NT-proBNP Predicts Cardiovascular, Renal Outcomes in ADVANCED CKD with Anemia

Hiroshi Nishi, PhD

Credit: WCN'24

A study found that N-terminal pro-brain natriuretic peptides (NT-proBNP) were linked to cardiovascular and renal outcomes among patients with advanced chronic kidney disease (CKD) experiencing anemia.¹

“A greater increase in NT-proBNP variability particularly shows a higher risk of renal events, regardless of the baseline NT-proBNP value,” wrote investigators, led by Hiroshi Nishi, PhD, from the University of Tokyo Graduate School of Medicine in Japan. “The trend was not true of cardiovascular outcomes. We posit that these differences could be attributable to the patient population, with CKD already having a low baseline eGFR in this study.”

Low renal clearance and anemia may modify blood levels of NT-proBNP, as previous research suggests.^2,3 Investigators sought to evaluate the impact of the blood level of NT-proBNP on cardiovascular and renal outcomes in patients who have advanced CKD and anemia.¹

The team conducted a post-hoc analysis of BRIGHTEN, the observational clinical research in chronic kidney disease patients with renal anemia: renal prognosis in patients with hyporesponsive anemia to erythropoiesis-stimulating agents, darbepoetin alfa. BRIGHTEN was a large prospective study examining patients with non-dialysis kidney disease who had anemia. Investigators used data from this study to examine the association of baseline NT-proBNP levels with cardiovascular outcomes, such as cardiac death, acute coronary syndrome, hospitalization due to heart failure or fatal arrhythmia, and renal outcomes, including the initiation of maintenance dialysis, kidney transplantation, a 50% decrease or ≤ 6 mL/min/1.73 m2 in the estimated glomerular filtration rate (eGFR).

The study included 1484 patients (40.6% females) with a mean age of 70.2 years, a mean eGFR of 0.3 ± 9.6 mL/min/1.73 m2, and a mean hemoglobin (Hb) level of 9.8 ± 0.9 g/dL. Participants had a median NT-proBNP level of 496.0 pg/mL (inter-quartile range [IQR], 235.0 – 1090.0 pg/mL). At baseline, participants had a weak association between NT-proBNP levels and eGFR (P < .001) or Hb levels (P < .001).

“These findings indicated that, while blood NT-proBNP levels may theoretically be influenced by renal clearance or Hb dynamics, such associations were not readily detected through correlation analysis in this large cohort,” investigators wrote.

During an average of 2.29 years (± 0.89), the study reported 92 cardiovascular and 573 renal events. An analysis adjusted for potential confounders, including eGFR and Hb level, showed a nonlinear relationship between NT-proBNP levels and both cardiovascular and renal outcomes. Patients who had a baseline NT-proBNP level ≥ 1000 pg/mL (hazard ratio [HR], 8.10; 95% confidence interval [CI], 2.80 – 23.40; P < .001) and 500 – 1000 pg/ML (HR, 3.35; 95% CI, 1.10 – 10.18; P = .033) demonstrated a greater risk for cardiovascular outcomes than patients with lower NT-proBNP levels (< 250 pg/mL).

Additionally, patients with a baseline NT-proBNP of ≥ 1000 pg/mL (HR, 1.77; 95% CI, 1.36 – 2.31; P < .001) and 500 – 1000 pg/mL (HR, 1.54; 95% CI, 1.19 – 2.00; P = .001) demonstrated a moderate risk for renal outcomes compared with patients who had NT-pro-NBP levels < 250 pg/ mL.

Furthermore, the team evaluated the link between NT-pro-BNP levels at baseline and the total eGFR slope. In the adjusted analysis, the total declining eGFR slope was increased, showing a quicker progression of CKD, while the NT-pro-BNP levels also increased (P = .007).

“Blood NT-proBNP level appears to be a valuable prognostic indicator for cardiovascular and renal outcomes in patients with advanced CKD experiencing anemia,” investigators concluded. “For patients with high blood levels of NT-proBNP, daily management that takes into account the status of cardiovascular and renal risks is essential. Future endeavors should focus on investigating whether utilizing the NT-proBNP level as a guiding factor in heart failure treatment can mitigate cardiovascular and renal outcomes in anemic patients with CKD.”

References

1. ^{Nishi H, Nangaku M, Sofue T, Kagimura T, Narita I. N-terminal pro-brain natriuretic peptide and cardiorenal outcome in patients with anaemia in chronic kidney disease. ESC Heart Fail. 2024 Dec 18. doi: 10.1002/ehf2.15042. Epub ahead of print. PMID: 39696837.}
2. ^{Tsutamoto T, Sakai H, Yamamoto T, Nakagawa Y. Renal Clearance of N-Terminal pro-Brain Natriuretic Peptide Is Markedly Decreased in Chronic Kidney Disease. Circ Rep. 2019 Aug 1;1(8):326-332. doi: 10.1253/circrep.CR-19-0063. PMID: 33693158; PMCID: PMC7892492.}
3. ^{Desai AS, Bibbins-Domingo K, Shlipak MG, Wu AH, Ali S, Whooley MA. Association between anaemia and N-terminal pro-B-type natriuretic peptide (NT-proBNP): findings from the Heart and Soul Study. Eur J Heart Fail. 2007 Sep;9(9):886-91. doi: 10.1016/j.ejheart.2007.06.005. Epub 2007 Jul 12. PMID: 17627881.}