Clinical implication of kidney injury molecule (KIM-1) in blood plasma of renal-cell cancer patients

Background. The most important task in the field of renal-cell cancer (RCC) treatment results improvement is the search and validation of the markers for its early diagnostics still absent in the clinical practice. It was established that even before the onset and/or detection of RCC the level of kidney injury molecule-1 (KIM-1) in blood plasma did increase. Objective of the study - comparative evaluation of KIM-1 levels in blood plasma of practically healthy persons, RCC cancer, benign kidney tumor patients, patients with non-oncological renal pathologies, and analysis of its role in RCC diagnostics and prognosis. Materials and methods. 125 RCC (age 33-81 years), 14 - benign kidney neoplasms (29-84 years) patients, 90 patients with chronic nephritis (28-82 years) and 68 practically healthy persons (18-71 years) were included in the study. Plasma KIM-1 content was measured using Human Serum TIM-1/KIM-1/HAVCR Quantikine (R) ELISA kit (R&D Systems Biotechne (R), USA). Results. KIM-1 level in blood plasma of RCC and chronic nephritis patients was significantly higher than in control (medians 305, 282 and 37.8 pg/ml respectively, p < 0.0001). The rate of KIM-1 elevation over cut-off value 90 pg/ml corresponding to the upper 95 % confidence interval of control in RCC patients comprised 79.2 %, in patients with nephritis - 83 %, in those with benign renal tumors - 50 %. Specificity in relation to healthy control was 96 %. KIM-1 level highly significantly increased with RCC progression, and already at stage I was 4.3-fold higher by median than in control (p < 0.0001). Sensitivity of stage I-II RCC detection at cut-off 90 pg/ml comprised 75 %; stage III-IV - 94 %. The highest plasma KIM-1 levels were detected in papillary cancer patients (median 644 pg/ml), that was more than 2-fold higher than in clear-cell and 32-fold higher than in chromophobic RCC. Plasma KIM-1 median level was 7-fold higher in patients with G(3-4) RCC than in those with G(1-2) (p < 0.0001). At the cut-off KIM-1 value of 163 pg/ml, corresponding to the median at stage I, significant differences in 3.5-years overall survival both in the total group: 49 % at high, 95 % at low marker level (p < 0.01), and at stage I RCC: 62 % and 100 % respectively (p < 0.05) - were revealed. Conclusion. Plasma KIM-1 may become the first highly sensitive marker for the early detection of RCC, but it does not allow differentiating between oncologic and non-oncologic renal pathologies. Increased basal plasma KIM-1 is an unfavorable prognostic factor irrespective of the stage of tumor progression.