Natural history, risk factors, and impact of subclinical rejection in kidney transplantation.
BACKGROUND
Subclinical rejection (SCR) is defined as histologically proven acute rejection in the absence of immediate functional deterioration.


METHODS
We evaluated the impact of SCR in 961 prospective protocol kidney biopsies from diabetic recipients of a kidney-pancreas transplant (n=119) and one kidney transplant alone taken regularly up to 10 years after transplantation.


RESULTS
SCR was present in 60.8%, 45.7%, 25.8%, and 17.7% of biopsies at 1, 3, 12, and greater than 12 months after transplantation. Banff scores for acute interstitial inflammation and tubulitis declined exponentially with time. SCR was predicted by prior acute cellular rejection and type of immunosuppressive therapy (P<0.05-0.001). Tacrolimus reduced interstitial infiltration (P<0.001), whereas mycophenolate reduced tubulitis (P<0.05), and the combination effectively eliminated SCR (P<0.001). Persistent SCR of less than 2 years duration on sequential biopsies occurred in 29.2% of patients and was associated with prior acute interstitial rejection (P<0.001) and requirement for antilymphocyte therapy (P<0.05). It resolved by 0.49 +/- 0.33 years and resulted in higher grades of chronic allograft nephropathy (CAN, P<0.05). True chronic rejection, defined as persistent SCR of 2 years or more duration and implying continuous immunologic activation was found in only 5.8% of patients. The presence of SCR increased chronic interstitial fibrosis, tubular atrophy, and CAN scores on subsequent biopsies (P<0.05-0.001). SCR preceded and was correlated with CAN (P<0.001) on sequential analysis.


CONCLUSIONS
Histologic evidence of acute rejection in the absence of clinical suspicion resulted in significant tubulointerstitial damage to transplanted kidneys and contributed to CAN.
Department of Renal Medicine, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. brian.nankivell@wsahs.nsw.gov.au
Brian J
BJ
Nankivell
Richard J
RJ
Borrows
Caroline L-S
CL
Fung
Philip J
PJ
O'Connell
Richard D M
RD
Allen
Jeremy R
JR
Chapman
D000208:Acute Disease; D001707:Biopsy, Needle; D002908:Chronic Disease; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery*; D006084:Graft Rejection / Q000145:classification / Q000453:epidemiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D016035:Pancreas Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology; D011183:Postoperative Complications / Q000145:classification / Q000473:pathology; D015995:Prevalence; D012189:Retrospective Studies
D007166:Immunosuppressive Agents