improve physical function in patients with CKD.

The ASCEND-NHQ randomized trial found positive effects of daprodustat on hemoglobin and quality of life in patients with non-dialysis chronic kidney disease.

The ASCEND-NHQ trial evaluated the effects of daprodustat on hemoglobin and the Medical Outcomes Study 36-item Short Form Survey (SF-36) Vitality score (fatigue) in a multicenter, randomized, double-blind, placebo-controlled trial. Adults with chronic kidney disease (CKD) stages 3-5, hemoglobin 8.5-10.0 g/dl, transferrin saturation 15% or more, and ferritin 50 ng/ml or more without recent erythropoiesis-stimulating agent use were randomized (1:1) to oral daprodustat or placebo to achieve and maintain target hemoglobin of 11-12 g/dl over 28 weeks. The primary endpoint was the mean change in hemoglobin between baseline and the evaluation period (Weeks 24-28). Principal secondary endpoints were proportion of participants with a 1 g/dl or more increase in hemoglobin and mean change in the Vitality score between baseline and Week 28. Outcome superiority was tested (1-sided alpha level of 0.025). Overall, 614 participants with non-dialysis-dependent CKD were randomized. The adjusted mean change in hemoglobin from baseline to the evaluation period was greater with daprodustat (1.58 vs 0.19 g/dl). The adjusted mean treatment difference (AMD) was significant at 1.40 g/dl (95% confidence interval 1.23, 1.56). A significantly greater proportion of participants receiving daprodustat showed a 1 g/dl or greater increase in hemoglobin from baseline (77% vs 18%). The mean SF-36 Vitality score increased by 7.3 and 1.9 points with daprodustat and placebo, respectively; a clinically and statistically significant 5.4 point Week 28 AMD increase. Adverse event rates were similar (69% vs 71%); relative risk 0.98, (95% confidence interval 0.88, 1.09). Thus, in participants with CKD stages 3-5, daprodustat resulted in a significant increase in hemoglobin and improvement in fatigue without an increase in the overall frequency of adverse events.

Regional Variation of Erythropoiesis-Stimulating Agent Hyporesponsiveness in the Global Daprodustat Dialysis Study (ASCEND-D).

INTRODUCTION: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) affects 10-15% of the chronic dialysis population. We explored baseline characteristics and predictors of ESA hyporesponsiveness in a global randomized cardiovascular outcomes study comparing an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), daprodustat, with conventional ESA treatment. METHODS: ASCEND-D (NCT02879305) recruited 2,964 chronic dialysis patients receiving ESA treatment (standardized to weekly intravenous [IV] epoetin) who were iron replete at baseline. The primary ESA hyporesponsiveness definition was an ESA Resistance Index (ERI, ESA units/kg/week/hemoglobin g/L) ≥2 or IV standardized ESA dose ≥450 units/kg/week. Predictors of ESA hyporesponsiveness were determined using a multivariable regression model. Alternative hyporesponder definitions were explored. RESULTS: Using the primary definition, 354 (12%) patients were ESA hyporesponsive. Geographic region, notably Latin America, lower baseline body mass index and transferrin saturation, younger age, lower albumin concentration, and a higher baseline IV iron dose were identified as strongly associated (p < 0.001) with ESA hyporesponsiveness. Additional predictors of ESA hyporesponsiveness included female sex (p = 0.010), history of heart failure (p = 0.035), longer dialysis vintage (p = 0.077), smoking status (p = 0.247), aspirin use (p = 0.121), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (p = 0.214). CONCLUSION: This is the first global HIF-PHI study to report prespecified definitions and predictors of ESA hyporesponsiveness. While most of the predictors identified in our study have been previously reported, geographic region stands out as an unexpected finding, meriting further investigation.

Estimated GFR, Albuminuria, and Physical Function: The Brain in Kidney Disease (BRINK) Cohort Study.

