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SIGNIFICANCE STATEMENT: Serum creatinine is a product of skeletal muscle metabolism. Differences in serum creatinine concentration between Black and non-Black individuals have been attributed to differences in muscle mass but have not been thoroughly examined. Furthermore, other race and ethnic groups have not been considered. If differences in body composition explain differences in serum concentration by race or ethnicity, then estimates of body composition could be used in eGFR equations rather than race. Adjustment for intracellular water (ICW) as a proxy of muscle mass among patients with kidney failure in whom creatinine clearance should minimally influence serum concentration does not explain race- and ethnicity-dependent differences. BACKGROUND: Differences in serum creatinine concentration among groups defined by race and ethnicity have been ascribed to differences in muscle mass. We examined differences in serum creatinine by race and ethnicity in a cohort of patients receiving hemodialysis in whom creatinine elimination by the kidney should have little or no effect on serum creatinine concentration and considered whether these differences persisted after adjustment for proxies of muscle mass. METHODS: We analyzed data from 501 participants in the A Cohort Study to Investigate the Value of Exercise in ESKD/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESKD study who had been receiving hemodialysis for >1 year. We examined the independent associations among race and ethnicity (Black, Asian, non-Hispanic White, and Hispanic), serum creatinine, and ICW (L/m 2 ), a proxy for muscle mass, derived by whole-body multifrequency bioimpedance spectroscopy, using multivariable linear regression with adjustment for several demographic, clinical, and laboratory characteristics. We examined the association of race and ethnicity with serum creatinine concentration with and without adjustment for ICW. RESULTS: Black, Asian, and Hispanic patients had higher serum creatinine concentrations (+1.68 mg/dl [95% confidence interval (CI), 1.09 to 2.27], +1.61 mg/dl [95% CI, 0.90 to 2.32], and +0.83 [95% CI, 0.08 to 1.57], respectively) than non-Hispanic White patients. Overall, ICW was associated with serum creatinine concentration (0.26 mg/dl per L/m 2 ICW; 95% CI, 0.006 to 0.51) but was not statistically significantly different by race and ethnicity. Black, Asian, and Hispanic race and ethnicity remained significantly associated with serum creatinine concentration after adjustment for ICW. CONCLUSION: Among patients receiving dialysis, serum creatinine was higher in Black, Asian, and Hispanic patients than in non-Hispanic White patients. Differences in ICW did not explain the differences in serum creatinine concentration across race groups.
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Creatinina , Etnicidad , Músculos , Grupos Raciales , Diálisis Renal , Humanos , Estudios de Cohortes , Creatinina/sangreRESUMEN
SIGNIFICANCE STATEMENT: The Advancing American Kidney Health Initiative aims to increase rates of utilization of peritoneal dialysis (PD) in the United States. One of the first steps to PD is successful catheter placement, which can be performed by surgeons, interventional radiologists, or nephrologists. We examined the association between operator subspecialty and risk of needing a follow-up procedure in the first 90 days after initial PD catheter implantation. Overall, we found that 15.5% of catheters required revision, removal, or a second catheter placement within 90 days. The odds of requiring a follow-up procedure was 36% higher for interventional radiologists and 86% higher for interventional nephrologists compared with general surgeons. Further research is needed to understand how to optimize the function of catheters across different operator types. BACKGROUND: The US government has implemented incentives to increase the use of PD. Successful placement of PD catheters is an important step to increasing PD utilization rates. Our objective was to compare initial outcomes after PD catheter placement by different types of operators. METHODS: We included PD-naïve patients insured by Medicare who had a PD catheter inserted between 2010 and 2019. We examined the association between specialty of the operator (general surgeon, vascular surgeon, interventional radiologist, or interventional nephrologist) and odds of needing a follow-up procedure, which we defined as catheter removal, replacement, or revision within 90 days of the initial procedure. Mixed logistic regression models clustered by operator were used to examine the association between operator type and outcomes. RESULTS: We included 46,973 patients treated by 5205 operators (71.1% general surgeons, 17.2% vascular surgeons, 9.7% interventional radiologists, 2.0% interventional nephrologists). 15.5% of patients required a follow-up procedure within 90 days of the initial insertion, of whom 2.9% had a second PD catheter implanted, 6.6% underwent PD catheter removal, and 5.9% had a PD catheter revision within 90 days of the initial insertion. In models adjusted for patient and operator characteristics, the odds of requiring a follow-up procedure within 90 days were highest for interventional nephrologists (HR, 1.86; 95% confidence interval [CI], 1.56 to 2.22) and interventional radiologists (odds ratio, 1.36; 95% CI, 1.17 to 1.58) followed by vascular surgeons (odds ratio, 1.06; 95% CI, 0.97 to 1.14) compared with general surgeons. CONCLUSIONS: The probability of needing a follow-up procedure after initial PD catheter placement varied by operator specialty and was higher for interventionalists and lowest for general surgeons.
