Patients with a failed renal transplant.

Despite the advances in the care of recipients and in immunosuppression, long-term graft survival has experienced little improvement in the last 10 years. An important number of recipients present progressive loss of graft function and have to be readmitted on dialysis therapy. Before starting dialysis, these patients are re-exposed to the complications of chronic renal failure but there are no specific guidelines for their treatment. The Kidney Disease Quality Initiative Advisory Board clinical practice guidelines given for the non-transplant chronic kidney disease patients have been recommended for ameliorating their clinical situation and the rate of progression of graft failure. The time when dialysis has to be restarted and the type of dialysis procedure, hemodialysis or peritoneal dialysis, are under discusion. But there is no evidence about the superiority of either type of dialysis procedure. Systematic graft nephrectomy has been considered to improve the inflammatory status of the patients with a failed graft which could contribute to a worse control of some complications such as anemia and to the increased rates of cardiovascular mortality. As in the patients with primary end-stage renal disease, retransplantation is the best treatment for a patient with a failed graft. Due to the shortage of organs for transplantation the number of patients who are retransplanted has remained stable. Recurrent diseases such as glomerulonephritis, lyphoproliferative diseases, BK virus nephopathy and previous non-adherence to the treatment do not necessarily preclude retransplantation.

[Treatment of uraemic anorexia with megestrol acetate]. / Tratamiento de la anorexia urémica con acetato de megestrol.

BACKGROUND: Anorexia is a common disorder in patients treated with regular haemodialysis and is a contributing factor to malnutrition. The aim of this study was to evaluate the effectiveness of megestrol acetate, an appetite stimulant used in cancer patients, as a treatment for anorexia in dialysis patients. MATERIAL AND METHOD: In 2009, 16 patients in our haemodialysis unit, three with diabetes mellitus, were treated with megestrol (160 mg/day single dose) for anorexia defined according to a Likert scale of appetite. The schedule and dialysis dose were not changed during the study. RESULTS: In the third month of treatment there was, in the overall group, an increase in dry weight (60.8 vs 58.9 kg, P<.01), in albumin concentration (4.02 vs 3.8 g/dl, P<.05), in creatinine concentration (9.73 vs 8.26 mg/dl, P<.01), and protein catabolic rate (1.24 vs. 0.97 g/kg/day, P<.0001). Non-significant variations in the concentration of haemoglobin, erythropoietin dose, and lipid concentrations were found. One patient with diabetes mellitus had to increase the dose of insulin and two other patients suffered mild hyperglycaemia. Megestrol acetate did not suppress the secretion of pituitary sex hormones, but in 3 of 10 patients studied was found inhibition of ACTH secretion. The response was not homogeneous: one patient did not respond and reduced his dry weight, in 5 the weight gain was minimal (less than 1 kg) and in the remaining ten the response was good, with an increase in dry weight ranging between 1.5 and 5.5 kg. CONCLUSIONS: Megestrol acetate can improve appetite and nutritional parameters in patients treated with periodic haemodialysis who report anorexia. Megestrol acetate may induce hyperglycaemia and inhibit the secretion of ACTH in some patients. These side effects should be assessed when administering this treatment.

Risk factors for early renal graft thrombosis: a case-controlled study in grafts from the same donor.

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.

Immunohumoral response during laparoscopic and open living donor nephrectomy: an experimental model.

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.

Comparative analysis of the hemodynamic and respiratory parameters during laparoscopic versus open living donor nephrectomy: an experimental model.

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."

Mycophenolate mofetil levels in stable kidney transplant recipients.

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.

Variability of mycophenolate mofetil trough levels in stable kidney transplant patients.

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.

High body mass index and posttransplant weight gain are not risk factors for kidney graft and patient outcome.

BACKGROUND: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Prevalence of osteoporosis, osteopenia, and vertebral fractures in long-term renal transplant recipients.

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Proliferation signal inhibitors in transplantation: questions at the cutting edge of everolimus therapy.

While advances in immunosuppressive therapy have allowed dramatic improvements in the control of acute allograft rejection, there is still a need to improve long-term graft and patient survival rates following renal and heart transplantation. Among the recognized threats to long-term organ survival are chronic allograft dysfunction in the form of chronic allograft nephropathy and cardiac allograft vasculopathy, with long-term patient morbidity and mortality further compromised by higher than normal rates of posttransplant cardiovascular disease, infection, and malignancy. A growing body of evidence finds that the selection and dosing of immunosuppressive therapies can have great influence on long-term transplantation outcomes. Early evidence suggests that the proliferation signal inhibitors (PSIs), everolimus and sirolimus, might offer effective immunosuppressive activity together with antiproliferative effects that may address some of the unmet needs in the long-term therapeutic management of the posttransplant patient. This review summarizes the emerging evidence for employing PSI-based immunosuppression to seek a balance between the goals of maximizing graft and patient survival, while minimizing the risks of adverse events and long-term complications. Based on the proceedings of an international gathering of nephrologists, cardiologists and surgeons at the inaugural PSI Forum meeting "Proliferation signal inhibitors in transplantation: questions at the cutting edge," this paper aims to provide both an evidence base and practical guidance for transplant physicians seeking to optimize their use of PSI treatment and highlights avenues of ongoing research into the clinical potential of this class of immunosuppressive therapy.

