31 results on '"Cruzado, J. M."'
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2. Clinical features and outcomes of tuberculosis in solid organ transplant recipients.
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Bodro M, Sabé N, Santín M, Cruzado JM, Lladó L, González-Costello J, and Carratalà J
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- Adult, Aged, Antitubercular Agents adverse effects, Chemical and Drug Induced Liver Injury etiology, Drug Resistance, Bacterial, Drug Therapy, Combination, Female, Graft Rejection immunology, Heart Transplantation, Humans, Immunosuppressive Agents adverse effects, Incidence, Interferon-gamma Release Tests, Kidney Transplantation adverse effects, Liver Transplantation adverse effects, Male, Microbial Sensitivity Tests, Middle Aged, Mycobacterium tuberculosis isolation & purification, Organ Transplantation mortality, Retrospective Studies, Spain epidemiology, Time Factors, Treatment Outcome, Tuberculin Test, Tuberculosis diagnosis, Tuberculosis epidemiology, Tuberculosis microbiology, Tuberculosis mortality, Antitubercular Agents therapeutic use, Organ Transplantation adverse effects, Tuberculosis drug therapy
- Abstract
Background: Tuberculosis (TB) remains a significant opportunistic infection in solid organ transplant (SOT) recipients. Moreover, its optimal treatment in SOT recipients is challenging due to the toxicity and potential drug-drug interactions of antituberculus drugs. We sought to assess the frequency, clinical characteristics, treatments, and outcomes of TB among SOT recipients., Methods: We reviewed retrospectively the medical charts of all TB cases occurring among SOT recipients from January 2000 to December 2011, retrieving data regarding baseline and clinical features, as well as treatment and outcomes., Results: Eighteen of 2005 SOT recipients developed TB (0.9%). The frequency according to the type of allograft was 0.9% (10 of 1120) for kidney, 1% (7 of 701) for liver, and 0.5% (1 of 184) for heart recipients. Six patients (33%) had prior exposure to TB: a positive tuberculin test (n = 3), a positive quantiferon-TB (n = 1) for a prior history of TB (n = 3). None of them received antituberculus prophylaxis. The mean time after transplantation to TB diagnosis was 64 months (range 2-169). Five patients (28%) developed TB within the first year posttransplantation. The mean duration of symptoms before diagnosis was 30 days (range 1-180). Nine patients (50%) displayed pulmonary TB; 7 (39%) had disseminated infections, and 2 (11%) had lymph node involvement. None of the Mycobacterium tuberculosis isolates were resistant to first-line antituberculus drugs. All patients were given isoniazide. Most of them received a 3-drug regimen. Rifampin was prescribed in 11 cases. Seven patients (5 liver and 2 kidney recipients) developed hepatotoxicity. One patient developed rejection without allograft loss. Mortality during antituberculus treatment was 17% (3/18)., Conclusions: In this study, 0.9% of SOT recipients developed TB, which frequently presented with extrapulmonary involvement, causing considerable mortality. Hepatotoxicity mainly among liver transplant recipients was a significant therapeutic drawback., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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3. Revisiting double kidney transplantation: two kidneys provide better graft survival than one.
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Cruzado JM, Fernandez L, Riera L, Bestard O, Carrera M, Torras J, Gil Vernet S, Melilli E, Ngango L, and Grinyó JM
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- Aged, Analysis of Variance, Chi-Square Distribution, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Proteinuria etiology, Risk Assessment, Risk Factors, Spain, Survival Rate, Time Factors, Treatment Outcome, Graft Survival, Kidney Transplantation adverse effects, Kidney Transplantation mortality, Tissue Donors supply & distribution
- Abstract
Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our "Dual Kidney Transplant program." Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our "old for old" renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the "old for old" program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)
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- 2011
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4. Tubular epithelial cells transfected with hHGF counteracts monocyte chemotactic protein-1 up-regulation after hypoxia/reoxygenation insult.
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Franquesa M, Riera M, Herrero-Fresneda I, Sola A, Hotter G, Lloberas N, Cruzado JM, Torras J, and Grinyó JM
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- Animals, Cell Division, Epithelial Cells cytology, Flow Cytometry, Gene Expression Regulation, Humans, Inflammation physiopathology, Kidney Tubules, Proximal cytology, Rats, Transfection, Up-Regulation, Chemokine CCL2 genetics, Epithelial Cells physiology, Hepatocyte Growth Factor genetics, Hypoxia physiopathology, Kidney Tubules, Proximal physiology
- Abstract
Acute kidney injury (AKI) which is mainly produced by nephrotoxic or ischemic insults is correlated with a high mortality and morbidity. Proximal tubular epithelial cells (PTEC) play a major role. They are the main target of ischemia/reperfusion injury. PTECs have also been proposed as the effectors of AKI reversibility, but also as the creator of the inflammatory milieu: cytokine, chemokine, and complement expression. An important chemokine implicated in this process is monocyte chemotactic protein-1 (MCP-1) due to its ability to recruit and activate monocytes. Hepatocyte growth factor (HGF) is a pleiotropic factor with mitogenic, anti-apoptotic, and proliferative effects which has recently been studied for its anti-inflammatory and antifibrogenic effects. Our aim was to evaluate the potential inflammatory effect of hypoxia and reoxygenation on rat PTECs. We created a stable human HGF (hHGF) expressing PTEC line that emulated in vivo transfection and analyzed the role of this cell type in the induction and reversibility of AKI. Our results showed the efficiency of transfection with the hHGF gene to promote sustained expression of the protein in the medium (7627.13 +/- 1144.078 to 8211.3 +/- 795.37 pg/mL). When rat PTECs were under a hypoxia/reoxygenation insult, MCP-1 was highly overexpressed (4479.3 +/- 154.3 pg/mL of protein and 5.099 +/- 1.23 times control gene expression). Transfected cells abrogated this effect (288.7 +/- 13.5 pg/mL and 1.169 +/- 0.0759 times control). In conclusion, we observed that the hypoxia/reoxygenation insult stimulated MCP-1 protein secretion in PTECs and that PTECs which were stably transfected and overexpressing hHGF abrogated the inflammatory reaction mediated by hypoxia/reoxygenation, being a suitable model for later studies.