Rationale & Objective: Chronic kidney disease (CKD) is associated with impaired physical performance. However, the association between albuminuria, a marker of vascular endothelial dysfunction, and physical performance has not been fully characterized. We hypothesized that estimated glomerular filtration rate (eGFR) and albuminuria would be independently associated with physical performance. Study Design: Cross-sectional analysis. Setting & Participants: A total of 571 adults with and without CKD. Predictors: Creatinine-based eGFR (eGFRCr) and cystatin C-based eGFR (eGFRCysC) and urine albumin to creatinine ratio (UACR). Outcome: Short Physical Performance Battery (SPPB). Analytical Approach: Univariate and multivariable logistic regression models were used to examine associations of eGFR and UACR with impaired physical performance. Results: Of the 571 participants (mean age, 69.3 years), 157 (27.5%) had eGFRCr (mL/min/1.73m2) <30, 276 (48.3%) had eGFRCr 30-<60, and 138 (24.2%) had eGFRCr ≥60; 303 (55.3%) participants had eGFRcysC <30, 141 (25.7%) had eGFRcysC 30-<60, and 104 (19.0%) had eGFRcysC ≥60. Impaired physical performance was observed in 222 (38.9%) participants. Separate univariate analyses showed that lower eGFRCr, lower eGFRCysC, and higher UACR were associated with higher odds of impaired physical performance. In the adjusted model with eGFRCr or eGFRCysC, UACR, and covariates, UACR retained a statistically significant association with impaired physical performance (adjusted odds ratio [OR], 2.04; 95% confidence interval [CI], 1.21-3.47 for UACR from 30-300 mg/g vs <30 mg/g and adjusted OR, 1.93; 95% CI, 1.01-3.69 for UACR >300 mg/g vs <30 mg/g), but eGFRCr and eGFRCysC did not. Limitations: Cross-sectional analysis, estimated rather than measured GFR. Conclusions: Only UACR was associated with worse physical performance in the fully adjusted model, suggesting that vascular endothelial function and inflammation may be important mechanisms of decreased physical function. Similar results were found using eGFRCr or eGFRCysC, suggesting that confounding based on muscle mass does not explain the lack of an association between eGFRCr and physical performance.

Comparison of 2021 CKD-EPI Equations for Estimating Racial Differences in Preemptive Waitlisting for Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Wait time for kidney transplantation can accrue when GFR is ≤20 ml/min. We examined whether using the race-free 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to guide preemptive waitlisting could attenuate racial differences in accruable preemptive wait time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our retrospective cohort study included Black or White Chronic Renal Insufficiency Cohort (CRIC) participants who were theoretically eligible for waitlist registration. We used Weibull accelerated failure time models to determine the association between race (Black or White) and time to kidney failure from the qualifying visit when the eGFR by creatinine or creatinine-cystatin C 2021 CKD-EPI equations fell to ≤20 ml/min per 1.73 m2. We then tested for differences in the time ratios from models using the 2021 creatinine- or creatinine-cystatin C-based CKD-EPI equation through a bootstrapping approach. RESULTS: By the creatinine equation, 472 CRIC participants were theoretically eligible for waitlist registration, and potential preemptive wait time was similar for Black versus White participants (time ratio, 1.05; 95% confidence interval, 0.81 to 1.35). The median wait time by the creatinine equation that could be accrued for Black participants was 23 versus 22 months in White participants. By the creatinine-cystatin C equation, 441 CRIC participants were eligible, and potential wait time was 20% shorter (95% confidence interval, 0.62 to 1.02) for Black than White participants. The median wait time that could be accrued for Black participants was 21 versus 26 months for White participants when using the creatinine-cystatin C equation. Using bootstrapping, the ratio of the time ratio of the models using the creatinine versus creatinine-cystatin C equation was statistically significantly different (ratio of the time ratios = 1.31 with 95% confidence interval, 1.06 to 1.62). CONCLUSIONS: Use of the 2021 creatinine-based CKD-EPI equation to determine preemptive waitlist eligibility reduced racial differences in preemptive wait time accrual more than use of the creatinine-cystatin C 2021 CKD-EPI equation within a theoretical context.

Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients: A Randomized Clinical Trial.

Importance: Daprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported. Objective: To evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients. Design, Setting, and Participants: This prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete. Interventions: Randomized 1:1 to daprodustat or darbepoetin alfa. Main Outcomes and Measures: The primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability. Results: A total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa. Conclusions and Relevance: This randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population. Trial Registration: ClinicalTrials.gov Identifier: NCT03029208.

Kidney transplant candidacy evaluation and waitlisting practices in the United States and their association with access to transplantation.

