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ABSTRACT: Renal graft thrombosis is an important cause of early graft loss. In a case-controlled analysis including only thrombosed kidneys and their counterparts from the same donors, we found that the right kidney as opposed to the left kidney was the only risk factor for early graft vascular thrombosis. No other recipient, donor, or perioperative factor was significantly associated with the complication. Our findings suggested that implantation of a right kidney might be followed by prophylactic anticoagulant or antiaggregant therapy.
Transplantation Proceedings 12/2008; 40(9):2891-3. · 1.00 Impact Factor
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ABSTRACT: Relapses of p-ANCA vasculitis during chronic dialysis treatment are infrequent. We report a patient with a pulmonary-renal syndrome and p-ANCA vasculitis who relapsed one year after starting hemodialysis treatment. Treatment with steroids and cyclosphosphamide successfully controlled the relapse, though cyclophosphamide had to be discontinued because of leucopenia. Clinical features of renal vasculitis, relapse after dialysis, the usefulness of ANCA titles as possible predictors and therapeutic options are discussed.
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2008; 28(4):457-60. · 1.00 Impact Factor
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Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 01/2008; 28 Suppl 2:40-1. · 1.00 Impact Factor
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A Fernández,
R Marcén, J Pascual,
J Martins,
J J Villafruela,
T Cano,
J Sabater,
C Puig,
B Gil-Casares,
A Muriel,
J Burgos,
J Ortuño
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ABSTRACT: The usefulness of mycophenolate mofetil (MMF) levels in stable kidney transplant patients is not well known. We measured MMF trough levels in 137 adult kidney recipients with more than 1 year of stable graft function. The MMF dose was adjusted according to hematological or gastrointestinal toxicity, it was 500 mg in 22 (16%) patients; 750 mg in 22 (16%); 1000 mg in 69 (50.5%); 1500 mg in 15 (11%); and 2000 mg in 9 (6.5%). We analyzed the total dose, virgule dose/kg, and MMF levels in relation to efficacy parameters (creatinine, proteinuria) and hematological toxicity (erythrocytes, leukocytes, and platelets) at the time of MMF level determinations and 3 months thereafter. Statistical analyses were performed with SSPS 12.0, including sensitivity and specificity analyses by ROC. Mean MMF levels were 3.68 mg/L (Pc25, 1.6-Pc75, 4.4 mg/L) with significant differences according to dose (P < .001). Trough MMF levels did not have discriminatory capacity in the area under the ROC for anemia, renal failure, or proteinuria at the time of determination or 3 months later. The percentage of patients without proteinuria was high among patients with MMF levels between 1.6 and 4.4 mg/L. The MMF levels were low in patients who had a major increase in creatinine (1.6 vs 3.8 mg/L, P < .05). In stable renal transplant patients the levels of MMF were related to the administered dose, and they are higher than those previously described in patients with less than a year follow-up with a functioning kidney. They did not have discriminatory value at the time of determination or 3 months later. Nevertheless, low MMF levels could help recognize patients at risk of developing chronic nephropathy.
Transplantation Proceedings 09/2007; 39(7):2182-4. · 1.00 Impact Factor
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ABSTRACT: High body mass constitutes a significant risk factor for morbidity and mortality in the general population, but it has been associated with an increased survival among dialysis patients. Its effects on renal transplant outcomes are controversial. The aim of our present work was to investigate the impact of high body mass and posttransplant weight gain on patient and graft outcomes.
One thousand consecutive renal transplant recipients (631 men and 369 women) were included in the study. Their mean age was 42.9 years and the follow-up was at least 2 years. Basal immunosuppression was azathioprine (Aza) and steroids in 196 patients, cyclosporine (CsA) without or with antiproliferative agent in 557, and 239 were presented tacrolimus (Tac).
At the time of transplantation the body mass index (BMI) was 23.7 +/- 3.9 kg/m2, namely, <18.5 kg/m2 in 6.3%; 18.5 to 25 in 61.7%; 25 to 30 in 25.4%; and >30 in 6.5%. Pretransplant obesity was associated with old age and female gender. Obese patients experienced a greater risk of delayed graft function (P < .01) and surgical wound complications (P < .01). After 1 year, 299 patients (29.9%) displayed weight gain >10% (mean 8.6% +/- 10.4% or 5.0 +/- 6.1 kg). Patients on Aza showed increased body weight by 11.9% +/- 10.9%; CsA patients by 9.5% +/- 10.3%, and Tac patients by 4.9% +/- 9.1% (P < .001). Univariate and multivariate analysis showed that pretransplant BMI had no effect on graft or patient survival either in the whole group or in the patients treated with CsA or TAC. Posttransplant weight gain above 5% or 10% did not influence graft or patient outcomes.
