Epidemiología de la patología tumoral en el trasplante renal / Epidemiology of tumoral pathology in renal transplantation

Introducción: La patología tumoral (PT) implica una morbimortalidad no despreciable después del trasplante renal, siendo la inmunosupresión un factor de riesgo potencialmente responsable de su desarrollo. El objetivo de nuestro estudio es determinar la prevalencia de malignidad durante el trasplante y estudiar su posible asociación con el uso de anticuerpos antilinfocitarios, infección por citomegalovirus y el antecedente de rechazo agudo. Métodos: Se trata de un estudio de cohorte, retrospectivo, en 1034 receptores de trasplante renal en el que se revisaron los eventos tumorales acontecidos entre abril de 1981 y marzo de 2010. Se consignaron el uso de anticuerpos antilinfocitarios (AAL), infección por CMV y episodios de rechazo agudo (RA), relacionando estas variables con el desarrollo posterior de patología tumoral. Resultados: NO se detectó mayor frecuencia de PT maligna en aquellos que recibieron AAL (13,8% vs. 17,6%, p=0,094) p=0,094). No hubo mayor frecuencia de PT en pacientes con infección por CMV (16,3% vs. 15,2%, p=0,69). Por último, hubo mayor frecuencia de PT en aquellos con antecedentes de RA, si bien con significación limítrofe (19,5% vs. 14,3%, p=0,05). Conclusiones: La patología tumoral maligna se ve potencialmente favorecida por la inmunosupresión cada vez más potente y duradera. No hemos encontrado asociación entre la administración de AAL, infección y / o enfermedad por CMV; si bien esta se ve ligeramente incrementada en aquellos pacientes con el antecedente de RA.(AU)

Introduction: Tumoral pathology (TP) implies morbidity which is significant after the renal transplantation; Immunosuppression is a risk factor which is potentially responsible for tumoral development. The aim of our study is to determine the prevalence of malignancy during transplantation and to study its possible relation with the usage of antillymphocvte antibodies, cytomegalovirus infection and the history of acute rejection. Methods: It is a cohort study, retrospective, in 1014 receptors of Kidney transplantation in which tumoral events were revised between April 1981 and March 2010. The development of tumoral pathology in recipients was related with the usage of AAL, CMV infection and AR episodes. Results: a greater frequency of malign TP was no recorded in those who received AAL (13.8% vs. 17.6%, p=0.094). There was not greater frequency of TP in patients with infection due to CMV (16,3% vs, 15.2%, p=0.69). Finally, there was greater frequency of TP in those with antecedent of AR, though with bordering significance (19.5%, vs. 14.3% p=0.05). Conclusions: Malign tumoral pathology is potentially favored by immunosuppression increasingly powerful lasting. We have not found any relationship between AAL use, infection and/ or disease due to CMV, although this is slightly increased in those patients with AR history.(AU)

Epidemiología de la patología tumoral en el trasplante renal / Epidemiology of tumoral pathology in renal transplantation

Introducción: La patología tumoral (PT) implica una morbimortalidad no despreciable después del trasplante renal, siendo la inmunosupresión un factor de riesgo potencialmente responsable de su desarrollo. El objetivo de nuestro estudio es determinar la prevalencia de malignidad durante el trasplante y estudiar su posible asociación con el uso de anticuerpos antilinfocitarios, infección por citomegalovirus y el antecedente de rechazo agudo. Métodos: Se trata de un estudio de cohorte, retrospectivo, en 1034 receptores de trasplante renal en el que se revisaron los eventos tumorales acontecidos entre abril de 1981 y marzo de 2010. Se consignaron el uso de anticuerpos antilinfocitarios (AAL), infección por CMV y episodios de rechazo agudo (RA), relacionando estas variables con el desarrollo posterior de patología tumoral. Resultados: NO se detectó mayor frecuencia de PT maligna en aquellos que recibieron AAL (13,8% vs. 17,6%, p=0,094) p=0,094). No hubo mayor frecuencia de PT en pacientes con infección por CMV (16,3% vs. 15,2%, p=0,69). Por último, hubo mayor frecuencia de PT en aquellos con antecedentes de RA, si bien con significación limítrofe (19,5% vs. 14,3%, p=0,05). Conclusiones: La patología tumoral maligna se ve potencialmente favorecida por la inmunosupresión cada vez más potente y duradera. No hemos encontrado asociación entre la administración de AAL, infección y / o enfermedad por CMV; si bien esta se ve ligeramente incrementada en aquellos pacientes con el antecedente de RA.

