Is the urinary kidney injury molecule an optimum biomarker for early detection of obstructive nephropathy? An experimental study

Abstract

Objectives: To evaluate the urinary kidney injury molecule-1 (KIM-1) as a predictor for early detection of acute kidney injury in cases with obstructive nephropathy in an animal model and to correlate urinary KIM-1 with the progress of obstructive nephropathy on a histopathological basis.

Materials and methods: Three models of obstruction were induced in 90 male rats: unilateral partial ureteral obstruction with a normal contra-lateral kidney, with nephrectomy of a contralateral kidney (solitary kidney), and bilateral partial ureteral obstruction. Each group was further divided into 2 subgroups; the sham-group (10 rats) and the disease group (20 rats). Serum creatinine, blood urea nitrogen, and urinary KIM-1 were collected on days 0, 7, and 14. Rats were sacrificed on the 7th and 14th day for histopathological examination of the obstructed kidney.

Results: By the end of first week, there was a significant rise of all biomarker levels in all groups when compared with basal levels. Similarly, biomarker levels at the 14th day were significantly higher than those obtained at the 7th day. The urinary KIM-1 level was not detected in the baseline condition. Expression of urinary KIM-1 showed a significant rise in all models ranging from 22 to 85 fold at the 7th day and even higher levels at the 14th day. Histopathological examination confirmed the presence of different forms of tubular injury.

Conclusions: Urinary KIM-1 is significantly elevated in obstructive uropathy. Such an elevation might be advantageous in the early diagnosis and subsequent early intervention of cases with partial ureteral obstruction.

Keywords

Biomarker / Injury / Kidney / Kidney injury molecule / Nephropathy / Obstruction / Uropathy

Acknowledgments

None.

Statement of ethics

The study gained ethical approval from local ethical committee in UNC, IRB Faculty of Medicine, Mansoura University. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All the experimental protocols for animal studies were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Conflict of interest statement

The authors declare that they have no financial conflict of interest.

Funding source

This study received an institutional funding.

Author contributions

ASE-H: Study design, manuscript writing, data analysis;

ME-H: Study design, chemical analysis, data analysis;

AAI: Chemical analysis, data collection;

KA: Histopathology analysis;

MA: Supervision, monitoring of data collection;

NB: Animal model surgeries;

AS: Supervision, reviewing final manuscript.

Data availability

The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.

References

[1] Huo W, Zhang K, Nie Z, Li Q, Jin F. Kidney injury molecule-1 (KIM-1): A novel kidney-specific injury molecule playing potential double-edged functions in kidney injury. TransplantRev (Orlando) 2010; 24(3):143-146.

[2] Fontanilla J, Han WK. Kidney injury molecule-1 (KIM-1) as an early detection tool for acute kidney injury and other renal diseases. Expert Opin Med Diagn 2011; 5(2):161-173.

[3] Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury. Kidney Int 2002; 62(1):237-244.

[4] Song J, Yu J, Prayogo GW, et al. Understanding kidney injury molecule 1: A novel immune factor in kidney pathophysiology. Am J Transl Res 2019; 11(3):1219-1229.

[5] Liangos O, Tighiouart H, Perianayagam MC, et al. Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers 2009; 14(6):423-431.

[6] Alharbi B, Fadda L, Ali HM. Evaluation of the renoprotective effect of nano turmeric against toxic dose of copper sulfate: Role of vascular cell adhesion molecule-1, kidney injury molecule-1, and signal transducer and activator of transcription 3 protein expressions. J Biochem Mol Toxicol 2019; 33(2):e22243.

[7] Nan-Ya K, Kajihara M, Kojima N, Degawa M. Usefulness of urinary kidney injury molecule-1 (KIM-1) as a biomarker for cisplatin-induced sub-chronic kidney injury. J Appl Toxicol 2015; 35(2):124-132.

[8] Wasilewska A, Taranta-Janusz K, Debek W, Zoch-Zwierz W, Kuroczycka-Saniutycz E. KIM-1 and NGAL: New markers of obstructive nephropathy. Pediatr Nephrol 2011; 26(4):579-586.

[9] Atilgan D, Parlaktas BS, Uluocak N, et al. Effects of melatonin on partial unilateral ureteral obstruction induced oxidative injury in rat kidney. Urol Ann 2012; 4(2):89-93.

[10] Luo QH, Chen ML, Sun FJ, et al. KIM-1 and NGAL as biomarkers of nephrotoxicity induced by gentamicin in rats. Mol Cell Biochem 2014; 397(1-2):53-60.

[11] McIlroy DR, Wagener G, Lee HT. Biomarkers of acute kidney injury: An evolving domain. Anesthesiology 2010; 112(4):998-1004.

[12] Mehta RL, Kellum JA, Shah SV, et al. Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11(2):R31.

[13] Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28(5):830-838.

[14] Han WK, Waikar SS, Johnson A, et al. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 2008; 73(7):863-869.

[15] van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA. Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol 2007; 212(2):209-217.

[16] Nejat M, Pickering JW, Devarajan P, et al. Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 2012; 81(12):1254-1262.

[17] Rouse R, Min M, Francke S, et al. Impact of pathologists and evaluation methods on performance assessment of the kidney injury biomarker, KIM-1. Toxicol Pathol 2015; 43(5):662-674.

[18] Mohammadjafari H, Rafiei A, Kosaryan M, Yeganeh Y, Hosseinimehr SJ. Determination of the severity of ureteropelvic junction obstruction using urinary epidermal growth factor and kidney injury molecule 1 levels. Biomark Med 2014; 8(10):1199-1206.