Value of N -terminal brain natriuretic peptide as a prognostic marker in patients with CKD: results from the CREATE study
ABSTRACT This study assessed plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) as a prognostic marker of cardiovascular risk in patients with chronic kidney disease stages 3-4 and anaemia treated with epoetin beta to two haemoglobin target ranges.
Of 603 patients enrolled in the Cardiovascular Risk Reduction by Early Anaemia Treatment with Epoetin Beta (CREATE) trial (baseline creatinine clearance 15-35 mL/min; haemoglobin 11.0-12.5 g/dL), 291 were included in this sub-study. Patients received subcutaneous epoetin beta either immediately after randomisation (target 13.0-15.0 g/dL; Group 1), or after their haemoglobin levels had fallen < 10.5 g/dL (target 10.5-11.5 g/dL; Group 2). Chronic heart failure New York Heart Association class III-IV was an exclusion criterion. (ClinicalTrials.gov Identifier: NCT00321919)
Cardiovascular event rates were higher in patients with baseline NT-proBNP > 400 vs. ≤ 400 pg/mL (39 vs. 13 events; p = 0.0002). Dialysis was initiated in 68 vs. 42 patients with NT-proBNP > 400 vs. ≤ 400 pg/mL (p = 0.0003). Amongst patients with NT-proBNP > 400 pg/mL, there was no significant difference between treatment groups in risk of cardiovascular events (HR = 0.57; p = 0.08) or time to dialysis (HR = 0.65; p = 0.08). The overall interpretation of this substudy is, however, limited by its relatively small sample size which, together with low clinical event rates, result in a lack of statistical power for some analyses and should be viewed as being hypothesis-generating in nature.
In chronic kidney disease patients with mild-to-moderate anaemia, elevated baseline plasma NT-proBNP levels are associated with a higher risk of cardiovascular events and an accelerated progression towards end-stage renal disease.
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ABSTRACT: The leading cause of mortality in dialysis patients is cardiovascular complications, including ventricular arrhythmias and sudden cardiac death. QT dispersion (QTd), a simple noninvasive arrhythmogenic marker, is used to assess homogeneity of cardiac repolarization. It was also significantly prolonged in continuous ambulatory peritoneal dialysis (CAPD) patients. The acute cardiac effect of increased abdominal pressure due to infused dialysate during CAPD is not clear yet. In this study we aimed to evaluate corrected QTd (cQTd) and cardiac injury markers such as plasma pro-brain natriuretic peptide (proBNP) and troponin I (TnI) in CAPD patients before and after an infusion of peritoneal dialysate fluid. Thirty subjects (16 women, 14 men; mean age, 40.21 ± 12.34 years) enrolled in our study. QTd, cQTd, maximum QT (QTmax), maximum corrected QT (cQTmax), minimum QT (QTmin), and minimum corrected QT (cQTmin) intervals were measured from standard 12-lead electrocardiography. We found that cQTmax, cQTmin, and cQTd were not changed from baseline measurement after infusion of dialysate in CAPD patients (460 ± 49 vs. 460 ± 38, p = 0.9; 410 ± 36 vs. 410 ± 41, p = 0.8; 470 ± 30 vs. 460 ± 25, p = 0.7, respectively). There were no statistically significant differences between before and after peritoneal dialysate according to the levels of proBNP and TnI (155.64 ± 76.41 vs. 208.30 ± 118.46, p = 0.2; 0.008 ± 0.007 vs. 0.01 ± 0.011; p = 0.4, respectively). In conclusion, we did not find any significant effect of peritoneal dialysate fluid infusion volume on QTd and cardiac injury markers in patients with chronic renal failure receiving CAPD therapy, which is thought to be a safer modality of dialysis.Renal Failure 07/2011; 33(6):568-71. DOI:10.3109/0886022X.2011.584648 · 0.78 Impact Factor
