early diagnosis of graft rejection in renal transplantation
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Early diagnosis of graft rejection in renal transplantation
Kidney solid organ rejection test (k- SORT)
Dr. Alaa Hussain Abd Awn
Consultant nephrologist
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Organ-i: Personalizing Treatment in Organ Transplantation
Current challenge is the absence of a highly sensitive, early and accurate molecular test that indicates the risk and
prevalence of AR in a peripheral blood sample independent of the invasive biopsy procedure.
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In kidney transplantation acute rejection (AR) occurs in about 15-20% of patients using the current standard of care for immunosuppressant treatment.
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AR (clinical and subclinical) represents major risk factors for developing chronic graft injury and graft loss, end with dialysis that it is coasty.
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Timely detection and treatment of rejection: an important goal
Renal Biopsy
Creatinine -Decreased UO -HTN -Graft tenderness
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The clinical period of AR:-Now practically, AR is only detected by invasive biopsy (Bx) to the graft after having increase in the patient’s S. creatinine (the only current peripheral marker for graft injury) and other non specific sings and symptoms.
-But the S. creat. is not specific marker for AR and only increase after substantive graft damage ( GFR decrease more than 50%)-Bx. results will be obtained after few days.
-The damage already happens and we will deal with the results of these changes.-What about the subclinical AR, when there is AR without increase in the S. creat., remain largely undetected until extensive graft damage develops.
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Timely detection and treatment of rejection: an important goal
Renal Biopsy
Creatinine -Decreased UO -HTN -Graft tenderness
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Histological period of AR :Some centers perform a protocol graft biopsies as means of frequent graft monitoring but,
-- Increasing the unnecessary risks of invasive procedures to patients who do not have AR (the majority of patients).
- Financial burden.- Bx. Sampling error and not predictive of AR
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A Kidney allograft biopsy
Low major complication rate (including transfusion requirement and catheterization) of between 0.4 and 1.0 percent
Only one graft lost in approximately 2500 biopsies
Schwarz A, Gwinner W, Hiss M, et al. Am J Transplant 2005; 5:1992.
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Page kidney after renal allograft biopsy
Heffernan E et. Al. J Clin Ultrasound. 2009 May;37(4):226-9.
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Timely detection and treatment of rejection: an important goal
Renal Biopsy
Creatinine -Decreased UO -HTN -Graft tenderness
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Pure molecular period of AR:The golden period for early Dx. And early treatment for AR (our goal).
The aim is to have specific, sensitive and non invasive test to Dx the AR (humeral and cellular) before having the histological and the clinical features of AR
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Gold Standard for diagnosis of acute rejection
The "tricorder" used by Bones McCoy to scan patients and get the right diagnosis
Graft biopsy currently the GOLD STANDARD for diagnosis of acute rejection.
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Recent technique:- Simple blood sample for quantitative real time PCR (QPCR) test, called the kidney solid organ rejection test (k- SORT),, ( organ- i).
- To predict AR and to treat those patients earlier, better outcome.
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Technique:-The peripheral blood is collected in 2.5 cc special tubes (PAXgene blood RNA tubes)or heparin- coated tubes, used for mononuclear cells isolation.(which are activated by the immune system secondary to the AR)
-Then the RNA (mRNA) extracted from these mononuclear cells by special lab. Technique (Qiagen technique).
- Quantitative real time PCR (QPCR) test used to detect abnormal exposure of 17 genes panel (from total 43 genes in the mRNA), which are abnormally exposed in AR .
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kidney Solid Organ Rejection Test: k-SORT
A 17 gene Quantitative real time PCR (QPCR) based assay:Easy collection of peripheral blood
sampling; no local processingNot impacted by post-transplant timeHigh specifications for sensitivity,
specificity of Acute RejectionPredicts Histological Acute Rejection
months before bx triggerApplicable to pediatric and adult
recipients
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Suggested Utilization Frequency of k-SORTfor Post-transplant Monitoring
Risk of acute rejection (AR) highest in 1st 12 months post transplantation
k-SORT reflects immune activity 3-4 months prior to histological
diagnosis of AR
Recommended testing schedule:Year 1: 5x
1) 1-2 week2) 1 month3) 3 months4) 6 months5) 12 months
Year 2 onwards: 2-3x / year; specially in high-risk patients
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OverviewOrgan-i is a transplant franchise developing and commercializing next generation (genomic and proteomic–based) diagnostic tools to advance the standard of care for patients with solid organ transplants.Operational since 2011.>15 years of researchs.
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Thank you