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- 2009
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5. Bone marrow transplantation induces normoglycemia in a type 2 diabetes mellitus murine model.
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Flaquer M, Franquesa M, Barquinero J, Lloberas N, Gutiérrez C, Torras J, Grinyo JM, and Cruzado JM
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- Animals, Bone Marrow Transplantation veterinary, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 veterinary, Disease Models, Animal, Female, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Receptors, Leptin genetics, Reference Values, Blood Glucose metabolism, Bone Marrow Transplantation methods, Diabetes Mellitus, Type 2 surgery
- Abstract
Objective: To study the cellular mechanisms involved in the regression of diabetic nephropathy, bone marrow-derived cells must be identified. The aim of this study was to obtain a diabetic chimeric model with bone marrow cells expressing enhanced green fluorecence protein (EGFP), without modifying the course of diabetic nephropathy., Materials and Methods: Bone marrow transplantation (BMT) was performed in an obese type 2 diabetic murine model (db/db) owing to a mutation in the leptin receptor gene. Whole bone marrow from female donor C57BL/6 EGFP+ mice was transplanted into 8-week-old C57BL/6 mice and into 8- and 24-week-old female C57BLKS (db/db) EGFP- mice. Recipient mice received total body irradiation (TBI) followed by bone marrow (BM) cell infusion. We tested various irradiation doses (Gy) and numbers of BM cells., Results: When a low TBI dose and a small number of BM cells were administered, only syngeneic C57BL/6 mice became chimeric, whereas allogeneic db/db mice showed rejection. When Gy dose and BM cells were increased, db/db mice became chimeric. However, 8-week-old db/db mice lost the obese phenotype and became normoglycemic, probably due to peripheral BM cell infiltration. Conversely, 24-week-old db/db mice remained obese showing similar blood glucose values, body weights, albuminuria, and glomerular lesions at nontransplanted db/db mice., Conclusions: Recipient age greatly influenced the peripheral repopulation after BMT in db/db mice. Only the adult chimeric db/db mice seemed to be a good model to study the cellular mechanisms involved in the regression of diabetic nephropathy.
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- 2009
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6. Preliminary results of treatment with pegylated interferon alpha 2A for chronic hepatitis C virus in kidney transplant candidates on hemodialysis.
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Casanovas-Taltavull T, Baliellas C, Llobet M, Cruzado JM, Castellote J, Casanova A, Niubó J, Valls C, and Serrano T
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- Adult, Biopsy, Female, Genotype, Hepacivirus drug effects, Hepacivirus genetics, Hepatitis C, Chronic complications, Hepatitis C, Chronic pathology, Humans, Interferon alpha-2, Male, Middle Aged, Prospective Studies, Recombinant Proteins, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy, Interferon-alpha therapeutic use, Kidney Transplantation physiology, Polyethylene Glycols therapeutic use, Renal Dialysis, Renal Insufficiency complications, Renal Insufficiency surgery
- Abstract
Introduction: At present, there is little published information on the outcome of treatment with pegylated interferon (Peg-IF alpha 2a) in hepatitis C virus (HCV)-infected hemodialysis patients awaiting renal transplantation. The objective of this study was to assess the efficacy and tolerance of Peg-IF alpha 2a in this population., Patients and Methods: Twelve noncirrhotic HCV-infected patients (10 men, 50 +/- 8 years of age, genotype 1b 84%), were prescribed Peg-IF alpha 2a, at 135 microg/wk for 48 weeks. Liver biopsy was performed in 11 of 12 cases., Results: Six patients completed 48 weeks of treatment, with one end of treatment response (ETR), two sustained viral responses (SVRs), and three HCV relapses. Treatment was shorter in the six remaining patients: two cases 24 weeks (one due to medical reasons with relapse, one due to nonresponse), one patient chose to discontinue at 14 weeks (with relapse), one patient died of stroke at 10 weeks, and in two additional patients interferon was withdrawn at 18 weeks because of severe anemia (SVR) and at 26 weeks due to prolonged fever (relapse). Other secondary treatment-related events included anemia (requiring transfusion in two patients and major erythropoietin administration in six), and fever in four patients., Conclusions: Peg-IF had limited efficacy in this group, with ETR in 83%, SVR in only 25%, and recurrence in 50%. Tolerance was moderate, with 4/12 (33%) discontinuing treatment due to adverse events, personal decision, or death. Large randomized controlled studies are needed to determine the role of Peg-IF treatment in this population.
