Acute kidney allograft Rj is a fundamental cause of allograft dysfunction. Certain allografts cannot resume function even after maximal anti-Rj therap
Clinical features & diagnosis of acute renal allograft rejection
o List of abbreviations:
o Rj: Rejection.
o PRA: Panel reactive antibody,
o HLA: human leukocyte antigen,
o DGF: delayed graft function,
o AKI: acute kidney injury,
o dd-cf DNA: Plasma donor-derived cell-free DNA,
o TCMR: acute T cell-mediated (cellular) rejection.
o ABM: antibody-mediated rejection,
o CMV: cytomegalovirus,
o im/m: immunosuppression,
o DSAs: Donor specific antibodies,
o ABOi: ABO-incompatible,
o KTx: Kidney transplantation,
o TR: Transplant recipients,
o SCr: serum creatinine,
o DD: differential diagnosis,
o GN: Glomerulonephritis,
o PTLD: posttransplant lymphoproliferative disease.
o IF/TA: interstitial fibrosis/tubular atrophy.
Acute kidney allograft Rj is a fundamental cause of allograft dysfunction. Certain allografts cannot resume function even after maximal anti-Rj therapy. Furthermore, in recovering TR, acute Rj episodes may reflected negatively on the long-term allograft survival.
Acute kidney allograft Rj can be defined as a sudden decline in allograft function that can be reflected as specific pathological alterations in the graft tissues. There are 2 major histological types of acute Rj, acute T cell-mediated (cellular) Rj (TCMR) and active ABMR. Both ABMR & acute TCMR may co-exist simultaneously in the allograft tissues. Moreover, subclinical Rj can be defined as the finding of histological evidence of acute Rj on biopsy specimen without associated rise in the SCr.
Risk factors triggering the evolution of acute Rj may include:
1) DGF.
2) HLA mismatching,
3) paediatric TR,
4) African American ethnicity,
5) Pre-sensitization (i.e., finding of DSAs or elevated PRA),
6) Incompatible blood grouping,
7) Extended cold ischemic time, &
Furthermore, ptns with a previous attack of Rj, TR receiving a 2nd or more tx, and those nonadherent to his/her medications are at increasing risk for acute Rj. Acute Rj episodes are generally complicated with a decline in the long-term allograft longevity, despite not all Rj episodes exerting the same effect on the long-term allograft function. Considering the significant decline in the acute Rj incidence rates along the last decade, there has not been associated advantages in the long-term allograft longevity. Most attacks of acute Rj observed within the 1st 6 mo post Tx, with so many episodes seen early post-operative. Rj after 12 mo is typically attributed to non-compliance or aggressively reduced im/m. Most ptns having acute Rj episodes can be presented with no symptoms. However, occasional manifestations can be seen e.g., pyrexia, malaise, oliguria, and allograft pain and/or tenderness. HT is also a commonly seen finding.
Ptns with acute allograft Rj can be presented with an acute elevation in SCr. A rising SCr level, however, is somehow a late finding in the Rj course and is an indicator of the presence of evident histological damage. Pyuria or newly found or worsened proteinuria can be also observed. Findings provided by kidney imaging are nonspecific, and such tests are usually performed to exclude other factors sharing in AKI development. Suspicion of acute allograft Rj should be considered with one or more of the following:
1) Newly raised SCr ≥ 25 % above baseline or higher than usual (e.g., recent TR with SCr stops decline too earlier than expected after Tx).
2) Any incremented rise in SCr in TR with higher risk for ABMR, e.g.,
1. ABOi transplant,
2. Highly sensitized TR,
3. TR with DSAs, or with
4. Inadequately given im/m.
3) Worsened HT.
4) Proteinuria >1 g/d.
5) Plasma donor-derived cell-free DNA (dd-cf DNA) >1 %.
The golden role for Dgx of kidney allograft Rj is an allograft biopsy that is used for proper grading the intensity of Rj, DD between TCMR & ABMR, and recognizing the magnitude of irreversible kidney damage (IF/TA). Biopsied renal allograft can also provide the other cause (s) of graft inflammation & injury, e.g., CMV, BK nephropathy, interstitial nephritis, pyelonephritis, de novo or recurrent GN disease, as well as PTLD. Chronically active ABMR was 1st identified in 2001 and nowadays a definite category in the Banff system. In contrary to active ABMR, chronic active ABMR is lacking an criterion of acute inflammation & show criteria that is consistent with matrix synthesis. Chronic ABMR generally observed late (>6 mo post-Tx) and can be seen in TR with or with no previous history of an active ABMR.
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