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.

Multitarget and suspect-screening of antimicrobials in vegetables samples: Uptake experiments and identification of transformation products.

This work provided an accurate analytical method to perform a multitarget analysis of a variety of antimicrobials (AMs) including sulfonamides, tetracyclines, macrolides, fluoroquinolones and quinolones, one imidazole and one nitroimidazole, one triazole, one diaminopyridine and one derivative of Penicillium stoloniferum in vegetables. The analysis is performed using liquid-chromatography coupled to a low-resolution triple quadrupole mass spectrometer (UHPLC-MS/MS) to detect the target analytesor coupled to a high-resolution q-Orbitrap (HRMS) to monitor the formed transformation products (TPs). Both instruments were compared in terms of limits of quantification and matrix effect at the detection. The method was applied to determine the presence of AMs in organic and non-organic vegetables, where sulfadiazine and mycophenolic acid were detected. On the other hand, the transference of four AMs (trimethoprim, sulfamethazine, enrofloxacin, and chlortetracycline) from soils to lettuces was evaluated through controlled uptake experiments. The choice of AMs was based on the classification into different families, and on the fact that those AM families are the most frequently detected in the environment. In this case, each of the AMs with which the soils were contaminated were found in the exposed lettuces. Moreover, in both studies, specific TPs of the AMs were identified, posing the necessity of assessing their effects in relation to food and human safety.

Comparison of conventional and dispersive solid phase extraction clean-up approaches for the simultaneous analysis of tetracyclines and sulfonamides in a variety of fresh vegetables.

The extensive use of antibiotics in agriculture has led to the occurrence of residual drugs in different vegetables frequently consumed by humans. This could pose a potential threat to human health, not only because of the possible effects after ingestion but also because the transmission of antibiotic-resistant genes could occur. In this work, two accurate sample preparation procedures were developed and validated for the simultaneous analysis of sulfonamides (SAs) and tetracyclines (TCs) in four of the most widely consumed vegetables (lettuce, onion, tomato, and carrot) in Europe. The evaluated protocols were based on QuECHERS for extraction and subsequent clean-up by SPE (solid phase extraction) or dispersive SPE. Parameters affecting both extraction and clean-up were carefully evaluated and selected for accuracy of results and minimal matrix effect. Overall, apparent recoveries were above 70% for most of the target analytes with both analytical procedures, and adequate precision (RSD<30%) was obtained for all the matrices. The procedural limits of quantification (LOQPRO) values for SPE clean-up remained below 4.4 µg kg-1 for TCs in all vegetables except for chlortetracycline (CTC) in lettuce (11.3 µg kg-1) and 3.0 µg kg-1 for SAs, with the exception of sulfadiazine (SDZ) in onion (3.9 µg kg-1) and sulfathiazole (STZ) in carrot (5.0 µg kg-1). Lower LOQPRO values (0.1-3.7 µg kg-1) were obtained, in general, when dSPE clean-up was employed. Both methods were applied to twenty-five market vegetable samples from ecological and conventional agriculture and only sulfamethazine (SMZ) and sulfapyridine (SPD) were detected in lettuce at 1.2 µg kg-1 and 0.5 µg kg-1, respectively.

[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.

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.

Variability of the Mammalian Target of Rapamycin Inhibitors Is Correlated With Long-Term Renal Graft Survival.

BACKGROUND: Many studies demonstrate the relationship between the high intrapatient variability of calcineurin inhibitor (CNI) levels and poor long-term renal graft outcome. Our objective is to analyze the intrapatient variability observed in the mammalian target of rapamycin inhibitors (mTOR-i) blood levels, to compare the variability of sirolimus (SRL) with that of everolimus (EVL) in kidney transplant patients converted to an mTOR-i, and to analyze whether the coefficient of variation (CV) was correlated with long-term graft survival. METHODS: We analyzed 279 adult renal transplant patients converted to an mTOR-i. CV was calculated using at least 3 blood trough levels between 3 and 18 months postconversion. RESULTS: The mean and median CV of the entire group was 25.54% and 23.7%, respectively. SRL and EVL mean CV was 23.8% and 27.1% (P = .03), respectively. The group of patients into the last tertile with CV> 28.52% presented a lower death-censored graft survival (75.26% vs. 93.01%, P < .0001) with a mean follow-up of 66.5 months. CONCLUSION: The CV of mTOR-i is correlated with long-term renal graft survival, so it should be considered a prognostic factor. SRL has a lower CV than EVL in renal transplant patients converted to mTOR-i in the stable posttransplant phase.

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.

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.

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.

Sampling variability on percutaneous liver biopsy.

Sampling variability of liver biopsy was determined in three consecutive biopsy specimens obtained from each of 118 patients immediately prior to autopsy. No sampling variability was found for fatty liver, alcoholic hepatitis, nonspecific hepatitis, fulminant hepatitis, leukemic infiltrate, and venous congestion. Cirrhosis was diagnosed in 80% of cases at the first biopsy but in all cases after three biopsies. Chronic aggressive and chronic persistent hepatitis were diagnosed correctly in two of three cases each at the first biopsy, and in all cases after three biopsies. Metastatic carcinoma was detected in 46% of cases at the first biopsy and in 69% after three biopsies. Granulomas were missed once on the first biopsy, but found on a subsequent biopsy. The amounts of fat and fibrosis in the biopsy specimens often were not representative of the amounts present at autopsy.

[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.

Oxalate-induced acute renal failure in Crohn's disease.

In a patient with long-standing Crohn's disease and bowel resection, acute reversible renal failure associated with hyperoxaluria developed. The renal biopsy specimen demonstrated marked oxalosis. Acute renal failure, although rare, is a complication of enteric hyperoxaluria of Crohn's disease. This type of renal failure may be reversible if recognized and treated early, since remission of symptoms occurred following hemodialysis.

