RESUMO
Enteric hyperoxaluria is a medical condition characterized by elevated urinary oxalate excretion due to increased gastrointestinal oxalate absorption. Causative features include fat malabsorption and/or increased intestinal permeability to oxalate. Enteric hyperoxaluria has long been known to cause nephrolithiasis and nephrocalcinosis, and, more recently, an association with CKD and kidney failure has been shown. Currently, there are no US Food and Drug Administration-approved therapies for enteric hyperoxaluria, and it is unclear what end points should be used to evaluate the efficacy of new drugs and biologics for this condition. This study represents work of a multidisciplinary group convened by the Kidney Health Initiative to review the evidence supporting potential end points for clinical trials in enteric hyperoxaluria. A potential clinical outcome is symptomatic kidney stone events. Potential surrogate end points include ( 1 ) an irreversible loss of kidney function as a surrogate for progression to kidney failure, ( 2 ) asymptomatic kidney stone growth/new stone formation observed on imaging as a surrogate for symptomatic kidney stone events, ( 3 ) urinary oxalate and urinary calcium oxalate supersaturation as surrogates for the development of symptomatic kidney stone events, and ( 4) plasma oxalate as a surrogate for the development of the clinical manifestations of systemic oxalosis. Unfortunately, because of gaps in the data, this Kidney Health Initiative workgroup was unable to provide definitive recommendations. Work is underway to obtain robust information that can be used to inform trial design and medical product development in this space.
Assuntos
Hiperoxalúria , Cálculos Renais , Insuficiência Renal , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/terapia , Oxalatos/urina , Cálculos Renais/etiologia , Oxalato de Cálcio/urina , Insuficiência Renal/complicaçõesRESUMO
BACKGROUND: Enteric hyperoxaluria is caused by increased intestinal oxalate absorption and can lead to kidney stones, chronic kidney disease, and kidney failure. Reloxaliase is an orally administered recombinant enzyme that degrades oxalate along the gastrointestinal tract, thereby preventing its absorption. METHODS: We randomly assigned participants with enteric hyperoxaluria to reloxaliase or placebo, three to five times per day with food for 4 weeks. The primary end point was percent change from baseline in 24-hour urinary oxalate (UOx) excretion during weeks 1 to 4. Secondary end points included the proportion of participants with more than a 20% reduction in 24-hour UOx and an efficacy assessment in the bariatric surgery subgroup. RESULTS: A total of 115 patients underwent randomization. The 24-hour UOx decreased from a baseline geometric mean of 83.2 to 67.4 mg/24 hr during weeks 1 to 4 in reloxaliase-treated participants. Corresponding data for placebo-treated participants were 84.2 to 78.1 mg/24 hr. Estimates from the mixed-effect model repeated-measures (MMRM) analysis showed a 22.6% reduction in geometric mean UOx during weeks 1 to 4 for reloxaliase and 9.7% for placebo, a difference of 14.3 percentage points (95% confidence interval [CI], 4.9 to 22.8; P=0.004). A 20% or greater reduction in 24-hour UOx was observed in 48.3% of reloxaliase-treated participants and 31.6% of placebo-treated participants (P=0.06). In the bariatric surgery subgroup, MMRM analysis showed a 21.2% reduction in geometric mean UOx for reloxaliase and a 6.0% reduction for placebo, for a difference of 16.2 percentage points (95% CI, 4.2% to 26.7%). Adverse events occurred in 69% of reloxaliase-treated participants versus 53% of individuals taking placebo and were most commonly gastrointestinal. All but one of the adverse events were grade 1 or 2 in severity; no reloxaliase-treated participants discontinued the study. CONCLUSIONS: Reloxaliase treatment for 4 weeks reduced UOx excretion in patients with enteric hyperoxaluria; adverse events were relatively common, but not dose-limiting. These data establish the foundation for a clinical trial to determine the impact of reloxaliase on nephrolithiasis in patients with enteric hyperoxaluria. (Funded by Allena Pharmaceuticals; ClinicalTrials.gov number, NCT03456830.)
Assuntos
Hiperoxalúria , Humanos , Masculino , Feminino , Adulto , Hiperoxalúria/tratamento farmacológico , Pessoa de Meia-Idade , Oxalatos/urina , Oxalatos/metabolismo , Método Duplo-Cego , Adulto Jovem , Idoso , Oxo-Ácido-LiasesRESUMO
Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative-sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.
