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 01/2011; 33(6):568-71. · 0.94 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. · 3.37 Impact Factor
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ABSTRACT: Abstract Background: In patients with heart failure plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are correlated to urine neutrophil gelatinase-associated lipocalin (NGAL) levels. We prospectively evaluated the relationship among glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (ACR), urine and serum NGAL and NT-proBNP levels in 20 type II diabetic patients with macroalbuminuria at 4-month intervals. Results: Compared with 20 age, gender-matched healthy controls, diabetic patients had higher urine and serum NGAL, serum NT-proBNP and lower eGFR. The eGFR of the patients at the baseline, the 4th and the 8th month were 29.6 ± 12.0, 27.8 ± 13.7 and 22.9 ± 10.4 mL/min/1.73 m(2), respectively. No significant change in urine NGAL levels was detected (p > 0.05), whereas there were significant increases in NT-proBNP, serum NGAL and urine ACR and significant decrease in eGFR as the study progressed (p < 0.05). Both the baseline and the 4th month urine ACR were positively correlated to NT-proBNP levels measured at the same periods (r: 0.451; p: 0.046; r: 0.489; p: 0.029 respectively). In all measurements, urine ACR was negatively correlated to serum albumin levels measured at the same periods (r: -0.792; p: 0.000; r: -0.716; p: 0.000; r: -0.531; p: 0.016 respectively). None of eGFR measurements was correlated with NT-proBNP (p > 0.05). Neither serum NGAL nor urinary NGAL levels are associated with NT-proBNP (p > 0.05). Conclusion: Our findings show an association between NT-proBNP and proteinuria in type II diabetic patients with macroalbuminuria but not with serum and urine NGAL.Renal Failure 08/2013; · 0.94 Impact Factor