KIDNEY FUNCTION AND RENAL DYSFUNCTION IN CHRONIC HEART FAILURE: CORRELATION WITH TUBULAR DAMAGE BIOMARKERS

Chronic heart failure (CHF) is frequently complicated by renal dysfunction, a condition collectively termed cardiorenal syndrome, which substantially increases morbidity and mortality. Traditional markers of renal function, such as serum creatinine and estimated glomerular filtration rate, often fail to detect early tubular injury before irreversible nephron damage occurs. Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) are novel urinary biomarkers that reflect tubular epithelial cell injury and are elevated early in the course of renal damage, potentially preceding changes in conventional parameters. In CHF, reduced cardiac output leads to renal hypoperfusion, neurohormonal activation, and inflammatory cascade initiation, all contributing to tubular ischemia and progressive kidney injury. Despite growing recognition of subclinical renal tubular damage in CHF, the clinical utility of KIM-1 and NGAL for early detection and risk stratification remains incompletely defined, particularly across different heart failure phenotypes. This study aimed to evaluate urinary concentrations of KIM-1 and NGAL in CHF patients with preserved or mildly reduced ejection fraction, compare levels between patients with and without overt renal dysfunction, and assess their potential as early biomarkers of tubular injury in cardiorenal syndrome.

This cross-sectional study enrolled 129 patients with chronic heart failure of various functional classes (NYHA I–III) and phenotypes (heart failure with mildly reduced ejection fraction [HFmrEF] or heart failure with preserved ejection fraction [HFpEF]) from [please specify institution] between [please specify dates]. Based on urinary concentrations of KIM-1 and NGAL, patients were stratified into two groups: Group I comprised 63 patients without evidence of renal dysfunction (normal serum creatinine, eGFR ≥60 mL/min/1.73m², and KIM-1/NGAL levels below predefined thresholds indicative of significant tubular injury), while Group II included 66 patients with confirmed renal dysfunction (elevated serum creatinine, eGFR <60 mL/min/1.73m², or significantly elevated KIM-1/NGAL concentrations). A control group of 20 relatively healthy individuals without clinical signs of CHF or renal disease served as the comparison cohort. All participants underwent comprehensive clinical evaluation including detailed medical history, physical examination, transthoracic echocardiography for ejection fraction determination and heart failure phenotype classification, and standard laboratory assessment. Urinary concentrations of KIM-1 and NGAL were quantified using enzyme-linked immunosorbent assay (ELISA) performed on an ELISA Kit immunoassay analyzer with reagents provided by Thermo Fisher Scientific (USA). Fresh urine samples were collected, processed within 2 hours, and stored at -80°C until analysis. All assays were performed in duplicate according to manufacturer protocols. Statistical analysis included descriptive statistics, independent t-tests or Mann-Whitney U tests for between-group comparisons depending on data distribution, and one-way ANOVA for multiple group comparisons. Significance was set at p<0.05. The study was approved by the institutional ethics committee, and all participants provided written informed consent.

Baseline characteristics were comparable between groups regarding age, sex distribution, and NYHA functional class distribution. The mean age across all CHF patients was 62±8 years, with 58% males. Heart failure phenotypes were distributed as 52% HFpEF and 48% HFmrEF. In the control group (n=20), mean urinary KIM-1 concentration was 0.86±0.15 ng/mL and NGAL was 16.8±4.2 ng/mL, representing normal baseline values in individuals without cardiovascular or renal disease. Group I patients (CHF without overt renal dysfunction, n=63) demonstrated significantly elevated biomarker levels despite preserved conventional renal function parameters. Urinary KIM-1 concentration was 1.56±0.42 ng/mL, representing an 81% elevation or approximately 1.8-fold increase compared to controls (p<0.01). NGAL levels were markedly elevated at 59.7±12.8 ng/mL, a 3.5-fold increase over control values (p<0.01). These findings indicate the presence of subclinical tubular ischemia and early nephron injury in CHF patients even when standard renal function tests remain within normal limits. Group II patients (CHF with confirmed renal dysfunction, n=66) exhibited substantially more pronounced biomarker elevations reflecting advanced tubular damage. Urinary KIM-1 concentration reached 3.7±0.63 ng/mL, which was 2.4 times higher than Group I (p<0.001) and 4.3 times higher than controls (p<0.001). NGAL levels were dramatically elevated at 196.4±46.7 ng/mL, exceeding Group I values by 3.3-fold (p<0.001) and control levels by 11.7-fold (p<0.001). Correlation analysis revealed significant positive associations between KIM-1 levels and NYHA functional class (r=0.54, p<0.001), as well as between NGAL and severity of renal dysfunction measured by eGFR (r=-0.68, p<0.001). Both biomarkers showed strong intercorrelation (r=0.71, p<0.001), suggesting shared pathophysiological mechanisms of tubular injury. Among HFpEF versus HFmrEF phenotypes, no significant differences in biomarker levels were observed within each group (p>0.05), indicating that tubular injury severity relates more closely to renal dysfunction status than to specific heart failure phenotype.

CHF patients with concomitant renal dysfunction demonstrated a marked elevation in KIM-1 and NGAL levels, reflecting the progression of cardiorenal syndrome, tubular ischemia, and ongoing inflammatory nephron damage.