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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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.
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.
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.
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.
KeywordsKIM-1 Renal transplantation Graft dysfunction
End-stage renal disease
Peripheral blood mononuclear cell
Chronic allograft dysfunction
Acute tubular necrosis
Interstitial fibrosis and tubular atrophy
Delayed graft function
Glomerular filtration rate
Kidney injury molecule-1
Area under the curve
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.
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.
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 was obtained from all individual participants included in the study.
- 3.Langone AJ, Chuang P. The management of the failed renal allograft: an enigma with potential consequences. In: Seminars in dialysis. Hoboken: Wiley Online Library; 2005.Google Scholar
- 27.Food U, Administration D. FDA, European Medicines Agency to consider additional test results when assessing new drug safety: Collaborative effort by FDA and EMEA expected to yield additional safety data. 2008. 2014.Google Scholar
- 36.Devarajan P. Emerging biomarkers of acute kidney injury. In: Acute kidney injury. Basel: Karger Publishers; 2007. pp. 203–212.Google Scholar
- 50.Nogare A, et al. Noninvasive analyses of kidney injury molecule-1 messenger RNA in kidney transplant recipients with graft dysfunction. In: Transplantation proceedings. Amsterdam: Elsevier; 2012.Google Scholar
- 53.Malyszko J, et al. Kidney injury molecule-1 correlates with kidney function in renal allograft recipients. In: Transplantation proceedings. Amsterdam: Elsevier; 2010.Google Scholar