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- 2007
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7. Donor structural and functional parameters are independent predictors of renal function at 3 months.
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Ibernon M, González-Segura C, Moreso F, Gomà M, Serón D, Fulladosa X, Torras J, Garcia-Huete L, Gil-Vernet S, Cruzado JM, Carrera M, Duarte V, and Grinyó JM
- Subjects
- Adolescent, Adult, Aged, Biopsy, Cadaver, Cause of Death, Female, Humans, Kidney pathology, Kidney Transplantation pathology, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Glomerular Filtration Rate physiology, Kidney Transplantation physiology, Tissue Donors
- Abstract
Introduction: Epidemiological studies have shown that demographic, clinical, and histological donor characteristics influence renal function after transplantation, but whether these variables are independent predictors has not been established. The aim of this study was to evaluate the relative contribution of different donor variables on glomerular filtration rates (GFRs) at 3 months., Patients and Methods: We analyzed single renal transplants performed at our center from January 2000 to July 2004. Donor variables included age, gender, weight and height, cause of death, duration of brain death, serum creatinine at admission and preprocurement, history of arterial hypertension or diabetes mellitus, and smoking habit. Donor chronic damage score was calculated in preimplantation biopsies as was the addition of interstitial fibrosis, fibrous intimal thickening, and glomerulosclerosis (<10% = 0, >10% = 1). Donor and recipient GFRs were calculated according to the Cockroft-Gault formula., Results: We analyzed 202 transplants obtained from 113 deceased donors. A renal biopsy was available in 111 transplants. Recipient GFR at 3 months correlated negatively with donor age (R = -0.32, P < .01) and donor chronic damage score (R = 0.32, P < .01). GFR was lower among recipients of female versus male donors (50 +/- 15 vs 60 +/- 20 mL/min; P < .01). Donor cerebrovascular accident death (53 +/- 19 vs 63 +/- 19 mL/min; P < .01) and hypertension (48 +/- 16 vs 59 +/- 20 mL/min; P < .01) were also associated with lower GFR at 3 months. There was a positive correlation between GFR at admission, GFR preprocurement, and GFR at 3 months (R = 0.32 and R = 0.18 respectively; P < .01). Stepwise regression analysis included chronic damage score, GFR at admission, and donor gender but not donor age as independent predictors of GFR at 3 months (R = 0.50; P < .01)., Conclusion: Donor structural and functional parameters are independent predictors of renal function at 3 months.
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- 2007
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8. Gastrointestinal complications in renal transplant recipients: MITOS study.
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Gil-Vernet S, Amado A, Ortega F, Alarcón A, Bernal G, Capdevila L, Crespo JF, Cruzado JM, De Bonis E, Esforzado N, Fernandez AM, Franco A, Hortal L, and Jiménez C
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- Adult, Aged, Drug Therapy, Combination, Female, Gastrointestinal Diseases chemically induced, Humans, Kidney Transplantation immunology, Male, Middle Aged, Prevalence, Spain epidemiology, Gastrointestinal Diseases epidemiology, Immunosuppressive Agents adverse effects, Kidney Transplantation adverse effects
- Abstract
Introduction and Methods: An epidemiologic multicenter study was performed to evaluate the prevalence and management of gastrointestinal (GI) complications in solid organ transplant patients. A total of 1788 recipients were included, 1132 of which corresponded to renal transplanted patients., Results: The mean age for the renal transplanted patients was 52 +/- 13.2 years. The mean time from the transplantation was 5.4 +/- 5.4 years. 17.7% showed some pretransplant GI disease, while 53% presented this type of complication in the posttransplant period. Diarrhea was the most prevalent GI complication (51.5%) and digestive perforation was the GI disorder that affected the patients daily living the most. From the patients with GI complications, 71% received pharmacological treatment, using gastric protectors in 91.3% of the cases. Regarding immunosuppressive drugs, in 30.9% of the cases the dose of the drug was reduced, in 9.3% discontinued temporarily and in 7.5% discontinued permanently. These changes mainly affected the MMF (89%, 83% and 74% for dose change, temporary and permanent discontinuation, respectively)., Conclusions: The prevalence of GI complications in renal transplant exceeded 50%, and affected patients' daily living. The management of these complications was based on treatment with gastric protectors, dose reduction and/or partial or definitive MMF discontinuation.
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- 2007
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9. Role of cold ischemia in acute rejection: characterization of a humoral-like acute rejection in experimental renal transplantation.
