1/ Want to continue the learning streak of #Kidneywk ?
#MedTwitter #NephTwitter, we bring another #ASPNFOAM group tweetorial based on pathology webinar @ASPNeph on T-cell mediated rejection(TCMR) in kidney transplant (Tx)
#MedTwitter #NephTwitter, we bring another #ASPNFOAM group tweetorial based on pathology webinar @ASPNeph on T-cell mediated rejection(TCMR) in kidney transplant (Tx)
2/
Let's start with a vignette! 13 yr M with CAKUT s/p DDKT 6mo ago, p/w with doubling of Cr from 0.7 to 1.5 mg/dl, normal vitals and PE. UA normal. A lot of recent stressors and concern for non-adherence.
Sounds like a familiar scenario?
Let's start with a vignette! 13 yr M with CAKUT s/p DDKT 6mo ago, p/w with doubling of Cr from 0.7 to 1.5 mg/dl, normal vitals and PE. UA normal. A lot of recent stressors and concern for non-adherence.
Sounds like a familiar scenario?
What is the potential cause of graft dysfunction in this patient?
3/ ⚡️Likely REJECTION!
Check out this awesome #tweetorial by @miketurk6 on “SCARI” causes of kidney graft dysfunction🎃👻
Check out this awesome #tweetorial by @miketurk6 on “SCARI” causes of kidney graft dysfunction🎃👻
4/
📌Kidney transplant rejection remains an independent risk factor for long term graft survival.
📌Despite robust immunosuppression regimen, TCMR and antibody mediated rejection (ABMR) is a concerning cause for graft loss
pubmed.ncbi.nlm.nih.gov
📌Kidney transplant rejection remains an independent risk factor for long term graft survival.
📌Despite robust immunosuppression regimen, TCMR and antibody mediated rejection (ABMR) is a concerning cause for graft loss
pubmed.ncbi.nlm.nih.gov
5/
TCMR typically occurs in 1st yr post Tx.
ABMR is the most common cause of late kidney allograft failure.
pubmed.ncbi.nlm.nih.gov
TCMR typically occurs in 1st yr post Tx.
ABMR is the most common cause of late kidney allograft failure.
pubmed.ncbi.nlm.nih.gov
What are some risk factors for kidney Tx rejection?
6/
🧐Let’s look into histopathology of TCMR
😄This is a pathology webinar, duh!!!
Off we go to heavenly Banff🧳🏔️
🧐Let’s look into histopathology of TCMR
😄This is a pathology webinar, duh!!!
Off we go to heavenly Banff🧳🏔️
7/
🔤The Banff lingo
Banff Lesion Score
▶️Interstitial inflammation
-mononuclear infiltrates involving unscarred cortical parenchyma
▶️Tubulitis
-mononuclear infiltrates in tubular basement membrane
▶️Arteritis
- inflammatory cells beneath the endothelial cells
🔤The Banff lingo
Banff Lesion Score
▶️Interstitial inflammation
-mononuclear infiltrates involving unscarred cortical parenchyma
▶️Tubulitis
-mononuclear infiltrates in tubular basement membrane
▶️Arteritis
- inflammatory cells beneath the endothelial cells
8/
Banff classification
♦️Borderline rejection added 2005
♦️< 10-25% inflammation
♦️foci of tubulitis + minor interstitial inflammation (Banff i0 or i1)
♦️ interstitial inflammation (i2 or i3) with minor tubulitis (t1)
i0(t1-t3), i1(t1-t3), i2t1 and i2t3
tinyurl.com
Banff classification
♦️Borderline rejection added 2005
♦️< 10-25% inflammation
♦️foci of tubulitis + minor interstitial inflammation (Banff i0 or i1)
♦️ interstitial inflammation (i2 or i3) with minor tubulitis (t1)
i0(t1-t3), i1(t1-t3), i2t1 and i2t3
tinyurl.com
9/
🔶Image shows mononuclear infiltrates in the interstitium, tubules and arteritis
🔶Light microscopy shows significant lymphocytic infiltrates
🔶Image shows mononuclear infiltrates in the interstitium, tubules and arteritis
🔶Light microscopy shows significant lymphocytic infiltrates
10/
💉Protocol biopsy done for early detection before change in GFR/proteinuria
🛑Pitfalls of biopsy(bx)
-Cost
-Invasive, potential complication
-Sampling error
-Labor intensive
renalfellow.org @RenalFellowNtwk @jadav_md
💉Protocol biopsy done for early detection before change in GFR/proteinuria
🛑Pitfalls of biopsy(bx)
-Cost
-Invasive, potential complication
-Sampling error
-Labor intensive
renalfellow.org @RenalFellowNtwk @jadav_md
What are the barriers to early diagnosis of kidney Tx rejection?
12/
💥This calls for non-invasive bio-marker!!!
💠One such biomarker recently studied is donor derived cell free DNA
💠% or total amount DNA released from injured donor kidney tissue (DD cf-DNA)
mdpi.com
💥This calls for non-invasive bio-marker!!!
