Short‐term prognostic implications of serum and urine neutrophil gelatinase‐associated lipocalin in acute heart failure: findings from the AKINESIS study

Abstract

Aims Kidney impairment has been associated with worse outcomes in acute heart failure (AHF), although recent studies challenge this association. Neutrophil gelatinase‐associated lipocalin (NGAL) is a novel biomarker of kidney tubular injury. Its prognostic role in AHF has not been evaluated in large cohorts. The present study aimed to determine if serum NGAL (sNGAL) or urine NGAL (uNGAL) is superior to creatinine for predicting short‐term outcomes in AHF. Methods and results The study was conducted in an international, multicentre, prospective cohort consisting of 927 patients with AHF. Admission and peak values of sNGAL, uNGAL and uNGAL/urine creatinine (uCr) ratio were compared to admission and peak serum creatinine (sCr). The composite endpoints were death, initiation of renal replacement therapy, heart failure (HF) readmission and any emergent HF‐related outpatient visit within 30 and 60 days, respectively. The mean age of the cohort was 69 years and 62% were male. The median length of stay was 6 days. The composite endpoint occurred in 106 patients and 154 patients within 30 and 60 days, respectively. Serum NGAL was more predictive than uNGAL and the uNGAL/uCr ratio but was not superior to sCr [area under the curve: admission sNGAL 0.61, 95% confidence interval (CI) 0.55–0.67, and 0.59, 95% CI 0.54–0.65; peak sNGAL: 0.60, 95% CI 0.54–0.66, and 0.57, 95% CI 0.52–0.63; admission sCr: 0.60, 95% CI 0.54–0.64, and 0.59, 95% CI 0.53–0.64; peak sCr: 0.61, 95% CI 0.55–0.67, and 0.59, 95% CI 0.54–0.64, at 30 and 60 days, respectively]. NGAL was not predictive of the composite endpoint in multivariate analysis. Conclusions Serum NGAL outperformed uNGAL but neither was superior to admission or peak sCr for predicting adverse events.

Cardiorenal syndrome in thalassemia patients

“…Elevation of urine or serum NGAL has also been observed in CRS patients, especially in cases of type 1 CRS, and may have been beneficial in the diagnosis of other types [18,[49][50][51][52][53]. However, recent large prospective cohort study AKINES IS has shown serum and urine NGAL was not superior to serum creatinine for predict worsening renal failure or need for renal-replacement therapy in patients with acute heart failure (CRS type 1) [54][55][56].…”

February 2020 at a glance: acute heart failure and cardio‐oncology

“…Biomarker measurements have a landmark role in patients with AHF. 3 Wettersten et al 4 evaluated the prognostic significance of serum and urine neutrophil gelatinase-associated lipocalin (NGAL) in 927 AHF patients. Serum NGAL outperformed urine NGAL but neither was superior to admission or peak serum creatinine for predicting adverse events.…”

“…Biomarker measurements have a landmark role in patients with AHF . Wettersten et al . evaluated the prognostic significance of serum and urine neutrophil gelatinase‐associated lipocalin (NGAL) in 927 AHF patients.…”

Neutrophil gelatinase‐associated lipocalin in acute heart failure: time to move on?

“…6 However, serum and urine NGAL demonstrated suboptimal performance as predictors of WRF in AHF with the respective AUC for both markers being below 0.7 and being lower than AUC for sCr. 7,8 In this issue of the Journal, Wettersten et al 9 expanded their original work 7,8 and evaluated prognostic value of serum and urine NGAL for the 30-and 60-day composite outcome of death, initiation of renal replacement therapy, heart failure readmission, and emergent heart failure outpatient visit in a large multicentre cohort study including 927 patients admitted for AHF. Multiple AUC for admission and peak sNGAL, uNGAL and uNGAL/urine creatinine ratio were similar or lower than AUC for admission and peak sCr and all were below 0.62 for the primary and individual outcomes, suggesting that serum or urine NGAL had at best only fair prognostic usefulness.…”

“…Rao et al 13 also demonstrated that patients developing elevation of uNGAL during the first 4 days of ADHF treatment had paradoxically better recovery of kidney function (adjusted odds ratio 6.3, P < 0.001) in a subgroup of 105 patients from the CARRESS-HF trial. Finally, Damman et al 14 9 further demonstrated that despite plausible biological rationale, NGAL measurements are insufficient in providing clinical guidance in AHF, especially, in individuals with preserved kidney function (eGFR > 60 mL/min/1.73 m 2 ). Therefore, NGAL continues to be 'just expensive creatinine' as was coined by Testani et al 15 Further research is needed to standardize the definition of WRF and to characterize the impact of WRF based on whether WRF is present on admission vs. it develops during treatment of AHF and if WRF is accompanied by changes in AKI biomarker(s).…”