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ABSTRACT: In patients with chronic kidney disease (CKD), as in other populations, elevations in cardiac biomarker levels predict increased risk of cardiovascular events. We examined the value of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in assessing the risk of developing end-stage renal disease (ESRD) in diabetic patients with CKD. Prospective cohort study nested within a randomized clinical trial. Patients with type 2 diabetes, CKD (estimated glomerular filtration rate [eGFR], 20-60 mL/min/1.73 m(2)), and anemia enrolled in TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy). Serum levels of the cardiac biomarkers TnT and NT-pro-BNP. Incidence of ESRD and the composite of death or ESRD. We measured TnT and NT-pro-BNP in baseline serum samples from the first 1,000 patients enrolled in TREAT. The relationship of these cardiac biomarker levels to the development of ESRD and death or ESRD was analyzed in multivariable regression models. Detectable TnT (≥0.01 ng/mL) was present in 45% of participants, and median NT-pro-BNP level was elevated at 605 pg/mL. Higher levels of both cardiac biomarkers were associated independently with higher rates of ESRD, as well as death or ESRD, and remained prognostically important after adjustment for eGFR, proteinuria, and other known predictors of CKD progression. The addition of cardiac biomarkers to a multivariable model for prediction of ESRD improved discrimination of those with and without an event by 16.9% (95% CI, 6.3%-27.4%). Observational study in a clinical trial cohort; results require validation. In ambulatory patients with type 2 diabetes, anemia, and CKD, TnT and NT-pro-BNP levels frequently are elevated. These cardiac-derived biomarkers enhance prediction of ESRD beyond established risk factors. Measurement of TnT and NT-pro-BNP may improve the identification of patients with CKD who are likely to require renal replacement therapy, supporting a link between cardiac injury and the development of ESRD.American Journal of Kidney Diseases 08/2011; 58(5):717-28. DOI:10.1053/j.ajkd.2011.05.020 · 5.76 Impact Factor
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ABSTRACT: Renin-angiotensin aldosterone system (RAAS) blockade only partly reduces blood pressure, proteinuria and renal and cardiovascular risk in chronic kidney disease (CKD) but often requires sodium targeting [i.e. low sodium diet (LS) and/or diuretics] for optimal efficacy. However, both under- and overtitration of sodium targeting can easily occur. We evaluated whether N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of volume expansion, predicts the benefits of sodium targeting in CKD patients. In a cross-over randomized controlled trial, 33 non-diabetic CKD patients (proteinuria 3.8 ± 0.4 g/24 h, blood pressure 143/86 ± 3/2 mmHg, creatinine clearance 89 ± 5 mL/min) were treated during 6-week periods with placebo, angiotensin receptor blockade (ARB; losartan 100 mg/day) and ARB plus diuretics (losartan 100 mg/day plus hydrochlorothiazide 25 mg/day), combined with LS (93 ± 52 mmol Na(+)/24 h) and regular sodium diet (RS; 193 ± 62 mmol Na(+)/24 h, P < 0.001 versus LS), in random order. As controls, 27 healthy volunteers were studied. NT-proBNP was elevated in patients during placebo + RS [90 (60-137) versus 35 (27-45) pg/mL in healthy controls, P = 0.001]. NT-proBNP was lowered by LS, ARB and diuretics and was normalized by ARB + diuretic + LS [39 (26-59) pg/mL, P = 0.65 versus controls]. NT-proBNP levels above the upper limit of normal (>125 pg/mL) predicted a larger reduction of blood pressure and proteinuria by LS and diuretics but not by ARB, during all steps of the titration regimen. Elevated NT-proBNP levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of sodium targeting, but not RAAS blockade, in proteinuric CKD patients. Importantly, this applies to the untreated condition, as well as to the subsequent treatment steps, consisting of RAAS blockade and even RAAS blockade combined with diuretics. NT-proBNP can be a useful tool to identify CKD patients in whom sodium targeting can improve blood pressure and proteinuria.Nephrology Dialysis Transplantation 08/2011; 27(3):983-90. DOI:10.1093/ndt/gfr408 · 3.49 Impact Factor