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Diálisis Peritoneal , Cirujanos , Humanos , Anciano , Estados Unidos/epidemiología , Nefrólogos , Medicare , Catéteres , Diálisis Peritoneal/métodos , Radiólogos , Catéteres de Permanencia/efectos adversosRESUMEN
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for several adverse outcomes among patients with diabetic kidney disease. Yet, optimal timing for SGLT2i after acute kidney injury (AKI) is uncertain, as are the providers responsible for post-AKI SGLT2i initiation. Using a retrospective cohort of United States Veterans with diabetes mellitus type 2 and proteinuria, we examined encounters by provider specialty before SGLT2i initiation and subsequent all-cause mortality after hospitalization with AKI, defined by a 50% or more rise in serum creatinine. Covariates included recovery, defined by return to a 110% or less of baseline creatinine, and time since AKI hospitalization. Among 21,330 eligible Veterans, 7,798 died (37%) and 6,562 received a SGLT2i (31%) over median follow-up of 2.1 years. Post-AKI SGLT2i use was associated with lower mortality risk [adjusted hazard ratio 0.63 (95% confidence interval 0.58-0.68)]. Compared with neither SGLT2i use nor recovery, mortality risk was similar with recovery without SGLT2i use [0.97 (0.91-1.02)] but was lower without recovery prior to SGLT2i use [0.62 (0.55-0.71)] and with SGLT2i use after recovery [0.60 (0.54-0.67)]. Finally, the effect of SGLT2i was stable over time (P for time-interaction 0.19). Thus, we observed reduced mortality with SGLT2i use after AKI among Veterans with diabetic kidney disease whether started earlier or later or before or after observed recovery. Hence, patients with diabetic kidney disease who receive a SGLT2i earlier after AKI experience no significant harm impacting mortality and experience a lower mortality risk than those who do not.
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Lesión Renal Aguda , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Veteranos , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/inducido químicamente , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/etiología , Veteranos/estadística & datos numéricos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/sangre , Estados Unidos/epidemiología , Factores de Tiempo , Creatinina/sangre , Proteinuria/mortalidad , Proteinuria/tratamiento farmacológico , Factores de Riesgo , Hospitalización/estadística & datos numéricosRESUMEN
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.).
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Anemia/tratamiento farmacológico , Barbitúricos/uso terapéutico , Darbepoetina alfa/uso terapéutico , Epoetina alfa/uso terapéutico , Glicina/análogos & derivados , Hematínicos/uso terapéutico , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Anciano , Anemia/etiología , Barbitúricos/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Darbepoetina alfa/efectos adversos , Epoetina alfa/efectos adversos , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Hematínicos/efectos adversos , Hemoglobinas/análisis , Humanos , Prolina Dioxigenasas del Factor Inducible por Hipoxia/antagonistas & inhibidores , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Accidente Cerebrovascular/epidemiologíaRESUMEN
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.).