The new immunosuppressive regimes reduce posttransplant weight gain. Pretransplant high body mass and 1-year posttransplant weight gain were not risk factors for graft or patient survival in our experience.
Transplantation Proceedings 09/2007; 39(7):2205-7. · 1.00 Impact Factor
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J Sáenz,
M S Asuero,
J Villafruela,
C Correa,
J Galindo,
B Cuevas,
A Páez,
A Linares, J Pascual,
R Marcén,
F J Burgos
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ABSTRACT: Measurement of interleukins (IL) and C-reactive protein (CRP) have demonstrated that a laparoscopic approach may induce less surgical stress than an open approach. The potential influence of this observation in living donor nephrectomy has scarcely been analyzed. The aim of the study was to analyze the immunohumoral response induced by laparoscopic versus open donor nephrectomy in an experimental model. Twenty pigs underwent left nephrectomy, 10 by laparoscopy and 10 by an open approach. In both groups the following parameters were measured: CRP, IL-2, IL-10, tumour necrosis factor alpha (TNF alpha), and endothelin-1 (ET-1). The determinations were done at different times: basal, immediately as well as on the first, third, fifth, and seventh days after the procedure. A comparative analysis between groups demonstrated a significant increases among the open group in the following markers: CRP (1.44 +/- 0.88 vs 1.32 +/- 0.14 mg/dL, P = .046); TNF alpha (131.14 +/- 41.37 vs 57.19 +/- 23.71 pg/mL; P > .001); and ET-1 (0.91 +/- 0.49 vs 0.56 +/- 0.5 fmol/mL; P = .001). The laparoscopic group showed higher levels of IL-2 than the open group. In conclusion, open donor nephrectomy produced a greater immunohumoral response than a laparoscopic approach. The influence of these observations on ischemia-reperfusion injury or on immediate graft function after kidney transplantation has not been clearly established.
Transplantation Proceedings 09/2007; 39(7):2102-4. · 1.00 Impact Factor
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J Sáenz,
M S Asuero,
C Correa,
J García,
J J Villafruela,
B Cuevas,
A Páez,
A Linares,
J Galindo, J Pascual,
R Marcén,
F J Burgos
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ABSTRACT: Increased intrabdominal pressure induced by pneumoperitoneum induces modifications in cardiovascular and respiratory systems. The aim of the study was to analyze the hemodynamic and respiratory modifications produced by pneumoperitoneum during living donor nephrectomy in a porcine experimental model. Twenty pigs underwent left nephrectomy, 10 by laparoscopy and 10 by an open approach. The following parameters were measured: mean arterial pressure (MAP), central venous pressure, cardiac output (CO), systemic vascular resistance (SVR), end tidal CO2 (ETCO2), minute volume (MV), respiratory airway pressure (RAP), and "compliance." Both groups were monitored for cardiac and respiratory systems at basal, 5, 30, and 60 minutes as well as postsurgery. The comparative analysis demonstrated increased CO with a higher difference at 30 minutes (4.33 +/- 0.73 vs 8.54 +/- 1.26 L/min, P < .001); decreased SVR (1118.81 +/- 302.52 vs 663.37 +/- 81.45 dinas x s x cm(-5), P < .001), and elevated MAP among the laparoscopic group (66.5 +/- 11.52 vs 80.25 +/- 2.49 mm Hg, P = .004). Analysis of respiratory modifications showed an initial increase in ETCO2 (44.3 +/- 2.6 vs 54.1 +/- 12.56 mm Hg, P < .035) and a higher MV administered (5.6 +/- 0.1 vs 7.01 +/- 0.96 L/min, P = .03) to the laparoscopy group. An increased RAP was observed at 5 minutes (22.11 +/- 2.76 vs 28.8 +/- 3.68 mm Hg, P < .001), in the laparoscopic group and lower levels of "compliance" at the same moment in that group (16 +/- 1.66 vs 14.9 +/- 4.07 cm H2O). Laparoscopic nephrectomy caused an increase in CO and MAP and decreased SVR. Likewise there were elevations of RAP, ETCO2, and MV and a slight decrease in the "compliance."
