ABSTRACT
In kidney transplantation, de novo donor-specific antibodies (DSA) correlate with poor graft survival, and Consensus Guidelines recommend a protocol biopsy. In pancreas transplantation, DSA are also associated with poor graft outcomes; however, there are no recommendations on protocol biopsies. We started an antibody screening protocol on pancreas transplant patients at 0, 3, 6, 12 months, and yearly. Patients with DSA or high MFI non-DSA were considered for protocol biopsies of both organs. Results: 143 pancreas recipients were screened. 84 patients had negative antibodies throughout the study, 11 patients were found to have antibodies at graft dysfunction, and 48 patients had positive antibodies at screening without acute organ dysfunction (study group). Among the 30 non-DSA patients, 9 had protocol simultaneous pancreas and kidney biopsies performed with negative results in all of them. In contrast, among the 18 DSA patients, 15 had these biopsies performed, and 47% presented with subclinical rejection of the kidney, the pancreas, or both. In addition, some of the DSA patients without a protocol biopsy presented with rejection during the first 15 months of follow-up. Conclusion: We conclude that protocol biopsies of both grafts may play a role in the follow-up of pancreas transplant patients with de novo DSA appearance.
Subject(s)
Pancreas Transplantation , Biopsy , Graft Rejection/diagnosis , Graft Rejection/etiology , Graft Survival , HLA Antigens , Humans , Isoantibodies , Tissue DonorsABSTRACT
Simultaneous pancreas and kidney transplants offer significant therapeutic advantages but present a diagnostic approach dilemma in the diagnosis of rejection. Because both organs are from the same donor, the kidney has been treated traditionally as the "sentinel" organ to biopsy, presumably representing the status of both allografts. Truly concurrent biopsy studies, however, are needed to confirm this hypothesis. We examined 101 concurrent biopsies from 70 patients with dysfunction in either or both organs. Results showed concurrent rejection in 23 of 57 (40%) of cases with rejection; 19 of 57 (33.5%) and 15 of 57 (26.5%) showed kidney or pancreas only rejection, respectively. The degree and type of rejection differed in the majority (13 of 23, 56.5%) of cases with concurrent rejection, with the pancreas more often showing higher rejection grade. Taking into account pancreas dysfunction, a positive kidney biopsy should correctly predict pancreas rejection in 86% of the instances. However, the lack of complete concordance between the 2 organs, the discrepancies in grade and type of rejection, and the tendency for higher rejection grades in concurrent or pancreas only rejections, all support the rationale for pancreas biopsies. The latter provide additional data on the overall status of the organ, as well as information on nonrejection-related pathologies.
Subject(s)
Graft Rejection/etiology , Graft Survival , Kidney Transplantation/adverse effects , Pancreas Transplantation/adverse effects , Postoperative Complications , Adult , Allografts , Biopsy , Female , Follow-Up Studies , Graft Rejection/pathology , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Retrospective Studies , Risk FactorsABSTRACT
Paracoccidioides brasiliensis is the cause of paracoccidioidomycosis, one of the most important systemic mycoses in Latin America. Human disease has been observed in a limited geographic and ecological niche, and it is attributed to exposure to the fungus in soil. Most primary infections are subclinical, as the infection is contained by the host mainly through cell-mediated immune response. However, as the fungus has the ability to survive in a dormant state for long periods, an impairment of the immune response may lead to reactivation and clinical disease. Surprisingly, paracoccidioidomycosis has rarely been reported in transplanted patients. The aim of this communication is to report a case occurring in a kidney recipient in an acute clinical form immediately after transplantation, and to review the available information on previously reported cases.
Subject(s)
Antifungal Agents/therapeutic use , Graft Rejection/therapy , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Lung Diseases, Fungal/diagnosis , Paracoccidioides/pathogenicity , Paracoccidioidomycosis/diagnosis , Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Antifungal Agents/administration & dosage , Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid/microbiology , Bronchoscopy , Female , Graft Rejection/immunology , Humans , Imipenem/administration & dosage , Imipenem/therapeutic use , Immunity, Humoral , Immunosuppression Therapy/methods , Immunosuppressive Agents/administration & dosage , Itraconazole/administration & dosage , Kidney Failure, Chronic/surgery , Latin America , Lung Diseases, Fungal/complications , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/microbiology , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Paracoccidioides/isolation & purification , Paracoccidioidomycosis/complications , Paracoccidioidomycosis/drug therapy , Paracoccidioidomycosis/microbiology , Plasmapheresis , Respiration, Artificial , Tomography, X-Ray Computed , Vancomycin/administration & dosage , Vancomycin/therapeutic useABSTRACT