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Herrero-Fresneda I, Franquesa M, Torras J, Vidal A, Aran J, Pluvinet R, Lloberas N, Rama I, Cruzado JM, Gulías O, and Grinyó JM
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- Acute Disease, Animals, Antibody Formation, Disease Models, Animal, Graft Survival immunology, Ischemia, Male, Rats, Rats, Inbred BN, Rats, Wistar, Renal Circulation, Graft Rejection immunology, Kidney Transplantation immunology
- Abstract
The aim of the study was to characterize the role of cold ischemia in the process of acute rejection using an experimental renal transplant model. Syngeneic renal transplants were performed between Wistar Agouti rats and allogeneic grafts using Wistar-Agouti rats as recipients of Brown-Norway kidneys. For cold ischemia (CI), kidneys were preserved in Euro-Collins (4 degrees C/ 2.5 hours). Rats were bilaterally nephrectomized at the moment of renal transplant and did not receive any immunosuppressant. The groups were NoAR (n = 6): immediate syngeneic transplant; CI-NoAR (n = 6): syngeneic transplant with CI; AR (n = 13): immediate allogeneic graft; CI-AR (n = 6): allogeneic graft with CI. Allogeneic rats were followed for the survival study. Syngeneic rats, with mean survival time beyond 6 months, were sacrificed on the day 7 to compare grafts with those in the allogeneic groups. H&E- and PAS-stained grafts were evaluated using the Banff criteria. Tissue INF-gamma and TNF-alpha were quantified by RT-real time-PCR on the kidney grafts. Renal insufficiency did not appear in the NoAR group, but it did from the posttransplant day 5 in both acute rejection groups. While NoAR kidneys showed well-conserved renal architecture, then AR group displayed variable degrees of tubular necrosis with scarce cellular infiltration, interstitial hemorrhage, vascular damage with fibrinoid necrosis, perivascular edema, and nuclear disruption. Cold ischemia in rejecting animals increased the mortality rate due to renal insufficiency and accelerated acute rejection. Independently of CI, the proinflammatory cytokines TNF-alpha and INF-gamma were increased in both rejection groups. In conclusion, addition of CI overactivates the acute rejection process via a humoral component.
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- 2005
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10. Arterial elasticity measurement in renal transplant patients under anticalcineurin immunosuppression.
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Martínez-Castelao A, Sarrias X, Bestard O, Gil-Vernet S, Serón D, Cruzado JM, Moreso F, Díez-Noguera A, and Grinyó JM
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- Adult, Aged, Arteries drug effects, Blood Pressure drug effects, Elasticity, Female, Humans, Kidney Transplantation immunology, Male, Middle Aged, Muscle, Smooth, Vascular drug effects, Renal Dialysis, Arteries physiopathology, Calcineurin Inhibitors, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use, Kidney Transplantation physiology, Muscle, Smooth, Vascular physiopathology, Tacrolimus therapeutic use, Vascular Resistance drug effects
- Abstract
Introduction: Calcineurin inhibitors may be associated with decreased arterial elasticity and increased vascular risk. We measured pulse wave velocity (PWV) in large or small arteries as an index of elasticity. The aim of our study was to determine aortic and radial arterial elasticity in 30 stable kidney transplant patients treated with calcineurin inhibitor immunosuppression., Patients and Methods: In stable kidney transplant patients we determined the usual biochemical parameters as well as lipid profiles, 24-hour blood pressure (BP) monitoring (CBPM) using a chronobiological program (Garapa), and PWV with a HDI-PWV CR-2000 monitor., Results: Sixteen patients received cyclosporine (CsA, G-1) and 14 tacrolimus (G-2) immunosuppression. There were no baseline differences regarding age (G-1: 56 +/- 12 years, G-2: 56 +/- 14 years), renal transplant follow-up (G-1: 7 +/- 3 years, G-2: 7.5 +/- 3 years), Systolic BP, pulse pressure or plasma creatinine (G-1: 163 +/- 35 umol/L, G-2: 173 +/- 26 umol/L). Patients in the G-1 showed higher diastolic BP (79 +/- 11 vs 74 +/- 8 mm Hg), greater proteinuria (1.26 +/- 0.4 vs 0.6 +/- 0.2 g/d, P < .05), total cholesterol (5.51 +/- 1.2 mmol/L) and low-density lipoprotein (3.08 +/- 0.3 vs 2.99 +/- 0.3 mmol/L, P = NS). Aortic arterial elasticity was decreased in G-1 patients (10.4 +/- 6 vs 14.3 +/- 2 mL/mm Hg x10, P < .05) as well as that in the radial artery (G-1: 5.52 +/- 1 vs 5.57 +/- 1.2 mL/mm Hg x100, P = NS). Almost 100% of the patients presented normal diurnal BP with high nocturnal BP in a nondipper pattern in both groups., Conclusion: Calcineurin immunosuppression may contribute to arterial stiffness in kidney transplant patients. No differences between CsA or tacrolimus were observed in our study. CBPM and PWV are useful tools to evaluate subclinical atherosclerosis in renal transplant patients.
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- 2005
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11. Therapy with plasmapheresis and intravenous immunoglobulin for acute humoral rejection in kidney transplantation.
