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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

  • Sanaz Keshavarz Shahbaz
  • Fatemeh Pourrezagholi
  • Mohesn Nafar
  • Pedram Ahmadpoor
  • Mehri Barabadi
  • Farshad Foroughi
  • Morteza Hosseinzadeh
  • Mir Saeed Yekaninejad
  • Aliakbar AmirzargarEmail author
Original article
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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.

Keywords

KIM-1 Renal transplantation Graft dysfunction 

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

Notes

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 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.

Compliance with ethical standards

Conflict of interest

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).

Informed consent

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

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Copyright information

© Japanese Society of Nephrology 2019

Authors and Affiliations

  • Sanaz Keshavarz Shahbaz
    • 1
    • 2
  • Fatemeh Pourrezagholi
    • 3
  • Mohesn Nafar
    • 3
  • Pedram Ahmadpoor
    • 3
  • Mehri Barabadi
    • 2
  • Farshad Foroughi
    • 4
  • Morteza Hosseinzadeh
    • 5
  • Mir Saeed Yekaninejad
    • 6
  • Aliakbar Amirzargar
    • 2
    • 7
    Email author
  1. 1.Department of Immunology, School of MedicineMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
  3. 3.Department of Nephrology, Chronic Kidney Disease Research CenterShahid Labbafinejad Medical Center and Shahid Beheshti University of Medical SciencesTehranIran
  4. 4.Cellular and Molecular Research CenterQazvin University of Medical SciencesQazvinIran
  5. 5.Department of Immunology, School of MedicineIlam University of Medical SciencesIlamIran
  6. 6.Department of Epidemiology and Biostatistics, School of Public HealthTehran University of Medical SciencesTehranIran
  7. 7.Molecular Immunology Research CenterTehran University of Medical SciencesTehranIran

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