Urinary Soluble Collagen Levels Are Associated With Moderate/Severe LUTS

ABSTRACT Background Expansion of the stromal compartment of the prostate concurrent with fibroblast activation and increased collagenization is now recognized as a pathobiology likely contributing to Lower Urinary Tract Symptoms (LUTS). However, approaches to quantitatively and, ideally, non‐invasively, assess prostatic collagenization in vivo are not currently available. This study sought to determine whether human urine could provide a suitable substrate for the identification of pro‐fibrotic collagen proteins associated with moderate/severe LUTS. Methods Whole urine from two separate age‐matched cohorts of men with or without severe LUTS was subjected to Sircol soluble collagen protein, specific gravity, and total protein assays. Samples were assayed fresh or after frozen storage at −20°C or −80°C. Results Both cohorts demonstrated statistically significantly ( p = 0.001) higher urinary soluble collagen levels in samples from men reporting moderate/severe LUTS (cases) compared to no/mild LUTS (controls). Urinary soluble collagen levels did not differ significantly different between the cases of the 2 cohorts or the controls of the 2 cohorts. In both cohorts, urinary specific gravity and whole protein content were modestly higher in cases than controls concurrent with higher collagen content. Responses to medical treatment varied in the LURN cohort, though responses to surgical treatment were overall beneficial. Assays performed using samples stored short‐ or long‐term at −80°C were highly reproducible. Conclusions Urinary soluble collagen levels increase concurrently with moderate/severe LUTS, and are stable in urine after long‐term storage at −80°C. These findings suggest that urinary soluble collagen levels may serve as suitable diagnostic biomarkers for prostatic collagenization consistent with fibrosis in association with LUTS. Potentially, urinary soluble collagen levels may be used as surrogate endpoint biomarkers to assess the efficacy of anti‐fibrotic medical or surgical therapies to decrease prostatic urethral obstruction or resistance, and alleviate LUTS.