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Dynamic variation of kidney injury molecule-1 mRNA and protein expression in blood and urine of renal transplant recipients: a cohort study

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Abstract

Background

Acute renal dysfunction still constitutes a highly significant obstacle to renal transplantation outcome. Kidney injury molecule-1 is highly upregulated in proximal tubular cells and shed into the urine and blood circulation following kidney injury. The aim of current cohort study was to evaluate the urine KIM-1 (uKIM-1) mRNA expression level and its protein concentration in blood and urine samples to determine whether sequential monitoring of KIM-1 in renal allograft recipients is a reliable biomarker for predicting the clinical status and outcome.

Methods

Both uKIM-1 mRNA expression level and the level of serum and uKIM-1 protein concentration in the 52 renal transplant recipients were respectively quantified using real-time PCR and ELISA methods at 2, 90 and 180 days after transplantation.

Result

KIM-1 mRNA and protein expression level in the blood and urine samples of patients with graft dysfunction was significantly higher than patients with well-functioning graft on days 2, 90 and 180 after transplantation. Receiver-operating characteristic curve analysis of mRNA and protein expression levels showed that urinary and blood KIM-1 at months 3 and 6 could predict acute renal dysfunction at 6 months and 1 year after transplantation.

Conclusion

Sequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury.

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Abbreviations

ESRD:

End-stage renal disease

PBMC:

Peripheral blood mononuclear cell

WFG:

Well-functioning graft

AR:

Acute rejection

CAD:

Chronic allograft dysfunction

GD:

Graft dysfunction

ATN:

Acute tubular necrosis

IF/TA:

Interstitial fibrosis and tubular atrophy

DGF:

Delayed graft function

CRE:

Creatinine

GFR:

Glomerular filtration rate

KIM-1:

Kidney injury molecule-1

ROC:

Receiver-operating characteristic

AUC:

Area under the curve

CI:

Confidence interval

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Acknowledgements

This study (MSc student thesis) was financially supported by (Grant no: 24286) Tehran University of Medical Sciences, research deputy, Tehran, Iran. The authors thank all staff members of the transplantation ward in Labbafi Nejad Hospital for their excellent assistance providing clinical data and samples from all patients.

Author information

Authors and Affiliations

  1. Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sanaz Keshavarz Shahbaz

  2. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Building No. 7, Poursina Ave, Tehran, Iran

    Sanaz Keshavarz Shahbaz, Mehri Barabadi & Aliakbar Amirzargar

  3. Department of Nephrology, Chronic Kidney Disease Research Center, Shahid Labbafinejad Medical Center and Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Fatemeh Pourrezagholi, Mohesn Nafar & Pedram Ahmadpoor

  4. Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran

    Farshad Foroughi

  5. Department of Immunology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran

    Morteza Hosseinzadeh

  6. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Mir Saeed Yekaninejad

  7. Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Aliakbar Amirzargar

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  1. Sanaz Keshavarz Shahbaz
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Contributions

SKS participated in collecting the samples, performing the experiments and writing the manuscript draft. FP, MN and PA are nephrologists, participated in acquisition of clinical data, interpreted the data with the clinical outcome. MSY contributed in statistical data analysis. MB, FF, and MH participated in sample collection and performed the experiments. AA, leading project manager, participated in designing the study and editing the final.

Corresponding author

Correspondence to Aliakbar Amirzargar.

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The authors confirm no conflict of interest.

Ethical approval

All the procedures performed in studies involving human participants were in accordance with Ethics Committee of Tehran University of medical science at which the studies were conducted (IRB approval number 92033024286).

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Informed consent was obtained from all individual participants included in the study.

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Keshavarz Shahbaz, S., Pourrezagholi, F., Nafar, M. et al. Dynamic variation of kidney injury molecule-1 mRNA and protein expression in blood and urine of renal transplant recipients: a cohort study. Clin Exp Nephrol 23, 1235–1249 (2019). https://doi.org/10.1007/s10157-019-01765-y

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