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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
LETTER TO THE EDITOR  
Year : 2019  |  Volume : 30  |  Issue : 3  |  Page : 752-753
Prognostication of acute kidney allograft rejection through urinary molecular signatures: A noninvasive approach to ameliorate kidney rejection dynamics


Renal Transplant Unit, National Institute of Solid Organ and Tissue Transplantation, Dow University of Health Sciences, Ojha Campus, Karachi, Pakistan

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Date of Submission28-Jul-2018
Date of Acceptance26-Dec-2018
Date of Web Publication26-Jun-2019
 

How to cite this article:
Hamid RB, Khan MT, Ali AS. Prognostication of acute kidney allograft rejection through urinary molecular signatures: A noninvasive approach to ameliorate kidney rejection dynamics. Saudi J Kidney Dis Transpl 2019;30:752-3

How to cite this URL:
Hamid RB, Khan MT, Ali AS. Prognostication of acute kidney allograft rejection through urinary molecular signatures: A noninvasive approach to ameliorate kidney rejection dynamics. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 15];30:752-3. Available from: http://www.sjkdt.org/text.asp?2019/30/3/752/261369


To the Editor,

Kidney transplantation is unquestionably the best existing therapeutic modality for patients enduring end-stage renal disease; however, acute kidney allograft rejection compromises its optimal therapeutic response. Considering the severity of pathology, absence of efficient diagnostic method, and availability of effective antirejection (immunosuppressive) agents, it is prudent to explore avenues of convenient, robust, and noninvasive diagnostic signatures that could prognosticate acute rejection well before irreversible allograft insult, and perhaps such an approach would bring several clinical advantages. It would (1) attenuate the necessity of needle biopsy; (2) aid in early prediction of acute kidney allograft rejection and might prevent irreversible allograft damage; (3) serve to determine the immune status (immune-patrolling tool) of the kidney allograft recipient before actual histopatholo-gical changes and guide preemptive antirejection therapy; and (4) assist in characterizing the immunopathological biomarkers to adjust the antirejection therapy, minimizing the risk of under- and over-immunosuppression.[1]

Lately, much interest has been generated by uncovering of noninvasive urinary diagnostic biomarkers of acute kidney allograft rejection. A study by Suthanthiran et al discovered that urinary biomarkers such as CD3ε mRNA, IP-10 mRNA, and 18S rRNA could foretell acute kidney rejections. Interestingly, they also found that abrupt rise in urinary biomarkers was specific to patients with rejection and was unaltered by urinary tract infection.[1] Similarly, Nissaisorakarn et al extensively reviewed literature and concluded that urinary biomarkers could be suggestive of precise immunopatho-logical events within the kidney allograft. For instance, elevated urinary levels of mRNAs for CD3ε, granzyme B, and perforin indicates the role of cytotoxic T cells; high expression of IP-10 and CXCR3 mRNAs is consistent with chemokines–chemokine receptors axis role; and augmented mRNA levels for FOXP3 suggest the T regulatory cells’ role in restricting acute kidney rejection.[2] The latter urinary cell biomarker was also demonstrated by Merhi et al in suggesting effective reversal of acute kidney rejection.[3] Erpicum et al also reported CXCL9; CXCL10; and a three-gene biomarker of CD3ą CXCL10, and 18S rRNA urinary levels as promising biomarkers for acute kidney rejection.[4]

The clinical importance of needle biopsy cannot be ignored in the assessment of kidney allograft histopathology; however, noninvasive urinary biomarkers have the ability to delineate the immunopathological mechanisms of acute rejection. Clearly, this simple method could provide a unique framework to guide antirejection therapy and improve individualized management of kidney allograft patients. The acute kidney allograft rejection rate in Pakistan is 14%, according to the report by Rizvi et al.[5] Although Pakistan has successfully established kidney transplant facilities and embraced high-end transplant technologies, we are yet to evidence any research and implementation of noninvasive urinary biomarker signatures for acute kidney rejection in our transplant settings. Hence, developing countries like Pakistan need to drive efforts to assess and validate such noninvasive yardsticks, evaluate its reproducibility in our population, and promote clinical application thereafter. Altogether, the diagnostic yield of noninvasive urinary biomarkers compared to other conventional methods would certainly transform the dynamics of the acute kidney allograft rejection in Pakistan and worldwide.

Conflict of interest: None declared.



 
   References Top

1.
Suthanthiran M, Schwartz JE, Ding R, et al. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med 2013;369:20-31.  Back to cited text no. 1
    
2.
Nissaisorakarn V, Lee JR, Lubetzky M, Suthanthiran M. Urine biomarkers informative of human kidney allograft rejection and tolerance. Hum Immunol 2018;79:343-55.  Back to cited text no. 2
    
3.
Merhi B, Bayliss G, Gohh RY. Role for urinary biomarkers in diagnosis of acute rejection in the transplanted kidney. World J Transplant 2015;5:251-60.  Back to cited text no. 3
    
4.
Erpicum P, Hanssen O, Weekers L, et al. Noninvasive approaches in the diagnosis of acute rejection in kidney transplant recipients, part II: Omics analyses of urine and blood samples. Clin Kidney J 2017;10:106-15.  Back to cited text no. 4
    
5.
Rizvi SA, Naqvi SA, Zafar MN, Akhtar SF. A kidney transplantation model in a low-resource country: An experience from Pakistan. Kidney Int Suppl (2011) 2013;3:236-40.  Back to cited text no. 5
    

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Correspondence Address:
Akbar Shoukat Ali
Renal Transplant Unit, National Institute of Solid Organ and Tissue Transplantation, Dow University of Health Sciences, Ojha Campus, Karachi
Pakistan
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DOI: 10.4103/1319-2442.261369

PMID: 31249250

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