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Anemia/tratamiento farmacológico , Barbitúricos/uso terapéutico , Darbepoetina alfa/uso terapéutico , Glicina/análogos & derivados , Hematínicos/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Anciano , Anemia/etiología , Barbitúricos/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Darbepoetina alfa/efectos adversos , Femenino , Glicina/efectos adversos , Glicina/uso terapéutico , Hematínicos/efectos adversos , Hemoglobinas/análisis , Humanos , Prolina Dioxigenasas del Factor Inducible por Hipoxia/antagonistas & inhibidores , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Insuficiencia Renal Crónica/sangre , Accidente Cerebrovascular/epidemiologíaRESUMEN
SIGNIFICANCE STATEMENT: Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications' ability to reduce risk of mortality and other adverse outcomes, there is concern that ACEi/ARB use may delay recovery of kidney function or precipitate recurrent AKI. Prior studies have provided conflicting data regarding the optimal timing of these medications after AKI and have not addressed the role of kidney recovery in determining appropriate timing. This study in US Veterans with diabetes mellitus and proteinuria demonstrated an association between ACEi/ARB use and lower mortality. This association was more pronounced with earlier post-AKI ACEi/ARB use and was not meaningfully affected by initiating ACEis/ARBs before versus after recovery from AKI. BACKGROUND: Optimal use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) after AKI is uncertain. METHODS: Using data derived from electronic medical records, we sought to estimate the association between ACEi/ARB use after AKI and mortality in US military Veterans with indications for such treatment (diabetes and proteinuria) while accounting for AKI recovery. We used ACEi/ARB treatment after hospitalization with AKI (defined as serum creatinine ≥50% above baseline concentration) as a time-varying exposure in Cox models. The outcome was all-cause mortality. Recovery was defined as return to ≤110% of baseline creatinine. A secondary analysis focused on ACEi/ARB use relative to AKI recovery (before versus after). RESULTS: Among 54,735 Veterans with AKI, 31,146 deaths occurred over a median follow-up period of 2.3 years. Approximately 57% received an ACEi/ARB <3 months after hospitalization. In multivariate analysis with time-varying recovery, post-AKI ACEi/ARB use was associated with lower risk of mortality (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.72 to 0.77). The association between ACEi/ARB use and mortality varied over time, with lower mortality risk associated with earlier initiation ( P for interaction with time <0.001). In secondary analysis, compared with those with neither recovery nor ACEi/ARB use, risk of mortality was lower in those with recovery without ACEi/ARB use (aHR, 0.90; 95% CI, 0.87 to 0.94), those without recovery with ACEi/ARB use (aHR, 0.69; 95% CI, 0.66 to 0.72), and those with ACEi/ARB use after recovery (aHR, 0.70; 95% CI, 0.67 to 0.73). CONCLUSIONS: This study demonstrated lower mortality associated with ACEi/ARB use in Veterans with diabetes, proteinuria, and AKI, regardless of recovery. Results favored earlier ACEi/ARB initiation.
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Lesión Renal Aguda , Diabetes Mellitus , Nefropatías Diabéticas , Veteranos , Humanos , Sistema Renina-Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/inducido químicamente , Lesión Renal Aguda/etiología , Proteinuria/tratamiento farmacológico , Proteinuria/inducido químicamente , Estudios Retrospectivos , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
Anemia is common in patients with chronic kidney disease and is associated with a high burden of morbidity and adverse clinical outcomes. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline for the diagnosis and management of anemia in chronic kidney disease. Since then, new data from studies assessing established and emerging therapies for the treatment of anemia and iron deficiency have become available. Beginning in 2019, KDIGO planned 2 Controversies Conferences to review the new evidence and its potential impact on the management of anemia in clinical practice. Here, we report on the second of these conferences held virtually in December 2021, which focused on a new class of agents-the hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs). This report provides a review of the consensus points and controversies from this second conference and highlights areas that warrant prioritization for future research.
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Anemia , Inhibidores de Prolil-Hidroxilasa , Insuficiencia Renal Crónica , Humanos , Anemia/diagnóstico , Anemia/etiología , Anemia/terapia , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/tratamiento farmacológico , Prolina Dioxigenasas del Factor Inducible por Hipoxia , Prolil Hidroxilasas , Inhibidores de Prolil-Hidroxilasa/uso terapéuticoRESUMEN
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.
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Hematínicos , Insuficiencia Renal Crónica , Adulto , Humanos , Calidad de Vida , Hemoglobinas/análisis , Barbitúricos/efectos adversos , Hematínicos/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
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.
