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ALL / Nephrology
Renal transplant: HLA typing and graft failure
Renal transplant: HLA typing and graft failure
The HLA system determines histocompatibility and is central to renal transplant outcomes. Graft dysfunction may reflect surgical complications, rejection, infection or recurrent renal disease.Pathophysiology and HLA
- HLA is the human major histocompatibility complex on chromosome 6
- class I antigens: HLA-A, HLA-B, HLA-C; class II antigens: HLA-DP, HLA-DQ, HLA-DR
- for renal transplantation, HLA matching importance is: DR > B > A
- rejection occurs when recipient immune responses recognise donor alloantigens
- antibody-mediated injury causes complement activation and vascular damage
- T-cell-mediated injury causes lymphocytic infiltration, cytokine release and fibrosis
Graft survival
- cadaveric transplant: 1-year survival about 90%, 10-year survival about 60%
- living-donor transplant: 1-year survival about 95%, 10-year survival about 70%
Early post-operative problems
- acute tubular necrosis of the graft
- vascular thrombosis
- urinary leak
- urinary tract infection
Hyperacute rejection (minutes to hours)
- due to pre-existing antibodies against ABO or HLA antigens
- an example of a type II hypersensitivity reaction
- leads to widespread thrombosis of graft vessels → ischaemia and necrosis of the transplanted organ
- no treatment is possible and the graft must be removed
Acute graft failure (< 6 months)
- usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)
- usually asymptomatic and is picked up by a rising creatinine, pyuria and proteinuria
- other causes include cytomegalovirus infection
- in a patient with rising creatinine and no reversible cause (e.g. obstruction, dehydration, drug toxicity), ultrasound-guided renal allograft biopsy is the definitive investigation
- may be reversible with steroids and immunosuppressants
Causes of chronic graft failure (> 6 months)
- both antibody and cell-mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)
- recurrence of original renal disease (MCGN > IgA > FSGS)
+PassMedicine Notes
The HLA system determines histocompatibility and is central to renal transplant outcomes. Graft dysfunction may reflect surgical complications, rejection, infection or recurrent renal disease.
Pathophysiology and HLA- HLA is the human major histocompatibility complex on chromosome 6
- class I antigens: HLA-A, HLA-B, HLA-C; class II antigens: HLA-DP, HLA-DQ, HLA-DR
- for renal transplantation, HLA matching importance is: DR > B > A
- rejection occurs when recipient immune responses recognise donor alloantigens
- antibody-mediated injury causes complement activation and vascular damage
- T-cell-mediated injury causes lymphocytic infiltration, cytokine release and fibrosis
- cadaveric transplant: 1-year survival about 90%, 10-year survival about 60%
- living-donor transplant: 1-year survival about 95%, 10-year survival about 70%
- acute tubular necrosis of the graft
- vascular thrombosis
- urinary leak
- urinary tract infection
- due to pre-existing antibodies against ABO or HLA antigens
- an example of a type II hypersensitivity reaction
- leads to widespread thrombosis of graft vessels --> ischaemia and necrosis of the transplanted organ
- no treatment is possible and the graft must be removed
- usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)
- usually asymptomatic and is picked up by a rising creatinine, pyuria and proteinuria
- other causes include cytomegalovirus infection
- in a patient with rising creatinine and no reversible cause (e.g. obstruction, dehydration, drug toxicity), ultrasound-guided renal allograft biopsy is the definitive investigation
- may be reversible with steroids and immunosuppressants
- both antibody and cell-mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)
- recurrence of original renal disease (MCGN > IgA > FSGS)