Transplantation Proceedings 09/2007; 39(7):2105-8. · 1.00 Impact Factor
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A Fernández,
J Martins,
J J Villlafruela,
R Marcén, J Pascual,
T Cano,
C Puig,
B Gil-Casares,
A Muriel,
F J Burgos,
J Ortuño
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ABSTRACT: Great interindividual variability in the pharmacokinetics of mycophenolate mofetil (MMF) exists among kidney transplanted patients. The within-patient variability in stable transplanted patients is not well established. We performed 258 determinations of trough MMF levels in 86 stable transplant patients without hematological or gastrointestinal toxicity after at least year of a functioning kidney and a fixed dose of MMF. We examined the within-patient variability of levels related with clinical factors (age, gender, underlying cause of kidney failure, time since transplant, associated immunosuppression, and MMF dose) and analytical factors (serum creatinine, proteinuria, hemoglobin). Trough MMF levels were 3.6 mg/L, percentile (Pc) 25 1.6 mg/L, Pc 75 4.4 mg/L with intraindividual variability median of 65% (Pc 25 14%, Pc 75 79%). For the data analysis a variation of 14% was chosen, which corresponded to the 25th percentile. We did not observed differences between patients with variation below or above the Pc 25 in age, gender, underling cause of kidney failure, basal MMF levels, and MMF dose. Patients with greater variations showed significantly higher serum creatinine and proteinuria values than the others (1.84 +/- 0.54 vs 1.46 +/- 0.44 mg/dL and 0.45 +/- 0.42 vs 0.19 +/- 0.14 g/L; P < .05). Therefore, great within-patient variability in trough MMF levels was associated with poor kidney function and proteinuria.
Transplantation Proceedings 09/2007; 39(7):2185-6. · 1.00 Impact Factor
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ABSTRACT: Osteopenia and osteoporosis are frequent complications early after transplantation. Their long-term prevalences and associations with the risk of fractures are not well known. The objective of the present work was to determine the incidence of osteopenia and osteoporosis versus vertebral fractures in renal transplant recipients with stable graft function and with a follow-up of at least 10 years.
Forty renal transplant recipients, 24 men and 16 women, were included in the study. The mean age was 41.8 years and the follow-up was 130 +/- 14 months. Initial immunosuppression consisted of cyclosporine with or without an antiproliferative agent. Measurements of bone mass density (BMD) were performed by dual-energy X-ray absorptiometry (DEXA). The assessment of vertebral fracture using conventional radiography was evaluated by semiquantitative criteria.
Eleven patients (27.5%) displayed lumbar spine osteoporosis (T-score < -2.5); 21 (52.5%), osteopenia (T-score > -2.5 and < -1) and 8 (20.0%), normal BMD. However, BMD was better preserved at the femoral neck: 14 patients (35.0%) had normal BMD; 20 (50.0%) osteopenia, and 6 (15.0%), osteoporosis. When analyzed together, patients with osteoporosis or osteopenia showed worse graft function at 1 and 8 years compared with normal BMD patients (1.75 +/- 0.634 vs 1.32 +/- 0.33 mg/dL at 1 year; P < .014) and (1.7 +/- 0.4 vs 1.2 +/- 0.2 mg/dL at 5 years; P < .01) and a greater number were prescribed vitamin D (50% vs 23%). Mild vertebral fractures were observed in 60.0% patients with osteoporosis; 70% with osteopenia; and 43% with normal lumbar BMD. Peripheral fractures were more common in patients with osteoporosis (P = .053).
Osteoporosis and osteopenia are common among long-term renal transplant recipients are associated with poorer graft function. Lumbar spine BMD osteoporosis is associated with peripheral fractures. However, mild vertebral deformities are not associated with the presence of osteopenia or osteoporosis.
Transplantation Proceedings 09/2007; 39(7):2256-8. · 1.00 Impact Factor
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Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2007; 27 Suppl 1:49-59. · 1.00 Impact Factor
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ABSTRACT: New immunosuppressive regimens have decreased acute rejection rates after kidney transplant. However, the use of these new agents has modified the profile of surgical complications. We compared the incidence of surgical complications in relation with the use of three types of drugs: calcineurin inhibitors, antiproliferative agents, and mammalian target of rapamycin (mTOR) inhibitors. This retrospective study included 359 cadaveric recipients who received an allograft between 1997 and 2004. The mean age was 54 years. The prevalence of diabetes was 8.5% and that of obesity (body mass index > 30 kg/m(2)) was 15.4%. The mean follow-up time was 44 +/- 5.6 months. The regimen most frequently used was tacrolimus (TACRO), mycophenolate mofetil (MMF), and prednisone (PRED) (n = 172), followed by TACRO-PRED (n = 49), cyclosporine (CSA) and MMF and PRED (n = 41), and CSA-azathioprine (AZA) and PRED (n = 24). A surgical complication was considered to be any type of event during the first year, although minimal, directly related to surgery. The rate of surgical complications was 34.8% (122/350). Collections and bleeding were higher in CSA than in TACRO regimens, 12% versus 3.8% (P < .05) and 11.5% versus 3% (P = .002), respectively. The incidence of lymphoceles was higher in regimens with than without mTOR inhibitors: 16% versus 3.7% (P = .012). The incidence of surgical complications was not influenced by the use of MMF or diabetes. In conclusion, the use of mTOR inhibitor-based immunosuppressive regimens leads to a higher incidence of lymphoceles, while the use of MMF does not increase the incidence of surgical complications.