Introduction: Tumoral pathology (TP) implies morbidity which is significant after the renal transplantation; Immunosuppression is a risk factor which is potentially responsible for tumoral development. The aim of our study is to determine the prevalence of malignancy during transplantation and to study its possible relation with the usage of antillymphocvte antibodies, cytomegalovirus infection and the history of acute rejection. Methods: It is a cohort study, retrospective, in 1014 receptors of Kidney transplantation in which tumoral events were revised between April 1981 and March 2010. The development of tumoral pathology in recipients was related with the usage of AAL, CMV infection and AR episodes. Results: a greater frequency of malign TP was no recorded in those who received AAL (13.8% vs. 17.6%, p=0.094). There was not greater frequency of TP in patients with infection due to CMV (16,3% vs, 15.2%, p=0.69). Finally, there was greater frequency of TP in those with antecedent of AR, though with bordering significance (19.5%, vs. 14.3% p=0.05). Conclusions: Malign tumoral pathology is potentially favored by immunosuppression increasingly powerful lasting. We have not found any relationship between AAL use, infection and/ or disease due to CMV, although this is slightly increased in those patients with AR history.

Comportamiento de la diabetes mellitus postrasplante en el Instituto de Nefrología Dr. Abelardo Buch López / Behavior of the post-transplantation diabetes mellitus in the Dr. Abelardo Buch López Institute of Nephrology

Se realizó un estudio observacional descriptivo de casos y controles que incluyó todos los pacientes que recibieron trasplantes renales en el Instituto de Nefrología entre 1970 y 2008 para conocer las características de los que desarrollaron diabetes mellitus postrasplante, los factores de riesgo para esta entidad y determinar la efectividad del tratamiento hipoglucemiante usado. Fueron revisadas todas las pancartas e historias clínicas de los casos y de 99 pacientes con DMPT, la mayoría tenía entre 40 y 59 años de edad y este factor de riesgo se asoció de forma significativa con la diabetes, 66 eran del sexo masculino, el mayor número de casos era de la raza blanca, estos factores no tuvieron significación estadística. Los antígenos HLA que se encontraron con más frecuencia fueron el A2, B35, B7 y el A3. El mayor número de casos debutó antes de 18 meses postrasplante, no eran obesos aunque, al comparar con el grupo control, este factor de riesgo sí tuvo significación estadística, el tratamiento con ciclosporina como inmunosupresor y los antecedentes familiares de diabetes también fueron factores de riesgo asociados con significación estadística al comienzo de la DMPT, no así el tratamiento con pulsos de metilprednisolona como terapia antirrechazo. El mejor control de la glucemia se logró con la dieta solamente, le siguió con el uso de glibenclamida como hipoglucemiante oral y, por último, los pacientes que eran tratados con insulina fueron los que peor control metabólico tuvieron

A descriptive and observational study was conducted in cases and controls including all patients underwent renal transplantation in the Institute of Nephrology between 1970 and 2008 to know the features of those patients developed post-transplantation diabetes mellitus, the risk factors for this entity and to determine the effectiveness of hypoglycemic treatment used. All placards and medical records of cases and from 99 patients with post-transplantation diabetes mellitus (PTDM) were reviewed, most aged 40 and 59 and this risk factor was associated in a significant way with diabetes, 66 were men and most of cases were of white race, these factors have not statistical significance. The more frequent HLA antigens were the A2, B35, B7 and A3. Most of cases debuted before the 18 months post-transplantation, non obese although compared with the control group, this risk factor had statistical significance, the treatment with cyclosporine as immunosuppressive agent and the family history of diabetes also were risk factors associated with the statistical significance at onset of PTDM, but not the treatment with impulse methylprednisolone like a anti-rejection therapy. The better control of the glycemia was achieved with the diet alone, followed by the use of glibenclamide as oral hypoglycemic agent and finally, the patients treated with insulin were those with the poorer metabolic control

Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients.