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Ibernón M, Gil-Vernet S, Carrera M, Serón D, Moreso F, Bestard O, Cruzado JM, and Grinyó JM
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- Acute Disease, Antibody Formation, Combined Modality Therapy, Drug Therapy, Combination, Female, Graft Rejection drug therapy, Graft Survival drug effects, Humans, Kidney Transplantation immunology, Male, Middle Aged, Prognosis, Transplantation, Homologous, Graft Rejection therapy, Immunoglobulins, Intravenous therapeutic use, Kidney Transplantation physiology, Plasmapheresis
- Abstract
Background: Acute humoral rejection (AHR) is characterized by acute graft dysfunction associated with de novo production of donor-specific alloantibodies (DSA) and C4d deposition in peritubular capillaries of the renal allograft. It has been reported the combination of plasmapheresis (PP) and intravenous gamma globulin (IVIG) as effective rescue therapy for established AHR., Methods: Between 1999 and 2004, seven kidney allografts recipients suffered from AHR diagnosed by severe rejection and C4d staining in peritubular capillaries. All patients had a negative cross-match before renal transplantation., Results: All patients were treated with daily sessions of PP and in four cases IVIG was added after the last PP session. Tacrolimus and mycophenolate mofetil were employed as maintenance immunosuppressive regimen. In one case, rituximab was added to PP and IVIG owing to refractory humoral rejection. At 1 year, patient survival was 100%, allograft survival was 70%, and the mean serum creatinine was 201 micromol/L., Conclusions: AHR is a severe form of rejection associated with a poor prognosis, but its early diagnosis and treatment with PP and IVIG allows reversal of AHR reaching a 70% graft survival at 1 year.
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- 2005
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12. Calcineurin-inhibitor-sparing immunosuppressive protocols.
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Bestard O, Cruzado JM, and Grinyó JM
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- Drug Administration Schedule, Humans, Immunosuppression Therapy methods, Immunosuppressive Agents administration & dosage, Mycophenolic Acid administration & dosage, Mycophenolic Acid therapeutic use, Pilot Projects, Calcineurin Inhibitors, Graft Survival drug effects, Immunosuppressive Agents therapeutic use, Mycophenolic Acid analogs & derivatives
- Abstract
Calcineurin inhibitors (CNI) have played an important role in improving graft survival. However, the balance between preventing immunologic allograft losses and the management of CNI-related nephrotoxicity is still an issue in renal transplantation. There are three major CNI-sparing strategies. CNI MINIMIZATION: The advent of mycophenolate mofetil (MMF) allows cyclosporine (CsA) reduction to ameliorate renal function in patients with chronic renal allograft dysfunction, without increasing acute rejection rates. In combination with mTOR inhibitors, very low CNI levels may be sufficient to prevent acute rejection. However, in this association, CNI nephrotoxicity is magnified by pharmacokinetic interaction. CNI WITHDRAWAL: CNI withdrawal has been attempted in regimens containing MMF or sirolimus (SRL). Introduction of MMF in patients with chronic allograft nephropathy (CAN) followed by CNI withdrawal resulted in stabilization or improvement of renal function and hypertension profile, although there is some risk of acute rejection. In regimes based on SRL, CNI withdrawal is a safety strategy, achieving a sustained improvement of renal function, histology, and graft survival. There is not consensus at all whether MMF should be added or not in patients converted from CNI to mTOR inhibitor. CNI AVOIDANCE: Polyclonal-based regimens with MMF and steroids have shown acceptable acute rejection rates, but high rates of cytomegalovirus (CMV) and opportunistic infections. Conversely, anti-IL-2R in combination with MMF and steroids resulted in 50% incidence of acute rejection, thus suggesting that CNI avoidance is not feasible in a regimen based on MMF. Alternatively, a protocol based on anti-IL-2R induction therapy combined with SRL, MMF, and prednisone has shown an efficient prevention of acute rejection, higher creatinine clearance and lower rate of CAN in comparison with a group treated with CNI. New strategies using costimulation blockade may help in the development of safe CNI-free regimens. In summary, in renal transplantation the new immunosuppressive medications have made feasible old aspirations such as minimization, withdrawal, or even avoidance of CNI.
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- 2005
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13. Long-term effect of hepatitis C virus chronic infection on patient and renal graft survival.
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Bestard O, Cruzado JM, Torras J, Gil-Vernet S, Serón D, Moreso F, Rama I, and Grinyó JM
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- Adult, Cause of Death, Female, Follow-Up Studies, Humans, Kidney Transplantation mortality, Male, Middle Aged, Patient Selection, Retrospective Studies, Survival Analysis, Time Factors, Graft Survival, Hepatitis C, Chronic complications, Kidney Transplantation adverse effects, Kidney Transplantation physiology
- Abstract
Background: Hepatitis C virus (HCV) infection increases morbimortality in renal transplantation. The immune response against the HVC is not predictable in a great proportion of patients developing into chronic liver disease, glomerulonephritis, or both., Patients: We analyzed the impact of posttransplant chronic hepatitis development on patient and graft survival in 200 HCV-positive/HBsAg-negative renal allograft recipients transplanted between 1981 and 2003., Results: Ninety-eight patients developed chronic ALT elevation (ALT+), while 102 did not (ALT-). There was no difference in acute rejection episodes (ARE), acute tubular necrosis, donor and recipient age, gender, HLA mismatches, and number of previous renal transplants. Development of ALT+ was associated with a worse patient survival (90% vs 65% at 15 years of follow-up, P = .007; RR = 3.8, CI = 1.4-10.1), an effect that was independent of other variables as time on dialysis and age. The main causes of death among ALT+ were chronic liver disease (52%), cardiovascular (26%), and infection (13%), whereas in ALT- they were cardiovascular (33%), cancer (33%), and chronic liver disease (16%). Conversely, graft survival (censoring for patient death with a functioning graft) was higher among ALT+ (50% vs 35% at 15 years of follow-up, P = .04; RR = 1.5, CI = 1.19-2.22). Causes of graft loss in ALT- patients were chronic allograft nephropathy (CAN, 53%), glomerulonephritis (GN, 18%), acute rejection episode (AR, 22%), and death (5%), whereas among ALT+ they were CAN (36%), GN (31%), ARE (10%), and death (21%; P = .01). By multivariate analysis, ALT- (RR = 1.6, CI = 1.07-2.55, P = .02) and de novo GN (RR = 2, CI = 1.29-3.09, P = .002) were associated with worse renal allograft survival., Conclusion: Our results suggested that a better immune response against the HCV lead to greater patient survival but poorer graft survival.
