Almost 3/4th of pancreatic Tx in the US are proceeded as a SPK Tx, with the observed remainder reported as either sequential PAK or PTA
Pancreas-kidney transplantation in DM: Pancreatic allograft
rejection
Abbreviations:
o
AB: antibodies.
o Ac Rj: acute rejection.
o ACR: acute cellular rejection.
o AMR: antibody-mediated rejection.
o
CyA: Cyclosporine.
o
DCD: deceased-donor.
o
GC: Glucocorticoids.
o
im/m: Immunosuppression.
o
IVIG: immune
globulin.
o
KTx: kidney transplant.
o
PAK: pancreas after kidney.
o
Prd: Prednisone.
o
PTA: pancreas transplants alone.
o
PE: plasmapheresis.
o
rATG: rabbit
Antithymocyte globulin.
o
Rtx: Rituximab.
o
SAB: single-antigen bead.
o
Sms: Symptoms.
o
SPK: simultaneous pancreas-kidney.
o
Tac:
Tacrolimus
o
TR: transplant recipient.
o
TR: Transplant recipients
o
FBS: fasting plasma glucose.
o
Tx: transplantation.
o
US: Ultrasound.
o
DCAL: death-censored allograft loss.
Almost 3/4th of pancreatic Tx in the US are proceeded as a SPK Tx,
with the observed remainder reported as either sequential PAK or PTA.
Pancreatic allograft Rj remains a crucial clinical challenge
and is the primary cause of pancreatic DCAL after 3 mo post-Tx.
Ptns with pancreas allograft Rj are mostly
asymptomatic, despite some ptns present with mild allograft tenderness and/or fever.
Other less commonly clinical manifestations of Ac
Rj may include painful abdomen, distension (typically induced by
ileus), or a bowel functional alterations. Lastly, the primary tools of
monitoring ptns with allograft Rj is
lab testing.
Pancreatic allograft Rj should
be suspected with either the aforementioned clinical criteria or with lab study
alterations (raised s. lipase and/or amylase
levels). The subsequent approach can be followed:
o
PAK or PTA seen with abdominal Sms or presenting within 6 weeks post-Tx,
> abdominopelvic US+CT
imaging with oral contrast to assess postsurgical sequelae &
intra-abdominal infections. If either pancreatic US
or CT imaging show an intra-abdominal
abnormality explaining the rise in pancreatic enzymes, then > appropriate antibiotics
+ follow up s. lipase & amylase. Ptns may need pancreatic graft biopsy with
lack of lipase and/or amylase lowering.
o
PAK or PTA with no intra-abdominal alterations on
either US or CT images,
or ptns presenting without abdominal Sms
and
presenting > 6
weeks post-Tx, recommended approach rely primarily
on blood Tac (or CyA) levels:
1) If Tac (or CyA) level is above the therapeutic range > reduce im/m
& monitor Tac (or CyA) level until returned to an accepted range. If lipase/amylase normalizes
with the im/m decline, pancreas
allograft Rj is unlikely, and enzymatic rise can be
attributed to Tac (or CyA) toxicity at supra-therapeutic range. Otherwise, pancreatic
allograft biopsy should be proceeded.
2) If Tac (or CyA) levels are within or below the therapeutic level, proceed to
> pancreatic allograft biopsy.
SPK Tx
presenting with
a new
rise in s. lipase and/or amylase and a new rise in SCr > renal biopsy to diagnose possible combined kidney/pancreas graft
Rj. If kidney allograft biopsy
showed > Ac Rj in SPK TR, we treat for Ac
Rj without the need for pancreatic
biopsy.
The gold standard for Dgx of pancreatic Rj is > pancreas biopsy that
is the only accurate tool for grading Rj
intensity & DD between ACR, AMR, and other causes of graft inflammation &
injury. Generally, we ttt most ptns with Ac Rj on biopsy irrespective to injurious chronicity or
magnitude of graft dysfunction. However, with abnormal graft function (e.g., raised FBS, lowered C-peptide, or HB
A1c >7 %) and histologically
reduced pancreatic islets, some clinicans
would not treat for Ac Rj. Therapy
for Ac Rj
relied primarily upon the type & intensity of Rj on
biopsy:
1) ACR therapy according to magnitude of inflammation per Banff classification:
o
Borderline ACR:
augment maintenance im/m for the coming 2-3 mo + pulse IV GC, followed by tapered oral Prd.
o
ACR grade I, II,
or III > rATG-TG > methylprednisolone
as pre-medication prior to the 1st 2-3 doses of rATG-TG, followed by a
tapered oral Prd. Do not give high-dose pulse GC with rATG-TG. Augment also maintenance im/m.
2) AMR: 3-5
sessions PE
followed by VIG, add also
anti-B cell e.g., Rtx Plus augmented maintenance im/m.
3) Mixed
AMR/ACR:
rATG-TG
+ 3
sessions PE
& IVIG, followed by low
dose Rtx.
In case of difficult pancreas biopsy, decision for
empirical therapy of Rj is usually relying on a case-by-case consideration.
Empirical therapy for ACR can be considered if the likelihood of Ac Rj is high.
Moreover, we can treat AMR with detected de novo DSAs
or rising DSA
as compared to pret-Tx level in the setting of allograft malfunction.
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