RESUMEN
Several organ allocation protocols give priority to wait-listed simultaneous kidney-pancreas (SPK) transplant recipients to mitigate the higher cardiovascular risk of patients with diabetes mellitus on dialysis. The available information regarding the impact of preemptive simultaneous kidney-pancreas transplantation on recipient and graft outcomes is nonetheless controversial. To help resolve this, we explored the influence of preemptive simultaneous kidney-pancreas transplants on patient and graft survival through a retrospective analysis of the OPTN/UNOS database, encompassing 9690 simultaneous transplant recipients between 2000 and 2017. Statistical analysis was performed applying a propensity score analysis to minimize bias. Of these patients, 1796 (19%) were transplanted preemptively. At ten years, recipient survival was significantly superior in the preemptive group when compared to the non-preemptive group (78.9% vs 71.8%). Dialysis at simultaneous kidney-pancreas transplantation was an independent significant risk for patient survival (hazard ratio 1.66 [95% confidence interval 1.32-2.09]), especially if the dialysis duration was 12 months or longer. Preemptive transplantation was also associated with significant superior kidney graft survival compared to those on dialysis (death-censored: 84.3% vs 75.4%, respectively; estimated half-life of 38.57 [38.33 -38.81] vs 22.35 [22.17 - 22.53] years, respectively). No differences were observed between both groups neither for pancreas graft survival nor for post-transplant surgical complications. Thus, our results sustain the relevance of early referral for pancreas transplantation and the importance of pancreas allocation priority in reducing patient mortality after simultaneous kidney-pancreas transplantation.
Asunto(s)
Diabetes Mellitus Tipo 1 , Trasplante de Riñón , Trasplante de Páncreas , Diabetes Mellitus Tipo 1/cirugía , Supervivencia de Injerto , Humanos , Trasplante de Riñón/métodos , Páncreas , Trasplante de Páncreas/efectos adversos , Estudios RetrospectivosRESUMEN
AIM: Acute antibody-mediated rejection (ABMR) after kidney transplantation (KT) is associated with poor allograft survival. Current therapies for ABMR are able to deplete B-lymphocytes but do not target plasma cells. Bortezomib is a proteasome inhibitor that can eliminate plasma cells and has demonstrated utility in the treatment of ABMR. METHODS: A retrospective study was carried out from 2010 to 2014, including all patients with ABMR refractory to conventional treatment who received bortezomib. Bortezomib (1.3 mg/m(2) ) was administered intravenously on days 1, 4, 8, and 11. Renal function, graft survival, follow-up biopsies, and donor-specific antibodies (DSA) were recorded. RESULTS: We identified seven patients. Of these, high immunological risk was found in 6 of 7, preformed DSA were found in 5 of 7, flow cytometry crossmatch was positive in 4 of 7, and desensitization before KTx was provided in 6 of 7 patients. ABMR was diagnosed at a median of 90 days (8-167) post-KT. After bortezomib therapy, renal function improved or stabilized in 5 of 7 patients and progressively deteriorated in 2 of 7, leading to haemodialysis after 7 and 11 months, respectively. Follow-up kidney biopsies showed persistence of ABMR in 2 of 7, chronic active ABMR 3 of 7 and inactive chronic lesions in 2 of 7. DSA titres significantly decreased after treatment (P = 0.028). All patients experienced mild adverse events. After a follow-up of 22 ± 18 months, three grafts were lost (42%) and four remained functioning. CONCLUSION: Bortezomib could be useful as an adjuvant therapy for ABMR refractory to conventional treatment with acceptable mid-term outcomes in these severe cases. More research is needed to develop strategies to better preserve graft function after refractory ABMR.