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- 2005
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14. Beneficial effect of concomitant induction with antilymphoblast globulin, cyclosporine, and steroids on long-term renal allograft outcome.
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Koga A, Moreso FJ, Seron D, Gil-Vernet S, Cruzado JM, Castelao AM, and Grinyó JM
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- Adrenal Cortex Hormones adverse effects, Adrenal Cortex Hormones therapeutic use, Adult, Antilymphocyte Serum adverse effects, Cadaver, Cyclosporine adverse effects, Drug Therapy, Combination, Female, Follow-Up Studies, Graft Survival drug effects, Humans, Immunosuppressive Agents therapeutic use, Kidney Transplantation physiology, Male, Regression Analysis, Time Factors, Tissue Donors, Treatment Outcome, Antilymphocyte Serum therapeutic use, Cyclosporine therapeutic use, Graft Survival immunology, Kidney Transplantation immunology
- Abstract
Background: The addition of induction therapy with antilymphocytic antibodies to cyclosporine (CsA) based immunosuppression, has reduced acute rejection incidence and improved short-term survivals, but has not had well-established effects on long-term renal transplant survival., Patients: We analyzed the long-term allograft outcome of patients included in a prospective randomized clinical study conducted in our center 15 years ago by comparing two strategies: (A) horse antilymphoblast globulin (ALG) given at 10 mg/kg on alternate days to a maximum of 6 doses with low-dose CsA started at 8 mg/kg per day and prednisone at 0.25 mg/kg per day, versus (B) CsA started at 15 mg/kg per day and prednisone at 0.5 mg/kg per day. Diabetic and highly sensitized patients (PRA > 70%) were excluded from the study., Results: The characteristics of the 50 patients enrolled in each group were not different. Although patient survival was not different (88% in group A vs 77% in group B), recipients treated with ALG showed a lower incidence of acute rejection episodes (20% vs 44%, P = .01) and better death-censored renal allograft survival (57% vs 41%, P = .03). Among rejection-free patients, graft survival was 15% higher in group A (60% vs 45%, P = .12). Multivariate Cox regression analysis showed that an acute rejection episode (relative risk [RR]: 2.44, 95% confidence interval [CI] 1.36-4.39; P = .0029) rather than ALG immunosuppression (RR 0.74, 95% CI 0.41-1.33; P = NS) was an independent predictor of death-censored graft survival., Conclusions: In summary, we confirmed that concomitant induction therapy with ALG, CsA, and steroids improves long-term renal allograft survival., (Copyright 2004 Elsevier Inc.)
- Published
- 2004
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15. Cyclosporine nephrotoxicity.
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Grinyó JM and Cruzado JM
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- Humans, Immunosuppressive Agents toxicity, Kidney drug effects, Kidney Transplantation pathology, T-Lymphocytes drug effects, T-Lymphocytes immunology, Cyclosporine toxicity, Kidney pathology, Kidney Transplantation immunology
- Abstract
The polypeptide immunosuppressant cyclosporine is a prodrug that binds an intracellular immunophilin. The complex cyclosporine-cyclophilin binds and inhibits the phosphatase activity of calcineurin interfering with the dephosphorilation of members of the nuclear factor of activated T cells, which is involved in the regulation of genes encoding many cytokines. However, calcineurin is not exclusive from T cells; it is also present in many organs, such as the kidney, and their inhibition accounts for both the immunosuppressive and the nephrotoxic effects of cyclosporine. In renal transplantation, it was shown that graft survival improved progressively between 1998 to 1996, mainly due to reduction of acute rejection episodes. There is no doubt that cyclosporine contributed to that success. After 20 years, cyclosporine targets for maintenance immunosuppression have not been defined and the magnitude of chronic cyclosporine nephrotoxicity in renal allografts is not known, in part by the limitations of histologic classification of chronic allograft nephropathy. In the future, the new technology based on DNA microarrays can be a valuable tool to separate chronic drug toxicity from other causes of graft deterioration. On the other hand, in the cyclosporine era, chronic renal failure has emerged as a frequent adverse event after transplantation of nonrenal organs and it is associated with increased risk of death. Although there is not yet enough evidence to support a generalization of calcineurin-free immunosuppression, we should open our minds to the upcoming new concepts on immunosuppression.
