Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma.

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are urinary biomarkers of diagnostic relevance in a wide variety of acute and chronic kidney diseases. Their diagnostic sensitivity and specificity for kidney cancer are largely unknown and therefore the subject of this investigation. METHODS: A prospective cohort study was performed to evaluate urine biomarkers for clear-cell and papillary subtypes of renal cancer (67 patients undergoing nephrectomy) and 55 control patients undergoing non-kidney surgery. Urinary KIM-1 and NGAL concentrations were determined by sensitive and specific ELISAs. RESULTS: In renal cancer patients, median NGAL excretion was 0.52 (1st to 3rd quartiles: 0.28-0.82) ng/mg urinary creatinine (U(Cr)) before nephrectomy compared to 0.15 (0.04-0.31) ng/mg U(Cr) in controls (p < 0.001), and there was a modest decrease of 30% after nephrectomy (p < 0.008). NGAL was not correlated to tumor size (r = 0.19, p = 0.27) or stage. Before nephrectomy, KIM-1 excretion was 0.68 (0.40-1.12) ng/mg U(Cr) compared to 0.03 (0.01-0.06) in controls (p < 0.001). There was a linear correlation between KIM-1 excretion before nephrectomy and tumor size (Spearman's r = 0.66, p < 0.001), tumor stage, and a 50% decrease in median KIM-1 concentration 1 month following tumor excision (p < 0.01). Biomarker concentration ranges for renal cancer patients and controls overlapped substantially for NGAL but not KIM-1. CONCLUSION: NGAL is not a sensitive or specific urinary biomarker of kidney cancer. Although KIM-1 had diagnostic sensitivity for kidney cancer, it is well known to reflect many types of kidney injuries, thus limiting its specificity as a diagnostic biomarker for renal cancer.

Urinary biomarkers for the early diagnosis of kidney cancer.

OBJECTIVE: To test the hypothesis that increased tumor expression of proteins such as aquaporin-1 (AQP1) and adipophilin (ADFP) in patients with renal cancer would result in increased urine AQP1 and ADFP excretion. PATIENTS AND METHODS: Prenephrectomy and postnephrectomy (pseudocontrol) urine samples were collected from 42 patients with an incidental radiographically discovered renal mass and presurgical presumptive diagnosis of kidney cancer from July 8, 2008, through March 10, 2009. Also enrolled were 15 control patients who underwent nonrenal surgery and 19 healthy volunteers. Urine AQP1 and ADFP concentrations normalized to urine creatinine were determined by sensitive and specific Western blot assays. RESULTS: Mean +/- SD preexcision urine AQP1 and ADFP concentrations (76+/-29 and 117+/-74 arbitrary units, respectively) in patients with a pathologic diagnosis of clear cell (n=22) or papillary (n=10) cancer were significantly greater than in patients with renal cancer of nonproximal tubule origin, control surgical patients, and healthy volunteers (combined values of 0.1+/-0.1 and 1.0+/-1.6 arbitrary units, respectively; n=44; P<.001). The AQP1 and ADFP concentrations decreased 88% to 97% in the 25 patients with clear cell or papillary cancer who provided postnephrectomy follow-up urine samples. In patients with clear cell and papillary carcinoma, a linear correlation (Spearman) was found between tumor size and preexcision urine AQP1 or ADFP concentration (r=0.82 and 0.76, respectively; P<.001 for each). CONCLUSION: Urine AQP1 and ADFP concentrations appear to be sensitive and specific biomarkers of kidney cancers of proximal tubule origin. These biomarkers may be useful to diagnose an imaged renal mass and screen for kidney cancer at an early stage. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00851994.