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Anemia , Hematínicos , Humanos , Femenino , Hematínicos/uso terapéutico , Hematínicos/farmacología , Diálisis Renal/efectos adversos , Anemia/tratamiento farmacológico , Eritropoyesis , Hemoglobinas , Hierro/uso terapéuticoRESUMEN
BACKGROUND: Mortality is high within the first few months of starting chronic dialysis. Pre-ESKD trajectory of kidney function has been shown to be predictive of early death after dialysis initiation. We aim to better understand how two key aspects of pre-dialysis kidney function-an abrupt transition pattern and an episode of dialysis-requiring AKI (AKI-D) leading directly to ESKD-are associated with early mortality after dialysis initiation. METHODS: We extracted national data from U.S. Veterans Health Administration cross-linked with the United States Renal Data System (USRDS) to identify patients who initiated hemodialysis during 2009-2013. We defined abrupt transition as having a mean outpatient eGFR ≥ 30 ml/min/1.73m2 within 1 year prior to ESKD. AKI-D was identified using inpatient serum creatinine measurements (serum Cr increase by at least 50% from baseline) along with billing codes for inpatient receipt of dialysis for AKI within 30 days prior to the ESKD start date. We used multivariable proportional hazards models to examine the association between patterns of kidney function prior to ESKD and all-cause mortality within 90 days after ESKD. RESULTS: Twenty-two thousand eight hundred fifteen patients were identified in the final analytic cohort of Veterans who initiated hemodialysis and entered the USRDS. We defined five patterns of kidney function decline. Most (68%) patients (N = 15,484) did not have abrupt transition and did not suffer an episode of AKI-D prior to ESKD (reference group). The remaining groups had abrupt transition, AKI-D, or both. Patients who had an abrupt transition with (N = 503) or without (N = 3611) AKI-D had the highest risk of early mortality after ESKD onset after adjustment for demographics and comorbidities (adjusted HR 2.10, 95% CI 1.66-2.65 for abrupt transition with AKI-D; adjusted HR 2.10, 95% CI 1.90-2.33 for abrupt transition without AKI-D). In contrast, patients who experienced AKI-D without an abrupt transition pattern (N = 2141 had only a modestly higher risk of early death (adjusted HR 1.19, 95% CI 1.01-1.40). CONCLUSIONS: An abrupt decline in kidney function within 1 year prior to ESKD occurred in nearly 1 in 5 incident hemodialysis patients (18%) in this national cohort of Veterans and was strongly associated with higher early mortality after ESKD onset.
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Lesión Renal Aguda , Fallo Renal Crónico , Veteranos , Humanos , Estados Unidos/epidemiología , Fallo Renal Crónico/terapia , Estudios de Cohortes , Diálisis , Diálisis Renal , Estudios RetrospectivosRESUMEN
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.
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Trasplante de Riñón , Índice de Masa Corporal , Humanos , Donadores Vivos , Sistema de Registros , Receptores de Trasplantes , Estados Unidos , Listas de EsperaRESUMEN
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.
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Aterosclerosis , Hipertensión Renovascular , Obstrucción de la Arteria Renal , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Aterosclerosis/terapia , Humanos , Hipertensión Renovascular/diagnóstico , Hipertensión Renovascular/epidemiología , Hipertensión Renovascular/etiología , Riñón , Arteria Renal , Obstrucción de la Arteria Renal/diagnóstico , Obstrucción de la Arteria Renal/epidemiología , Obstrucción de la Arteria Renal/terapia , Sistema Renina-AngiotensinaRESUMEN
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.
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Disfunción Cognitiva , Insuficiencia Renal Crónica , Anciano , Albuminuria/epidemiología , Bicarbonatos , Dióxido de Carbono , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Estudios Transversales , Tasa de Filtración Glomerular , Humanos , Riñón , Proyectos Piloto , Factores de RiesgoRESUMEN
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.
Asunto(s)
Anemia , Eritropoyetina , Hematínicos , Insuficiencia Renal Crónica , Anemia/tratamiento farmacológico , Anemia/etiología , Darbepoetina alfa/uso terapéutico , Epoetina alfa/efectos adversos , Eritropoyetina/uso terapéutico , Femenino , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapiaRESUMEN
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.
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Anemia , Eritropoyetina , Hematínicos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Inhibidores de Prolil-Hidroxilasa , Insuficiencia Renal Crónica , Anciano , Femenino , Humanos , Masculino , Anemia/tratamiento farmacológico , Anemia/etiología , Darbepoetina alfa/uso terapéutico , Eritropoyetina/efectos adversos , Hematínicos/uso terapéutico , Hemoglobinas , Hierro , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/inducido químicamenteRESUMEN
OBJECTIVES: The importance of muscle wasting as a predictor of mortality in the hemodialysis population is not clear. Lack of association of muscle mass with survival in some studies could be related to reliance on single measures or to incorporation of excess extracellular water (ECW) into estimates of muscle mass. We examined changes in body composition over a 2-year period and the association of body composition with survival. DESIGN AND METHODS: We analyzed data from 325 adults receiving hemodialysis in the Bay Area. We estimated ECW, intracellular water (ICW), and fat mass by whole-body bioimpedance spectroscopy (BIS) at 0, 12, and 24 months from enrollment. We used linear mixed modeling to examine changes in body mass index and BIS-derived estimates of body composition and Cox modeling with BIS-derived estimates as time-varying independent variables to examine associations between body composition and survival in multivariable analyses. RESULTS: Body mass index declined over time. Considering individual components of body composition, ICW declined (-0.09 kg/m2 per year, 95% confidence interval -0.14 to -0.04), but fat mass and ECW did not change significantly. There were 120 deaths over a median of 5.2 years. The relationship between ICW and mortality was not linear such that the association was steeper at low values of ICW, whereas higher ICW was associated with better survival that was relatively stable above 9 kg/m2. Higher ECW was associated with higher mortality, and fat mass was not associated with survival. These associations were independent of markers of inflammation and nutritional status. CONCLUSIONS: ICW declined over 2 years in this cohort, whereas fat mass and ECW remained relatively stable. Higher ICW was associated with better survival, but higher fat mass was not. Higher ECW was associated with worse survival. These results suggest that muscle mass may predict survival among patients on hemodialysis.
