Early diagnosis of graft rejection in renal transplantation
1. Early diagnosis of graft rejection in renal
transplantation
Kidney solid organ rejection test (k- SORT)
Dr.
Alaa Hussain Abd Awn
Consultant nephrologist
2. 2
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.
3. In kidney transplantation acute rejection (AR)
occurs in about 15-20% of patients using the
current standard of care for immunosuppressant
treatment.
4. AR (clinical and subclinical) represents major risk
factors for developing chronic graft injury and graft
loss, end with dialysis that it is coasty.
5. Timely detection and treatment of rejection: an important goal
Renal Biopsy
Creatinine
-Decreased UO
-HTN
-Graft tenderness
6. 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.
7. Timely detection and treatment of rejection: an important goal
Renal Biopsy
Creatinine
-Decreased UO
-HTN
-Graft tenderness
8. 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
9. 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.
10. Page kidney after renal allograft biopsy
Heffernan E et. Al. J Clin Ultrasound. 2009 May;37(4):226-9.
11. Timely detection and treatment of rejection: an important goal
Renal Biopsy
Creatinine
-Decreased UO
-HTN
-Graft tenderness
12. 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
13. 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.
14. 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.
15. 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 .
16. 16
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 processing
Not impacted by post-transplant time
High specifications for sensitivity, specificity of
Acute Rejection
Predicts Histological Acute Rejection months
before bx trigger
Applicable to pediatric and adult recipients
17.
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Suggested Utilization Frequency of k-SORT
for 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 week
2) 1 month
3) 3 months
4) 6 months
5) 12 months
Year 2 onwards: 2-3x / year; specially in high-risk patients
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Overview
Organ-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.