Abstract 19795: Clinical Determinants and Relation to Prognosis of Progressive Tubular Damage and Glomerular Decline in Chronic Heart Failure (Bio-SHiFT Study)

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Introduction: Tubular damage and glomerular decline predict clinical outcome in chronic heart failure (CHF). Yet, which patients are prone to these renal changes and how their joint assessment relates to prognosis is unknown.

Hypothesis: We hypothesized that progressive tubular damage and glomerular decline in CHF have different clinical determinants, and that joint assessment of these dynamic renal indices improves risk stratification.

Methods: During a median of 2.2 years, we simultaneously collected blood and urine in 263 CHF patients at fixed 3-month intervals (per patient median (IQR) 9 [5-10] and 8 [5-10] samples, respectively). We estimated the annual slopes (change/year) of markers of tubular damage: urinary NAG and KIM-1, and glomerular filtration: creatinine and Cystatin C. The endpoint was a composite of cardiac death, LVAD-placement, heart transplantation, and HF-hospitalization.

Results: Patients with progressive tubular damage had higher baseline NT-proBNP and TnT (each p<0.001), lower eGFR (p=0.001), more diabetes (p=0.018), NYHA class III/IV (p=0.001), more cardiac resynchronization therapy (p=0.009), higher age (p=0.045), and lower survival rates (Fig. A). Patients with glomerular decline also had higher NT-proBNP (p=0.028) and TnT (p=0.005), but also higher NAG (p=0.001), more hypertension (p=0.003), atrial fibrillation (p=0.006), higher diuretics doses (p=0.017), and lower survival rates (Fig. B). Patients in whom both renal compartments had deteriorated prior to the endpoint had the lowest survival; patients without tubular deterioration had the highest survival regardless of creatinine slope (log-rank p=0.007, Fig. C).

Conclusions: When combined, progressive tubular damage and glomerular decline improve risk stratification. Slopes of tubular markers are clinically important even if GFR remains stable. Clinical determinants differ between the two renal indices, which also supports that they should be jointly assessed.

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