RESUMEN
Despite improvement in early outcome, rejection particularly chronic allograft enteropathy continues to be a major barrier to long-term visceral engraftment. The potential role of donor specific antibodies (DSA) was examined in 194 primary adult recipients. All underwent complement-dependent lymphocytotoxic crossmatch (CDC-XM) with pre- and posttransplant solid phase HLA-DSA assay in 156 (80%). Grafts were ABO-identical with random HLA-match. Liver was included in 71 (37%) allografts. Immunosuppression was tacrolimus-based with antilymphocyte recipient pretreatment in 150 (77%). CDC-XM was positive in 55 (28%). HLA-DSA was detectable before transplant in 49 (31%) recipients with 19 continuing to have circulating antibodies. Another 19 (18%) developed de novo DSA. Ninety percent of patients with preformed DSA harbored HLA Class-I whereas 74% of recipients with de novo antibodies had Class-II. Gender, age, ABO blood-type, cold ischemia, splenectomy and allograft type were significant DSA predictors. Preformed DSA significantly (p < 0.05) increased risk of acute rejection. Persistent and de novo HLA-DSA significantly (p < 0.001) increased risk of chronic rejection and associated graft loss. Inclusion of the liver was a significant predictor of better outcome (p = 0.004, HR = 0.347) with significant clearance of preformed antibodies (p = 0.04, OR = 56) and lower induction of de novo DSA (p = 0.07, OR = 24). Innovative multifaceted anti-DSA strategies are required to further improve long-term survival particularly of liver-free allografts.
Asunto(s)
Antígenos HLA/inmunología , Intestinos/trasplante , Trasplante de Hígado/inmunología , Adulto , Análisis de Varianza , Biopsia con Aguja , Estudios Transversales , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Prueba de Histocompatibilidad , Humanos , Inmunohistoquímica , Isoanticuerpos/inmunología , Trasplante de Hígado/métodos , Masculino , Persona de Mediana Edad , Trasplante de Órganos/métodos , Valores de Referencia , Medición de Riesgo , Factores de Tiempo , Donantes de Tejidos , Trasplante Homólogo/inmunología , Resultado del TratamientoRESUMEN
Despite continuous improvement in long-term survival, there is no knowledge about risk of bone health impairment and management strategies before and after intestinal transplantation. Therefore, 147 adults were retrospectively studied via chart review; 70 long-term survivors, 53 candidates and 24 recipients with longitudinal follow-up. Evaluation process included measurement of bone mineral density (BMD) and allied biochemical markers. Both long-term survivors and candidates showed low bone mass with lower (p < 0.05) z-scores at hip, femoral neck and spine. Vitamin D deficiency and secondary hyperparathyroidism were observed in both groups. Prevalence of osteoporosis was 44% among long-term survivors and 36% in candidates with age, BMD, duration of parenteral nutrition, type of immunosuppression and rejection being significant risk factors. Fragility fractures occurred at a higher (p = 0.02) rate among long-term survivors (20%) compared to candidates (6%). The longitudinal study documented acceleration (p = 0.025) of bone loss after transplantation with a decline of 13.4% (femoral neck), 12.7% (hip) and 2.1% (spine). Alendronate reduced (p < 0.05) but did not prevent bone loss. In conclusion, intestinal transplant recipients are at risk of osteoporosis secondary to bone loss before and after transplantation. Accordingly, current management includes comprehensive preventive measures with prompt therapeutic intervention utilizing intravenous bisphosphonates or subcutaneous human PTH.