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d⁻, patients with ABMR C4d⁺ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients / Correlações clinico-patológicas da marcação de C4d e sua influência na evolução de receptores de transplante renal

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31 percent) biopsies, of which 23 (14.7 percent) had diffuse and 25 (16 percent) focal distribution. Pre-transplantation panel reactive antibodies ( percentPRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d-, patients with ABMR C4d+ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high percentPRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.

INTRODUÇÃO: A fração do complemento C4d é um marcador de rejeição mediada por anticorpos (RMA) em aloenxertos renais, embora na rejeição celular também se observem depósitos de C4d. OBJETIVOS: Correlacionar a expressão de C4d com parâmetros clínicopatológicos e a evolução do enxerto renal em três anos. MÉTODOS: Foram incluídos 146 receptores de transplante renal com biópsias por indicação. A marcação de C4d foi feita por imuno-histoquímica em parafina. Foram medidas a função e a sobrevida do enxerto e determinadas as variáveis preditivas de sua evolução por meio de modelo de regressão de Cox. RESULTADOS: A marcação positiva para C4d foi detectada em 48 (31 por cento) biópsias, das quais 23 (14,7 por cento) tinham marcação difusa e 25 (16 por cento), focal. A reatividade contra painel ( por centoPRA) de classe I e II pré-transplante foi significativamente maior nos pacientes C4d+ quando comparada aos C4d-. Tanto glomerulite quanto pericapilarite foram associadas com C4d (p = 0,002 e p < 0,001, respectivamente). A presença de C4d em biópsias sem rejeição (SR), rejeição celular aguda (RCA) ou fibrose intersticial/atrofia tubular (FI/AT) não teve impacto na função ou na sobrevida do enxerto. Comparados a indivíduos com SR, RCA e FI/AT C4d-, pacientes com RMA C4d+ tiveram pior sobrevida do enxerto em 3 anos (p = 0,034), mas não houve diferença entre RMA versus SR, RCA e FI/AT C4d+ (p = 0,10). Na regressão de Cox, função do enxerto no momento da biópsia e por centoPRA alto foram preditores de perda do enxerto. CONCLUSÕES: A pesquisa de C4d em biópsias do enxerto renal é útil para identificar RMA, com correlações clínicopatológicas bem definidas. O impacto do C4d em outros diagnósticos histológicos necessita de investigação adicional.

Steroid or tacrolimus withdrawal in renal transplant recipients using sirolimus.

BACKGROUND: Calcineurin inhibitor (CNI) and steroid (ST) withdrawal are strategies under investigation to reduce long-term toxicities associated with current immunosuppressive regimens. We conducted a single center, prospective trial comparing the efficacy and safety of CNI or ST withdrawal in kidney transplant recipients receiving sirolimus-based immunosuppressive regimen. METHODS: Forty-seven recipients of first renal transplant with non-HLA-identical living donors received sirolimus (SRL), tacrolimus (TAC), and ST without induction therapy and were randomized to undergo ST (TAC/SRL group, n = 24) or TAC (SRL/ST group, n = 21) withdrawal 3 months after transplantation. Primary efficacy and safety endpoints were the incidence of biopsy-confirmed acute rejection (BCAR) and renal function at 12 months. RESULTS: No differences were observed in the incidence of BCAR (4.2% vs. 9.5%), graft (95.8% vs. 95.6%), and patient (95.8% vs. 95.6%) survivals or in renal function (60 ± 11.5 vs. 63.4 ± 10.5 ml/min, P = 0.361). Higher mean cholesterol concentration was observed in the SRL/ST group (191.9 ± 63.3 vs. 241.6 ± 61.5 mg/dl, P = 0.019). Treatment discontinuation due to adverse events occurred in 12.5% of patients in TAC/SRL group and 21.7% in SRL/ST group. CONCLUSION: Within this short period of observation, our study was unable to detect any significant difference in major transplant outcomes comparing CNI and ST elimination strategies.

