TY - JOUR
TI - Assessment of Proximal Tubular Function by Tubular Maximum Phosphate
Reabsorption Capacity in Heart Failure
AU - Emmens, Johanna E.
AU - de Borst, Martin H.
AU - Boorsma, Eva M. and
AU - Damman, Kevin
AU - Navis, Gerjan
AU - van Veldhuisen, Dirk J. and
AU - Dickstein, Kenneth
AU - Anker, Stefan D.
AU - Lang, Chim C. and
AU - Filippatos, Gerasimos
AU - Metra, Marco
AU - Samani, Nilesh J. and
AU - Ponikowski, Piotr
AU - Ng, Leong L.
AU - Voors, Adriaan A.
AU - ter Maaten,
AU - Jozine M.
JO - Clinical Journal of The American Society of Nephrology
PY - 2022
VL - 17
TODO - 2
SP - 228-239
PB - AMER SOC NEPHROLOGY
SN - 1555-9041, 1555-905X
TODO - 10.2215/CJN.03720321
TODO - proximal tubule; heart failure; outcomes; renal dysfunction
TODO - 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.
ER -