BACKGROUND: Multiple factors have been implicated in the process of ischemia-reperfusion injury (IRI) in organ transplantation. Among these factors, oxidative damage seems to initiate the injury. α-lipoic acid (ALA) is a potent antioxidant that is used in patients with diabetic polyneuropathy. The aim of the present study was to determine the effect of ALA in patients undergoing simultaneous kidney-pancreas transplant by evaluating the functional recovery of the graft and biochemical markers of IRI. METHODS: Twenty-six patients were included in the following groups: (i) untreated control; (ii) donor and recipient (DR) ALA-treated, in which ALA was administered both to the deceased donor and to the recipients; and (iii) recipient ALA-treated group. The expression of inflammatory genes, as observed in biopsies taken at the end of surgery, as well as the serum cytokines, secretory leukocyte protease inhibitor, regenerating islet-derived protein 3ß/pancreatitis-associated protein, amylase, lipase, glucose, and creatinine levels were quantified as markers of organ function. RESULTS: The DR group showed high levels of TGFß and low levels of C3 and TNFα in the kidneys, whereas high levels of C3 and heme oxygenase were identified in pancreas biopsies. Decreases in serum IL-8, IL-6, secretory leukocyte protease inhibitor, and regenerating islet-derived protein 3 ß/pancreatitis-associated protein were observed after surgery in the DR group. Serum lipase and amylase were lower in the DR group than in the control and recipient groups. Early kidney dysfunction and clinical pancreatitis were higher in the control group than in either treatment group. CONCLUSIONS: These results show that ALA preconditioning is capable of reducing inflammatory markers while decreasing early kidney dysfunction and clinical posttransplant pancreatitis.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antioxidants/therapeutic use , Kidney Diseases/prevention & control , Kidney Transplantation , Pancreas Transplantation , Pancreatic Diseases/prevention & control , Reperfusion Injury/prevention & control , Thioctic Acid/therapeutic use , Adult , Argentina , Biomarkers/blood , Female , Humans , Inflammation Mediators/blood , Kidney Diseases/blood , Kidney Diseases/diagnosis , Kidney Diseases/etiology , Kidney Transplantation/adverse effects , Male , Middle Aged , Oxidative Stress/drug effects , Pancreas Transplantation/adverse effects , Pancreatic Diseases/blood , Pancreatic Diseases/diagnosis , Pancreatic Diseases/etiology , Pancreatitis-Associated Proteins , Prospective Studies , Reperfusion Injury/blood , Reperfusion Injury/diagnosis , Reperfusion Injury/etiology , Time Factors , Treatment Outcome , Young AdultABSTRACT
La inmunoglobulina intravenosa (IVIg) ha sido utilizada en el pasado en pacientes con enfermedades autoinmunes, y también ha sido recientemente usada en pacientes sensibilizados que se encuentran en lista de espera para transpalnte renal, con el fin de reducir sus niveles de anticuerpos reactivos contra panel (PRA). Basados en estos reportes, se ha postulado también que la IVIg podría ser utilizada como un agente de rescate ene el tratamiento de rechazos refractarios en el transplante renal. Este trabajo reporta a cuatro pacientes, quienes se encontraban cursando su primer transplante renal. Tres de ellos habían sido trasplantados con donante vivo, dos relacionados y uno no relaiconado (esposo), y el cuarto había recibido un riñón cadavérico. El diagnóstico de rechazo, fue efectuado por biopsia renal y punción aspirativa renal. Inicialmente a todos los pacientes se les suministró esteroides y luego terapia antilinfocitaria, tres de ellos con anticuerpos monoclonales (OKT3), y el rescate con globulina antilinfocitaria (GAL). Luego del fracaso de la terapia antilinfocitaria, IVIg fue administrada a dosis de 500 mg/Kg/d durante siete días consecutivos. todos los rechazos fueron exitosamente revertidos. el mecanismo de acción de la IVIg puede estar relacionada con los anticuerpos antiidiotípicos. IVIg aparece como una alternativa útil para el rescate de receptores de transplantes renales con rechazos refractarios.
Subject(s)
Humans , Immunoglobulins, Intravenous/therapeutic use , Graft Rejection , Kidney Transplantation/adverse effectsABSTRACT
La inmunoglobulina intravenosa (IVIg) ha sido utilizada en el pasado en pacientes con enfermedades autoinmunes, y también ha sido recientemente usada en pacientes sensibilizados que se encuentran en lista de espera para transpalnte renal, con el fin de reducir sus niveles de anticuerpos reactivos contra panel (PRA). Basados en estos reportes, se ha postulado también que la IVIg podría ser utilizada como un agente de rescate ene el tratamiento de rechazos refractarios en el transplante renal. Este trabajo reporta a cuatro pacientes, quienes se encontraban cursando su primer transplante renal. Tres de ellos habían sido trasplantados con donante vivo, dos relacionados y uno no relaiconado (esposo), y el cuarto había recibido un riñón cadavérico. El diagnóstico de rechazo, fue efectuado por biopsia renal y punción aspirativa renal. Inicialmente a todos los pacientes se les suministró esteroides y luego terapia antilinfocitaria, tres de ellos con anticuerpos monoclonales (OKT3), y el rescate con globulina antilinfocitaria (GAL). Luego del fracaso de la terapia antilinfocitaria, IVIg fue administrada a dosis de 500 mg/Kg/d durante siete días consecutivos. todos los rechazos fueron exitosamente revertidos. el mecanismo de acción de la IVIg puede estar relacionada con los anticuerpos antiidiotípicos. IVIg aparece como una alternativa útil para el rescate de receptores de transplantes renales con rechazos refractarios. (AU)