There are limited data on the degree of variability in practices surrounding prioritization of referrals for transplant evaluation and criteria for transplant candidacy and their association with transplantation rates. We surveyed transplant programs across the United States between January 2020 and May 2020 to determine current pre-transplantation practices. We examined the relation between these reported practices and the outcomes of waitlisted patients at responding programs between January 2015 and March 2021 using Scientific Registry of Transplant Recipients data. We used adjusted Cox models with random effects to accommodate clustering by program. Primary outcomes included living or deceased donor transplantation. Of 172 surveyed programs, 90 participated. Substantial variations were noted in when the candidacy evaluation began (13% reported when eGFR was <30 mL/min/1.73 m2 and 17% reported no set policy) and the approach to pre-transplantation cardiac workup (multi-modality [58%], stress echocardiogram [20%]). Using adjusted models, a program policy of using other measures of body habitus to determine transplant candidacy rather than requiring patients to meet a body mass index (BMI) threshold of ≤35 kg/m2 (reference group) for candidacy was associated with a higher hazard of living donor transplantation (HR 1.83 [95% CI 1.10-3.03]). Pre-transplant practices vary substantially across the United States, and select practices were associated with transplantation rates.

The ASCEND-ND trial: study design and participant characteristics.

BACKGROUND: Anaemia is common in chronic kidney disease (CKD) and assessment of the risks and benefits of new therapies is important. METHODS: The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3-5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8-10 g/dL or receiving ESAs with screening Hb of 8-12 g/dL. Participants were randomized to daprodustat or darbepoetin alfa (1:1) in an open-label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28-52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials. RESULTS: Overall, 3872 patients were randomized from 39 countries (median age 67 years, 56% female, 56% White, 27% Asian and 10% Black). The median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and estimated glomerular filtration rate was 18 mL/min/1.73 m2. Among randomized patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin-angiotensin system blockers, 55% were taking statins and 49% were taking oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials. CONCLUSION: ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.

Study design and baseline characteristics of patients on dialysis in the ASCEND-D trial.

BACKGROUND: The Anemia Studies in chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Dialysis (ASCEND-D) trial will test the hypothesis that daprodustat is noninferior to comparator epoetin alfa or darbepoetin alfa for two co-primary endpoints: hemoglobin (Hb) efficacy and cardiovascular (CV) safety. METHODS: We report the trial design, key demographic, clinical and laboratory findings, and baseline therapies of 2964 patients randomized in the open-label (sponsor-blinded) active-controlled, parallel-group, randomized ASCEND-D clinical trial. We also compare baseline characteristics of ASCEND-D patients with patients who are on dialysis (CKD G5D) enrolled in other large CV outcome trials (CVOTs) and in the most relevant registries. RESULTS: The median age of patients was 58 years, 43% were female; 67% were White and 16% were Black. The median Hb at baseline was 10.4 g/dL. Among randomized patients, 89% were receiving hemodialysis and 11% peritoneal dialysis. Among key comorbidities, 42% reported a history of diabetes mellitus and 45% a history of CV disease. Median blood pressure was 134/74 mmHg. The median weekly dose of epoetin was 5751 units. Intravenous and oral iron uses were noted in 64 and 11% of patients, respectively. Baseline demographics were similar to patients with CKD G5D enrolled in other CVOTs and renal patient registries. CONCLUSIONS: ASCEND-D will evaluate the efficacy and safety of daprodustat compared with epoetin alfa or darbepoetin alfa in the treatment of patients with anemia with CKD G5D.This trial is registered with ClinicalTrials.gov: NCT02879305. EudraCT Number: 2016-000541-31; Sponsor Protocol Number: 200807.

Atherosclerotic Renovascular Disease: A KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference.

The diagnosis and management of atherosclerotic renovascular disease (ARVD) is complex and controversial. Despite evidence from the ASTRAL (2009) and CORAL (2013) randomized controlled trials showing that percutaneous renal artery revascularization did not improve major outcomes compared with best medical therapy alone over 3-5 years, several areas of uncertainty remain. Medical therapy, including statin and antihypertensive medications, has evolved in recent years, and the use of renin-angiotensin-aldosterone system blockers is now considered the primary means to treat hypertension in the setting of ARVD. However, the criteria to identify kidneys with renal artery stenosis that have potentially salvageable function are evolving. There are also data suggesting that certain high-risk populations with specific clinical manifestations may benefit from revascularization. Here, we provide an overview of the epidemiology, diagnosis, and treatment of ARVD based on consensus recommendations from a panel of physician experts who attended the recent KDIGO (Kidney Disease: Improving Global Outcomes) Controversies Conference on central and peripheral arterial diseases in chronic kidney disease. Most focus is provided for contentious issues, and we also outline aspects of investigation and management of ARVD that require further research.