Assuntos
Hiperoxalúria/fisiopatologia , Hiperoxalúria/terapia , Gastroenteropatias/complicações , Humanos , Hiperoxalúria/etiologiaRESUMO
Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited. Therefore, we assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate. Mean ± standard deviation age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6-73.0) mg/24 h and 81 patients had one or more stone event during a median follow-up time of 4.9 (2.8-7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event. Thus, these data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group. BACKGROUND: Data directly demonstrating the relationship between urinary oxalate (UOx) excretion and stone events in those with enteric hyperoxaluria (EH) are limited. METHODS: We assessed the relationship between UOx excretion and risk of kidney stone events in a retrospective population-based EH cohort. In all, 297 patients from Olmsted County, Minnesota were identified with EH based upon having a 24-h UOx ≥40 mg/24 h preceded by a diagnosis or procedure associated with malabsorption. Diagnostic codes and urologic procedures consistent with kidney stones during follow-up after baseline UOx were considered a new stone event. Logistic regression and accelerated failure time modeling were performed as a function of UOx excretion to predict the probability of new stone event and the annual rate of stone events, respectively, with adjustment for urine calcium and citrate. RESULTS: Mean ± SD age was 51.4 ± 11.4 years and 68% were female. Median (interquartile range) UOx was 55.4 (46.6-73.0) mg/24 h and 81 patients had ≥1 stone event during a median follow-up time of 4.9 (2.8-7.8) years. Higher UOx was associated with a higher probability of developing a stone event (P < 0.01) and predicted an increased annual risk of kidney stones (P = 0.001). Estimates derived from these analyses suggest that a 20% decrease in UOx is associated with 25% reduction in the annual odds of a future stone event. CONCLUSIONS: These data demonstrate an association between baseline UOx and stone events in EH patients and highlight the potential benefit of strategies to reduce UOx in this patient group.
Assuntos
Hiperoxalúria , Cálculos Renais , Cálculos Urinários , Adulto , Feminino , Humanos , Hiperoxalúria/diagnóstico , Hiperoxalúria/epidemiologia , Hiperoxalúria/etiologia , Cálculos Renais/diagnóstico , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Pessoa de Meia-Idade , Oxalatos , Estudos Retrospectivos , Cálculos Urinários/epidemiologia , Cálculos Urinários/etiologiaRESUMO
IgA nephropathy (IgAN) is an important cause of ESKD for which there are no approved therapies. A challenge for evaluating treatments for IgAN is the usual long time course for progression to ESKD. The aim of this Kidney Health Initiative project was to identify surrogate end points that could serve as reliable predictors of a treatment's effect on long-term kidney outcomes in IgAN and be used as a basis for approval. Proteinuria was identified as the most widely recognized and well studied risk factor for progression to ESKD in IgAN. The workgroup performed a critical review of the data on proteinuria reduction as a surrogate end point for a treatment's effect on progression to ESKD in IgAN. Epidemiologic data indicate a strong and consistent relationship between the level and duration of proteinuria and loss of kidney function. Trial-level analyses of data from 13 controlled trials also show an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death. We conclude that data support the use of proteinuria reduction as a reasonably likely surrogate end point for a treatment's effect on progression to ESKD in IgAN. In the United States, reasonably likely surrogate end points can be used as a basis for accelerated approval of therapies intended to treat serious or life-threatening conditions, such as IgAN. The clinical benefit of products approved under this program would need to be verified in a postmarketing confirmatory trial.