Transplantation Proceedings 11/2006; 38(8):2445-7. · 1.00 Impact Factor
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ABSTRACT: Conceptually, pancreas islet transplantation (PIT) associated with renal transplantation (RT) should resolve not only chronic renal failure but also diabetes. Although the most frequently used site for PIT is the portal vein, genitourinary locations could be technically feasible during RT. Seventeen pigs (age 3 to 4 months; mean weight 34.5 kg) underwent the following experimental steps: On day 1 a left nephrectomy was performed and the kidney was perfused with cold Wisconsin solution. This was followed by a caudal pancreatectomy and islet isolation by means of digestion with intraductal collagenase. Islets were stained with Dithizone and cultured overnight al 37 degrees C and 5% CO(2). On day 2 a right nephrectomy and orthotopic RT of the preserved left kidney were performed. The islets were transplanted into four different sites: subcapsular in the kidney graft, in the bladder submucosa, in the testis by puncture, and in the testis by infusion through the vas deferens. On day 7 the animals were sacrificed. Islet viability was determined by histological examination with insulin immunostaining and determination of insulin in the blood of the veins draining the implantation sites. The mean weight of the pancreatic specimens was 27.8 g (13 to 46). The mean number of islets was 536,000 (16,600 to 1,5000,000). Islets were shown in the bladder submucosa and the testes after vas deferens infusion. The number of viable islets in the other implantation sites was very scarce. The insulin levels of the venous effluents were: 15.1 microU/mL for bladder submucosa, 10.2 microU/mL for intradeferential injection in the testis, 7.3 microU/mL for intratesticular injection by puncture, and 2.6 microU/mL for subcapsular implantation in the graft. In conclusion, the bladder submucosa and testis via the vas deferens might represent alternative sites for PIT. The latter route may benefit from the immunoprivileged and special trophic conditions of the testis. For the first time, the feasibility of the bladder submucosa as an implantation site for pancreas islets was demonstrated.
Transplantation Proceedings 11/2006; 38(8):2585-7. · 1.00 Impact Factor
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ABSTRACT: Cancer has been reported to be more common among kidney transplant recipients than waiting-list patients or the general population. Use of anticalcineurin agents and azathioprine are relevant risk factors. Nine renal allograft recipients (seven men and two women) of mean age 67.6 (55-77) years and mean time after transplantation of 30.7 (58-216) months were switched to everolimus-based immunosuppression because of the presence of biopsy-proven malignancies (eight patients) or neurological tacrolimus toxicity (one patient). One patient with posttransplant lymphoproliferative disease also received chemotherapy with a good evolution at 6 months. He showed an initial increase in the protein to creatinine ratio (peak 3.3 mg/mg at 3 months) that was controlled by increasing the enalapril dose. One patient with skin cancer and severe atheromatosis (baseline SCr 2.5 mg/dL, creatinine clearance 17 mL/min, and protein to creatinine ratio 3.2 mg/mg), had cyclosporine and everolimus overlapped for 25 days, showing a continued poor evolution requiring dialysis initiation at 3 months after switch. The other six patients with recurrent skin cancers had good cancer evolution, with no new skin tumors and regression of skin lesions in three, including not biopsied actinic keratosis. Sudden switching from calcineurin inhibitors to everolimus is safe and may be used in long-term transplant recipients with malignancies. In patients with advanced chronic nephropathy this approach appeared to be less beneficial.