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- 2004
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16. The ether phospholipids trail: blood timing in renal ischemia-reperfusion injury.
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Lloberas N, Torras J, Herrero I, Cruzado JM, Riera M, and Grinyó JM
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- Animals, Biomarkers blood, Male, Platelet Activating Factor analysis, Rabbits, Time Factors, Phospholipid Ethers blood, Renal Circulation, Reperfusion Injury blood
- Published
- 2002
- Full Text
- View/download PDF
17. Gene therapy in organ transplantation.
- Author
-
Torras J, Cruzado JM, and Grinyo JM
- Subjects
- Humans, National Library of Medicine (U.S.), Organ Transplantation standards, Transfection, United States, Genetic Therapy, Organ Transplantation methods
- Published
- 2002
- Full Text
- View/download PDF
18. Ischemic preconditioning improves postischemic acute renal failure.
- Author
-
Riera M, Herrero I, Torras J, Cruzado JM, Fatjo M, Lloberas N, Alsina J, and Grinyo JM
- Subjects
- Acute Kidney Injury blood, Acute Kidney Injury pathology, Animals, Creatinine blood, Ischemia blood, Ischemia complications, Kidney pathology, Male, Rats, Rats, Sprague-Dawley, Acute Kidney Injury prevention & control, Ischemia physiopathology, Ischemic Preconditioning, Kidney blood supply
- Published
- 1999
- Full Text
- View/download PDF
19. Effect of ETA/ETB receptor antagonist administration on iNOS gene expression in a rat renal transplantation model.
- Author
-
Herrero I, Torras J, Bover J, Espinosa LI, Cruzado JM, Riera M, Hueso M, Lloberas N, Alsina J, and Grinyo JM
- Subjects
- Animals, Antihypertensive Agents pharmacology, Bosentan, Nitric Oxide Synthase Type II, RNA, Messenger genetics, Rats, Receptor, Endothelin A, Receptor, Endothelin B, Transcription, Genetic drug effects, Endothelin Receptor Antagonists, Gene Expression Regulation, Enzymologic drug effects, Kidney, Kidney Transplantation physiology, Nitric Oxide Synthase genetics, Organ Preservation, Sulfonamides pharmacology
- Published
- 1999
- Full Text
- View/download PDF
20. Ischemia and reperfusion injury in transplantation.
- Author
-
Torras J, Cruzado JM, and Grinyo JM
- Subjects
- Apoptosis, Humans, Kidney Transplantation methods, Kidney Transplantation pathology, Ischemia, Kidney Transplantation physiology, Reperfusion Injury
- Published
- 1999
- Full Text
- View/download PDF
21. Hyperacute rejection models: ex vivo xenoperfusion systems.
- Author
-
Grinyo JM, Cruzado JM, and Torras J
- Subjects
- Animals, Humans, Mice, Models, Immunological, Organ Transplantation, Perfusion, Swine, Graft Rejection immunology, Graft Rejection prevention & control, Immunosuppression Therapy methods, Transplantation, Heterologous immunology
- Published
- 1999
- Full Text
- View/download PDF
22. Functional and pathologic outcome after complement inactivation in a pig kidney-human blood xenoperfusion model.
- Author
-
Grinyo JM, Cruzado JM, Riera M, Martorell J, Condom E, Borobia FG, Muñoz J, Herrero I, Lloberas N, Gimeno A, Alsina J, and Torras J
- Subjects
- Animals, Blood, Humans, Perfusion, Swine, Transplantation, Heterologous, Graft Rejection, Kidney Transplantation
- Published
- 1997
- Full Text
- View/download PDF
23. Prophylaxis of urinary tract infection in renal transplantation: comparison of three different protocols using ceftriaxone-cloxacillin, aztreonam-cloxacillin, or aztreonam-amoxycillin-clavulanic acid.
- Author
-
Castelao AM, Soto K, Grinyó JM, Gilvernet S, Serón D, Torras J, Riera L, Cruzado JM, and Alsina J
- Subjects
- Adult, Female, Follow-Up Studies, Gram-Negative Bacterial Infections epidemiology, Gram-Positive Bacterial Infections epidemiology, Histocompatibility Testing, Humans, Male, Postoperative Complications prevention & control, Urinary Tract Infections epidemiology, Amoxicillin therapeutic use, Aztreonam therapeutic use, Ceftriaxone therapeutic use, Cloxacillin therapeutic use, Drug Therapy, Combination therapeutic use, Kidney Transplantation immunology, Urinary Tract Infections prevention & control
- Published
- 1995
24. Hepatic preservation with a cold-storage solution containing fructose-1,6-diphosphate and mannitol: evaluation with the isolated perfused rat liver and comparison with University of Wisconsin solution.
