For a study, it was determined that in heart failure, the estimated glomerular filtration rate (eGFR) was a critical measure. The role of tubular function was far less well understood. In patients with heart failure, researchers looked at the influence of tubular maximum phosphate reabsorption capacity (TmP/GFR), a proximal tubular function metric. TmP/GFR (Bijvoet formula) was established in 2,085 patients with heart failure, and its relationship with kidney function deterioration (>25% eGFR decrease from baseline) and plasma neutrophil gelatinase-associated lipocalin (NGAL) doubling (baseline to 9 months) was investigated using logistic regression analysis and clinical outcomes using Cox proportional hazards regression. They also used analysis of covariance to see how sodium-glucose transport protein 2 (SGLT2) inhibition by empagliflozin affected tubular maximal phosphate reabsorption capacity in 78 patients with acute heart failure.
Low TmP/GFR (0.80 mmol/L) was seen in 1,392 (67%) and 21 (27%) patients, respectively. Patients with a decreased TmP/GFR ratio had advanced heart failure, a lower eGFR, and increased tubular damage indicators. Higher urea fractional excretion was the primary driver of reduced TmP/GFR (P<0.001). Lower TmP/GFR was related with a greater probability of plasma NGAL doubling (odds ratio, 2.20; 95% CI, 1.05 to 4.66; P=0.04) but not with kidney function degradation (odds ratio, 2.20; 95% CI, 1.05 to 4.66; P=0.04). After multivariable adjustment, lower TmP/GFR was linked to a higher risk of all-cause mortality (hazard ratio, 2.80; 95% CI, 1.37 to 5.73; P=0.005), heart failure hospitalization (hazard ratio, 2.29; 95% CI, 1.08 to 4.88; P=0.03), and the combination of the two (hazard ratio, 1.89; 95% CI, 1.07 to 3.36; P=0.03). After 1 day, empagliflozin substantially raised TmP/GFR compared to placebo (P=0.004), but not after adjusting for eGFR change.
TmP/GFR, a measure of proximal tubular function, was typically diminished in patients with heart failure, particularly in those with severe heart failure. Lower TmP/GFR was also linked to an increased risk of plasma NGAL doubling and poor clinical outcomes, regardless of glomerular function.