Incidence of AR, defined as increase in serum creatinine more than 0.3 mg/dl is 14.7% in 2001-2003 period. Pathologically interstitium is diffusely edematous and infiltrated by CD4 and CD8 lymphocyte. Tubulitis occurs when lymphocyte and monocyte extend into the walls and Lumina of tubules. In cell mediated vascular ejection that can be seen with tubulointerstitial rejection, lymphocyte&monocyte undermine arterial swollen endothelium, without arterial wall necrosis. Presence of leukocyte suggests infection or antibody mediated rejection. Typically C4d staining is negative. Differential diagnosis of acute allograft dysfunction is: Pre renal, interstitial nephritis, viral and bacterial infection, ATN, drug’s toxicity and obstructive uropathy. Assessment includes the history, adherence to drugs, physical examination and blood& urine tests, drugs level and sonography. Volume depletion, drugs and UTI constitute the common causes of allograft dysfunction. Diagnosis of ACR depends on biopsy, CD20 staining for refractory cases, negative C4d staining, presence of markers of activating lymphocyte and proteomic study.
Sub clinical rejection describes a morphologic pattern of acute cell mediated ejection that may occur in 30% of patients without clinical sign and symptoms of rejection diagnosed with advent of protocol biopsy.
Treatment of ACR, include pulse steroid (125-1000 mg for 3-5 days) can reverse 75% of first rejection episode. It can be repeated for recurrent or resistant rejection. Thymoglobulin and OKT3 used as the second line of treatment if graft function was deteriorating. For Banff IIB or greater, Thymoglobulin or OKT3 can be used from the beginning. With refractory rejection second course can be given in selected patient with 40-50% success of long term graft function. Changing the protocol from cyclosporine to tacrolimus or adding MMf, sirolimus and Anti CD, 20 (Rituximab) may be effective. Prognosis depends on recurrent rejection, episodes using potent drugs, occurs beyond 6 months or lack of response.