To evaluate the sensitivity, specificity, and false-positive rate of the nuclear matrix protein-22 (NMP22) test in patients with end-stage renal disease (ESRD) and microscopic hematuria in order to avoid unnecessary follow-up tests for patients with false-positive NMP22 test results.
Patients and methods:
Patients with ESRD were screened for microscopic hematuria as part of the pre-transplant workup. Patients with documented microscopic hematuria underwent workup as recommended by the American Urological Association.
Between January 2006 and April 2012, 277 patients with ESRD were referred to the Department of Urology for pre-transplant evaluation. Fifty-seven (22.6%) patients were found to have microscopic hematuria and underwent further testing. Nineteen (33.3%) patients demonstrated a positive NMP22 test result and 38 (66.7%) had a negative NMP22 test result. The false-positive rate was 32.7%. The sensitivity and specificity of the NMP22 test in this patient population were 50% and 67%, respectively. The positive predictive value of the test was 52.6% and the negative predictive value 97.3%. Especially noteworthy, the two detected transitional cell cancers of the urinary bladder were both demonstrated during cystoscopy, independent of their NMP22 or urine cytology test result.
Our study revealed a significantly increased NMP22 test false-positive rate, low sensitivity, and specificity in the setting of high prevalence of microscopic hematuria, proteinuria, and low glomerular filtration rate in patients with ESRD. Therefore, cystoscopy remains the gold standard for patients with ESRD and microscopic hematuria for pre-transplant evaluation.
"However we took precautions in our study to minimize renal dysfunction as a confounder by excluding subjects with a history of renal dysfunction as well as exclude subjects with grossly elevated urinary protein levels. Recently, researchers have reported that impaired renal function (i.e., reduced glomerular filtration rate) may adversely affect urinary biomarkers performance
[33,34]. This is an excellent point and should be taken into consideration in future studies. "
[Show abstract][Hide abstract] ABSTRACT: In this study, we further investigated the association of two biomarkers, CCL18 and A1AT, with bladder cancer (BCa) and evaluated the influence of potentially confounding factors in an experimental model.
In a cohort of 308 subjects (102 with BCa), urinary concentrations of CCL18 and A1AT were assessed by enzyme-linked immunosorbent assay (ELISA). In an experimental model, benign or cancerous cells, in addition to blood, were added to urines from healthy controls and analyzed by ELISA. Lastly, immunohistochemical staining for CCL18 and A1AT in human bladder tumors was performed.
Median urinary protein concentrations of CCL18 (52.84 pg/ml vs. 11.13 pg/ml, p < 0.0001) and A1AT (606.4 ng/ml vs. 120.0 ng/ml, p < 0.0001) were significantly elevated in BCa subjects compared to controls. Furthermore, the addition of whole blood to pooled normal urine resulted in a significant increase in both CCL18 and A1AT. IHC staining of bladder tumors revealed CCL18 immunoreactivity in inflammatory cells only, and there was no significant increase in these immunoreactive cells within benign and cancerous tissue and no association with BCa grade nor stage was noted. A1AT immunoreactivity was observed in the cytoplasm of epithelia cells and intensity of immunostaining increased with tumor grade, but not tumor stage.
Further development of A1AT as a diagnostic biomarker for BCa is warranted.
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