- Author
-
Torras J, Borobia FG, Herrero I, Carrera M, Riera M, Bartrons R, Figueras J, Alsina J, Cruzado JM, and Jaurrieta E
- Subjects
- Adenosine, Adenosine Triphosphate metabolism, Alanine Transaminase metabolism, Allopurinol, Animals, Aspartate Aminotransferases metabolism, Bile metabolism, Glutathione, Insulin, Male, Oxygen Consumption, Perfusion, Portal System, Raffinose, Rats, Rats, Sprague-Dawley, Solutions, Time Factors, Vascular Resistance, Fructosediphosphates, Liver cytology, Liver physiology, Mannitol, Organ Preservation methods, Organ Preservation Solutions
- Published
- 1995
25. Course of three biochemical bone markers after kidney transplantation.
- Author
-
Gonzalez MT, Bonnin R, Cruzado JM, Garcia R, Moreso F, Fulladosa X, Alsina J, Navarro MA, and Griñó JM
- Subjects
- Adrenal Cortex Hormones therapeutic use, Biomarkers blood, Creatinine blood, Cyclosporine therapeutic use, Female, Follow-Up Studies, Humans, Kidney Transplantation immunology, Male, Parathyroid Hormone blood, Time Factors, Alkaline Phosphatase blood, Kidney Transplantation physiology, Osteocalcin blood, Peptide Fragments blood, Procollagen blood
- Published
- 1995
26. Evaluation of interstitial lesions in well-functioning renal allografts.
- Author
-
Serón D, Moreso F, Condom E, Carrera M, Cañas C, Cruzado JM, Soto K, Gil-Vernet S, Torras J, and Castelao AM
- Subjects
- Adult, Analysis of Variance, Biopsy, Creatinine blood, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Transplantation immunology, Kidney Transplantation physiology, Male, Retrospective Studies, Transplantation, Homologous, Kidney Transplantation pathology
- Published
- 1995
27. Metastatic pulmonary calcifications in severe secondary hyperparathyroidism: evolution after renal transplantation.
- Author
-
Fulladosa X, González MT, Cruzado JM, Andrés E, Castelao AM, Griñó JM, and Alsina J
- Subjects
- Adolescent, Adult, Bone and Bones diagnostic imaging, Calcinosis blood, Calcinosis physiopathology, Diphosphonates, Female, Follow-Up Studies, Humans, Hyperparathyroidism blood, Hyperparathyroidism physiopathology, Kidney Failure, Chronic blood, Kidney Failure, Chronic surgery, Lung Diseases blood, Lung Diseases physiopathology, Male, Parathyroid Hormone blood, Peritoneal Dialysis, Continuous Ambulatory, Radiography, Technetium Compounds, Calcinosis etiology, Hyperparathyroidism complications, Kidney Failure, Chronic complications, Kidney Transplantation physiology, Lung Diseases etiology
- Published
- 1995
28. Secondary hyperparathyroidism and acute ischemic posttransplant renal failure.
- Author
-
Cruzado JM, González MT, Gil-Vernet S, Serón D, Castelao AM, Andrés E, Bonnin R, Fulladosa X, Torras J, and Moreso F
- Subjects
- Adult, Cadaver, Chi-Square Distribution, Creatinine blood, Female, Glomerular Filtration Rate, Humans, Hyperparathyroidism epidemiology, Male, Reoperation, Retrospective Studies, Tissue Donors, Treatment Failure, Hyperparathyroidism etiology, Kidney Transplantation physiology, Parathyroid Hormone blood, Postoperative Complications
- Published
- 1995
29. Effect of pravastatin in the treatment of hypercholesterolemia after renal transplantation under cyclosporine and prednisone.
- Author
-
Castelao AM, Grinyó JM, Castiñeiras MJ, Fiol C, Gilvernet S, Seron D, Torras J, Cruzado JM, and Alsina J
- Subjects
- Adult, Apolipoprotein A-I blood, Cholesterol blood, Cholesterol, HDL blood, Cholesterol, LDL blood, Drug Administration Schedule, Female, Humans, Hypercholesterolemia blood, Hypercholesterolemia etiology, Immunosuppression Therapy methods, Kidney Transplantation adverse effects, Kidney Transplantation immunology, Male, Middle Aged, Cyclosporine therapeutic use, Hypercholesterolemia drug therapy, Kidney Transplantation physiology, Muromonab-CD3 therapeutic use, Pravastatin therapeutic use, Prednisone therapeutic use
- Published
- 1995
30. Multivariate analysis of prognostic factors in renal transplantation.
- Author
-
Moreso F, Gallén M, García-Osuna R, Torras J, Gil-Vernet S, Castelao AM, Serón D, Cruzado JM, Alsina J, and Grinyó JM
- Subjects
- Actuarial Analysis, Adult, Female, Follow-Up Studies, Histocompatibility Testing, Humans, Kidney Transplantation immunology, Male, Multivariate Analysis, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Retrospective Studies, Time Factors, Transplantation, Homologous, Graft Survival, Immunosuppressive Agents therapeutic use, Kidney Transplantation physiology
- Published
- 1995
31. Automatic evaluation of renal interstitial volume fraction.
- Author
-
Moreso F, Gratin C, Vitriá J, Condom E, Poveda R, Cruzado JM, Grinyó JM, Alsina J, and Serón D
- Subjects
- Adult, Automation methods, Biopsy methods, Female, Humans, Kidney Cortex pathology, Male, Regression Analysis, Kidney pathology, Kidney Diseases pathology
- Published
- 1995
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