Uso de riñones para trasplante renal provenientes de donantes de 55 o más años / Use of kidneys for renal transplant from donors aged 55 and over

Introducción: Uno de los principales obstáculos para el trasplante renal es la escasez de donantes ante el incremento del número receptores, por lo que se ha requerido la utilización de vísceras provenientes de donantes de edades avanzadas. Objetivos: Conocer cuál es la frecuencia de utilización de los donantes de 55 años o más en nuestro centro, los resultados logrados y las principales complicaciones que se pueden presentar. Métodos: Estudio descriptivo, retrospectivo y de tipo casos y controles, incluyendo todos los trasplantes realizados en el Hospital Hermanos Ameijeiras desde el año 1984 al 2008, la muestra se separó en 2 grupos según la edad del donante, 55 años o más y menores de 55. Resultados: La frecuencia de utilización del donantes de 55 años constituyó solo el 10,6 por ciento de la muestra, 2,8 por ciento para el dador vivo y 12,5 por ciento para el cadáver, el tiempo de isquemia fría y la edad de los receptores fue mayor en el grupo que utilizó los donantes de mayor edad, lo que justifica una más frecuente y duradera aparición de complicaciones como la necrosis tubular aguda, así como menor tasa de función al alta en este grupo. Las complicaciones vasculares y urológicas fueron más frecuentes e influyeron en la pérdida de los trasplantes al compararlas con el grupo control. Aunque la supervivencia del injerto fue menor en este estudio, en el grupo cuyos trasplantes provenían de donantes más añosos, no cabe duda que si se mejoran las condicionales que han envuelto esta práctica en nuestro centro, el empleo de donantes de edad avanzada es una opción válida

Introduction: One of the major obstacles for renal transplantation is the donor shortage versus the increasing number of recipients, being necessary the use of viscera from old age donors. Objectives: To know what the use frequency of donors aged 55 or more in our center, the results obtained and the potential main complications. Methods: A retrospective and descriptive and of cases-control study was conducted including all transplantations carried out in the Hermanos Ameijeiras Clinical Surgical Hospital from 1984 to 2008, sample was divided into two groups according to donor's age, 55 years or more and under 55. Results: Use frequency of donors aged 55 was only of the 10,6 percent of sample, 2,8 percent for live donor and 12,5 percent for cadaver, time of cold ischemia and the recipient's age was great in the group where were used old age donors, justifying a more frequent and lasting appearance of complications like the acute tubular necrosis, as well as a low rate of discharge function in this group. The urologic and vascular complications were more frequent and influenced on the lost of transplantations compared to control group. Although graft survival was less in present study, in group whose transplantations came from older donors there`s not doubt that if conditions involved in this practice in our institution are improved, the use of old age donors is a valid option

Rituximab in the treatment of acute cellular rejection of renal allograft with CD20-positive clusters in the infiltrate.