💠One such biomarker recently studied is donor derived cell free DNA
💠% or total amount DNA released from injured donor kidney tissue (DD cf-DNA)
mdpi.com
13/
dd-cf-DNA clinical assay uses Single nucleotide polymorphism (SNP) for donor and recipient identification
Check out this article with beautiful cartoons @NatRevNeph
nature.com
dd-cf-DNA clinical assay uses Single nucleotide polymorphism (SNP) for donor and recipient identification
Check out this article with beautiful cartoons @NatRevNeph
nature.com
14/ Lets review few big studies on DD-cf-DNA
🎯DART-> Allosure testing platform
🔸Median dd-cfDNA in ABMR 2.9%;
🔸1.2% in TCMR grade 1B or worse
🔸0.2% for TCMR 1A
♦️ 1% cut-off used for test positivity
👉Better for predicting ABMR (AUC 0.87) than TCMR
PMID # 28280140
🎯DART-> Allosure testing platform
🔸Median dd-cfDNA in ABMR 2.9%;
🔸1.2% in TCMR grade 1B or worse
🔸0.2% for TCMR 1A
♦️ 1% cut-off used for test positivity
👉Better for predicting ABMR (AUC 0.87) than TCMR
PMID # 28280140
15/
♦️Initial Prospera study
🔸median cf-DNA for ABMR (2.2%), TCMR( 2.7%) and mixed rejection(2.6%) did not differ significantly.
pubmed.ncbi.nlm.nih.gov
♦️Initial Prospera study
🔸median cf-DNA for ABMR (2.2%), TCMR( 2.7%) and mixed rejection(2.6%) did not differ significantly.
pubmed.ncbi.nlm.nih.gov
16/
🧬Viracor Transplant Rejection Allograft Check(TRAC) analyzes 70,000 SNP’s, initial study promising with AUC for detection ~ 0.85
🧬Ongoing TRULO study looks at gene expression assay TruGraf and TRAC dd-cfDNA
tinyurl.com
🧬Viracor Transplant Rejection Allograft Check(TRAC) analyzes 70,000 SNP’s, initial study promising with AUC for detection ~ 0.85
🧬Ongoing TRULO study looks at gene expression assay TruGraf and TRAC dd-cfDNA
tinyurl.com
17/
Meta-analysis of cf-DNA in TCMR, the median level did not differ between pts with TCMR and those without rejection, thus limiting its utility
pubmed.ncbi.nlm.nih.gov
Meta-analysis of cf-DNA in TCMR, the median level did not differ between pts with TCMR and those without rejection, thus limiting its utility
pubmed.ncbi.nlm.nih.gov
18/
❓Why was cf-DNA not high in TCMR in these studies?
⚡️No direct endothelial injury
⚡️Mostly tubulointerstitial damage
⚡️Classifying TCMR into mixed rejection
❓Why was cf-DNA not high in TCMR in these studies?
⚡️No direct endothelial injury
⚡️Mostly tubulointerstitial damage
⚡️Classifying TCMR into mixed rejection
19/
▶️Borderline TCMR/1A rejection makes up ¾ of all ACR
▶️Does affect long term graft function
▶️cf-DNA could differentiate although at lower detection levels (<1%)
pubmed.ncbi.nlm.nih.gov
▶️Borderline TCMR/1A rejection makes up ¾ of all ACR
▶️Does affect long term graft function
▶️cf-DNA could differentiate although at lower detection levels (<1%)
pubmed.ncbi.nlm.nih.gov
20/
🔸Improvement in cf-DNA after IV pulse steroids for TCMR
💊Could be used to guide therapy
🧒Recent studies showed effectiveness of using cfDNA in ped kidney Tx
👇
PMID #
●36302566
●33217125
●35340104
🔸Improvement in cf-DNA after IV pulse steroids for TCMR
💊Could be used to guide therapy
🧒Recent studies showed effectiveness of using cfDNA in ped kidney Tx
👇
PMID #
●36302566
●33217125
●35340104
What the potential confounders of DD-cf-DNA?
21/
🔥Trifecta study in 300 kidney bx ->relationships b/w dd-cfDNA(%) at the time of indication biopsy and the genome-wide molecular findings assessed by microarrays
🔥Molecular rejection correlated with elevated cf-DNA better than histologic changes
tinyurl.com
🔥Trifecta study in 300 kidney bx ->relationships b/w dd-cfDNA(%) at the time of indication biopsy and the genome-wide molecular findings assessed by microarrays
🔥Molecular rejection correlated with elevated cf-DNA better than histologic changes
tinyurl.com
22/
Treatment TCMR
⚕️Banff BL, IA, IB→ Steroid pulse 10 mg/kg q daily x 3 doses OR oral steroid cycle over 3mo
⚕️Banff IIA,IIB, III→ Rabbit ATG 3-5 doses
Treatment TCMR
⚕️Banff BL, IA, IB→ Steroid pulse 10 mg/kg q daily x 3 doses OR oral steroid cycle over 3mo
⚕️Banff IIA,IIB, III→ Rabbit ATG 3-5 doses
23/
Chronic active TCMR is newly described entity with long term graft loss and variable treatment response
sciencedirect.com
Chronic active TCMR is newly described entity with long term graft loss and variable treatment response
sciencedirect.com
For a case-based clinical discussion on #TCMR with an expert - login to @ASPNeph website, Sept 2022 webinar #Membereducation
aspneph.org
Special thanks to #ASPNFOAM group members @drM_sudha @CatherineJ20 for reviewing!
aspneph.org
Special thanks to #ASPNFOAM group members @drM_sudha @CatherineJ20 for reviewing!
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