Neutrophil gelatinase-associated lipocalin curve and neutrophil gelatinase-associated lipocalin extended-range assay: a new biomarker approach in the early diagnosis of acute kidney injury and cardio-renal syndrome.
Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which multiple causative factors are involved. The time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the effects of the insult become evident with a loss or decline of renal function. For this reason, pharmaceutical interventions for AKI that have been shown to be renoprotective or beneficial when tested in experimental conditions do not display similar results in the clinical setting. In most cases patients with AHF are admitted with clinical signs and symptoms of congestion and fluid overload. Loop diuretics, typically used to induce an enhanced diuresis in these congested patients, often are associated with a subsequent significant decrease in glomerular filtration rate and cause a creatinine increase that is apparent within 72 hours. Early detection of AKI is not possible with the use of serum creatinine and there is a need for a timely diagnostic tool able to address renal damage while it is happening. We need to define the diagnosis of both AHF and AKI in the early phases of CRS type 1 by coupling a kidney damage marker such as neutrophil gelatinase-associated lipocalin (NGAL) with B-type natriuretic peptide (BNP). Indeed, it would be ideal to make available a panel including whole blood or plasma cardiac and renal biomarkers building specific, pathophysiologically based, molecular profiles. Based on current knowledge and consensus, we can use kidney damage biomarkers such as plasma NGAL for an early diagnosis of AKI. However, differences in individual patient values and uncertainties about the ideal cut-off values may currently limit the application of these biomarkers. We propose that NGAL may increase its usefulness in the diagnosis and prevention of CRS if a curve of plasma values rather than a single plasma measurement is determined. To apply the concept of measuring an NGAL curve in AHF patients, however, assay performance in the lower-range values becomes a critical factor. For this reason, we propose the use of the new extended-range plasma NGAL assay that may contribute to remarkably improve the sensitivity of AKI diagnosis in AHF and lead to more effective intervention strategies.
Ronco C
，Cruz D
，Noland BW
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Comparison of Neutrophil Gelatinase-Associated Lipocalin Versus B-Type Natriuretic Peptide and Cystatin C to Predict Early Acute Kidney Injury and Outcome in Patients With Acute Heart Failure.
Neutrophil gelatinase-associated lipocalin (NGAL) has been described in chronic heart failure (HF) as marker of tubular damage and renal dysfunction; however, less data are available in patients with acute HF. Because of high rate of acute kidney injury (AKI) development, we aimed to investigate the role of NGAL in predicting early AKI development; second, we compared NGAL with respect to cystatin C, B-type natriuretic peptide (BNP), renal function, and blood urea nitrogen (BUN) for outcome prediction. We measured admission serum NGAL, cystatin C, and BNP in 231 patients affected to acute HF; all patients were submitted to daily creatinine, estimated glomerular filtration rate, and measurement to identify inhospital AKI defined by Risk, Injury, Failure, Loss, End-Stage Kidney Disease and Acute Kidney Injury Network criteria. We also measured admission and discharge estimated glomerular filtration rate, creatinine, and BUN to evaluate their prognostic role during a 6-month follow-up period; 78 patients developed AKI during hospitalization. In these subjects, NGAL levels were significantly increased respect to patients without AKI (295 ± 228 vs 129 ± 108 ng/ml, p <0.001). A cutoff of 134 ng/ml has been related to AKI with good sensibility and specificity (85% and 80%, respectively; area under the curve 0.81, p <0.001). BNP was also mildly increased (1,000 ± 906 vs 746 ± 580 pg/ml, p = 0.03) but not cystatin C. Patients with chronic kidney disease demonstrated higher NGAL levels compared with subjects with preserved renal function (258 ± 249 and 120 ± 77 ng/ml, p <0.001). The receiver-operating characteristic curve analysis demonstrated that increased NGAL values were associated with increased mortality (cutoff 170 ng/ml, sensibility 60%, specificity 82%, accuracy 71%, area under the curve 0.77, p <0.001). The same significant correlation was also found for BUN at discharge (cutoff 100 mg/dl, sensibility 65%, specificity 85%, accuracy 71%, area under the curve 0.77, p <0.001). Multivariable Cox regression analysis showed that cutoff 170 ng/ml was related with adverse outcome (hazard ratio 1.77, confidence interval 1.24 to 2.83, p = 0.01). In conclusion, NGAL measurement is a sensible tool to predict AKI during hospitalization. Elevated NGAL levels appear to be related to BUN increase and post-discharge outcome. This suggests a prognostic role of tubular damage beyond renal dysfunction.
Palazzuoli A
，Ruocco G
，Pellegrini M
，De Gori C
，Del Castillo G
，Franci B
，Nuti R
，Ronco C
... -
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A combined cardiorenal assessment for the prediction of acute kidney injury in lower respiratory tract infections.
The accurate prediction of acute kidney injury (AKI) is an unmet clinical need. A combined assessment of cardiac stress and renal tubular damage might improve early AKI detection.
A total of 372 consecutive patients presenting to the Emergency Department with lower respiratory tract infections were enrolled. Plasma B-type natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured in a blinded fashion at presentation. The potential of these biomarkers to predict AKI was assessed as the primary endpoint. AKI was defined according to the AKI Network classification.
Overall, 16 patients (4%) experienced early AKI. These patients were more likely to suffer from preexisting chronic cardiac disease or diabetes mellitus. At presentation, BNP (334 pg/mL [130-1119] vs 113 pg/mL [52-328], P <.01) and NGAL (269 ng/mL [119-398] vs 96 ng/mL [60-199], P <.01) levels were significantly higher in AKI patients. The predictive accuracy of presentation BNP and NGAL levels was comparable (BNP 0.74; 95% confidence interval [CI], 0.64-0.84 vs NGAL 0.74; 95% CI, 0.61-0.87). In a combined logistic model, a joint BNP/NGAL approach improved the predictive accuracy for early AKI over either biomarker alone (area under the receiver operating characteristic curve: 0.82; 95% CI, 0.74-0.89). The combined categorical cut point defined by BNP >267 pg/mL or NGAL >231 ng/mL correctly identified 15 of 16 early AKI patients (sensitivity 94%, specificity 61%). During multivariable regression analysis, the combined BNP/NGAL cutoff remained the independent predictor of early AKI (hazard ratio 10.82; 95% CI, 1.22-96.23; P = .03).
A model combining the markers BNP and NGAL is a powerful predictor of early AKI in patients with lower respiratory tract infection.
Breidthardt T
，Christ-Crain M
，Stolz D
，Bingisser R
，Drexler B
，Klima T
，Balmelli C
，Schuetz P
，Haaf P
，Schärer M
，Tamm M
，Müller B
，Müller C
... -
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