Assuntos
Ensaios Clínicos Controlados como Assunto/métodos , Determinação de Ponto Final , Glomerulonefrite por IGA/terapia , Proteinúria/prevenção & controle , Projetos de Pesquisa , Progressão da Doença , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/mortalidade , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Proteinúria/diagnóstico , Proteinúria/etiologia , Proteinúria/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Iron deficiency anemia is a common complication in patients with chronic kidney disease (CKD). Currently available intravenous (IV) iron replacement therapies have either inconvenient regimens of administration or adverse event profiles that limit their utility in the outpatient setting. Ferumoxytol is a novel, semisynthetic, carbohydrate-coated, superparamagnetic iron oxide nanoparticle that is administered IV as an injection. The main objective of this study was to assess the safety of ferumoxytol for the treatment of patients with CKD stages 1 to 5 and 5D. STUDY DESIGN: Phase 3, randomized, double-blind, placebo-controlled, crossover, multicenter study of a single 510-mg dose of ferumoxytol versus saline as placebo. SETTING & PARTICIPANTS: 750 patients with CKD stages 1 to 5 and 5D. INTERVENTION: An IV injection of either 17 mL of ferumoxytol or saline placebo over 17 seconds on day 0 and the alternate agent on day 7. OUTCOMES & MEASUREMENTS: Descriptive comparison of adverse events, laboratory tests, and vital signs. RESULTS: Of 750 randomly assigned patients with CKD, 60% were not on dialysis therapy. 713 patients received ferumoxytol, and 711 received placebo. There were 420 adverse events reported; 242 in 152 patients (21.3%) with ferumoxytol and 178 in 119 patients (16.7%) with placebo. The incidence of related adverse events was 5.2% with ferumoxytol and 4.5% with placebo. The most common related adverse events after each treatment included symptoms related to the injection/infusion site, dizziness, pruritus, headache, fatigue, and nausea. Serious adverse events occurred in 21 patients (2.9%) after ferumoxytol and 13 patients (1.8%) after placebo. Serious related adverse events were observed in 1 patient (0.1%) after each treatment. There was no meaningful decrease in blood pressure after administration of ferumoxytol or placebo. LIMITATIONS: Follow-up was 7 days after each study treatment. CONCLUSIONS: Ferumoxytol is well tolerated and has a safety profile similar to placebo in anemic patients with CKD stages 1 to 5 and 5D.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/etiologia , Óxido Ferroso-Férrico/uso terapêutico , Nefropatias/complicações , Idoso , Doença Crônica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Óxido Ferroso-Férrico/efeitos adversos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Iron deficiency is an important cause of anemia in patients with chronic kidney disease (CKD), but intravenous iron is infrequently used among patients who are not on dialysis. Ferumoxytol is a novel intravenous iron product that can be administered as a rapid injection. This Phase III trial randomly assigned 304 patients with CKD in a 3:1 ratio to two 510-mg doses of intravenous ferumoxytol within 5 +/- 3 d or 200 mg of elemental oral iron daily for 21 d. The increase in hemoglobin at day 35, the primary efficacy end point, was 0.82 +/- 1.24 g/dl with ferumoxytol and 0.16 +/- 1.02 g/dl with oral iron (P < 0.0001). Among patients who were not receiving erythropoiesis-stimulating agents, hemoglobin increased 0.62 +/- 1.02 g/dl with ferumoxytol and 0.13 +/- 0.93 g/dl with oral iron. Among patients who were receiving erythropoiesis-stimulating agents, hemoglobin increased 1.16 +/- 1.49 g/dl with ferumoxytol and 0.19 +/- 1.14 g/dl with oral iron. Treatment-related adverse events occurred in 10.6% of patients who were treated with ferumoxytol and 24.0% of those who were treated with oral iron; none was serious. In summary, a regimen of two doses of 510 mg of intravenous ferumoxytol administered rapidly within 5 +/- 3 d was well tolerated and had the intended therapeutic effect. This regimen may offer a new, efficient option to treat iron deficiency anemia in patients with CKD.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Óxido Ferroso-Férrico/uso terapêutico , Insuficiência Renal Crônica/complicações , Oligoelementos/uso terapêutico , Administração Oral , Idoso , Anemia Ferropriva/etiologia , Feminino , Óxido Ferroso-Férrico/administração & dosagem , Óxido Ferroso-Férrico/efeitos adversos , Humanos , Injeções Intravenosas , Ferro/administração & dosagem , Ferro/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oligoelementos/administração & dosagemRESUMO
Infections are a major cause of death in end-stage renal disease (ESRD) patients, second only to cardiovascular disease, and also contribute to significant morbidity in patients with earlier stages of chronic kidney disease (CKD). Vaccines are a strategy to attempt to reduce morbidity related to infections. Patients with CKD and ESRD may not respond as well to vaccines as patients without kidney failure, but adequate seroresponse with standard or augmented regimens for vaccinations against influenza, hepatitis B, pneumococcus, and varicella have been documented. Influenza, in particular, seems to provide adequate protection with standard dosing regimens. Despite somewhat reduced effectiveness of certain vaccines in patients with CKD, there is emerging evidence of benefit to vaccination in these populations. However, vaccination rates are relatively low. Given the accumulating evidence of benefit, continuing quality improvement programs focused on increasing vaccination rates in patients with all levels of CKD are needed.
