The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma

Abstract

Purpose: Renal cancer is frequently asymptomatic until late stages of the disease and it has a poor prognosis when not discovered early. AQP1 and PLIN2 are recently discovered, sensitive urine biomarkers of clear cell and papillary kidney cancer. We validated these biomarkers in a second cohort of patients and determined the effect of common kidney diseases on specificity.

Materials and methods: Urine samples were obtained from 36 patients with clear cell or papillary kidney cancer, 43 controls, 44 patients with documented urinary tract infection, 24 diagnosed with diabetic nephropathy and 18 diagnosed with glomerulonephritis. Urine levels of AQP1 and PLIN2 normalized to urine creatinine were determined by a sensitive, specific Western blot procedure.

Results: Compared with controls, urine AQP1 and PLIN2 levels in patients with kidney cancer were 23-fold and fourfold greater, respectively, and they decreased 83% to 84% after tumor excision. There was a linear correlation between urine AQP1 and PLIN2 levels, and tumor size (each p <0.001). Urine AQP1 and PLIN2 levels in patients with kidney cancer were 11 to 23-fold and 17 to 25-fold greater, respectively, than in patients with the common kidney diseases.

Conclusions: The ability of urine AQP1 and PLIN2 to identify patients with kidney cancer compared to controls was validated in a second cohort of patients. Common kidney diseases do not adversely increase urine AQP1 and PLIN2 levels or decrease their specificity to screen for renal cancer.

Trial registration: ClinicalTrials.gov NCT00851994.

Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Dot- and box-plot of urinary biomarker concentrations in the 43 control, 44 patients with urinary tract infections (UTI), 24 patients with diabetic nephropathy (DN), 18 patients with glomerulonephritis (GN) and 36 patients with renal cancer. (A) AQP-1 (B) ADFP. (+) outliers > 1.5 and 3 interquartile range. For statistical significance see Table 1.

Figure 1

Dot- and box-plot of urinary biomarker concentrations in the 43 control, 44 patients with urinary tract infections (UTI), 24 patients with diabetic nephropathy (DN), 18 patients with glomerulonephritis (GN) and 36 patients with renal cancer. (A) AQP-1 (B) ADFP. (+) outliers > 1.5 and 3 interquartile range. For statistical significance see Table 1.

Figure 2

Urinary biomarker concentrations as a function of tumor size. (A) AQP-1 Spearman correlation coefficient of the 36 patients with clear cell and papillary kidney cancer is 0.89 (95% Confidence Interval, 0.79-0.94, P

Figure 2

Urinary biomarker concentrations as a function of tumor size. (A) AQP-1 Spearman correlation coefficient of the 36 patients with clear cell and papillary kidney cancer is 0.89 (95% Confidence Interval, 0.79-0.94, P

Figure 3

Pre- and post-nephrectomy urine AQP-1 and ADFP concentrations. Results are shown for only the twenty seven patients who provided both a pre- and post-nephrectomy urine sample. Each line represents an individual patient. The biomarker concentrations were corrected for the urinary creatinine excretion.

Figure 4

Urinary AQP-1 and ADFP levels in patients with diabetic nephropathy (DN) (upper) or urinary tract infections (UTI) (lower). Two patients with renal cancer (RCC) are shown for comparison.

Figure 5

Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers to detect kidney cancer. (A) AQP-1 application to diagnose T1a kidney cancer (clear cell and papillary) compared to control patients (ROC area 0.99, 95% confidence interval 0.97 to 1.00, P

Figure 5

Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers to detect kidney cancer. (A) AQP-1 application to diagnose T1a kidney cancer (clear cell and papillary) compared to control patients (ROC area 0.99, 95% confidence interval 0.97 to 1.00, P

Figure 5

Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers to detect kidney cancer. (A) AQP-1 application to diagnose T1a kidney cancer (clear cell and papillary) compared to control patients (ROC area 0.99, 95% confidence interval 0.97 to 1.00, P

Figure 5

Receiver Operating Characteristic Curve analysis of the sensitivity and specificity of urinary biomarkers to detect kidney cancer. (A) AQP-1 application to diagnose T1a kidney cancer (clear cell and papillary) compared to control patients (ROC area 0.99, 95% confidence interval 0.97 to 1.00, P