Static Cold Storage vs Ex Vivo Machine Perfusion: Results From a Comparative Study on Renal Transplant Outcome in a Controlled Donation After Circulatory Death Program.

INTRODUCTION: We aimed to evaluate if ex vivo machine perfusion could minimize the negative impact of cold ischemia on those renal grafts obtained from controlled donation after circulatory death (cDCD). MATERIAL AND METHODS: Prospective observational paired study of kidney transplants from cDCD performed in our center. The kidney from each pair preserved on ice was transplanted first within the first few hours following procurement, while the contralateral kidney was machine-perfused with a LifePort device (Organ Recovery Systems, Brussels, Belgium) and transplanted the following day. RESULTS: A total of 12 cDCDs were included. No differences were observed in delayed graft dysfunction or graft survival between the 2 groups. CONCLUSION: The use of ex vivo perfusion devices is simple and they do not require any large infrastructural or high economic investments, considering the fact that it allows a better selection of recipients and viable organs no longer need to be discarded because of prolonged warm ischemia times.

Effect of Cold Ischemia Time on Kidney Graft Function and Survival: Differences Between Paired Kidney Transplants From the Same Donor.

INTRODUCTION: Kidney transplantation procedures commonly result in a cold ischemia time (CIT) gap when both kidney grafts are implanted in the same center. Owing to logistics, the procedure is usually consecutive, first accomplishing one surgery and then the other. CIT constitutes an independent risk factor for the development of delayed graft function (DGF) in kidney transplants. The effect that CIT exerts on graft and patient survival is still unclear. This study evaluates the relation of CIT and transplant outcomes by comparing paired kidney transplants in terms of survival and graft function. METHODS: We accomplished a retrospective analysis of 402 kidney transplants performed in our center between 2000 and 2017. We selected all transplants where both organs from the same donor were implanted at our hospital, establishing 2 study groups (group 1: first graft implanted and group 2: second graft implanted) to compare by paired data statistical methods. RESULTS: We found an increase in the incidence of DGF in group 2 (42% vs 28.8%; P < .05). Group 2 had significantly worse graft function on day 5 posttransplant (4.7 ± 2.88 vs 3.86 ± 2.8 mg/dL of serum creatinine; P < .05). No significant differences in graft function were found on days 30 and 90 posttransplant. We didn't find any difference in graft survival between both groups. Length of hospitalization stay (17.6 days [± 13] vs 21.6 days [± 17]) and hemodialysis sessions (mean of 2.8 [± 2] vs 3.6 [± 2.2]) were higher in group 2. CONCLUSION: CIT acts as an independent risk factor for the development of DGF in kidney transplantation. CIT had no isolated effect on graft survival.

Usefulness of Delayed Introduction of Tacrolimus in Kidney Transplants Using Type-III Donors After Circulatory Death.

INTRODUCTION: Our study compares 2 immunosuppressive strategies to reduce tacrolimus nephrotoxicity and its risk of acute tubular necrosis: delayed introduction of tacrolimus plus thymoglobulin vs initial tacrolimus plus basiliximab on the results of kidney transplant (KT) using type-III donation after circulatory death (III-DCD). MATERIAL AND METHODS: We analyzed all the transplants performed using type-III DCD in our hospital (42 cases). They were distributed in a first stage with delayed tacrolimus (3°-4° day) + thymoglobulin and a second one with initial tacrolimus + basiliximab, with a follow-up of 6 months. The rate of delayed graft function, the evolution of renal function, and the incidence of rejection were compared. RESULTS: 28 patients received thymoglobulin with delayed tacrolimus, and 13 patients received basiliximab and tacrolimus from day 0 (1 excluded). There were no significant differences in delayed graft function (27% group 1 and 23% group 2) or in rejection (10.7% and 15.4%), respectively. Serum creatinine at day 3, 7, 14, 30, and 180 showed no statistically significant differences. The levels of tacrolimus measured at 10, 30, 90, and 180 days after transplantation were similar, except for the first month: 10.10 ± 2.3 in group 1 and 12 ± 1.7 ng/mL in group 2 (P = .007). CONCLUSIONS: Delayed introduction of tacrolimus does not seem to suppose a benefit in KT using type-III DCD; therefore, the use of thymoglobulin, with its higher profile of adverse effects, seems unjustified in patients with normal immunological risk.

