Temporal Trajectory of B-Type Natriuretic Peptide in Patients with CKD Stages 3 and 4, Dialysis, and Kidney Transplant

Abstract

Background and objectives B-type natriuretic peptide (BNP) concentration predicts outcome in patients undergoing dialysis. Because survival and cardiovascular risk change across the CKD continuum, serial changes in BNP were compared in patients at different CKD stages and after kidney transplantation.Design, setting, participants, & measurements Patients with CKD stages 3 and 4 (CKD 3-4), dialysis patients, and kidney transplant recipients (KTRs) from one center had two measurements of BNP taken a median of 161 days apart in 2003-2004 and were followed until July 2012. Both BNP-32 (Triage BNP; Biosite Diagnostics) and NT-BNP-76 (proBNP; Roche Diagnostics) were assayed. The interaction between change in log-transformed BNP concentration over time and patient group was tested by fitting regression models on panel data with random effects. Survival after the second measurement was compared by tertile of change in BNP.Results Patients with CKD 3-4 (n=48), dialysis patients (n=102), and KTRs (n=73) were followed for a median of 5.7, 4.8, and 5.9 years, respectively. The interaction between patient group and BNP measurements over time was significant for NT-BNP-76 (P,0.001) and BNP-32 (P,0.01). Median NT-BNP-76 increased in dialysis patients and those with CKD 3-4 from 3850 pg/ml (interquartile range [IQR], 1776-12,323 pg/ml) to 18,830 pg/ml (IQR, 6114-61,009 pg/ml; P,0.001) and from 698 pg/ml (IQR, 283-2922 pg/ml) to 2529 pg/ml (IQR, 347-9277 pg/ml; P=0.002), respectively. Change was not significant for KTRs or comparisons made with BNP-32. Survival rate was significantly lower for patients with the highest tertile of change in NT-BNP-76 among patients with CKD 3-4 (P=0.02), but not in the dialysis or KTR groups. In 11 patients who received a kidney transplant during the study, median NT-BNP-76 decreased from 9607 pg/ml (IQR, 2292-31,282 pg/ml) to 457 pg/ml (IQR, 203-863 pg/ml) after transplant (P,0.01).Conclusions The temporal trajectory of BNP differs between dialysis patients and those with CKD 3-4 and KTRs. This has important implications for the development of BNP-guided management strategies in CKD.

Carvedilol and Cardiac Biomarkers in Dialysis Patients: Secondary Analysis of a Randomized Controlled Trial

“…Although not statistically significant, our findings with BNP (and NT-proBNP) were dissimilar to these studies as the levels of these biomarkers increased over time in both groups, but to a greater degree if receiving carvedilol. This increase in BNP (and NT-proBNP) over time has been demonstrated in observational studies of dialysis patients [30, 31]. The major difference between these two intervention studies and our RCT was the much shorter duration of therapy in these studies (3 months in the carvedilol RCT and 4 months in the metoprolol study).…”

B-Type Natriuretic Peptide and Cardiac Troponin I Are Associated With Adverse Outcomes in Stable Kidney Transplant Recipients

“…Roberts et al followed BNP levels in 48 patients with CKD, in 102 dialysis patients, and in 73 kidney transplant recipients for over five years and concluded that while temporal changes in BNP were predictive of survival in CKD, they did not predict survival in dialysis patients and kidney transplant recipients. 34 Similarly, Bodlaj et al measured NT-proBNP in 76 kidney transplant recipients before, shortly after and 2–3 weeks after transplant and found that NT-proBNP levels measured 2–3 weeks after transplantation were significantly correlated with eGFR at 1 year after transplantation. 35 However, these two patient populations differ from our patients who are more remote from the actual kidney transplantation with a median graft vintage of 4.0 years.…”

Effect Modification of Chronic Kidney Disease on the Association of Circulating and Imaging Cardiac Biomarkers With Outcomes

“…This suggests that elevation in hs‐TnT and association with cardiovascular outcomes in CKD is not merely because of decreased clearance, and may reflect other mechanisms such as underlying myocardial strain, endothelial dysfunction, or subendocardial ischemia in albuminuric CKD . NT‐pro‐BNP has been associated with death and cardiovascular events in CKD samples . Elevated BNP, which has a shorter half‐life than NT‐pro‐BNP, was associated with cardiovascular events in 1 Japanese cohort with known CVD .…”

“…These were limited by small sample sizes and event rates, inadequate control for confounding, and ethnic homogeneity . Moreover, few data are available evaluating the prognostic value of TnT measured with new high‐sensitivity assays (hs‐TnT) in CKD . Importantly, most prior studies do not include stages 1 to 2 CKD as defined by albuminuria with preserved glomerular filtration rate (GFR), when early interventions might make the largest impact on cardiovascular outcomes.…”