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.).

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

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

Association of Cognitive Function Screening Results with Adherence and Performance in a Pedometer-Based Intervention.

INTRODUCTION: A randomized, controlled trial of a pedometer-based walking intervention with weekly activity goals led to increased walking among dialysis patients. We examined whether impairment per cognitive function screening is associated with adherence and performance in the intervention. METHODS: Thirty dialysis patients were randomly assigned to a 3-month pedometer-based intervention with weekly goals. Participants were administered the Telephone Interview of Cognitive Status (TICS), a test of global mental status. We examined the association of levels of impairment on the TICS (≥33: unimpaired, 26-32: ambiguous impairment, 21-25: mild cognitive impairment [MCI]) with adherence, achieving weekly goals, and increasing steps, physical performance (Short Physical Performance Battery, SPPB), and self-reported physical function (PF) through multivariable linear mixed-model and logistic regression analyses adjusted for age, sex, BMI, dialysis modality, baseline steps, baseline SPPB, and stroke status. RESULTS: One-third of participants were unimpaired, and 13% had MCI. Participants with worse results on cognitive function screening missed more calls and completed fewer weekly goals than participants with better results. During the intervention, a worse result on cognitive function screening was associated with smaller increases in steps compared to those without impairment: (ambiguous: -620 [95% CI -174, -1,415], MCI: -1,653 [95% CI -120, -3,187]); less improvement in SPPB (ambiguous: -0.22 points [95% CI -0.08, -0.44], MCI: -0.45 [95% CI -0.13, -0.77]); and less improvement in PF (ambiguous: -4.0 points [95% CI -12.2, 4.1], MCI: -14.0 [95% CI -24.9, -3.1]). During the postintervention period, a worse result on cognitive function screening was associated with smaller increases in SPPB (ambiguous: -0.54 [95% CI -1.27, 0.19], MCI: -0.97 [95% CI -0.37, -1.58]) and PF (ambiguous: -3.3 [95% CI -6.5, -0.04], MCI: -10.5 [95% CI -18.7, -2.3]). DISCUSSION/CONCLUSION: Participants with worse results on cognitive function screening had worse adherence and derived less benefit from this pedometer-based intervention. Future exercise interventions should be developed incorporating methods to address cognitive impairment, for example, by including caregivers when planning such interventions.

Central and peripheral arterial diseases in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Chronic kidney disease (CKD) affects about 10% of all populations worldwide, with about 2 million people requiring dialysis. Although patients with CKD are at high risk of cardiovascular disease and events, they are often underrepresented or excluded in clinical trials, leading to important knowledge gaps about how to treat these patients. KDIGO (Kidney Disease: Improving Global Outcomes) convened the fourth clinical Controversies Conference on the heart, kidney and vasculature in Dublin, Ireland, in February 2020, entitled Central and Peripheral Arterial Diseases in Chronic Kidney Disease. A global panel of multidisciplinary experts from the fields of nephrology, cardiology, neurology, surgery, radiology, vascular biology, epidemiology, and health economics attended. The objective was to identify key issues related to the optimal detection, management, and treatment of cerebrovascular diseases, central aortic disease, renovascular disease, and peripheral artery disease in the setting of CKD. This report outlines the common pathophysiology of these vascular processes in the setting of CKD, describes best practices for their diagnosis and management, summarizes areas of uncertainty, addresses ongoing controversial issues, and proposes a research agenda to address key gaps in knowledge that, when addressed, could improve patient care and outcomes.

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.

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

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

An overview of frailty in kidney transplantation: measurement, management and future considerations.

The construct of frailty was first developed in gerontology to help identify older adults with increased vulnerability when confronted with a health stressor. This article is a review of studies in which frailty has been applied to pre- and post-kidney transplantation (KT) populations. Although KT is the optimal treatment for end-stage kidney disease (ESKD), KT candidates often must overcome numerous health challenges associated with ESKD before receiving KT. After KT, the impacts of surgery and immunosuppression represent additional health stressors that disproportionately impact individuals with frailty. Frailty metrics could improve the ability to identify KT candidates and recipients at risk for adverse health outcomes and those who could potentially benefit from interventions to improve their frail status. The Physical Frailty Phenotype (PFP) is the most commonly used frailty metric in ESKD research, and KT recipients who are frail at KT (~20% of recipients) are twice as likely to die as nonfrail recipients. In addition to the PFP, many other metrics are currently used to assess pre- and post-KT vulnerability in research and clinical practice, underscoring the need for a disease-specific frailty metric that can be used to monitor KT candidates and recipients. Although frailty is an independent risk factor for post-transplant adverse outcomes, it is not factored into the current transplant program risk-adjustment equations. Future studies are needed to explore pre- and post-KT interventions to improve or prevent frailty.

