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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; P50.04) 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; P50.005), heart failure hospitalization (hazard ratio, 2.29; 95% confidence interval, 1.08 to 4.88; P50.03), and their combination (hazard ratio, 1.89; 95% confidence interval, 1.07 to 3.36; P50.03) after multivariable adjustment. Empagliflozin significantly increased TmP/GFR compared with placebo after 1 day (P50.004) 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.
Original language | English |
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Pages (from-to) | 228-239 |
Number of pages | 12 |
Journal | Clinical Journal of the American Society of Nephrology |
Volume | 17 |
Issue number | 2 |
Early online date | 7 Feb 2022 |
DOIs | |
Publication status | Published - Feb 2022 |
Keywords
- proximal tubule
- heart failure
- TmP/GFR
- tubular damage
- outcome
- outcomes
- renal dysfunction
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine
- Nephrology
- Transplantation
- Epidemiology
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Aref#d: 21596. BIOSTAT-CHF: A Systems Biology Study to Tailored Treatment in Chronic Heart Failure
Doney, A. (Investigator), Guthrie, B. (Investigator), Lang, C. (Investigator), Morris, A. (Investigator), Palmer, C. (Investigator) & Struthers, A. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/04/10 → 31/03/15
Project: Research