Transplantation Proceedings 11/2006; 38(8):2453-5. · 1.00 Impact Factor
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ABSTRACT: Mycophenolate mofetil (MMF) reduces acute rejection episodes (AREs) and may be associated with better renal graft survival than azathioprine. However, MMF-related adverse events are frequent; dose reduction or even withdrawal are quite common. Between 1999 and 2003, 115 renal transplantation patients were treated with tacrolimus, MMF, and steroids. An observational study was undertaken until graft loss (n = 7), death with a functioning graft (n = 2), or October 31, 2005 (mean follow-up-50 months). We assessed MMF dose reductions due to adverse events with the possible consequences on AREs and graft function. Treated acute ARE occurred in 11.3% of recipients, all of which were steroid-responsive. The median MMF initial daily dose was 1000 mg. In 44 patients (38.3%), the MMF dose was not changed; in 48 (41.7%) it was reduced; and in 23 (20%), withdrawn. The causes for dose modification were diarrhea (n = 33, 28.7% of all patients), leukopenia (n = 22, 19.1%), both of these (n = 7, 6.1%), or other events (n = 9, 7.8%). No AREs were attributed to MMF dose changes. Tacrolimus blood levels were higher at 3 years and serum creatinine values at 4 years among patients with dose changes (8.43 +/- 2.42 vs 7.37 +/- 2.23 ng/mL; P = .051 and 1.75 +/- 0.71 vs 1.48 +/- 0.38 mg/dL; P = .038, respectively). The need for MMF dose reduction or withdrawal was frequent in our patients with diarrhea or leukopenia during treatment with tacrolimus, MMF, and steroids. These adverse event-related changes were not associated with AREs, but produced deleterious effects on long-term graft function.
Transplantation Proceedings 11/2006; 38(8):2398-9. · 1.00 Impact Factor
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Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2006; 26(3):304-14, 316. · 1.00 Impact Factor
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Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2006; 26(1):25-30. · 1.00 Impact Factor
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C Quereda, J Pascual,
F García-López,
R Alcázar,
P Aljama,
J J Amenábar,
M Arias,
V Barrio,
A Fernández-Rodríguez,
G Fernández Juárez, [......],
R Pérez García,
M Praga,
R Saracho,
R Selgas,
M Rivera,
J C Rodríguez Pérez,
J L Teruel,
A Tato,
A Torres,
F Valdés
Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2006; 26(2):163-72. · 1.00 Impact Factor
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Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2006; 26 Suppl 3:82-7. · 1.00 Impact Factor
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ABSTRACT: The incidence of post-renal transplantation ureteral stenosis ranges from 2%-12%. Because the role of self-expanding ureteral metallic stents for its treatment has been scarcely reported, the aim of this study was to evaluate the efficacy of Nitinol stents. Eleven ureteral stenoses in patients with chronic graft dysfunction (8 cases) or high surgical risk (3 cases) were treated by antegrade percutaneous implantation of Nitinol stents through a nephrostomy tract. The mean follow-up period was 48 +/- 7 months (range, 3-85 months). The patency rate at the moment of return to dialysis, death, or last check-up was 73% (8/11). Three patients (27%) developed stent occlusion. Two patients were treated using a trans-stent double-J catheter and 1 patient using stent removal and pyeloureterostomy using the native ureter. The mean percentage decrease in serum creatinine (Cr) level after stent implantation was 41% (range, 14%-63%). Nitinol ureteral stent implantation is an effective alternative for the treatment of ureteral stenosis in patients with chronic graft dysfunction or high surgical risk.
Transplantation Proceedings 12/2005; 37(9):3828-9. · 1.00 Impact Factor
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ABSTRACT: During the 1990s two metaanalysis of randomized clinical trials of steroid withdrawal after renal transplantation showed significant increases in acute rejection episodes and graft failure rates. A recently published metaanalysis of steroid withdrawal in patients on a calcineurin inhibitor and MMF included randomized clinical trials. We have updated this study, searching more publications during the last 2 years. Finally, the same six trials were included, four in patients receiving cyclosporine and two tacrolimus. Risk ratio (RR) for acute rejection was 2.28 [95%CI 1.65-3.16, P < .00001], and pooled risk difference (RD) was 0.08 [0.05-0.11, P < .001], indicating that the proportion of patients with acute rejection episodes after prednisone withdrawal was significantly higher compared with controls. RR for graft failure was 0.73 [0.42-1.28, P = .27], and RD was -0.01 [-0.03-0.01, P = .28], indicating that the proportion of patients with graft failure after withdrawal was not significantly different from that of controls. Total cholesterol was significantly lower after steroid withdrawal (weighted mean difference -0.53 mumol/L [-0.70--0.36, P < .0001]). Renal allograft recipients on triple therapy with a calcineurin inhibitor, MMF, and steroids are at low but significant risk of acute rejection after steroid withdrawal, but do not suffer an increased risk of early graft failure. It is necessary to extend controlled follow-up to confirm graft function stabilization.
Transplantation Proceedings 11/2005; 37(9):3746-8. · 1.00 Impact Factor
