High Soluble CD30 Serum Levels Are Associated with Inflammatory Infiltrate in Renal Graft Protocol Biopsies and Predict Dysfunction of the Graft

Abstract

In a previous study we showed, in recipients (R) with a functional kidney graft for at least three years, that high sCD30 serum levels (≥70 U/mL) are markers for long-term graft loss. In the present study we evaluated the relationship between sCD30 levels in R with stable renal function three months after transplantation (Tx) and the presence of inflammatory infiltrate in protocol biopsies (PBx) and renal function 3 and 6 months thereafter. The study was conducted in 127 first graft R with pre-Tx peak PRA < 30%, negative T and B CDC crossmatches and no donor-specific antibodies detected with Luminex assays. sCD30 levels were determined by ELISA (Bender MedSystems), in a sample drawn at the day or up to 28 days before the PBx. Graft lesions were graded according to Banff'07, C4d was evaluated by immunofluorescence. Serum creatinine levels (Cr) and proteinuria/Cr ratios (PCR) nearest to the PBx and 3 and 9 months thereafter were recorded. Estimated glomerular filtration rate (eGFR) was calculated with the Cockroft-Gault formula. Statistics: Mann-Whitney and Fisher's exact tests. Results: Inflammatory infiltrate was present in 30 (23.6%) biopsies (9 had acute cellular rejection; 7, borderline rejection; 14, tubulo-interstitial nephritis/inflammatory infiltrate without quantification; none had antibody mediated rejection). R with and without inflammatory infiltrate did not differ regarding serum Cr or PCR. sCD30 levels were higher in patients with inflammatory infiltrate (69.7 vs 37.5 U/mL, p< 0.05). sCD30 levels ≥70 U/mL were associated with the presence of inflammatory infiltrate (p< 0.02, RR=2.2), but not with Cr >1.5 mg/dL, proteinuria/Cr ≥ 0.1, or CMV infection. The eGFR did not differ between cases with sCD30 ≥ or < 70 U/mL at the time of the PBx, but was lower 3 and 9 months thereafter in R with sCD30 ≥ 70 U/mL, while no significant differences in eGFR were observed in relation to the presence of inflammatory infiltrate or acute rejection. In conclusion, the results showed that high sCD30 serum levels are associated with inflammatory infiltrate in PBx and may predict graft dysfunction 6 to 9 months after the biopsy, independently of the histological findings.