Asunto(s)
Bortezomib/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Inmunosupresores/uso terapéutico , Isoanticuerpos/sangre , Trasplante de Riñón/efectos adversos , Inhibidores de Proteasoma/uso terapéutico , Enfermedad Aguda , Administración Intravenosa , Biomarcadores/sangre , Biopsia , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/fisiopatología , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/efectos adversos , Recuperación de la Función , Diálisis Renal , Estudios Retrospectivos , España , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management. METHODS: Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples. dd-cfDNA was measured using the Prospera test (Natera, Inc.) and reported both as a fraction of the total cfDNA (fraction; %) and as concentration in the recipient's plasma (quantity; copies/mL). RESULTS: In the absence of P-BPAR, dd-cfDNA was significantly higher in samples collected within the first 45 d after SPKTx compared with those measured afterward (median, 1.00% versus 0.30%; median, 128.2 versus 35.3 cp/mL, respectively with both; P = 0.001). In samples obtained beyond day 45, P-BPAR samples presented a significantly higher dd-cfDNA fraction (0.83 versus 0.30%; P = 0.006) and quantity (81.3 versus 35.3 cp/mL; P = 0.001) than stable samples. Incorporating dd-cfDNA quantity along with dd-cfDNA fraction outperformed dd-cfDNA fraction alone to detect active rejection. Notably, when using a quantity cutoff of 70 cp/mL, dd-cfDNA detected P-BPAR with a sensitivity of 85.7% and a specificity of 93.7%, which was more accurate than current biomarkers (area under curve of 0.89 for dd-cfDNA (cp/ml) compared with 0.74 of lipase and 0.46 for amylase). CONCLUSIONS: dd-cfDNA measurement through a simple noninvasive blood test could be incorporated into clinical practice to help inform graft management in SPKTx patients.
Asunto(s)
Ácidos Nucleicos Libres de Células , Rechazo de Injerto , Trasplante de Riñón , Trasplante de Páncreas , Biomarcadores , Ácidos Nucleicos Libres de Células/genética , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/genética , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Páncreas/efectos adversos , Proyectos Piloto , Complicaciones Posoperatorias , Donantes de TejidosRESUMEN
AIMS: Information on the impact of insulin therapy before pancreas donation on pancreas outcomes is scarce. We aim to explore the influence of insulin therapy before donation on recipient and pancreas graft survival. METHODS: Registry study including 12,841 pancreas recipients from the OPTN/UNOS registry performed between 2000 and 2017. Inverse probability of treatment weighting (IPTW) was used to account for covariate imbalance between recipients from a donor with and without insulin requirements. RESULTS: A total of 7765 (60%) patients received a pancreas from a donor with insulin before donation (IBD). Pancreas graft survival (death-censored) was similar between recipients from IBD and non-IBD donors at 1, 5 and 10 years (89% vs 89%, 78% vs 79 and 69% vs 70%, respectively, P = 0.35). Recipients from IBD donors presented a similar 90-days pancreas graft survival. After IPTW weighting, IBD donors were neither associated with any post-transplant surgical complication (HR 1.11 [95% CI 0.98-1.24], P = 0.06), nor with risk for recipient death (HR 0.94 [95% CI 0.85-1.04], P = 0.26), nor pancreas graft failure (HR 1.06 [95% CI 0.98-1.16], P = 0.15). CONCLUSIONS: Insulin therapy before donation in accepted pancreas donors was not associated, per se, with an impaired pancreas graft and patient survival.
Asunto(s)
Insulina , Trasplante de Páncreas , HumanosRESUMEN
UNLABELLED: From a theoretical point of view, an alloimmune response can not take place, still some type of standard immunosuppression is used in about 60% of patients receiving kidney grafts from their monozygotic twins. We aimed at assessing clinical response in patients receiving renal grafts from a living monozygotic twin donor when no immunosuppressive therapy is used. METHODS: This is a retrospective observational study of patients receiving kidney grafts from their monozygotic twins from 1969 to 2013. The following data were recorded: age, renal graft recipient's primary disease, renal function, renal survival and overall survival. Immunosuppressive therapy included a single intraoperative dose of methylprednisolone 500 mg and no maintenance immunosuppression. RESULTS: Five patients with kidney grafts from their monozygotic twins were dentified in our centre. Mean age at transplantation was 33 years (27-39). One-year overall survival and graft survival were 100%. Mean creatinine level was 0.96 ± 0.2 one year after transplantation, and 1.2 ± 0.37 mg/dl at most recent follow-up. Two patients died with a functional graft more than 15 years after kidney transplantation (causes were melanoma and cardiovascular event respectively). Follow-up was lost in a patient one year after transplantation. Two patients are alive with a functioning graft at 18 months and 42.5 years after transplantation respectively. CONCLUSION: Kidney transplantation from a living monozygotic twin is associated to outstanding clinical outcomes. Immunossuppresive therapy to suppress alloimmune response in probably unnecessary 11 zygosity has been confirmed.
