Diuretic response and worsening renal function in obese patients with acute heart failure: a ROSE-AHF substudy
M Van Es, J Erzeel, P Martens, W H W Tang, W MullensAbstract
Background
The ROSE AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure) trial found that low-dose dopamine and nesiritide failed to enhance decongestion or improve renal function in acute heart failure (AHF).(1) The impact of obesity on renal hemodynamics, risk of renal injury, diuretic response and clinical outcomes in AHF remains insufficiently understood. This substudy investigates whether the presence of obesity influences diuretic response and markers of renal function and injury.
Methods
ROSE AHF enrolled 360 hospitalized patients with AHF and renal dysfunction. Patients were stratified by obesity (BMI ≥ 30 kg/m2). Diuretic response was evaluated as the 72-hour cumulative urine volume and sodium output per mg furosemide equivalents. Changes in filtration markers (cystatin C and estimated glomerular filtration [eGFRcr-cys]), and markers of tubular injury (N-acetyl-β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and kidney injury molecule 1 [KIM-1]) were compared. Multivariable linear models were adjusted for treatment allocation, cumulative loop diuretic dose, age, eGFRcr-cys, and other relevant clinical covariates. Six-month all-cause mortality was compared using Cox proportional hazards models.
Results
The cohort included 353 patients (55.2% obese; median BMI 30.9 kg/m2). Obese participants were younger, had higher diabetes prevalence, lower NT-proBNP, and received higher cumulative loop diuretic doses compared to non-obese patients (596 vs 480 mg, p = 0.004). Obese patients maintained a similar diuretic response for both urine volume and sodium output per mg furosemide compared to non-obese patients (both p > 0.05). Obesity was associated with a greater rise in cystatin C (+0.16 mg/L, 95% CI 0.09-0.24, p < 0.001) and a steeper decline in eGFRcr-cys (-4.99 mL/min/1.73m2; 95% CI -7.71 to -2.28, p < 0.001) after covariate adjustment. Crucially, this phenomenon was not associated with tubular injury, as the changes in NGAL, KIM-1, or NAG were similar between groups (all p > 0.05). Obesity was independently associated with improved 6-month survival (aHR 0.41; 95% CI 0.20–0.83, p =0.012) after adjustment. Importantly, the development of eGFRcr-cys decline was not associated with increased mortality in obese patients (p interaction = 0.980).
Conclusions
Obese patients with AHF demonstrated a similar diuretic response compared to non-obese patients despite higher median doses of loop diuretics. However, the presence of obesity predicted a greater decline in glomerular filtration, but this phenomenon was not associated with tubular injury or worse clinical outcomes. These findings suggest that eGFR declines during decongestion in obese AHF patients are likely benign and should not limit the administration of diuretic therapy.Diuretic response and renal changesFor image description, please refer to the figure legend and surrounding text.Obesity, WRF and survivalFor image description, please refer to the figure legend and surrounding text.