Assuntos
Infecções Bacterianas/prevenção & controle , Falência Renal Crônica/complicações , Vacinação , Infecções Bacterianas/etiologia , HumanosRESUMO
BACKGROUND: Current recommendations for initiating dialysis therapy are based on level of kidney function and clinical evidence of uremia. Several studies reported no benefit in patient survival from initiating dialysis therapy with a greater glomerular filtration rate (GFR). Whether this is explained by a greater comorbidity burden or detrimental effect of early initiation remains unclear. We thus undertook an evaluation of the impact of comorbidity on the association between GFR at initiation and death. METHODS: Data from the Center for Medicare & Medicaid Services were used to derive 3 incident dialysis populations: (1) general population aged 18+ years, (2) older patients aged 67+ years, and (3) a "low-risk" subgroup without diabetes, heart failure, or atherosclerotic heart disease. A Cox proportional hazard regression technique was used. RESULTS: Greater GFR at initiation of dialysis therapy was associated with a greater risk for death in all populations, and sequential adjustment for additional covariates attenuated the effect. Patients in the general dialysis population who initiated dialysis therapy at a GFR greater than 10 mL/min/1.73 m2 (>0.17 mL/s) had a 42% increased risk for death compared with patients with a GFR less than 5 mL/min/1.73 m2 (<0.08 mL/s) at initiation of dialysis therapy after adjusting for all covariates. In the older and healthier populations, adjusted increased risks were 25% and 39%, respectively. CONCLUSION: Patients initiating dialysis therapy at greater GFRs have an increased risk for death not fully explained by comorbidity. Additional research is required to determine the reasons for poor survival in patients who start dialysis therapy with significant residual renal function.
Assuntos
Comorbidade , Falência Renal Crônica/terapia , Mortalidade , Diálise Renal , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Complicações do Diabetes/epidemiologia , Etnicidade/estatística & dados numéricos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Medicare , Pessoa de Meia-Idade , Modelos Teóricos , Modelos de Riscos Proporcionais , Diálise Renal/estatística & dados numéricos , Risco , Análise de Sobrevida , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Overweight and obesity are well-established risk factors for cardiovascular disease and decline in kidney function in individuals with existing chronic kidney disease (CKD). Conversely, their association with the development of CKD is less clear. METHODS: We evaluated the association between body mass index (BMI) and risk for CKD in a cohort of 11,104 initially healthy men who participated in the Physicians' Health Study and provided a blood sample after 14 years. BMI was calculated from self-reported weight and height. We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study and defined CKD as GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). RESULTS: After an average 14-year follow-up, 1,377 participants (12.4%) had a GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). Higher baseline BMI was associated consistently with increased risk for CKD. Compared with participants in the lowest BMI quintile (<22.7 kg/m2), those in the highest quintile (>26.6 kg/m2) had an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.19 to 1.76; P trend <0.001) after adjusting for potential confounders. We found similar associations by using different categories of BMI. Compared with men who remained within a +/-5% range of their baseline BMI, those who reported a BMI increase greater than 10% had a significant increase in risk for CKD (OR, 1.27; 95% CI, 1.06 to 1.53). CONCLUSION: In this large cohort of initially healthy men, BMI was associated significantly with increased risk for CKD after 14 years. Strategies to decrease CKD risk might include prevention of overweight and obesity.
