Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants.
BACKGROUND
Subclinical rejection (SCR) causes chronic allograft damage, which may be prevented by antirejection therapy.


METHODS
A pilot study of the effect of routine treatment of SCR was performed in 88 recipients of either a kidney (n=59) or combined kidney-pancreas transplant (n=29) undergoing protocol biopsy (PBX) surveillance at 1 and 3 months, using calcineurin inhibitors, mycophenolate mofetil, and corticosteroid therapy.


RESULTS
SCR was seen in 46.6% (41/88 patients), as 30 borderline and 11 acute SCR. From 279 transplant biopsies, the prevalence of SCR was 25% (22/88) at 1 month, 10.2% (9/88) at 3 months, and 8.3% (2/24) at 12 months PBX. Treatment included bolus intravenous or oral corticosteroids (n=20) and augmented immunosuppression, either by conversion to tacrolimus (n=6) or increased doses of maintenance therapy (n=14), whereas OKT3 was used in one case of subclinical vascular rejection. Borderline episodes were not treated in 12 patients. In biopsies taken to assess therapeutic response, persistent SCR was present in 46.1% (6/13). Treatment of SCR at 1 month was followed by lower acute Banff sum scores at 3 months PBX (P<0.01-0.0001). Early chronic damage was already present in the 1 month PBX, associated with SCR (P<0.0005 versus without SCR), although by 3 months these differences were lost. Rates of opportunistic infections and BK nephropathy were not increased by SCR treatment.


CONCLUSIONS
Early chronic allograft damage was associated with SCR and therapy appeared to ameliorate further immune-mediated injury, although the efficacy of corticosteroids alone may be inadequate. A controlled trial of therapy for SCR is warranted.
Kee
Terence Y-S
TY
Department of Renal Medicine, University of Sydney, Westmead Hospital, Sydney, Australia.
Chapman
Jeremy R
JR
O'Connell
Philip J
PJ
Fung
Caroline L-S
CL
Allen
Richard D M
RD
Kable
Kathryn
K
Vitalone
Matthew J
MJ
Nankivell
Brian J
BJ
D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006084:Graft Rejection / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D016035:Pancreas Transplantation; D020551:Pulse Therapy, Drug; D016559:Tacrolimus / Q000627:therapeutic use
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016559:Tacrolimus; D008775:Methylprednisolone