A 31-year-old woman with nephronophthisis received a cadaveric kidney transplant, and was immunosuppressed with cyclosporine, azathioprine and steroids. Twelve days after transplant a biopsy showed acute rejection with vascular damage. She was treated with 3 pulses of methylprednisolone and change of immunosuppression to mycophenolate mofetil and tacrolimus, without improving graft function. At day 21, a second biopsy showed accentuation of interstitial and vascular rejection. Antibody-mediated rejection was suspected and plasmapheresis and rituximab were prescribed. Graft function improved rapidly. Staining for C4d was negative and there were no circulating antibodies against the donor. In the interstitial infiltrate there were clusters of B lymphocytes that accounted for 40% of cells, which was thought to be an ominous sign, as it has been associated with poor graft outcome. Acute T-cell-mediated rejection grade III (Banff 07) was diagnosed. Thirty-nine months after transplant her kidney function is stable with no other complication. This clinical case generates the hypothesis that rituximab may have a beneficial role in the therapy of acute cellular rejection when there are clusters of B lymphocytes in the infiltrate and a good response has not been obtained to conventional anti-rejection therapy.

Risk factors for Banff borderline acute rejection in protocol biopsies and effect on renal graft function.

INTRODUCTION: The interpretation and handling of Banff borderline acute rejection observed in protocol biopsies from patients with stable renal function continues to be controversial. Our objective was to identify the risk factors for borderline acute rejection on 1-year protocol biopsies and to evaluate their effect on renal graft function after 2 years' follow-up. METHODS: We included 82 kidney transplant recipients (KTR), who underwent 1-year protocol biopsies with normal or stable graft function. All KTR had follow-up of at least 2 years posttransplantation. We formed three groups: (1) KTR with a normal biopsy, (2) KTR with borderline changes, and (3) KTR with interstitial fibrosis/tubular atrophy (IF/TA). We searched for risk factors related to borderline injury. The main outcome to evaluate was renal function at 1 month, at protocol biopsy, and 2 years posttransplant. RESULTS: The 82 patients included in this study showed no differences in immunosuppression, gender, etiology of renal failure, or percentage of panel-reactive antibodies. The risk factors associated with borderline lesions were: at least one biopsy due to allograft dysfunction and acute rejection events during the first year posttransplant (P = .011 and P = .021, respectively). Increased serum creatinine and estimated glomerular filtration rate decline were greater among the borderline lesion than the normal group, but similar to patients with IF/TA. CONCLUSION: Renal function decline was greater among borderline and IF/TA groups. However, the sum of insults, and not only the borderline injury itself, produces greater declines in renal function with greater risk for graft loss.

Application of artificial neural networks in renal transplantation: classification of nephrotoxicity and acute cellular rejection episodes.

Complications associated with kidney transplantation and immunosuppression can be prevented or treated effectively if diagnosed in the early stages by posttransplant monitoring. One of the major problems is diseases that occur during the first year after kidney transplantation. For this purpose, we used different classifiers to predict events of nephrotoxicity versus acute cellular rejection episodes. The classifiers were evaluated according to values of sensitivity, specificity and area under ROC curves (RCA). The classifier with better accuracy rate for nephrotoxicity achieved the value of 75.68% and RCA classifier reached the accuracy of 80.89%. These results are encouraging, with rates of accuracy and error consistent with work purpose.

Evaluation of the stages involved in cold ischemia time in renal transplants in Chile.

INTRODUCTION: Cold ischemia time (CIT) is one of the factors that determine the evolution of a renal transplant; taking measures to reduce this time requires knowledge of its stages. The objective of this study was to evaluate the times in the stages that determine CIT in renal transplants. METHODS: We analyzed 108 donors and 201 kidney transplantations performed in Chile in 2008, establishing the CIT for the kidney transplanted by the center that extracted the kidneys (local kidney) and for the kidney transplanted in another center (shared kidney). RESULTS: Average CIT was 18.8 hours: namely, 16.9 hours for local and 20.2 hours for shared kidneys (P = .0001484). CIT for cases in which samples were sent to histocompatibility laboratory prior to nephrectomy was 7.3 hours less than for those sent postnephrectomy. The mean time between the allocation of the kidney and the transplant was 7.3 hours; 5.6 hours for local kidneys and 8.4 hours for shared kidneys (P = .000007124). CONCLUSION: We identified the stages at which intervention is possible to reduce the CIT, mainly for shared kidneys. All involved parties should make an effort to reduce this time.

