Predicting cisplatin-induced acute kidney injury by urinary neutrophil gelatinase-associated lipocalin excretion: a pilot prospective case-control study.
OBJECTIVE
Nephrotoxicity is the major limitation to cisplatin therapy for solid tumors. We aimed at evaluating whether early increases in serum/urine levels of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of tubular damage and regeneration, predict cisplatin-induced acute kidney injury (AKI).


METHODS
We compared changes in serum creatinine and serum/urine NGAL levels (ELISA assay) at 1 and 4 h and 1, 2, 3, 7 and 15 days after cisplatin infusion (70-80 mg/m(2)) versus baseline in 12 consecutive cancer patients (cases) with AKI (>25% serum creatinine increase vs. baseline) and 12 consecutive controls without AKI.


RESULTS
Baseline characteristics and posttreatment serum NGAL levels were similar in both groups. Urinary NGAL levels increased significantly more in cases than in controls at 1, 2, 3 and 15 days after cisplatin. The NGAL increase preceded AKI by 4.5 days and the NGAL increase at day 2 after cisplatin independently predicted AKI (p < 0.05). Six cases with residual kidney dysfunction at 15 days showed a trend to earlier and higher increase in urinary NGAL levels compared to cases with renal function recovery.


CONCLUSIONS
An early increase in urinary NGAL excretion may help in identifying patients at risk of cisplatin-induced AKI who might benefit from innovative treatments to prevent cisplatin nephrotoxicity.
Gaspari
Flavio
F
Department of Medicine and Transplantation, Ospedali Riuniti, Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Cravedi
Paolo
P
Mandalà
Mario
M
Perico
Norberto
N
de Leon
Felipe Rodríguez
FR
Stucchi
Nadia
N
Ferrari
Silvia
S
Labianca
Roberto
R
Remuzzi
Giuseppe
G
Ruggenenti
Piero
P
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis / Q000652:urine*; D000209:Acute-Phase Proteins / Q000652:urine*; D000368:Aged; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D002945:Cisplatin