Asunto(s)
Trasplante de Riñón , Donadores Vivos , Gemelos Monocigóticos , Adulto , Estudios de Seguimiento , Supervivencia de Injerto , Histocompatibilidad , Humanos , Terapia de Inmunosupresión , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Cuidados Intraoperatorios , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Estudios Retrospectivos , Análisis de SupervivenciaAsunto(s)
Bortezomib/efectos adversos , Rechazo de Injerto/tratamiento farmacológico , Inmunidad Humoral , Inmunosupresores/efectos adversos , Seudoobstrucción Intestinal/inducido químicamente , Trasplante de Riñón/efectos adversos , Inhibidores de Proteasoma/efectos adversos , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Humanos , Incidencia , Seudoobstrucción Intestinal/diagnóstico , Seudoobstrucción Intestinal/fisiopatología , Seudoobstrucción Intestinal/terapia , Masculino , Persona de Mediana Edad , Recuperación de la Función , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Complemento C5/antagonistas & inhibidores , Síndrome Hemolítico-Urémico/prevención & control , Trasplante de Riñón , Síndrome Hemolítico Urémico Atípico , Factor H de Complemento/genética , Inactivadores del Complemento/uso terapéutico , Femenino , Síndrome Hemolítico-Urémico/genética , Síndrome Hemolítico-Urémico/inmunología , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/inmunología , Donadores Vivos , Mutación Missense , Adulto JovenRESUMEN
BACKGROUND: Graft survival depends on adequate immunosuppression. To evaluate the effect on the immune system of immunosuppressive therapies using calcineurin inhibitors (CNIs), several pharmacodynamic indices have been proposed to complement pharmacokinetic data. In this preliminary study we compared some of these parameters during combined immunosuppressant therapies. METHODS: We treated 65 stable renal transplant recipients with cyclosporin A (CsA; n = 16), tacrolimus (TRL; n = 10); CsA + mycophenolate mofetil (MMF; n = 14); TRL + MMF (n = 13), and MMF (n = 12). Twelve nontreated healthy controls were also included. Calcineurin activity (CNA) in peripheral blood mononuclear cells was measured using (32)P-labeled peptide. Interleukin-2 (IL-2) and interferon-gamma production in phytohemagglutinin-activated whole blood were measured at 0 and 2 h postdose. The areas under the curves, c(min), c(max), and concentration at 2 h (c(2 h)) were also measured. RESULTS: We found no differences in CNA between groups receiving CNIs alone or combined with MMF [median (25th-75th percentiles)]: CsA(2 h), 3.87 (3.00-6.85)% alkaline phosphatase (AP); CsA+MMF(2 h), 3.90 (1.78-5.19)% AP; TRL(2 h), 5.68 (3.02-16.00)% AP; TRL+MMF(2 h), 11.80 (4.05-14.63)% AP. In vitro IL-2 production was significantly lower in the groups receiving combined therapy than in groups receiving CNIs alone [median (25th-75th percentiles)]: CsA(2 h), 276.52 (190.41-385.25) ng/L; CsA+MMF(2 h), 166.48 (81.06-377.01) ng/L (P <0.001); TRL(2 h), 249.34 (127.48-363.50) ng/L; TRL+ MMF(2 h), 122.13 (51.02-180.00) ng/L (P <0.001). The correlations (r) between c(2 h) and CNA 2 h postdose were as follows: CsA, r = -0.74; CsA+MMF, r = -0.84; TRL, r = -0.70; TRL+ MMF, r = -0.70 (P <0.001 in all cases). CONCLUSIONS: The measurement of CNA may be of help in following the effect on the immune system of CNI treatments, even in combined therapies, but does not reflect the additional effect of MMF. In contrast, IL-2 in vitro production reflects the effect of both MMF and CNIs.