Parameters of Doppler ultrasound at five days posttransplantation as predictors of histology and renal function at one year.

INTRODUCTION: In our center, a Doppler ultrasound (DU) is performed at 5 days after transplantation. The normal upper limit of flow velocity (FV) in the renal artery is 200-250 cm/s. The resistance index (RI) is considered elevated when >0.8. Elevation of the RI can be shown in all the forms of graft dysfunction. OBJECTIVE: The objective of this study was to evaluate the capacity of the DU to predict the prognosis of graft function and histological damage at 1 year. METHODS: We examined a retrospective cohort of patients undergoing renal transplantation between January 2004 and May 2007. The renal function was evaluated with serum creatinine measurements and glomerular filtration rate (GFR) estimates by the quadratic Modification of Diet in Renal Disease study equation. The biopsy specimen was evaluated according to the Banff 1997 classification. RESULTS: The overall average age was 35 years, and 58% of the subjects were men. Eight cases (25.8%) showed abnormal DU. The Delta among those with normal DU was -0.94 versus 0.27 +/- 0.39 with abnormal DU (P < .005). There was no significance as far as the biopsy at 1 year. CONCLUSIONS: Renal DU allows physicians to suspect complications at the first posttransplantation year. It shows a tendency to elevated blood pressure, as well as increased deterioration of renal function over the first year.

Conversion to sirolimus allows preservation of renal function in kidney and kidney-pancreas allograft recipients.

The major causes of graft failure are chronic allograft nephropathy (CAN) and patient mortality. Sirolimus (SRL) is a powerful immunosuppressant with a less nephrotoxic profile as well as a lower incidence of cancer. The aim of this study was to evaluate the impact of conversion to SRL from calcineurin inhibitor (CNI)-based therapy in kidney (KT) and kidney-pancreas (SPK) allograft recipients. We analyzed renal function, allograft and patient survival, and SRL-associated adverse effects in 93 adult patients (86 KT and 7 SPK), who were converted to SRL between January 2001 and November 2008. The main reason for conversion was CAN (76; 9%) and 52 (7%) were receiving tacrolimus. Conversion occurred at a median 26.2 months. There was a significant improvement in creatinine clearance (CCr) at 6 months after conversion (CCr(baseline) 51.4 vs CCr(6m) 60.4 mL/min; P < .0001), without changes at 12 and 24 months. However, proteinuria increased significantly at 6 months compared with the baseline: 150 mg/24 hours (0-453) versus 0 mg/24 hours (range, 0-309), respectively (P < .0001), but did not progress at 12 or 24 months. At the same time we observed more extensive use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers: 60/5%; 65/3% and 70/2% at 6, 12, and 24 months. There were no changes in blood pressure control. Cholesterol significantly increased at 6 months (218.2 +/- 37 vs. 186.6 +/- 44 mg/dL; P < .0001). Graft and patient survivals at 4 years were 88% and 95%, respectively. Our experience suggested that conversion to SRL constituted a safe alternative with excellent results in patient and graft survival.

Sirolimus in kidney transplant donors and clinical and histologic improvement in recipients: rat model.

BACKGROUND: Ischemia-reperfusion (I/R) injury is one of the risk factors for delayed graft function, acute rejection episodes, and impaired long-term allograft survival after kidney transplantation. This antigen-independent inflammatory process produces tissue damage. Isogeneic transplantation in a rat model is a useful method for study of nonimmunologic risk factors for kidney damage. OBJECTIVE: To study the effect of sirolimus on I/R injury using only 1 dose of the drug in the donor. MATERIALS AND METHODS: Eighteen rats were allocated to 3 groups of 6 rats each: sham group, control group, and rapamycin group. RESULTS: Improved renal function and systemic inflammatory response were observed in the rapamycin group compared with the control group (Deltaurea, Deltacreatinine, and DeltaC3, all P < .01). The number of apoptotic nuclei in the renal medulla in the control group was higher than in the rapamycin group (P < .01). Tubular damage was less severe in the rapamycin group compared with the control group (P < .01). Complement 3 and tumor necrosis factor-alpha expression in the kidney samples were significantly decreased when rapamycin was given to the donor rats (P > .01). Bcl-2 protein was upregulated in the rapamycin group compared with the control group (P < .01). CONCLUSION: Administration of rapamycin in donors attenuates the I/R injury process after kidney transplantation in a rat model.

