Elevated Brain Natriuretic Peptide Predicted Kidney Disease and Death Even Without Heart Failure or Diabetes

What the researchers found

In 197 patients without heart failure or diabetes followed for a median of 10.6 years, NT-proBNP >125 pg/mL was associated with a 2.54-fold increased risk (HR 2.54, 95% CI 1.34-4.82, p=0.004) of developing chronic kidney disease (eGFR <60 mL/min/1.73 m²) or dying from any cause. After multivariate adjustment, the association remained significant (adjusted HR 2.23, 95% CI 1.10-4.52, p=0.026), confirming NT-proBNP as an independent predictor of renal and mortality outcomes.

Why it matters

NT-proBNP is widely available and routinely measured in clinical practice for heart failure. Discovering that this peptide biomarker also independently predicts kidney disease and death in people without heart failure or diabetes means it could be used as a broader screening tool for identifying high-risk patients who might benefit from early preventive intervention.

How the study worked

This was a prospective cohort study enrolling patients without diabetes who underwent oral glucose tolerance testing between 2011 and 2013. Patients with heart failure or existing CKD (eGFR <60) were excluded. NT-proBNP was measured at baseline and dichotomized at 125 pg/mL. Cox proportional hazards models assessed the association with composite outcome of incident CKD and all-cause mortality over a median 10.6-year follow-up.

What this study cannot tell us

The sample size of 197 patients is small, limiting statistical power and the ability to adjust for multiple confounders. The study combined CKD incidence and all-cause mortality as a composite endpoint, making it difficult to assess each outcome independently. The single-center design and specific population (patients undergoing glucose tolerance testing) may limit generalizability. Repeat NT-proBNP measurements were not assessed.

How to read the evidence

This is a prospective cohort study with long follow-up (10.6 years) and multivariate adjustment, which is a reasonable study design for biomarker validation. However, the small sample size (n=197) and composite endpoint limit the strength of the conclusions.

When this study was published

Published in 2025 with patients enrolled 2011-2013, this study benefits from over a decade of follow-up, providing long-term prognostic data on NT-proBNP beyond heart failure.

The bigger picture

Natriuretic peptides like BNP and NT-proBNP are increasingly recognized as biomarkers for cardiovascular risk beyond heart failure. This study extends their predictive value to kidney disease, highlighting the interconnected nature of cardiorenal biology. As the kidney-heart connection (cardiorenal syndrome) gains clinical attention, peptide biomarkers like NT-proBNP could become central to integrated cardiorenal risk assessment.

Questions still open

• Could NT-proBNP screening identify patients at risk for CKD early enough to prevent disease progression?
• Is there a dose-response relationship between NT-proBNP levels and CKD risk, or is 125 pg/mL the optimal threshold?
• Would serial NT-proBNP measurements provide better risk prediction than a single baseline measurement?

Common questions

Read the original research

Associations of N-Terminal Pro-Brain Natriuretic Peptide with Incident Chronic Kidney Disease and All-Cause Mortality in Patients with No History of Heart Failure and Diabetes.

Nigerian journal of clinical practice, 28(12), 1470-1477

Citation

Kuo, Y N; Lin, C H; Wang, J S. (2025). Associations of N-Terminal Pro-Brain Natriuretic Peptide with Incident Chronic Kidney Disease and All-Cause Mortality in Patients with No History of Heart Failure and Diabetes.. Nigerian journal of clinical practice, 28(12), 1470-1477. https://doi.org/10.4103/njcp.njcp_567_25