Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury.

Pubmed ID: 29352071

Pubmed Central ID: PMC6066176

Journal: Circulation

Publication Date: May 8, 2018

MeSH Terms: Humans, Male, Female, Aged, Aged, 80 and over, United States, Middle Aged, Heart Failure, Treatment Outcome, Creatinine, Time Factors, Glomerular Filtration Rate, Kidney, Acute Disease, Acute Kidney Injury, Sodium Potassium Chloride Symporter Inhibitors, Diuresis, Biomarkers, Cystatin C, Hepatitis A Virus Cellular Receptor 1, Lipocalin-2, Acetylglucosaminidase

Grants: K23 HL114868, L30 HL115790, K23 HL128933, K23 DK097201, P30 DK079310, R01 DK072381, R01 DK113191

Authors: Testani JM, Coca SG, O'Connor CM, Felker GM, Chen HH, Hernandez AF, Wilson FP, Ahmad T, Tang WHW, Jackson K, Rao VS, Brisco-Bacik MA, Sabbisetti VS, Bonventre JV

Cite As: Ahmad T, Jackson K, Rao VS, Tang WHW, Brisco-Bacik MA, Chen HH, Felker GM, Hernandez AF, O'Connor CM, Sabbisetti VS, Bonventre JV, Wilson FP, Coca SG, Testani JM. Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury. Circulation 2018 May 8;137(19):2016-2028. Epub 2018 Jan 19.

Studies:

Abstract

BACKGROUND: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, <i>N</i>-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation-Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. METHODS: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C. RESULTS: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300-815 mg), which induced a urine output of 8425 mL (interquartile range, 6341-10 528 mL) over the 72-hour intervention period. Levels of <i>N</i>-acetyl-β-d-glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both <i>P</i>&gt;0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (-8.7 ng/mg; interquartile range, -169 to 35 ng/mg; <i>P</i>&lt;0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin (<i>P</i>=0.21), <i>N</i>-acetyl-β-d-glucosaminidase (<i>P</i>=0.46), or kidney injury molecule 1 (<i>P</i>=0.22). Increases in neutrophil gelatinase-associated lipocalin, <i>N</i>-acetyl-β-d-glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69-0.91; <i>P</i>=0.001). CONCLUSIONS: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.