Assuntos
Índice de Massa Corporal , Nefropatias/epidemiologia , Obesidade/epidemiologia , Adulto , Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Doença Crônica , Estudos de Coortes , Complicações do Diabetes/epidemiologia , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Sobrepeso , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fumar/epidemiologia , Estados Unidos/epidemiologia , beta Caroteno/uso terapêuticoRESUMO
Suboptimal health care during advancing chronic kidney disease (CKD) may result in greater morbidity and cost once dialysis is started and may preclude future transplantation. Medicare data were examined for the prevalence of selected general health, diabetes, and CKD interventions in a national cohort of patients in the 2 yr before dialysis initiation and compared with a contemporaneous non-CKD cohort. A total of 24,778 individuals who were aged > or =67 yr composed the CKD cohort, and 1,046,136 individuals who were aged > or =67 yr did not have CKD. Among patients with diabetes and CKD, fewer than two thirds had claims for eye examinations, 75% for HbA(1C) testing, and 68% for lipid testing, with similar proportions in the non-CKD cohort. Among those without diabetes, 47 and 54% of the CKD and non-CKD cohorts, respectively, had claims for lipid testing. Fewer than 50 and 15% had claims for influenza and pneumococcal vaccination, respectively, with slightly lower proportions among patients with CKD. Claims for cancer tests were found for 14 to 41% and 29 to 52% of individuals with and without CKD, respectively, depending on the type of cancer. A greater proportion of patients with diabetes tended to have claims for tests in both cohorts. In the CKD cohort, claims for anemia testing and parathyroid hormone levels were available in fewer than 50 and 15%, respectively, and claims for permanent vascular access were found for only 30% of hemodialysis patients. This study provides further evidence that patients with CKD may not be receiving general health and CKD care according to current recommendations.
Assuntos
Nefropatias/terapia , Falência Renal Crônica/terapia , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doença Crônica , Testes Diagnósticos de Rotina/estatística & dados numéricos , Feminino , Humanos , Nefropatias/complicações , Falência Renal Crônica/complicações , Masculino , Neoplasias/diagnóstico , Neoplasias/etiologiaRESUMO
BACKGROUND: Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS: Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic renovascular disease in the 2 years preceding December 31, 1999 (N= 1,085,250), followed until December 31, 2001. RESULTS: The incidence of atherosclerotic renovascular disease was 3.7 per 1000 patient-years. Major antecedent associations [P < 0.05, with adjusted hazards ratios (HR) > 1.5] included chronic kidney disease (adjusted HR 2.54), hypertension (2.42), peripheral vascular disease (2.00), and atherosclerotic heart disease (1.70). Adverse event rates after incident atherosclerotic renovascular disease greatly exceeded those in the general population (P < 0.0001): atherosclerotic heart disease, 303.9 per 1000 patient-years (vs. 73.5 in the general population); peripheral vascular disease, 258.6 (vs. 52.2); congestive heart failure, 194.5 (vs. 56.3); cerebrovascular accident or transient ischemic attack, 175.5 (vs. 52.9); death, 166.3 (vs. 63.3); and renal replacement therapy, 28.8 (vs. 1.3). Among atherosclerotic renovascular disease patients, 16.2% underwent a renal revascularization procedure, percutaneously in 96%. Revascularization was not associated with renal replacement therapy, congestive heart failure, or death but was associated with atherosclerotic heart disease (adjusted HR 1.42) (P= 0.004) and peripheral vascular disease (adjusted HR 1.38) (P= 0.002). CONCLUSION: Atherosclerotic renovascular disease is strongly associated with cardiovascular disease, both past and future. Absolute cardiovascular risk exceeds that of renal replacement therapy. Renal revascularization is used selectively and shows inconsistent associations with cardiovascular outcomes, renal replacement therapy, and death.
Assuntos
Arteriosclerose/epidemiologia , Falência Renal Crônica/epidemiologia , Obstrução da Artéria Renal/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Falência Renal Crônica/terapia , Masculino , Medicare/estatística & dados numéricos , Prevalência , Prognóstico , Obstrução da Artéria Renal/terapia , Circulação Renal , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Most incident hemodialysis (HD) patients who initiate dialysis therapy with anemia usually can achieve a hemoglobin (Hb) level of 11 g/dL or greater (> or =110 g/L) within a few months of the initiation of recombinant human erythropoietin (EPO) therapy. However, patients unable to achieve this level may be at greater risk for adverse outcomes. Whether intractable anemia is a modifiable problem or a marker for other conditions is unclear. This question was addressed in a cohort of 130,544 incident HD patients from 1996 to 2000 who were administered EPO regularly. METHODS: Medicare claims data were used to determine demographic characteristics, comorbidities, hospitalizations, and related events. Patients who did not achieve an Hb level of 11 g/dL or greater (> or =110 g/L; n = 19,096; 14.6%) during months 4 to 9 after dialysis therapy initiation were compared with those who did. RESULTS: Patients unable to achieve an Hb level of 11 g/dL (110 g/L) were younger and more often of nonwhite race. In addition, these patients had more comorbid conditions; experienced more hospitalizations with longer stays, more infectious hospitalizations, and more catheter insertions; and were administered more blood transfusions. EPO was administered in higher and increasing doses during the years of study among patients with intractable anemia compared with those with an Hb level of 11 g/dL or greater (> or =110 g/L), likely denoting increasing attempts to correct anemia over the years. CONCLUSION: It is apparent that incident HD patients unable to achieve an Hb level of 11 g/dL or greater (> or =110 g/L) have a greater disease burden. The independent association of intractable anemia with such future outcomes as cardiovascular events and hospitalizations remains to be determined.
