Rechazo crónico mediado por anticuerpos

Contexto el rechazo crónico mediado por anticuerpos (cABMR, chronic antibody-mediated rejection) se considera una de las principales causas de disfunción crónica del injerto. Objetivo profundizar en la comprensión de los mecanismos que la ocasionan para diseñar tratamientos efectivos, dado que es muy poco lo que se ha avanzado en el tratamiento de esta patología. Metodología en esta revisión narrativa de la literatura, presentamos los factores de riesgo relacionados con la disfunción crónica del injerto, haciendo énfasis en la fisiopatología, el diagnóstico y el tratamiento del cABMR. Resultados el factor de riesgo más relevante para el desarrollo de disfunción crónica del injerto es el desarrollo de anticuerpos donante específicos (DSA) y ABMR. Para el diagnóstico de cABMR activo, se requieren los criterios de Banff 2017 (los tres deben estar presentes: Evidencia histológica de lesión tisular crónica, evidencia de inflamación actual en el endotelio vascular ocasionada por anticuerpos y evidencia serológica de DSA. El cABMR no tiene un tratamiento efectivo. Conclusiones dado que cABMR no tiene un tratamiento efectivo, es importante disminuir la exposición a los factores de riesgo y hacer un diagnóstico y un tratamiento oportuno de los eventos agudos de lesión renal que contribuyen a la progresión de disfunción crónica del injerto.

Context Chronic antibody-mediated rejection (cABMR) is considered one of the main causes of chronic graft. Objective To review the mechanisms that cause cABMR to design effective treatments, since it is very little what has been advanced in it treatment of this pathology. Methodology In this narrative review of the literature, we present the risk factors related to the chronic dysfunction of the injection, emphasizing the pathophysiology the diagnosis and treatment of cABMR. Results The most relevant risk factor for the development of chronic graft dysfunction is the development of specific donor antibodies (DSA) and ABMR. For the diagnosis of active cABMR, the criteria of Banff 2017 are required (three must be present: histological evidence of chronic tissue injury, evidence of current inflammation in the vascular endothelium caused by antibodies and serological evidence of DSA. The cABMR does not have an effective treatment. Conclusions Since cABMR does not have an effective treatment, it is important reduce exposure to risk factors and carry out a diagnosis and treatment of the acute events of kidney injury that contribute to the progression of chronic injection dysfunction.

The study of effect of Human macrophage polarization on Mouse Pericyte-to-Myofibroblast Transition in vitro / 中华器官移植杂志

Objective:To explore the role of macrophage polarization on pericyte-to-myofibroblast transition and renal allograft fibrosis after kidney transplantation(KT).Methods:Allograft tissues were harvestedfrom recipients with chronic allograft dysfunction(CGD)and normal kidney tissues.The expression and distribution of M1/M2 macrophages in kidney tissues were detected by routine and immunofluorescent staining; mRNA of CD68, CD206 and iNOS detected by polymerase chain reaction(PCR); Murine vascular pericytes subjected to TGF-β1 in vitro and the expressions of α-SMA and PDGFR-β in perivascular cells detected by immunoblotting and cellular fluorescence; The co-culturing models of vascular pericytes and M1/M2 macrophages were constructed.The expressions of α-SMA and PDGFR-β in pericytes were detected by immunoblotting, cellular fluorescence and PCR.Results:A marked infiltration of CD68+ iNOS+ M1 macrophages was present in allograft tissues of recipients with CGD while no obvious infiltration of CD68 + CD206 + was observed.The mRNA levels of CD68, iNOS and CD206 were significantly higher in CGD group than those in control group( P<0.05); In CGD allograft tissues, protein expressions of α-SMA and PDGFR-β spiked markedly( P<0.05)while cells with double staining of α-SMA and PDGFR-β were markedly infiltrated in interstitial area of CGD allograft.TGF-β1 could induce a marked elevation of PMT-related markers in a time-dependent manner( P<0.05); Immunoblotting and cellukar fluorescence indicated that M1 macrophages could promote the elevations of α-SMA and PDGFR-β in pericytes in vitro while M2 macrophages showed no effect on pericyte-to-myofibroblast transition in pericytes. Conclusions:M1 macrophage polarization may promote the formation of renal allograft interstitial fibrosis through promoting PMT.

