The fate of C4d positive kidney allografts lacking histological signs of acute rejection.

BACKGROUND: C4d deposits in renal transplants are known to be an independent risk factor of graft failure. The current analysis evaluates the impact of C4d deposits on graft function and survival in renal transplants without morphological signs of rejection.

METHODS: We retrospectively analyzed diagnostic transplant biopsies performed due to allograft dysfunction from June 1994 to June 2001 at the University Hospital in Basel.

STUDY GROUP: Grafts/patients with focal or diffuse positivity of C4d along peritubular capillaries; absence of morphological signs of acute cellular and/or humoral rejection; up to 3 year follow-up analysis post index biopsy. Patients treated with anti-rejection therapy or an increase in maintenance immunosuppression post biopsy (intervention group = IG) were compared to patients with unaltered immunosuppression (standard group = SG).

RESULTS: Study group: 22 biopsies/patients out of 400 biopsies (5%) were included into the study, 17 in the SG and 5 in the IG. Patient survival (1-/3-years): SG: 100/94%, IG: 80/80%; graft survival censored for death (1-/3-years): SG: 82.5/68.8%, IG: 100/100%; serum creatinine (micromol/l) at index biopsy/1-year/3-years: SG: 221 +/- 70/231 +/- 103/245 +/- 124, IG: 217 +/- 100/143 +/- 28/177 +/- 55; acute rejection episodes within 1 year post index biopsy: SG: 4 (4 patients), IG: 1 (1 patient); all differences not significant. Lowest serum creatinine within 4 weeks post index biopsy (IG vs. SG): 108 +/- 25 vs. 181 +/- 61, p = 0.02.

CONCLUSIONS: C4d positivity in kidney transplants lacking histological evidence of acute rejection is not associated with rapid functional graft deterioration, even in untreated cases. However, anti-rejection therapy results in the improvement of kidney function. Thus, even in grafts with normal histology, the detection of C4d in diagnostic biopsies can be interpreted as a sign of "smoldering" rejection that benefits from therapy.