@article{3034330,
    title = "Assessment of Proximal Tubular Function by Tubular Maximum Phosphate
Reabsorption Capacity in Heart Failure",
    author = "Emmens, Johanna E. and de Borst, Martin H. and Boorsma, Eva M. and and Damman, Kevin and Navis, Gerjan and van Veldhuisen, Dirk J. and and Dickstein, Kenneth and Anker, Stefan D. and Lang, Chim C. and and Filippatos, Gerasimos and Metra, Marco and Samani, Nilesh J. and and Ponikowski, Piotr and Ng, Leong L. and Voors, Adriaan A. and ter Maaten, and Jozine M.",
    journal = "Clinical Journal of The American Society of Nephrology",
    year = "2022",
    volume = "17",
    number = "2",
    pages = "228-239",
    publisher = "AMER SOC NEPHROLOGY",
    issn = "1555-9041, 1555-905X",
    doi = "10.2215/CJN.03720321",
    keywords = "proximal tubule; heart failure; outcomes; renal dysfunction",
    abstract = "Background and objectives The estimated glomerular filtration rate
(eGFR) is a crucial parameter in heart failure. Much less is known about
the importance of tubular function. We addressed the effect of tubular
maximum phosphate reabsorption capacity (TmP/GFR), a parameter of
proximal tubular function, in patients with heart failure.Design,
setting, participants, & measurements We established TmP/GFR (Bijvoet
formula) in 2085 patients with heart failure and studied its association
with deterioration of kidney function (> 25% eGFR decrease from
baseline) and plasma neutrophil gelatinase-associated lipocalin (NGAL)
doubling (baseline to 9 months) using logistic regression analysis and
clinical outcomes using Cox proportional hazards regression.
Additionally, we evaluated the effect of sodium-glucose transport
protein 2 (SGLT2) inhibition by empagliflozin on tubular maximum
phosphate reabsorption capacity in 78 patients with acute heart failure
using analysis of covariance.Results Low TmP/GFR (< 0.80 mmol/L) was
observed in 1392 (67%) and 21 (27%) patients. Patients with lower
TmP/GFR had more advanced heart failure, lower eGFR, and higher levels
of tubular damage markers. The main determinant of lower TmP/GFR was
higher fractional excretion of urea (P < 0.001). Lower TmP/GFR was
independently associated with higher risk of plasma NGAL doubling (odds
ratio, 2.20; 95% confidence interval, 1.05 to 4.66; P=0.04) but not
with deterioration of kidney function. Lower TmP/GFR was associated with
higher risk of all-cause mortality (hazard ratio, 2.80; 95% confidence
interval, 1.37 to 5.73; P=0.005), heart failure hospitalization (hazard
ratio, 2.29; 95% confidence interval, 1.08 to 4.88; P=0.03), and their
combination (hazard ratio, 1.89; 95% confidence interval, 1.07 to 3.36;
P=0.03) after multivariable adjustment. Empagliflozin significantly
increased TmP/GFR compared with placebo after 1 day (P=0.004) but not
after adjustment for eGFR change.Conclusions TmP/GFR, a measure of
proximal tubular function, is frequently reduced in heart failure,
especially in patients with more advanced heart failure. Lower TmP/GFR
is furthermore associated with future risk of plasma NGAL doubling and
worse clinical outcomes, independent of glomerular function."
}