Renal function in patients with cadaveric kidney transplants treated with tacrolimus or cyclosporine.

INTRODUCTION: Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone. METHODS: We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results. RESULTS: At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 +/- 0.7 vs 1.8 +/- 0.8 mg/dL, P < .001) and GFR (60.5 +/- 20.9 mL/min vs 47.9 +/- 10.0, P < .001) than the cyclosporine group. Additionally, recipients with ideal graft donors (23.5 +/- 2.8 vs 24.0 +/- 2.9 years) had a better serum creatinine at 2 years (1.23 +/- 0.2 vs 1.5 +/- 0.4 mg/dL, P < .05). Multivariate analysis showed that tacrolimus was an independent factor associated with better renal function: odds ratio 1.6, 95% confidence interval (1.2 to 2.2), P < .001. CONCLUSIONS: Patients with a renal transplant treated with tacrolimus in combination with MMF and prednisone displayed better renal function at 2 years than those who received cyclosporine.

[The Cockcroft-Gault equation is better than MDRD equation to estimate the glomerular filtration rate in patients with advanced chronic renal failure]. / La ecuación de Cockcroft-Gault es preferible a la ecuación MDRD para medir el filtrado glomerular en la insuficiencia renal crónica avanzada.

ABSTRACT The aim of this study was to compare the accuracy of three kidney function estimating equations: classic Cockcroft-Gault (classic CG), corrected Cockcroft-Gault (corrected CG) and simplified Modification of Diet in Renal Disease (MDRD), in patients with advanced chronic renal failure. The study was made in 84 nondialyzed patients with chronic renal disease in stage 4 or 5. The glomerular filtration rate was measured on a 24-hour urine collection as the arithmetic mean of the urea and creatinine clearances (CUrCr). In each patient, the difference between each estimating equation and the measured glomerular filtration rate was calculated. The absolute difference expressed as a percentage of the measured glomerular filtration rate indicates the intermethod variability. In the total group the glomerular filtration rate measured as the CUrCr was de 13,5+/-5,1 ml/min/1.73 m(2); and the results of the estimating equations were: classic CG 14,2+/-5 (p<0,05); corrected CG 12+/-4,2 (p<0,01) and MDRD : 12,1+/-4,8 ml/min/1.73 m(2) (p<0,01). The variability of the estimating equations was 15,2+/-12,2%, 17,1+/-13,4 % and 19,3+/-13,3% (p<0,05), for classic CG, corrected CG and MDRD respectively. The percent of estimates falling within 30% above o below the measured glomerular filtration rate was 90% for CG classic, 87% for corrected CG and 79% for MDRD. The intraclass correlation coefficients respect to CUrCr were 0,86 for classic CG, 0,81 for corrected CG and 0,77 for MDRD. The MDRD variability, but not classic CG variability or corrected CG variability, showed a positive correlation with the glomerular filtration rate (r=0,25, p<0,05). In patients with chronic renal disease in stage 5, the variability of the different estimating equations was similar. We conclude that in our population with advanced chronic renal failure the classic CG equation is more accurate than the MDRD equation. Corrected CG equation has not any advantage respect to classic CG equation.

[Control of the dialysis dose by ionic dialysance and bioimpedance]. / Control de la dosis de diálisis mediante dialisancia iónica y bioimpedancia.

INTRODUCTION: The ionic dialysance monitor allows an automated measure of Kt in each dialysis session. Bioelectrical impedance analysis (BIA) determines the total body water which it is equivalent to the urea volume of distribution (V). If the Kt, determined by ionic dialysance, is divided by the V, estimated by bioelectrical impedance, a Kt/V at the end of dialysis session (Kt/VDiBi) is obtained. AIM OF THE STUDY: To evaluate the agreement between the Kt/VDiBi and the Kt/V obtained by two simplified formulas: the monocompartimental (Kt/Vm) and the equilibrated (Kt/Ve) Daugirdas equations. METHODS: The Kt/VDiBi, the Kt/Vm and the Kt/Ve were determined in 38 hemodialysis patients (27 males and 11 females) in the same hemodialysis session. The patients were on dialysis three times a week for 3.5 to 4 hours. The V was determined by monofrequency bioelectrical impedance (50 kHz) at the end of the dialysis session. RESULTS: The Kt/VDiBi, Kt/Vm and Kt/Ve were 1.29+/-0.26, 1.54+/-0.29 and 1.36+/-0.25, respectively (p<0.001 between the Kt/VDiBi and the KtVm, and p<0.001 between the KtV/DiBi and the Kt/Ve). The intraclass correlation coefficient showed better concordance between the KtV/DiBi and the Kt/Ve (coefficient 0.88) than between the Kt/VDiBi and the KtVm (coefficient 0.65). The relative difference of the Kt/VDiBi was 8.3+/-6.4% with respect to the Kt/Ve and 18.4+/-7.8 % with respect to the Kt/Vm (p<0.001). The relative difference between the Kt/VDiBi and the Kt/Ve was lower than 15% in the 84% of the patients and lower than 10% in the 64% of the patients. CONCLUSIONS: If the V obtained by bioelectrical impedance analysis is included in the ionic dialysance monitor, we can obtain a Kt/V for each patient in real time, which is similar to the equilibrated Kt/V obtained from the Daugirdas equation.

