KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients
https://doi.org/10.17650/1726-9776-2020-16-3-21-28
Abstract
Objective: to assess the potential clinical significance of KIM-1 (kidney injury molecule 1) as a urinological marker for kidney cancer.
Materials and methods. An enzyme-linked immunosorbent assay was used to assess urinary KIM-1 (uKIM-1 — kidney injury molecule 1) levels in 67 patients with renal cell carcinoma (RCC) and 36 healthy volunteers (a control group).
Results. Both in patients and in healthy individuals, uKIM-1 levels were age independent. A difference between mean uKIM-1 values in RCC patients (2.4 ± 0.2 ng/ml) and the control group (0.7 ± 0.1 ng/ml) was statistically significant (p <0.0001). In RCC patients the higher uKIM-1 level was observed at more advanced clinical disease stages: the values increasedfrom 2.0 ± 0.2 ng/ml at the stage I and 3.0 ± 0.5 ng/ml at the stage II—III to 4.4 ± 1.2 ng/ml at the stage IV. In the group of patients with stage IRCC, most representative by the number of cases (n = 44) the uKIM-1 levels correlated with the tumor size and were increased in patients with different histological subtypes of the tumor, including clear cell, papillary and chromophobe RCC. After nephrectomy, a monotonous decrease in uKIM-1 level was observed, and after 6 days its values approached the mean value in the control group. Two days after kidney resection, uKIM-1 increased and then decreased, remaining elevated after 6 days.
Conclusion. This study demonstrates that uKIM-1 can be attributed to potentially significant urine tumor-associated markers of RCC.
About the Authors
K. Yu. KanukoevRussian Federation
3 2 nd Botkinskiy Proezd, Moscow 125284.
Competing Interests:
The authors declare no conflict of interest.
N. S. Sergeeva
Russian Federation
3 2 nd Botkinskiy Proezd, Moscow 125284; 1 Ostrovityanovа St., Moscow 117997.
Competing Interests:
The authors declare no conflict of interest.
T. A. Karmakova
Russian Federation
3 2 nd Botkinskiy Proezd, Moscow 125284.
Competing Interests:
The authors declare no conflict of interest.
N. V. Marshutina
Russian Federation
3 2 nd Botkinskiy Proezd, Moscow 125284.
Competing Interests:
The authors declare no conflict of interest.
M. P. Solokhina
Russian Federation
3 2 nd Botkinskiy Proezd, Moscow 125284.
Competing Interests:
The authors declare no conflict of interest.
K. M. Nyushko
Russian Federation
3 2 nd Botkinskiy Proezd, Moscow 125284.
Competing Interests:
The authors declare no conflict of interest.
B. Ya. Alekseev
Russian Federation
4 Koroleva St., Obninsk 249031; 11 Volokolamskoe Shosse, Moscow 125080.
Competing Interests:
The authors declare no conflict of interest.
A. D. Kaprin
Russian Federation
4 Koroleva St., Obninsk 249031.
Competing Interests:
The authors declare no conflict of interest.
References
1. Malignant tumors in Russia in 2018 (morbidity and mortality). Eds.: A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsena -filial FGBU “NMITS radiologii” Minzdrava Rossii, 2019. 250 p. (In Russ.).
2. Solokhina M.P., Sergeeva N.S., Marshutina N.V. et al. KIM-1 as a potential serological/urinological tumor-associated marker of renal cell carcinoma and chemotherapy nephrotoxicity. Onkourologiya = Cancer Urology 2019;15(3):132-42. (In Russ.).
3. Gershtein E.S., Kushlinskii N.E. Marker KIM-1 in the early diagnosis of renal cell carcinoma. Tekhnologiya zhivykh system = Technologies of Living Systems 2019;16(1):5-20. (In Russ.).
4. Yin C., Wang N. Kidney injury molecule-1 in kidney disease. Ren Fail 2016;38(10):1567-73. DOI: 10.1080/0886022X.2016.1193816.
5. Ichimura T., Hung C.C., Yang S.A. et al. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 2004;286(3):F552-63. DOI: 10.1152/ajprenal.00285.2002.