Influence of Proportion of Normal Saline Administered in the Perioperative Period of Renal Transplantation on Kalemia Levels.

BACKGROUND: The hyperchloremic metabolic acidosis triggered by the infusion of normal saline (NS) significantly increases the level of extracellular potassium. In this study we assessed the influence of proportion of NS administered in the perioperative period of renal transplantation on potassium levels in usual clinical practice. METHODS: This study was a retrospective cohort analysis of patients undergoing renal transplantation during a 24-month period (2015-2016). To determine the influence of NS on K+ levels, simple linear regression and multiple linear regression analyses were performed, adjusted for the total volume of fluids administered, establishing the difference in serum K+ levels for each 20% increase in the proportion of NS. RESULTS: As the proportion of NS administered increased, K+ levels at 24 hours were significantly increased (P = .026) (0.69 mEq/L K+ increase per 20% increase in NS ratio). Mean K+ values at 24 hours (adjusted for total volume of fluids administered) ranged from 4.17 mEq/L (95% confidence interval [CI] 3.7-4.56) in patients who did not receive NS to 4.85 mEq/L (95% CI 4.56-5.15) in those administered exclusively NS. CONCLUSION: The risk of developing hyperkalemia in patients who receive a balanced solution with potassium in its formulation compared with NS in the perioperative period of renal transplantation is not increased, but the volume of NS administered is significantly associated with increases in K+ levels at 24 hours.

Improving the Outcomes of Organs Obtained From Controlled Donation After Circulatory Death Donors Using Abdominal Normothermic Regional Perfusion.

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients' outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty-seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty-seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1-year death-censored kidney survival was 91%, and delayed graft function rate was 27%. The 1-year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.

Relationship Between Albuminuria During the First Year and Antibody-Mediated Rejection in Protocol Biopsies in Kidney Transplant Recipients.

BACKGROUND: Antibody-mediated rejection is the main cause of deterioration of kidney transplants and frequently is detected only by means of protocol biopsies. The aim of this study was to relate the presence of albuminuria throughout the 1st year to the histologic findings detected by 1-year protocol biopsies in kidney graft recipients. METHODS: Retrospective observational study of 86 protocol biopsies 1 year after transplantation. Albuminuria was measured at 3, 6, 9, and 12 months in urine samples and expressed as albumin/creatinine (mg/g). RESULTS: Analysis of biopsies, reflected according to the Banff criteria, the following categories: fibrosis and tubular atrophy, 35 (40.7%); cellular rejection, 13 (15.1%); antibody-mediated rejection, 8 (9.3%); chronic glomerulopathy, 10 (11.6%); normal, 14 (16.3%); recurrence, 1 (1.2%); and other, 5 (5.8%). The proportions of patients with albuminuria for Banff scale scores (0 vs ≥1, respectively) at 6 and 12 months, respectively, after transplantation, were: for marker glomerulitis, 45.5% versus 59.3% (P = .021) and 36.4% versus 70.4% (P < .001); for marker glomerulopathy, 49.1% versus 50.0% (P = .051) and 42.1% versus 58.3% (P = .019); for marker peritubular capillaritis, 45.8% versus 60.9% (P = .047) and 39.0% versus 69.6% (P = .276); and for marker C4d, 49.2% versus 56.3% (P = .894) and 46.2% versus 56.3% (P = .774). CONCLUSIONS: The presence of albuminuria after renal transplantation is common, especially in patients with proteinuria. Persistent albuminuria after transplantation, even at low levels, can be indicative of subclinical antibody-mediated rejection. Additional broader studies to relate the albuminuria to histologic changes observed in protocol biopsies are required.

[Changes in the pre-transplant bone-mineral metabolism do not affect the initial progress of the renal graft]. / Las alteraciones del metabolismo óseo-mineral pretrasplante no influyen en la evolución inicial del injerto renal.

