RESUMO
BACKGROUND: In chronic kidney disease, intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase acute kidney injury risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allograft function remains unknown. Thus, in FAVORIT, we investigated the relationship of SBP and diastolic blood pressure (DBP) with risk of kidney allograft failure and estimated glomerular filtration rate (eGFR) slope among stable KTRs. METHODS: Cox proportional hazards and multivariable linear regression models adjusted for demographics, transplant characteristics, comorbidities, baseline eGFR, and urine albumin-to-creatinine ratio were used to determine associations of SBP and DBP with time to a composite kidney outcome of ≥50% eGFR decline or dialysis dependence, and with annualized eGFR change, respectively. Multivariable restricted cubic spline plots were developed to evaluate the functional form of the relationships. RESULTS: Among 3,598 KTRs, mean age was 52 ± 9 years, SBP was 136 ± 20 mm Hg, DBP was 79 ± 12 mm Hg, and eGFR was 49 ± 18 ml/minute/1.73 m2. There were 369 events of ≥50% eGFR decline or dialysis dependence during a mean follow-up of 4.0 ± 1.5 years. There was no association of either SBP (compared with SBP 120 to <130 mm Hg, hazard ratio (HR) for the SBP < 110 was 1.01 (95% confidence interval (CI) 0.60 to 1.70) and 130 to <140 was 0.89 (0.64 to 1.24)) or DBP (compared with DBP 70 to <80 mm Hg, HR for the DBP 60 to <70 was 1.00 (95% CI 0.74 to 1.34) and 80 to <90 was 0.90 (0.68 to 1.18)) with the kidney failure outcome or annualized eGFR slope, and, when examined using restricted cubic splines, there was no evidence of "J"- or "U"-shaped relationships. CONCLUSIONS: In a large sample of stable KTRs, we found no evidence of thresholds at which lower BPs were related to higher risk of allograft failure or eGFR decline. In light of prior findings of mortality benefit at low SBP, these observational findings suggest lower BP may be beneficial in KTRs. This important question requires confirmation in future randomized trials in KTRs.
Assuntos
Pressão Sanguínea , Taxa de Filtração Glomerular , Hipertensão/etiologia , Transplante de Rim/efeitos adversos , Rim/fisiopatologia , Insuficiência Renal Crônica/etiologia , Adulto , Idoso , Brasil , Canadá , Progressão da Doença , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
PURPOSE: Research examining the relationship between physical activity (PA) and cardiovascular disease (CVD) risk factors among kidney transplant recipients (KTR) is limited. Accordingly, we sought to 1) describe the levels of PA in KTR and 2) analyze the associations between PA levels and CVD risk factors in KTR. METHODS: Baseline data from KTR participants in a large multiethnic, multicenter trial (the Folic Acid for Vascular Outcome Reduction in Transplantation) were examined. PA was categorized in tertiles (low, moderate, and high) derived from a modified PA summary score from the Yale Physical Activity Survey. CVD risk factors were examined across levels of PA by ANOVA, Kruskal-Wallis rank test, and hierarchical multiple regression. RESULTS: The 4034 participants were 37% female (mean ± SD = 51.9 ± 9.4 yr of age, 75% White, 97% with stage 2T-4T chronic kidney disease, and 20% with prevalent CVD. Participants in the "high" PA tertile reported more vigorous PA and walking, compared with participants in moderate and low tertiles (both P < 0.001). No differences were observed in daily household, occupational, or sedentary activities across PA tertiles. More participants in the "low" PA tertile were overweight/obese, had a history of prevalent diabetes, and/or had CVD compared with more active participants (all P < 0.001). Hierarchical modeling revealed that younger age (P = 0.002), cadaveric donor source (P = 0.006), shorter transplant vintage (P = 0.025), lower pulse pressure (P < 0.001), and no history of diabetes (P < 0.001) were associated with higher PA scores. CONCLUSION: The most active KTR engaged in more intentional exercise. Lower levels of PA were positively associated with more CVD risk factors. Higher PA levels were associated with younger age and with more positive KTR outcomes.