Assuntos
Anemia/tratamento farmacológico , Diálise Renal/efeitos adversos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/etiologia , Estudos de Coortes , Comorbidade , Eritropoetina/uso terapêutico , Etnicidade , Feminino , Hemoglobinas/metabolismo , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Diálise Renal/métodos , Tempo , Falha de Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Late nephrology referral has been associated with adverse outcomes among patients with end-stage renal disease; however, its relationship to mortality is unclear. We examined the impact of timing of nephrology care relative to initiation of dialysis on mortality after initiation of dialysis. METHODS: Data from the Dialysis Morbidity and Mortality Study - Wave II, a prospective study of incident dialysis patients, were used. Late referral (LR) was defined as first nephrology visit <4 months and early referral (ER) as first nephrology visit >or=4 months prior to initiation of dialysis. Propensity scores (PS) were estimated using logistic regression to predict the probability that a given patient was LR. A Cox proportional hazards model was built to examine the association between timing of nephrology referral and mortality. RESULTS: The cohort was comprised of 2195 patients: 54% were males, 66% were Caucasians, 26% were African-Americans and 33% were referred late. A Cox proportional hazards analysis demonstrated that compared with ER patients, LR patients had a 44% higher risk of death at 1 year after initiation of dialysis [hazards ratio (HR) = 1.44; 95% confidence interval (CI): 1.15-1.80], which remained significant after adjusting for quintiles of PS (HR = 1.42; 95% CI: 1.12-1.80). CONCLUSIONS: Among patients with chronic kidney disease (CKD) who initiated dialysis, LR was associated with higher risk of death at 1 year after initiation of dialysis compared with ER.
Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Encaminhamento e Consulta/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
Iron therapy maintains iron stores and optimizes the response to recombinant human erythropoietin (r-HuEPO) in patients with end-stage renal failure. Information is limited, however, regarding the preferential route of iron administration in pediatric patients receiving hemodialysis. Therefore, we prospectively randomized 35 iron-replete patients (aged >1 to <20 years) to receive up to 16 weeks of maintenance i.v. ( n=17) or daily oral ( n=18) iron. Eligible patients had received hemodialysis for >2 months, had a baseline transferrin saturation [TSAT] >20%, and were receiving maintenance r-HuEPO. Treatment arms were evenly distributed with respect to baseline demographic and clinical characteristics, with no statistically significant differences in baseline hemoglobin (Hb), hematocrit (Hct), reticulocyte Hb content (CHr), serum ferritin (SF), TSAT, or r-HuEPO dose. In the 35 patients, i.v. iron dextran and not oral iron was associated with a significant increase (138.5 to 259.1 ng/ml, P=0.003) in SF. A comparison of the change in SF between the i.v. iron group and the oral iron group was also significant ( P=0.001). Whereas only i.v. iron was associated with a significant decrease in the dose of r-HuEPO (234.0 to 157.6 U/kg per week, P=0.046) and an increase of the CHr (29.2 to 30.1 pg, P=0.049), these changes were not significantly different from those experienced by patients in the oral iron group. In both groups, the Hct remained stable and in neither group was there a significant change in the TSAT. In summary, although both oral and i.v. iron maintained patients in an iron-replete state in this short-term study, only i.v. therapy allowed for a significant improvement in iron stores.
