Subclinical Lesions and Donor-Specific Antibodies in Kidney Transplant Recipients Receiving Tacrolimus-Based Immunosuppressive Regimen Followed by Early Conversion to Sirolimus.
BACKGROUND
There is no evidence on the incidence of subclinical inflammation and scaring lesions in patients receiving tacrolimus (TAC) minimization and elimination immunosuppressive regimens.


METHODS
This study analyzed preimplantation, 3 and 24 months protocol biopsies and anti-HLA donor-specific antibodies (DSA) in 140 low immunological risk kidney transplant recipients receiving reduced TAC exposure, prednisone, and mycophenolate, randomized at 3 months to be converted or not to sirolimus (SRL).


RESULTS
Mean TAC concentrations were 6.0 ± 2.4 ng/mL and 5.8 ± 2.2 ng/mL at 3 and 24 months. The incidence of subclinical inflammation lesions at 3 months was 9.3%. The incidence of (interstitial fibrosis) IF/(tubular atrophy) TA at month 24 was 57.6%, higher in SRL compared to TAC group (68.8 vs 44.4%; P = 0.022). Patients converted to SRL showed higher incidence of acute rejection (7.3% vs 0%), proteinuria (59.6% vs 25%; P = 0.001), and DSA (17.8% vs 7.3%; P = 0.201), respectively. Biopsy-proven acute rejection (odds ratio [OR] 2.32, 95% confidence interval [95% CI], 0.979-5.518, P = 0.056), subclinical inflammation lesions at 3 months (OR, 11.75; 95% CI, 1.286-107.474; P = 0.029) and conversion to SRL (OR, 2.72; 95% CI, 1.155-6.383; P = 0.022) were associated with IF/TA at month 24. Black ethnicity (OR, 0.22; 95% CI, 0.058-0.873; P = 0.031), donor age (OR, 2.74; 95% CI, 1.329-5.649; P = 0.006), and conversion to SRL (OR, 2.34; 95% CI, 1.043-5.267; P = 0.039) were associated with inferior renal function at 24 months.


CONCLUSIONS
In kidney transplant recipients receiving reduced TAC exposure, subclinical inflammation lesions at 3 months were associated with IF/TA at 24 months. Conversion from TAC to SRL was associated with inferior renal function, higher incidence of IF/TA, and trends to higher incidence of DSA at 24 months.
1 Nephrology Division, Hospital do Rim/Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil. 2 Instituto de Imunogenética, AFIP, São Paulo, Brazil. 3 Pathology Division, Universidade Federal do Paraná, Curitiba, Brazil. 4 Pathology Division, Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil. 5 Urology Division, Hospital do Rim/Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil.
Tainá Veras
TV
de Sandes-Freitas
Cláudia Rosso
CR
Felipe
Érika Fernandes
ÉF
Campos
Maria Gerbasi
MG
de Lima
Maria Fernanda
MF
Soares
Marcello Fabiano
MF
de Franco
Wilson Ferreira
WF
Aguiar
Hélio
H
Tedesco-Silva
José Osmar
JO
Medina-Pestana
D000328:Adult; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D057915:Drug Substitution; D005260:Female; D005355:Fibrosis; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007518:Isoantibodies / Q000097:blood*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009393:Nephritis / Q000139:chemically induced; D016017:Odds Ratio; D011507:Proteinuria / Q000139:chemically induced; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D020123:Sirolimus; D016559:Tacrolimus