Assuntos
Doenças Cardiovasculares/epidemiologia , Exercício Físico , Transplante de Rim , Adulto , Fatores Etários , Brasil/epidemiologia , Canadá/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sedentário , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Elevated uric acid concentration is associated with higher rates of cardiovascular (CV) morbidity and mortality in the general population. It is not known whether hyperuricemia increases the risk for CV death or transplant failure in kidney transplant recipients. STUDY DESIGN: Post hoc cohort analysis of the FAVORIT Study, a randomized controlled trial that examined the effect of homocysteine-lowering vitamins on CV disease in kidney transplantation. SETTING & PARTICIPANTS: Adult recipients of kidney transplants in the United States, Canada, or Brazil participating in the FAVORIT Study, with hyperhomocysteinemia, stable kidney function, and no known history of CV disease. PREDICTOR: Uric acid concentration. OUTCOMES: The primary end point was a composite of CV events. Secondary end points were all-cause mortality and transplant failure. Risk factors included in statistical models were age, sex, race, country, treatment assignment, smoking history, body mass index, presence of diabetes mellitus, history of CV disease, blood pressure, estimated glomerular filtration rate (eGFR), donor type, transplant vintage, lipid concentrations, albumin-creatinine ratio, and uric acid concentration. Cox proportional hazards models were fit to examine the association of uric acid concentration with study end points after risk adjustment. RESULTS: 3,512 of 4,110 FAVORIT participants with baseline uric acid concentrations were studied. Median follow-up was 3.9 (IQR, 3.0-5.3) years. 503 patients had a primary CV event, 401 died, and 287 had transplant failure. In unadjusted analyses, uric acid concentration was significantly related to each outcome. Uric acid concentration was also strongly associated with eGFR. The relationship between uric acid concentration and study end points was no longer significant in fully adjusted multivariable models (P=0.5 for CV events; P=0.09 for death, and P=0.1 for transplant failure). LIMITATIONS: Unknown use of uric acid-lowering agents among study participants. CONCLUSIONS: Following kidney transplantation, uric acid concentrations are not independently associated with CV events, mortality, or transplant failure. The strong association between uric acid concentrations with traditional risk factors and eGFR is a possible explanation.
Assuntos
Doenças Cardiovasculares/mortalidade , Hiper-Homocisteinemia/tratamento farmacológico , Hiperuricemia/epidemiologia , Falência Renal Crônica/epidemiologia , Transplante de Rim , Vitaminas/uso terapêutico , Adulto , Brasil , Canadá , Causas de Morte , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Estados UnidosRESUMO
BACKGROUND: Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD. OBJECTIVES: To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trial of homocysteine lowering with a standard multivitamin containing high doses of folic acid and vitamins B(6) and B(12) aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine concentration, and prevalence of diabetes and previous cardiovascular disease (CVD). STUDY DESIGN: Cross-sectional survey within a randomized controlled trial cohort. SETTING & PARTICIPANTS: Participants were recruited from kidney transplant clinics in the United States, Canada, and Brazil. Eligible participants had increased levels of homocysteine (> or =12.0 micromol/L in men and > or =11.0 micromol/L in women) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater. RESULTS: Of 4,110 randomly assigned participants, 38.9% had diabetes and 19.5% had previous CVD. Mean total homocysteine concentration was 17.1 +/- 6.3 (SD) micromol/L, whereas mean creatinine clearance was 66.4 +/- 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD (i.e., 30 to 89 mL/min). LIMITATIONS: Analysis is based on cross-sectional data from a randomized controlled trial, self-report of comorbid illnesses, and level of kidney function was estimated. CONCLUSIONS: A large population of stable renal transplant recipients who are at high risk of the development of CVD (both de novo and recurrent) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial.