12 research outputs found
Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage
Akutes Nierenversagen (AKI) ist nach wie vor ein hÀufiger und ernst zu
nehmender klinischer Befund. Besonders oft fĂŒhrt eine Form des
Nierenversagens, das Intrinsische Nierenversagen (iAKI) zu ungĂŒnstigen
klinischen VerlÀufen. Diese Form des Nierenversagens ist mit strukturellen
NierenschÀdigungen assoziiert, was im Unterschied zu anderen Formen des
Nierenversagens andere therapeutische Konsequenzen hat. Deshalb ist eine
möglichst frĂŒhe Unterscheidung der einzelnen Formen des Nierenversagens
notwendig. Die herkömmliche Diagnostik beruht gröĂtenteils auf Messungen von
Kreatininwerten, wobei eine Unterscheidung der verschiedenen Formen des
Nierenversagens kaum möglich ist. In den letzten Jahren wurden deshalb
verschiedene Urin-Biomarker auf die Detektion von Intrinsischem Nierenversagen
hin untersucht. In der vorliegenden Arbeit wird der diagnostische und
prognostische Wert von fĂŒnf verschiedenen Urin-Biomarker untersucht und mit
der konservativen Diagnostik mit Serum-Kreatinin verglichen. Die in der
vorliegenden Arbeit untersuchten Urin-Biomarker sind: Urin-Neutrophilen-
Gelatinase- assoziiertes Lipocalin [uNGAL], Urin-Kidney Injury Molecule 1
[uKIM-1], Urin-Leber-Typ- FettsÀure-bindendes Protein [uLFABP], Urin-
Interleukin 18 [uIL 18] und Urin-Cystatin C [uCysC]. Es wurde eine
prospektiven Kohortenstudie mit 543 unselektierten Notaufnahmepatienten
durchgefĂŒhrt. Diese Kohorte war Teilkohorte einer multizentrischen Studie [1]
von 1635 Notaufnahmepatienten. Ziel war es, Angaben ĂŒber den Wert jedes
einzelnen Biomarkers im Vergleich zum Serum- Kreatinin bei der
Diagnosestellung von Intrinsischem Nierenversagen, bei der Vorhersage von
Schwere und Dauer von iAKI und bei der Vorhersage klinischer Ergebnisse wie
Tod oder Dialysebeginn zu erhalten. Es wurde im Ergebnis deutlich, dass jeder
der fĂŒnf Biomarker mit unterschiedlicher Signifikanz bei iAKI erhöht war. Der
beste Marker war uNGAL (WB) mit einer SpezifitÀt von 83% und SensitivitÀt von
68% bei einem Cutoff von 90 ”g/ml. Auch fĂŒr die Schwere und die Dauer von iAKI
erwies sich uNGAL als der beste PrÀdiktor. Bekanntlich ist iAKI sehr hÀufig
mit ungĂŒnstigen klinischen Endpunkten assoziert. Auch in der vorliegenden
Studie wurde das belegt. Die hÀufigsten FÀlle von Tod oder Dialysebeginn
wurden bei Patienten mit iAKI im Vergleich zu Patienten mit anderen Formen des
Nierenversagens verzeichnet. Die Urin-Biomarker uNGAL in Kombination mit
uLFABP waren dabei die besten PrĂ€diktoren fĂŒr ein negatives klinisches
Ergebnis. Jeweils in Kombination mit sCr-Werten konnte sowohl uNGAL als auch
uLFABP die RisikoeinschÀtzung verbessern. Eine Gruppe in der Kohorte wurde
gefunden, die zwar niedrige sCr-Werte, aber hohe Biomarkerwerte von uNGAL und
uLFABP zeigten. Diese Patienten wÀren bei der alleinigen Messung von Serum-
Kreatinin mit der konventionellen Diagnostik nicht der richtigen Risikoklasse
zugeordnet und als Risikopatienten ĂŒbersehen worden. Im Ergebnis kann gesagt
werden, dass die Biomarker die diagnostische und auch prognostische Einteilung
der Patienten in der Notaufnahme verbessern können.Acute kidney injury (AKI) is a ubiquitous event in clinical practice,
frequently with severe consequences. Intrinsic acute kidney injury (IAKI) is a
variant of it. It is associated with structural kidney damage (nephron injury)
and leads frequently to an unfavorable clinical outcome.The usual diagnostics
with creatinine exhibits deficits in the ability to distinguish different
forms of kidney injury. That motivated studies with a variety of urine
biomarkers with respect to detection of iAKI. In this prospective cohort
study, we determine the diagnostic and prognostic value of several urinary
biomarkers for iAKI in the emergency department and compare it with currently
used diagnostics. Five biomarkers (urinary neutrophil gelatinaseâassociated
lipocalin [uNGAL],kidney injury molecule-1 [uKim-1], urinary liver-type fatty
acid binding protein[LFABP], urinary interleukin-18 [u-IL-18], and cystatin C
[u-cysC])were measured in 543 unselected emergency department patients at the
time of hospital admission. We assesed the performance of the biomarkers for
detection of severity and duration of iAKI and the predictive power for poor
clinical outcome. UNGAL performed best in diagnosing iAKI out of the 5
(specifity 83%, sensitivity 68% withacutoff at 90 ”g/l).It also proved to be
the best predictor of the severity and duration of iAKI. iAKI was more
frequently associated with the negative combined clinical outcome death or in-
hospital dialysis compared to other clinical diagnoses.The best predictive
value for negative clinical outcome had uNGAL combined with uLFABP.Risk
assessment of both uNGAL and uLFABP individually was imporved if each was
combined with sCr-values. We also identified a subgroup in the cohort with low
creatinine values but elevated uNGAL and uLFABP. The biomarker values allowed
for correct patient classification. This group would have gone unnoticed as
patients at risk with currently used diagnostics. In summary, prognostic and
diagnostic stratification in the emergency department is possible by the use
of biomarkers
Urinary NGAL-Positive Acute Kidney Injury and Poor Long-term Outcomes in Hospitalized Patients
Neutrophil gelatinaseâassociated lipocalin (NGAL) is a widely studied biomarker of renal tubular injury. Urinary NGAL (uNGAL) during acute kidney injury (AKI) predicts short-term adverse outcomes. However, the long-term predictive value is unknown.
Methods: We performed a prospective observational study of 145 patients with hospital-acquired AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria and analyzed the long-term predictive value of uNGAL at the time of AKI. We defined a composite outcome of all-cause mortality and the development of end-stage renal disease (ESRD).
Results: In all, 61 AKI patients died and 22 developed ESRD within 6 months. The uNGAL levels were significantly higher in patients with poor long-term outcomes. uNGAL levels â„362 ÎŒg/l (highest quartile) and uNGAL levels between 95 and 362 ÎŒg/l (third quartile) were associated with hazard ratios of 3.7 (95% confidence interval, 2.1â6.5) and 1.9 (1.1â3.5), respectively, compared with uNGAL levels <95 ÎŒg/l (lower quartiles). After 6 months, 67% and 43% of patients within the highest and third uNGAL quartile, respectively, had either progressed to ESRD or died, compared to only 21% of patients with uNGAL in the lower 2 quartiles (P < 0.001). In multivariable Cox regression analyses accounting for conventional predictors, uNGAL was the strongest independent predictor of adverse long-term outcomes. The association of uNGAL levels and poor long-term outcomes remained significant in the subgroup of 107 AKI survivors discharged without requiring dialysis (P = 0.002).
Discussion: These data indicate that elevated uNGAL levels at AKI diagnosis predict poor long-term outcomes
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Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.
Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone.A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr â„1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated.For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were 950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were 408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs.Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone
Correction: Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.
[This corrects the article DOI: 10.1371/journal.pone.0178091.]
Simulation model.
<p>A cost simulation model was developed for competing testing strategies to evaluate for AKI; 1) Scr alone, vs. 2) uNGAL plus Scr (uNGAL+Scr). Since the uNGAL+Scr treatment arm provided more diagnostic information, it was regarded as the âgold standardâ relative to Scr alone in terms of whether patients should be treated or whether treatment should be delayed.</p
Sensitivity analysis.
<p>The sensitivity analysis recalculates the net expected cost of each strategy (Scr vs. uNGAL+Scr), varying one model input at a time to its high and low values relative to its baseline value. At both sites, costs of uNGAL+Scr remain lower for each scenario examined in the sensitivity analysis. At NYP-Allen and SIUH, the results are most sensitive to hospital costs and length of stay, costs of additional testing, and the percent of patients with CKD.</p
Effects on cost per patient.
<p>Effects on Cost Per Patient at NYP-Allen and SIUH. At NYP-Allen, the use of uNGAL+Scr would lead to an expected cost savings of 522 per patient at SIUH. These savings were reflected in lower per patient hospitalization costs and lower additional testing costs.</p