Role of peritubular capillaries and vascular endothelial growth factor in chronic allograft nephropathy.

OBJECTIVE: To investigate the role of peritubular capillary damage and vascular endothelial growth factor (VEGF) in chronic allograft injury and to evaluate their correlation with clinical factors. PATIENTS AND METHODS: The study included 56 patients who underwent transplantation between 1987 and 2004 and experienced chronic graft dysfunction. CD34 (peritubular capillaries) and VEGF were evaluated at histologic analysis. Patients were classified into 3 groups: 47 with chronic allograft injury, 9 with pure cyclosporine toxicity, and 26 who served as the control group (time 0 biopsy). RESULTS: Compared with the control group, CD34 total expression in chronic nephropathy was indirectly proportional to Banff stage (P < .05), and VEGF was increased in chronic allograft injury grade I or II or nephrotoxicity (P < .05). CD34 expression was correlated with age (P < .007) and number of acute rejection episodes (P = .005). A negative correlation was observed between expression of CD34 and of VEGF (P < .001). Low expression of CD34 was associated with risk of graft loss of 1.45 (95% confidence interval, 1.15-7.24; P = .04). CONCLUSION: Peritubular capillaries decreased progressively with development of chronic allograft injury. The VEGF demonstrated a bimodal behavior, increasing at the onset of nephropathy and decreasing in the final stages. Loss of peritubular capillaries was associated with worse graft survival and overexpression of VEGF.

Asynchronous kidney allograft loss after simultaneous pancreas-kidney transplantation: impact on pancreas allograft outcome at a single center.

OBJECTIVE: We analyzed the clinical evolution of pancreas allografts in simultaneous pancreas-kidney transplantation (SPKT) cases after asynchronous kidney allograft loss and kidney retransplantation at a single non-United States center. PATIENTS AND METHODS: We performed a retrospective analysis of 168 SPKT from December 2000 to June 2007. RESULTS: The 5-year kidney allograft survival rate was 71%. Excluding cases of death with a functioning graft after SPKT (n = 35; 74.4%), 12 kidney allografts were lost due to acute rejection (n = 7; 15%) or chronic allograft nephropathy (n = 5; 10.6%). Delayed graft function contributed to kidney allograft loss. Five of 12 patients underwent kidney retransplantation. Sixty percent of pancreas allografts were lost after this procedure, which was attributed to either the diabetogenic effects of the immunosuppressive regimen or to the perioperative stress. Oral glucose tolerance tests performed before kidney retransplantation identified patients with good pancreas allograft function versus those with intolerance on glucose tests who received reduced glucocorticoid doses. CONCLUSIONS: In SPKT, pancreas allograft function was seriously affected by kidney retransplantation. Oral glucose tolerance tests performed before kidney retransplantation were helpful to assess beta-cell function and suggest prescription of lower steroid doses to decrease the pancreas allograft dysfunction.

Delayed graft function in renal transplant recipients: risk factors and impact on 1-year graft function: a single center analysis.