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Tejido Adiposo , Composición Corporal , Tejido Adiposo/metabolismo , Adulto , Índice de Masa Corporal , Agua Corporal/metabolismo , Impedancia Eléctrica , Humanos , Agua/metabolismoRESUMEN
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.
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Tasa de Filtración Glomerular , Disparidades en Atención de Salud , Trasplante de Riñón , Racismo , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/cirugía , Listas de Espera , Negro o Afroamericano , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Política de Salud , Disparidades en Atención de Salud/estadística & datos numéricos , Humanos , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Racismo/estadística & datos numéricos , Factores de Tiempo , Estados Unidos , Población BlancaRESUMEN
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.
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COVID-19/complicaciones , Fallo Renal Crónico/complicaciones , SARS-CoV-2 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/etnología , COVID-19/mortalidad , COVID-19/prevención & control , Vacunas contra la COVID-19/provisión & distribución , Causas de Muerte , Etnicidad/estadística & datos numéricos , Femenino , Disparidades en Atención de Salud , Hospitalización/estadística & datos numéricos , Humanos , Fallo Renal Crónico/etnología , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Trasplante de Riñón , Masculino , Medicaid , Medicare , Persona de Mediana Edad , Mortalidad/etnología , Grupos Raciales/estadística & datos numéricos , Diálisis Renal , Estudios Retrospectivos , Análisis de Supervivencia , Triaje , Estados Unidos/epidemiología , Adulto JovenRESUMEN
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.
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COVID-19/epidemiología , Fallo Renal Crónico/epidemiología , Adolescente , Adulto , Anciano , Cateterismo Venoso Central/estadística & datos numéricos , Tasa de Filtración Glomerular , Humanos , Incidencia , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/terapia , Trasplante de Riñón/estadística & datos numéricos , Modelos Logísticos , Persona de Mediana Edad , Oportunidad Relativa , Utilización de Procedimientos y Técnicas , Diálisis Renal/estadística & datos numéricos , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Transplant candidates may gain an advantage by traveling to receive care at a transplant center that may have more favorable characteristics than their local center. Factors associated with longer travel distance for transplant care and whether the excess travel distance (ETD) is associated with access to transplantation or with graft failure are unknown. METHODS: This study of adults in the United States wait-listed for kidney transplantation in 1995-2015 used ETD, defined as distance a patient traveled beyond the nearest transplant center for initial waiting list registration. We used linear regression to examine patient and center characteristics associated with ETD and Fine-Gray models to examine the association between ETD (modeled as a spline) and time to deceased or living donor transplantation or graft failure. RESULTS: Of 373,365 patients, 11% had an ETD≥50 miles. Traveling excess distance was more likely among patients who were of non-Black race or those whose nearest transplant center had lower annual living donor transplant volume. At an ETD of 50 miles, we observed a lower likelihood of deceased donor transplantation (subhazard ratio [SHR], 0.85; 95% confidence interval [95% CI], 0.84 to 0.87) but higher likelihood of living donor transplantation (SHR, 1.14; 95% CI, 1.12 to 1.16) compared with those who received care at their nearest center. ETD was weakly associated with higher risk of graft failure. CONCLUSIONS: Patients who travel excess distances for transplant care have better access to living donor but not deceased donor transplantation and slightly higher risk of graft failure. Traveling excess distances is not clearly associated with better outcomes, especially if living donors are unavailable.