Hyperfiltration Affecting the Outcome of Living-related Renal Allograft / 대한신장학회잡지

It is well known that immunologic factors like rejection episode and HLA missmatch influence allograft loss and prognosis. However, non-immu- nologic factors such as glomerular hyperfiltration may also have an effect on the survival of the allograft. We measured relative kidney function(dkRF) by DMSA scan, GFR(dGFR) using EDTA and CCr dCCr) by 24-hour urine collection in donors of 70 adult living-related renal allografts engrafted at a single center between December 1992 and January 1994 as a donor work-up before transplantation, and calculated donated kidney GFR(dkGFR=dGFRxdkRF) and CCr(dkCCr=dkCCrxdkRF). We observed graft function for 5 years and analyzed the prognostic factors for the graft. Graft dysfunction was defined as the increase of serum creatinine 5 years after transplantation more than 1.5 times of stabilized serum creatinine at 3 months after transplantation. 1) Sixty patients were followed up for 5 years. Graft dysfunction was observed in 22 patients(37%) and maintenance renal replacement therapy was required in 9(15%) of them. 2) Of the non-immunologic factors, donor age was older in patients with graft dysfunction(51 +/- 12 years) than those without it(34 +/- 11 years, p<0.01), but dkGFR(54.1 +/- 12.2ml/min vs. 58.5 +/- 11.9mVmin), dkCCr(44.8 +/- 14.3mVmin vs. 50.74 13.4ml/min) and the ratio of body surface area(recipient/donor, 0.964 0.14 vs. 0.990.12) were not different in the two groups. Age of recipients and occurrence of graft glomerulopathy also were not different in the two groups. The episode of acute rejection was more frequent in patients with graft dysfunction(32%, 7/ 22) than those without it(3%, 1/38, p<0.01), but the degree of HLA missmatch was not different. In multivariate analysis, donor age(p<0.01) and the episode of acute rejection(p<0.05) were independent factors affecting graft dysfunction. 3) Donor age was older(52 +/- 12 vs. 3814 years, p<0.01) and the episode of acute rejection was more frequent(56%, 5/9 vs. 696, 3/51, p<0.01) in 9 patients with graft loss than those without it. However, dkGFR, dkCCr, body surface area ratio, recipient age, occurrence of glomerulopathy and HLA missmatch were not different. In multivariate analysis, donor age(p<0.05) and the experience of acute rejection(p<0.01) were independent factors affecting graft loss. We therefore conclude that donor age is more important as non-immunologic prognostic factors in graft dysfunction than GFR of the donated kidney and the difference in body mass between recipient and donor.

Clinical Risk Factors of Chronic Renal Allograft Dysfunction / 대한신장학회잡지

Chronic renal allograft dysfunction (CRAD) has been the rnost frequent cause of graft failure for last decade. Even in cycloporine era the incidence of CRAD has not changed. From Jan 1992 to Dec 1994 118 kidney transplants performed in Seoul National University Hospital had been entered into our database. All patients had been followed for at least 1 year. CRAD is defined if there had been progressive deterioration of renal function that was not explained by other causes and finally serum creatinine (Scr) had doubled from basal Scr after transplantation and has been maintained. Analyzed factors as follows; HLA misrnatch, living or cadaver transplant, ABO mismatch, acute rejecton (AR), frequency and timing of AR, donor age, recipient age, cold ischmic time, delayed graft function, proteinuria, infection. A CRAD has developed in 27 (23%) patients. The incidence of CRAD with time was analyzed by Kaplan-Meier survival analysis and compared with log-rank test. We concluded that in univariate anlaysis the risk factors are acute rejection, frequency of AR, AR after 3 months after tranplantation, age of recipient 40rnin for living transplants. Although HLAMM=0 significantly decreased the risk of CRAD (P1. AR and HLAMM (HLAMM=O vs. HLAMM>1) were related each other (P=0.02).