BACKGROUND: Abnormalities in serum calcium, phosphate, and Parathyroid Hormone (PTH) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. One of the most common problems in the first weeks after renal transplantation is Delayed Graft Function (DGF). There are several well-known risk factors for DGF development, but the role of calcium phosphate-PTH homeostasis as a risk factor for early graft dysfunction is controversial. This issue was addressed in the current study. METHODS: Pretransplant PTH, calcium and phosphate values were gathered in 449 patients that received a renal transplant in our center between 1994 and 2007. Other variables expected to influence the risk for delayed graft function were included from the clinical charts. RESULTS: The incidence of DGF was 27.3%. DGF development was significantly associated with recipient age, type and need of renal replacement therapy, peak panel reactive antibodies, transfusion number and donor age. There were no significant differences in the mean pretransplant values of calcium (9.4 +/- 1.0 vs. 9.5 +/- 0.9 mg/dl, p = 0.667), phosphate (5.7 +/- 1.8 vs. 5.5 +/- 1.5 mg/dl, p = 0.457), calcium-phosphate product (53.5 +/- 17.2 vs. 51.8 +/- 14.6 mg(2)/dl(2), p = 0.413) and PTH (315 +/- 312 vs. 340 +/- 350 pg/ml, p = 0.530) between patients with and without DGF. CONCLUSIONS: In our study population pretransplant serum PTH, calcium and phosphorus levels have no influence on the risk for DGF.

Las alteraciones del metabolismo óseo-mineral pretrasplante no influyen en la evolución inicial del injerto renal / No disponible

Antecedentes: el Retraso en la Función del Injerto (RFI) es uno delos problemas más frecuentes en las primeras semanas del trasplante renal, afectando a su evolución. Conocer los factores de riesgo de RFI puede ayudar a reducir su incidencia. Las alteraciones en los niveles séricos de calcio, fósforo y Hormona Paratiroidea (HPT) son muy frecuentes en los pacientes en lista de espera de trasplante y podrían favorecer la aparición de RFI. Sin embargo, diversos estudios que han analizado la relación entre los niveles pretrasplante de calcio, fósforo y HPT y el desarrollo de RFI han obtenido resultados dispares que no permiten confirmar ni descartar que influyan en el mismo. Métodos: estudiamos los valores pretrasplante de calcio, fósforo y HPT en 449 pacientes trasplantados renales realizados entre 1994 y 2007. Se definió RFI en aquellos pacientes que precisaron diálisis durante la primera semana postrasplante. De las historias clínicas se recogieron los datos clínicos y analíticos relacionados con RFI. Resultados: un 27,3%presentó RFI. Los factores significativos de riesgo para desarrollar RFI fueron la edad del receptor, el tipo y la necesidad de tratamiento sustitutivo renal, el título de anticuerpos anti-HLA máximos, el número de trasfusiones pretrasplante y la edad del donante. No detectamos diferencias significativas en los valores medios de calcio (9,4 ± 1,0 vs. 9,5 ± 0,9 mg/dl, p = 0,667), fósforo(5,7 ± 1,8 vs. 5,5 ± 1,5 mg/dl, p = 0,457), producto fosfocálcico (53,5± 17,2 vs. 51,8 ± 14,6 mg2/dl2, p = 0,413) y HPTi (315 ± 312 vs. 340± 350 pg/ml, p = 0,530) en los pacientes con y sin RFI. Conclusiones: en nuestro estudio, los parámetros séricos pretrasplante del metabolismo óseo-mineral no favorecen el desarrollo de RFI (AU)