UNLABELLED: Delayed graft function (DGF), a frequent complication after kidney transplantation, occurs among about 60% of recipients of kidneys from deceased donors. DGF has a multifactorial etiology. It is characterized by acute tubular necrosis (ATN) upon biopsy. In this study we sought to identify among a group of recipients of kidneys from deceased donors, the incidence, risk factors, and impacts on patient and graft survivals of DGF. MATERIALS AND METHODS: We retrospectively analyzed medical records from renal transplant recipients aged >18 years who received a deceased donor kidney graft between January 2003 and December 2006. Kidneys lost during the first week posttransplantation were excluded from this series. RESULTS: Among 165 transplants, 111 (67%) displayed DGF, defined as the need for dialysis during the first week posttransplantation. The incidence of DGF was higher among patients with a cold ischemia time (CIT) > 24 hours: 85% vs 60%, DGF vs no DGF (P < .05), as well as for grafts from older donors. After 1-year follow-up, the DGF group showed worse graft function (serum creatinine 1.6 +/- 0.7 vs 1.3 +/- 0.4 mg/dL; P < .05) as well as a greater incidence of graft loss. CONCLUSION: Prolonged cold ischemia and older donor age were associated with a greater incidence of DGF in this series, leading to prolonged hospitalization, increased risk for an acute rejection episode, and reduced graft function and survival after 1 year.

Analysis of different staining techniques for c4d detection in renal allograft biopsies.

Capillary C4d deposition has been recognized as a marker of antibody-mediated rejection (AMR). Although the detection of capillary C4d by means of immunofluorescence (IF) in cryostat sections is well established, frozen tissue is not always available, thus limiting the diagnosis of AMR. The aim of the present study was to analyze different techniques for C4d staining and the prevalence of C4d in renal allograft biopsies. Detection of C4d was carried out using IF or immunohistochemistry (IHC) on frozen and paraffin sections of renal allograft biopsies available from the same patients. Biopsies obtained from 20 patients were classified into 3 groups: no rejection, acute rejection, and chronic allograft nephropathy (CAN). The capillary C4d deposition prevalence in frozen-IF, considered the gold standard technique for C4d detection, was 45% (9/20 cases). Compared with frozen-IF, the frozen-IHC technique presented an 85% concordance rate (17/20 cases; r = .70; P < .001; sensitivity = 77.8%; specificity = 90.9%). The paraffin-IF technique showed similar results, with an 80% concordance rate (16/20 cases; r = .64; P < .005; sensitivity = 55.6%; specificity = 100%), whereas C4d detection occurred in only 65% of paraffin-IHC cases (13/20; r = .30; not significant; sensitivity = 66.7%; specificity = 63.6%). No capillary C4d deposition was detected in cases without evidence of rejection. However, 4/7 cases (57%) of acute rejection were C4d positive. In the CAN group, 5/11 cases (45%) were C4d positive. In conclusion, these results demonstrated that frozen-IHC and paraffin-IF can be considered alternative techniques to frozen-IF for C4d detection. The paraffin-IHC technique displayed the lowest concordance rate for C4d detection.

Urinary CD20 mRNA as a surrogate of CD20-positive cells infiltration during allograft dysfunction in renal transplant patients.

B lymphocyte infiltration in renal acute allograft rejection has been associated with steroid resistance and poor outcomes. We aimed to measure CD20 mRNA in urine of renal transplant patients with graft dysfunction and correlate with the histological diagnosis and immunohistochemical (IH) staining for CD20. A total of 48 urine samples were analyzed (21 with acute rejection, 10 with chronic allograft nephropathy, 11 with unspecific tubular lesions, 3 with acute pyelonephritis and 3 with polyomavirus nephropathy). Higher urinary CD20 levels associated with a positive IH staining for CD20 (>50 positive cells/HPF) in renal tissue (p=0.04), with a sensitivity of 83.3% and a specificity of 51.6%. Within the acute rejection group, a positive staining for CD20 was not associated with graft loss, steroid resistance or lack of return to basal creatinine after treatment, but was associated with higher serum creatinine at 3 and 6 months, 1 and 2 years after the acute episode (p<0.05). In conclusion, we showed that urinary levels of CD20 detected by RT-PCR had a high sensitivity for CD20+ staining in the corresponding renal tissue, but with a low specificity. Patients with clusters of CD20+ cells >50/HPF had higher serum creatinine after 2 years of follow up.