Assuntos
Ferro/administração & dosagem , Falência Renal Crônica/tratamento farmacológico , Diálise Renal , Administração Oral , Adolescente , Criança , Eritropoetina/uso terapêutico , Feminino , Ferritinas/sangue , Ferritinas/efeitos dos fármacos , Hematócrito , Hemoglobinas/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Proteínas Recombinantes , Transferrina/efeitos dos fármacosRESUMO
There has been much attention directed toward the high mortality of patients with end-stage renal disease (ESRD), with much of the focus on cardiovascular disease. However, infectious disease is the second most common cause of death in late-stage chronic kidney disease (CKD) patients. Although CKD patients are immunocompromised, some vaccines such as influenza, retain their efficacy and reduce infection rates with a standard immunization schedule. Other vaccines, such as hepatitis B and pneumococcal vaccines, require more frequent and/or higher doses to produce and maintain protective antibody levels. Attention has recently been given to the efficacy of influenza vaccination in ESRD patients in reducing morbidity and mortality. Centers with vaccination protocols have demonstrated reduced infection rates and resultant decreased morbidity and mortality. It could be extrapolated from this that widespread vaccination would reduce the total cost of ESRD patient care, and potentially improve patient well-being. However, vaccination appears to be underutilized in CKD patients, and it is a readily available intervention to improve outcomes.
Assuntos
Nefropatias/complicações , Vacinação , Doença Crônica , Hepatite B/prevenção & controle , Vacinas contra Hepatite B , Humanos , Vacinas contra Influenza , Influenza Humana/complicações , Influenza Humana/prevenção & controle , Falência Renal Crônica/complicações , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/prevenção & controle , Vacinas PneumocócicasRESUMO
BACKGROUND: The care of patients with end-stage renal disease (ESRD) is associated with substantial costs to society, much of which is accounted for by a high rate of hospitalization. However, the influence of declining kidney function on hospitalization as ESRD approaches is not well understood. METHODS: We performed a retrospective cohort study of national data to evaluate the frequency of hospitalizations among patients with chronic kidney disease (CKD) who reached ESRD and had at least 2 years of Medicare eligibility before initiation of dialysis therapy. The study period for each patient extended from 2 years before to 6 months after the initiation of dialysis therapy. RESULTS: The study cohort was composed of 109,321 patients with a mean age of 75 years, all of whom initiated long-term dialysis therapy between 1995 and 1998. Mean hospitalization rate was 134 hospitalizations/1,000 patient-months at risk (PMAR). Hospitalization rates gradually increased as ESRD approached, peaking in the 3 months immediately after the initiation of dialysis therapy at 487 hospitalizations/1,000 PMAR. Cause-specific hospitalization rates mirrored this trend and were greatest for placement of vascular access and diagnoses related to cardiovascular (CVD) and infectious disease. CONCLUSION: Hospitalizations during CKD become more frequent with the approach of ESRD. The majority of these hospitalizations, both before and after the initiation of dialysis therapy, are caused by comorbidity related to CKD. These hospitalizations may be favorably impacted on by heightened attention to the prevention and management of CVD and timely placement of vascular access during CKD.
Assuntos
Hospitalização/estatística & dados numéricos , Nefropatias/terapia , Idoso , Doença Crônica , Estudos de Coortes , Nefropatias Diabéticas/terapia , Progressão da Doença , Feminino , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Nefropatias/etiologia , Falência Renal Crônica/terapia , Tempo de Internação , Masculino , Medicare , Diálise Renal , Estudos Retrospectivos , Fatores SexuaisRESUMO
Cardiovascular disease is a leading cause of death among kidney transplant recipients. Anemia, a risk factor for cardiovascular complications among patients with chronic kidney disease, has not been well characterized in kidney transplant recipients. We performed a retrospective cohort study of the prevalence of and factors associated with anemia among 240 patients who underwent kidney transplantation at our institution. The mean hematocrit (Hct) rose from 33% at 1 month after transplantation to 40% at 12 months after transplantation. The proportion of patients with Hct < 36% was 76% at transplantation and 21% and 36%, 1 year and 4 years after transplantation, respectively. Six months after transplantation, women had higher likelihood (OR = 3.61) of Hct < 36%, while higher Hct at 3 months (OR = 0.67 for 1% higher Hct) and diabetes (OR = 0.14) were associated with a lower likelihood of Hct < 36%. Similar associations were seen 12 months after transplantation. Even among patients with Hct < 30%, only 36% had iron studies, 46% received iron supplementation and 40% received recombinant human erythropoietin. Awareness of factors associated with a lower Hct may prompt better anemia screening and management, potentially improving cardiovascular outcomes among kidney transplant recipients.
Assuntos
Anemia/etiologia , Transplante de Rim , Complicações Pós-Operatórias , Adolescente , Adulto , Estudos de Coortes , Eritropoetina/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Hematócrito , Humanos , Ferro/sangue , Nefropatias/sangue , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Fatores de TempoRESUMO
Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.