Background: abnormalities in serum calcium, phosphate, and Parathyroid Hormone (HPT) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. One of the most common problems in the first weeks after renal transplantation is Delayed Graft Function (DGF). There are several well-known risk factors for DGF development, but the role of calciumphosphate-HPT homeostasis as a risk factor for early graft dysfunction is controversial. This issue was addressed in the current study. Methods: Pretransplant HPT, calcium and phosphate values were gathered in 449patients that received a renal transplant in our center between 1994 and 2007. Other variables expected to influence the risk for delayed graft function wereincluded from the clinical charts. Results: The incidence of DGF was 27.3%. DGF development was significantly associated with recipient age, type and need of renal replacement therapy, peak panel reactive antibodies, transfusion number and donor age. There were no significant differences in the mean pretransplant values of calcium (9.4 ± 1.0 vs. 9.5 ± 0.9 mg/dl, p = 0.667),phosphate (5.7 ± 1.8 vs. 5.5 ± 1.5 mg/dl, p = 0.457),calcium-phosphate product (53.5 ± 17.2 vs. 51.8 ± 14.6mg2/dl2, p = 0.413) and HPT (315 ± 312 vs. 340 ± 350pg/ml, p = 0.530) between patients with and without DGF. Conclusions: In our study population pretransplant serum HPT, calcium and phosphorus levels have no influence on the risk for DGF (AU)

Evaluation of the efficacy and safety of the conversion from a calcineurin inhibitor to an everolimus-based therapy in maintenance renal transplant patients.

Everolimus has recently been introduced into clinical practice with promising perspectives due to its efficacy, lack of nephrotoxicity, and antitumor effects. Experience in clinical trials associated with low-dose cyclosporine showed good results, but there is almost no experience in calcineurin inhibitor (CNI) elimination learning it as the primary immunosuppressant. We describe our experience in a series of 78 stable renal transplant patients who were switched to Everolimus with complete and quick elimination of the CNI: the procedure of conversion, pharmacokinetic results after conversion, evolution of renal parameters (renal function, proteinuria, and others), and safety data (acute rejection and adverse events). An initial dose of 3 mg/d was adequate to obtain the recommended trough levels between 5 and 10 ng/mL. Our results demonstrated that conversion to Everolimus was a simple, safe procedure that must be considered in patients CNI toxicity, especially those with malignant neoplasms and progressive deterioration of renal function due to chronic allograft nephropathy.

[Microscopic polyangiitis in a patient with rheumatoid arthritis]. / Poliangeítis microscópica en paciente con artritis reumatoide.

Rheumatoid arthritis (RA) is a systemic disorder that primary involves joints, although renal disease has also been associated it is not common that rapidly progressive glomerulonephritis (RPGN) appears. We report the case of a patient with nodular and aggressive RA who had an acut renal failure secondary to ANCA positive RPGN due to a Microscopic polyangiitis who was not responsive to steroids and cyclophosphamide therapy.

Immunoprophylaxis with Simulect (basiliximab) in kidney transplantation: results from routine clinical practice at 18 kidney transplant units.

OBJECTIVE: The objective of this study is to assess a Simulect (basiliximab) regimen in routine clinical practice in the Spanish kidney transplantation units to evaluate efficacy and safety. METHODS: In this prospective, observational study, data on demographics, parameters of efficacy, and safety in patients who under with kidney transplantation treated with Simulect (basiliximab) were collected through an on-line collection system. RESULTS: One hundred sixty three patients at 18 kidney transplant units included 12 months follow-up. The patient mean age was 52 years (DS 13,67) including 96 (58.90%) men and 67 (41.10%) women. Cold ischemia time was 19 hours (DS 6,79). Only 2 patients presented with PRA >50%. For prophylactic immunosuppression, 67.13% of patients received triple therapy with CNI (cyclosporine 49.65% or tacrolimus 17.48%), MMF (66.43%) or AZA (10.49%), and steroids. Incidence of acute rejection (AR) at 12 months was 12.27% (1.84% steroid-resistant). In subgroup analysis, AR was 13.5% in nondiabetics and 4.5% in diabetics, including 3 steroid-resistant episodes (1.84%) in nondiabetics and none in diabetics. In relation to donor age, AR was incidence 10.3% in patients with kidneys from donors aged 50 years or younger and 10.6% when donors were older than 50 years, including 1 (1.73%) and 2 (1.93%) steroid-resistant episodes, respectively. The graft and patient survival rates at 12 months were 90% and 98%, respectively. CONCLUSIONS: Simulect (basiliximab) used in routine clinical practice provided good prophylaxis against acute rejection in several kidney transplant patient populations, similar to that observed in randomized clinical studies with excellent tolerability and safety.