Conversion from cyclosporine microemulsion to tacrolimus in stable kidney transplant patients with hypercholesterolemia is related to an improvement in cardiovascular risk profile: a prospective study.

The aim of this prospective multicenter study was to evaluate the effect of conversion from cyclosporine (CsA) to tacrolimus (Tac) on cardiovascular risk factors in stable kidney transplant patients with hyperlipidemia. Twenty-six patients were switched from CsA to Tac at 81.7 +/- 44.4 months after transplantation. Tac was started at 0.15 mg/kg/d. Patient outcomes were evaluated up to 6 months after conversion. Significant reductions were seen in systolic blood pressure (143 +/- 13 baseline to 136 +/- 9 mm Hg at 6 months, P = .026) as well as the need for antihypertensive medication, with no changes in diastolic blood pressure. There was a significant reduction in total cholesterol (247 +/- 41 to 221 +/- 35 mg/dL, P = .003), low-density lipoprotein cholesterol (150 +/- 24 to 127 +/- 27 mg/dL, P = .001), total cholesterol/high-density lipoprotein (HDL) cholesterol ratio (4.9 +/- 1.9 to 3.9 +/- 1, P = .02), and triglyceride levels (228 +/- 175 to 148 +/- 71 mg/dL, P = .026). No significant modifications in HDL cholesterol, Apo A1 and Apo-B levels, or in the need for lipid-lowering medication were observed. Glucose levels did not change, but an increase in HbAC1 took place (5.8 +/- 1.1 to 6.2 +/- 1, P = .002). In men Framingham risk score significantly decreased from 11.5 +/- 11.3 to 8.4 +/- 7.2. (P = .0023). In conclusion, elective conversion from CsA to Tac in stable kidney transplant patients with hyperlipidemia was related to an improved blood pressure and lipid profile, both suggesting a decrease in the estimated 10-year coronary heart disease risk in men.

Post-kidney transplant surgical complications under new immunosuppressive regimens.

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.

Mycophenolate mofetil tolerability and dose changes in tacrolimus-treated renal allograft recipients.

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.

Conversion from calcineurin inhibitors to everolimus in kidney transplant recipients with malignant neoplasia.

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.

Pancreas islet transplantation in the genitourinary tract associated with renal transplantation: an experimental study.

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.

Posttransplant diabetes mellitus in renal allograft recipients: A prospective multicenter study at 2 years.

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P < .05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P < .001), body mass index (BMI) > 30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P < .001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

[Temperature dialysate and hemodialysis tolerance]. / Temperatura del baño y tolerancia a la hemodiálisis.

In this study, the effect of dialysate temperature on hemodynamic stability, patients' perception of dialysis discomfort and postdialysis fatigue were assessed. Thirty-one patients of the morning shift were eligible to participate in the study. Three patients refused. Patients were assessed during 6 dialysis sessions: in three sessions the dialysate temperature was normal (37 degrees C) and in other three sessions the dialysate temperature was low (35.5 degrees C). To evaluate the symptoms along the dialysis procedure and the postdialysis fatigue, specific scale questionnaires were administered in each dialysis session and respective scores were elaborated. Low temperature dialysate was associated with higher postdialysis systolic blood pressure (122 +/- 24 vs. 126 +/- 27 mmHg, p < 0.05), and lower postdialysis heart rate (82 +/- 13 vs. 78 +/- 9 beats/min, p < 0.05) with the same ultrafiltration rate. Dialysis symptoms score and postdialysis fatigue score were better with the low dialysate temperature (0.7 +/- 0.9 vs. 0.4 +/- 1 vs. p < 0.05, and 1.3 +/- 1 vs. 1 +/- 0.9 p < 0.05, respectively). Furthermore, low temperature dialysate shortened the post-dialysis fatigue period (5.4 +/- 6.3 vs. 3.1 +/- 3.3 vs. hours, p < 0.05). The clinical improvement experimented with the low temperature dialysate was not universal. A beneficial effect was exclusively observed in the patients with higher dialysis symptoms and postdialysis fatigue scores or having more than one episode of hypotension in a week. The patients were asked about their temperature preference, 7 patients (23%) request a dialysate at 37 degrees C, 19 patients (61%) prefered to be dialysed with the low temperature dialysate, and 5 patients (16%) were indifferent. The later two groups of the patients continued with the low temperature dialysate during other 4 weeks. At the end of that period, the clinical improvement remained unchanged. In summary, low temperature dialysate is particularly beneficial for highly symptomatic patients.