6. Wasung M.E., Chawla L.S., Madero M. Biomarkers of renal function, which and when? Clin Chim Acta 2015;438:350-7. DOI: 10.1016/j.cca.2014.08.039.
7. Moresco R.N., Bochi G.V., Stein C.S. et al. Urinary kidney injury molecule-1 in renal disease. Clin Chim Acta 2018;487:15-21. DOI: 10.1016/j.cca.2018.09.011.
8. Tajima S., Yamamoto N., Masuda S. Clinical prospects of biomarkers for the early detection and/or prediction of organ injury associated with pharmacotherapy. Biochem Pharmacol 2019;170:113664. DOI: 10.1016/j.bcp.2019.113664.
9. Han W.K., Alinani A., Wu C.L. et al. Human kidney injury molecule-1 a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol 2005;16(4):1126-34. DOI: 10.1681/ASN.2004070530.
10. Lin F., Zhang P.L., Yang X.J. et al. Human kidney injury molecule-1 (hKIM-1): a useful immunohistochemical marker for diagnosing renal cell carcinoma and ovarian clear cell carcinoma. Am J Surg Pathol 2007;31(3):371-81. DOI: 10.1097/01.pas.0000213353.95508.67.
11. Dong Y.C., Wu B., Wang J.D. et al. Expression and clinical significance of kidney injury molecule-1 in renal epithelial neoplasms. Zhonghua Bing Li Xue Za Zhi 2010;39(1):35-9. [Article in Chinese].
12. Morrissey J.J., London A.N., Lambert M.C. et al. Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma. Am J Nephrol 2011;34(5):391-8. DOI: 10.1159/000330851.
13. Cuadros T., Trilla E., Vila M.R. et al. Hepatitis A virus cellular receptor 1/ kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/ kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression. Eur J Cancer 2013;49(8):2034-47. DOI: 10.1016/j.ejca.2012.12.020.
14. Zhang P.L., Mashni J.W., Sabbisetti V.S. et al. Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma. Int Urol Nephrol 2014;46(2):379-88. DOI: 10.1007/s11255-013-0522-z.
15. Mijugkovic M., Stanojevic I., Milovic N. et al. KIM-1 and AQP-1 in patients with clear renal cell carcinoma: potential noninvasive biomarkers. Vojnosanit Pregl 2016;73(3):266-72. DOI: 10.2298/vsp150124006m.
16. Mijugkovic M., Stanojevic I., Milovic N. et al. Tissue and urinary KIM-1 relate to tumor characteristics in patients with clear renal cell carcinoma. Int Urol Nephrol 2018;50(1):63-70. DOI: 10.1007/s11255-017-1724-6.
17. Kushlinskii N.E., Gershtein E.S., Naberezhnov D.S. et al. Kidney Injury Molecule-1(KIM-1) in blood plasma of patients with clear-cell carcinoma. Bull Exp Biol Med 2019;167(3):388-92. DOI: 10.1007/s10517-019-04533-w.
18. Scelo G., Muller D.C., Riboli E. et al. KIM-1 as a blood-based marker for early detection of kidney cancer: a prospective nested case-control study. Clin Cancer Res 2018;24(22):5594-601. DOI: 10.1158/1078-0432.CCR-18-1496.
19. Shalabi A., Abassi Z., Awad H. et al. Urianary NGal and KIM-1: potential association with histopathologic features in patients with renal cell carcinoma. World J Urol 2013;31:1541-5. DOI: 10.1007/s00345-013-1043-1.
20. Frantsiyants E.M., Ushakova N.D., Kit O.I. et al. The dynamics of acute renal impairment markers during a surgery for kidney cancer. Obshchaya reanimatologiya = General Reanimatology 2017;13(6):38-47. (In Russ.).
Review
For citations:
Kanukoev K.Yu., Sergeeva N.S., Karmakova T.A., Marshutina N.V., Solokhina M.P., Nyushko K.M., Alekseev B.Ya., Kaprin A.D. KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients. Cancer Urology. 2020;16(3):21-28. (In Russ.) https://doi.org/10.17650/1726-9776-2020-16-3-21-28