Racial and Ethnic Disparities in Kidney Transplant Access Within a Theoretical Context of Medical Eligibility.

BACKGROUND: Non-Hispanic black (NHB) and Hispanic patients have lower access to kidney transplantation compared to non-Hispanic whites (NHWs). We examined whether differences in the prevalence of comorbidities that affect eligibility for transplant contribute to disparities in receipt of transplantation. METHODS: We performed a retrospective study of 986 019 adults who started dialysis between 2005 and 2014, according to the United States Renal Data System. We compared prevalence of comorbidities that could influence transplant eligibility by race/ethnicity. We examined time to first transplant by race/ethnicity in this overall cohort and in a very healthy sub-cohort without conditions that could be contraindications to transplantation. RESULTS: During 2.3 years of mean follow-up, 64 892 transplants occurred. NHBs and Hispanics had a lower prevalence of medical barriers to transplantation at the time of dialysis initiation than NHWs, including age >70 years (26% in NHB versus 47% in NHW) and malignancy (4% in Hispanics versus 10% in NHWs). Access to transplant was 65% lower (95% CI, 0.33-0.37) in NHBs and 43% lower (95% CI, 0.54-0.62) in Hispanics (versus NHWs) in the first year after end-stage renal disease, but by Year 4, access to transplantation was not statistically significantly different between Hispanics or NHBs (versus NHWs). In our very healthy cohort, racial and ethnic disparities in access to transplantation persisted up to Year 5 in NHBs and Year 4 in Hispanics after end-stage renal disease onset. CONCLUSIONS: Differences in medical eligibility do not appear to explain racial/ethnic disparities in receipt of kidney transplantation and may mask the actual magnitude of the inequities that are present.

Validation of a New Physical Activity Instrument Against Pedometers Among Dialysis Patients.

OBJECTIVE(S): The newly developed Low Physical Activity Questionnaire (LoPAQ) was designed to capture the low activity level among typically sedentary patients undergoing dialysis and correlated well with a physical activity questionnaire used in the general population. However, this instrument has not been validated against a more objective measure. METHODS: We recruited patients receiving dialysis for ≥3 months from 3 dialysis facilities in San Francisco. Spontaneous walking activity was measured by pedometers over 7 days including a weekend and used as the standard reference. Patients were instructed to record their activities and step count readings. Study coordinators administered the LoPAQ during a dialysis session (hemodialysis [HD]) or clinic visit (peritoneal dialysis [PD]). The LoPAQ ascertains time and energy expended in walking activity, as well as light, moderate, and vigorous activity, and total physical activity during a 1-week recall period with 11 simple questions and requires approximately 10 minutes to administer. The LoPAQ also asks about time spent in sitting activities over 1 week. Spearman correlation was used to determine whether the LoPAQ results correlate with step counts. RESULTS: Sixty dialysis patients (HD = 48, PD = 12) completed the LoPAQ and wore a pedometer for 1 week. Mean age was 58.0 ± 12.7 years, 78.3% were men, and median dialysis vintage was 3.1 (IQR, 1.1-5.8) years. Median step count was 2,630.5 (1,270.7-5,137) steps/day. Most patients (82.8%) reported walking activity around the neighborhood, for transportation, and/or for fitness or pleasure, with a median of 595 (70-1,566.3) kcal/week. Total kilocalories per week of physical activity reported on the LoPAQ were 655 (422.8-2,336.8). Participants reported an average of 5 (3-8) sedentary hours per day. Energy expenditure in walking by the LoPAQ was highly correlated with weekly step counts (rho = 0.53, P < .001). In addition, the overall activity reported on the LoPAQ correlated with weekly pedometer readings (rho = 0.35, P = .01) and did not differ between HD and PD patients. CONCLUSIONS: The LoPAQ was easier and less time-consuming than previously validated physical activity questionnaires. LoPAQ demonstrated a good correlation with objective pedometer step counts among dialysis patients, similar to other physical activity instruments used in healthier and more active populations.