Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

Abstract

Background/Aim. Kidney injury molecule-1 (KIM-1) and aquaporin-1 (AQP-1) are potential early urinary biomarkers of clear renal cell carcinoma (cRCC). The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy) in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1) and urinary AQP-1 (uAQP-1) were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr)] were significantly greater compared with controls (healthy volunteers) (0.210 ± 0.082 ng/mgUcr) (p = 0.0227). Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively). The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr) compared with the control group (0.202 ± 0.078 ng/mgUcr) (p = 0.0014). Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy.

Uvod/Cilj. Molekul oštećenja bubrega-1 (KIM-1) i akvaporin-1 (AQP-1) su potencijalni rani biomarkeri karcinoma svetlih ćelija (cRCC). Cilj ove studije bio je da se utvrdi povezanost između koncentracija KIM-1 i AQP-1 u urinu i veličine, gradusa, stadijuma i vrste operacije (radikalna ili parcijalna nefrektomija) kod bolesnika sa cRCC. Metode. Urinarne koncentracije KIM-1 i AQP-1 određene su primenom komercijalnih ELISA kitova. Analizom je bilo obuhvaćeno 40 bolesnika koji su bili podvrgnuti parcijalnoj ili radikalnoj nefrektomiji zbog tumora bubrega i 40 zdravih odraslih ispitanika. Grupe su bile komparabilne po polu i godinama života. Rezultati. Srednja preoperativna koncentracija urinarnog KIM-1 (uKIM-1) u cRCC grupi [0,724 ± 1,120 ng/mg kreatinia u urinu (Ucr)] bila je statistički značajno viša u poređenju sa koncentracijom u kontrolnoj grupi (0,210 ± 0,082 ng/mgUcr ) (p = 0,0227). Postoperativno, koncentracija uKIM-1 značajno je padala i približavala se vrednosti u kontrolnoj grupi (0,177 ± 0,099 ng/mgUcr nasuprot 0,210 ± 0,082 ng/mgUcr). Veličina, gradus i stadijum tumora bili su u pozitivnoj korelaciji sa preoperativnim koncentracijama uKIM-1. Nasuprot ovim rezultatima, koncentracija urinarnog AQP-1 (uAQP-1) u cRCC grupi bila je značajno niža (0,111 ± 0,092 ng/mgUcr) u poređenju sa kontrolnom grupom zdravih osoba (0,202 ± 0,078 ng/mgUcr) (p = 0,0014). Postoperativno, koncentracija uAQP-1 progresivno se povećavala, približno do vrednosti u kontrolnoj grupi. Nismo našli značajnu korelaciju između preoperativnih koncentracija uAQP-1 i veličine, gradusa i stadijuma tumora. Zaključak. uKIM-1 bi mogao biti dodatni pouzdani dijagnostički marker za cRRC na osnovu njegove značajno više preoperativne koncentracije i sniženja vrednosti nakon nefrektomije.