Pathology of high dose intermittent cyclophosphamide therapy.

Pathologic changes induced by high dose intermittent cyclophosphamide therapy are described in 39 patients with solid tumors, lymphohematopoietic malignant disease, and bone marrow transplants. Patients receiving 50 to 120 mg. per kg. daily for one to four days showed transmural bladder injury affecting all component tissue; toxic vasculitis involving small arteries, capillaries, and venules; and interstitial, myocardial, and vascular changes in the heart. Myocardial necrosis with heart failure was the dose limiting factor of very high dose therapy. Patients receiving 15 to 30 mg. per kg. for four days showed variable degrees of bladder injury limited to the mucosa and lamina propria and vascular changes consisting only of telangiectasia. Both groups showed atypia of transitional urinary and esophageal epithelia as well as of mesenchymal cells in the lamina propria of the bladder, persistent and total ablation of spermatogenesis, and long lasting absence of ovarian follicular maturation. Bone marrow hypoplasia and lymphoid depletion developing after cyclophosphamide therapy completely disappeared an average of 3.5 weeks after the last dose.

Influence of estrogen replacement therapy on plasma lipid peroxidation.

OBJECTIVE: To observe whether any relationship exists between the concentration of plasma estradiol (E2) and the plasma concentrations of malondialdehyde (MDA) or whether a relationship exists between the concentration of plasma E2 and the activity of the erythrocyte enzymes, superoxide dismutase (SOD) and catalase, in ovariectomized female Wistar rats (treated and untreated with E2). DESIGN: We used 40 ovariectomized Wistar rats randomly assigned to four groups. The first group was allowed to evolve freely with no treatment. A gel containing 17beta-estradiol was administered transdermally to the other three groups at doses of 4, 8, and 16 microg/day, respectively. After 15 days of treatment, blood samples were obtained from the four groups. The concentrations of plasma MDA and E2 and the activities of erythrocyte catalase and SOD were determined. RESULTS: There were significant correlations between the MDA levels and the logarithm (base 10) of the plasma E2 concentrations in both linear (p = 0.00093) and quadratic (p = 0.000001) regression analyses. No relationship was found between the E2 concentrations and the catalase and SOD activities. CONCLUSIONS: There was a clear relationship between the plasma levels of MDA and the logarithm of the plasma E2 concentrations, which was best demonstrated with a quadratic regression. This model may explain the contradictory findings presented by estrogens with respect to their pro-or antioxidant action.

The efficacy and tolerability of triclabendazole in Cuban patients with latent and chronic Fasciola hepatica infection.

Current chemotherapy for the treatment of infections caused by the liver fluke Fasciola hepatica is not satisfactory. Therefore, the efficacy and tolerability of triclabendazole (TCZ) was assessed for this indication. Eighty-two patients (51 female, 31 male, age 15-81 yr, mean 42 yr) with chronic or latent F. hepatica infection refractory to previous anti-helminthic chemotherapy were enrolled in a 60-day open, non-comparative trial. Patients received 20 mg/kg TCZ as two doses of 10 mg/kg administered after food 12 hr apart. Efficacy of treatment was assessed by stool microscopy, determination of Fasciola excretory-secretory antigen (FES) in feces, and by ultrasonography (US) which were systematically performed pre-therapy and on Days 1-7, 15, 30, and 60 post-therapy. For continuous safety assessment, patients were hospitalized during the first week after therapy and then monitored at home for the appearance of any adverse events. Clinical chemistry and hematology tests were carried out on Days 1, 3, 7, 15, and 60, and whenever an adverse effect occurred possibly related to therapy. Seventy-one (92.2%) of the 77 patients who completed the 60-day follow-up period became egg-negative. Efficacy of therapy was supported by the disappearance or decrease of FES antigen and of ultrasonography abnormalities. In the 6 remaining patients, parasitological cure was achieved by another single TCZ dose of 10 mg/kg on Day 60. A total of 74 adverse events possibly related to therapy was reported by 54 patients. The most important adverse event was colic-like abdominal pain (40 patients [49%]) consistent with the expulsion of the parasite through the bile ducts as confirmed by US on Days 2-7. Most adverse events (53) were graded as mild, 20 as moderate, and only 1 as severe (a biliary colic responding to spasmolytic therapy within two hours). Triclabendazole 20 mg/kg is an effective therapy for the treatment of F. hepatica infection in patients who have failed to respond to other antihelminthic agents. Biliary colics reflecting the expulsion of dead or damaged parasites usually occur during Day 3-7 and respond well to spasmolytic therapy.

Disseminated Curvularia infection. Additional therapeutic and clinical considerations with evidence of medical cure.

A previously reported case of cerebral infection due to Curvularia lunata is more fully described. Medical cure was apparently achieved after 30 months' treatment with amphotericin B. Success was achieved only when the drug was given in a dose of 40 mg, three times per week, and was continued for six months after enhanced computed tomographic scans no longer showed cerebral lesions. Immunologic studies suggested the infection was accompanied by an unexplained defect in cell-mediated immunity.

Retinoic acid binding protein in human and experimental pancreatic carcinomas in hamsters.

Cytoplasmic retinoic acid binding protein (cRABP) is present in human fetal pancreas and becomes nondetectable in the normal adult pancreas. The binding protein for retinoic acid becomes apparent again in pancreatic cancer. Similar fluctuations in the content of cRABP occur in the hamster. The binding protein is undetectable in the normal adult hamster pancreas, while it was detected in several transplantable adenocarcinomas in the Syrian golden hamster.

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.