Association between plasma NT-proBNP level and the risk of acute kidney injury: a retrospective cohort study

Technical Summary: Association between Plasma NT-proBNP Level and the Risk of Acute Kidney Injury

Problem Statement
Acute kidney injury (AKI) is a frequent and serious complication in patients with acute decompensated heart failure (ADHF), occurring in 20–30% of hospitalizations. This condition is often driven by cardiorenal syndrome (CRS), where cardiac and renal dysfunctions exacerbate one another through hemodynamic, neurohormonal, and inflammatory mechanisms. AKI in this context is independently associated with increased mortality, prolonged hospitalization, and progression to chronic kidney disease (CKD) or end-stage kidney disease (ESKD). While N-terminal pro-brain natriuretic peptide (NT-proBNP) is a well-established biomarker for heart failure severity and volume status, its specific utility in predicting AKI risk and adverse renal outcomes in ADHF patients remains under-investigated. Furthermore, because NT-proBNP is partially cleared by the kidneys, its prognostic value in patients with pre-existing CKD is uncertain, creating a need to determine if baseline renal function modifies the relationship between NT-proBNP levels and AKI risk.

Methodology
This study employed a retrospective, single-centre cohort design conducted at Prince of Wales Hospital in Hong Kong between October 2021 and September 2022.

• Population: The study enrolled 669 adult patients (≥18 years) admitted with ADHF who had both a measured plasma NT-proBNP level and a baseline serum creatinine level within six months prior to admission. Patients were excluded if they lacked these specific measurements or were under 18.
• Data Collection: Clinical data, including demographics, comorbidities (diabetes, hypertension, cardiovascular disease), medication use (RAAS inhibitors, SGLT-2 inhibitors), and exposure to sepsis or contrast agents, were extracted from the Hospital Authority's electronic records.
• Outcomes:
  • Primary Outcome: Development of AKI during hospitalization, defined by Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria.
  • Secondary Outcomes: AKI severity (maximal stage attained), renal recovery (return to within 50% of baseline eGFR within 3 months), and length of hospitalization.
• Statistical Analysis: Plasma NT-proBNP levels, which exhibited a skewed distribution, were log-transformed (base 2) for analysis. Multivariate logistic regression was used to assess the association between NT-proBNP and AKI risk, adjusting for age, gender, baseline eGFR, comorbidities, and medication use. Multinomial regression analyzed AKI severity, and negative binomial regression analyzed hospitalization duration. Receiver operating characteristic (ROC) curves were constructed to identify optimal NT-proBNP cut-off values for predicting AKI. Interaction terms were used to evaluate whether baseline CKD stage modified the predictive value of NT-proBNP.

Key Results

• AKI Incidence: Of the 669 patients, 289 (43%) developed AKI. The distribution of severity was 53% Stage 1, 31% Stage 2, and 16% Stage 3.
• Association with AKI Risk: Multivariate analysis confirmed that elevated plasma NT-proBNP levels were independently associated with an increased risk of AKI. Specifically, every doubling of the NT-proBNP level was associated with an adjusted odds ratio (OR) of 1.470 (95% CI 1.347–1.604, p < 0.001) for developing AKI.
• Effect of Baseline CKD: A significant interaction was found between NT-proBNP levels and baseline CKD stage (p for interaction = 0.023).
  • In patients with CKD Stage 1–2, the adjusted OR for AKI per doubling of NT-proBNP was 1.488 (p < 0.001).
  • In patients with CKD Stage 3, the adjusted OR was 1.376 (p = 0.001).
  • The association was not statistically significant in patients with CKD Stage 4–5, likely due to the small sample size (n=27) and the dominance of reduced renal clearance over cardiac stress in elevating NT-proBNP levels in advanced renal failure.
• Predictive Thresholds: ROC analysis identified an overall NT-proBNP cut-off of 1450 pg/mL for predicting AKI (AUC 0.74, sensitivity 71.3%, specificity 65%). Stratified analysis suggested lower thresholds for earlier CKD stages: 1000 pg/mL for CKD Stage 1–2 and 2000 pg/mL for CKD Stage 3.
• Secondary Outcomes: Higher NT-proBNP levels were significantly associated with more severe AKI stages (adjusted ORs ranging from 1.344 for Stage 1 to 1.878 for Stage 3) and prolonged hospitalization (adjusted incidence rate ratio 1.087, p < 0.001). However, no significant association was found between NT-proBNP levels and renal recovery within 3 months.

Significance and Claims
The authors claim that this study provides evidence that elevated plasma NT-proBNP levels are independently associated with the risk of AKI and adverse renal outcomes in patients with acute decompensated heart failure. The study highlights that this predictive capability persists even in patients with mild to moderate pre-existing CKD (Stages 1–3), suggesting NT-proBNP can be a useful tool for renal risk stratification in this population.

The paper posits that establishing specific NT-proBNP cut-off thresholds (1450 pg/mL generally, with adjustments for CKD stage) could assist clinicians in identifying high-risk patients early. This identification may facilitate targeted interventions and more focused care to prevent kidney complications. The authors explicitly state that while their findings suggest an association, the retrospective nature of the study limits causal inference. They conclude that larger prospective studies are necessary to confirm NT-proBNP's role as a predictive biomarker in cardiorenal syndrome and to further validate its utility in guiding fluid management and renoprotective strategies.