Controlled-Dose Versus Fixed-Dose Mycophenolate Mofetil for Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Transplantation - Current Issue Controlled-Dose Versus Fixed-Dose Mycophenolate Mofetil for Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundAlthough mycophenolate mofetil (MMF) is recommended at a fixed dose, there is increasing interest in controlled-dose (CD) MMF based on therapeutic drug monitoring. We systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of CD versus fixed-dose MMF for kidney transplant recipients. MethodsThe electronic databases Medline, Embase, and Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two reviewers independently applied the study selection criteria, examined the study quality, and extracted the data. Dichotomous measures were expressed as relative risk (RR) and continuous outcomes were expressed as weighted mean difference, both with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager 5.1.6. ResultsFour RCTs met our selection criteria and included 1755 de novo recipients. The differences between CD and fixed-dose MMF in treatment failure (RR, 0.95; 95% CI, 0.82–1.10; P=0.52), serum creatinine clearance (weighted mean difference, 2.46; 95% CI, −1.15 to 6.07; P=0.18), total gastrointestinal adverse events (RR, 1.23; 95% CI, 0.65–2.35; P=0.53), diarrhea (RR, 1.08; 95% CI, 0.92–1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95–1.64; P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93–1.35; P=0.25), thrombocytopenia (RR, 0.80; 95% CI, 0.47–1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27–1.38; P=0.23) were not statistically significant. Furthermore, total infections were more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03–1.30; P=0.01). ConclusionsBased on current evidence, CD MMF administration cannot be recommended as routine practice for kidney transplant recipients. Therapeutic drug monitoring for MMF may be targeted toward high-risk recipients, who should be identified in future studies.


http://journals.lww.com/transplantjournal/Fulltext/2013/08270/Controlled_Dose_Versus_Fixed_Dose_Mycophenolate.4.aspx

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Alberto Reino Buelvas

Médico Internista Nefrólogo

Hospital San Vicente de Paul

Grupo Trasplantes Renales

Director Médico Unidad Renal

Extrarenal Factors Influencing Resistance Index in Stable Kidney Transplant Recipients

Transplantation - Current Issue Extrarenal Factors Influencing Resistance Index in Stable Kidney Transplant Recipients

BackgroundIncreased intrarenal resistance index (RI) has been associated with decreased long-term allograft and patient survival in kidney transplant recipients. Taking into account the potential role of endothelial dysfunction, systemic inflammation, arteriosclerotic lesions, and left ventricle remodeling, we performed a cross-sectional study that aimed to evaluate extrarenal factors that may have influence on kidney graft RI in a large cohort of stable kidney transplant recipients. MethodsOne hundred seventy-four kidney transplant recipients were enrolled into the study. Mean time after transplantation was 8.4±1.8 years. Echocardiography, carotid ultrasound (intima-media thickness), pulse wave velocity, and Doppler examination of kidney graft were performed. The inflammatory markers, adhesion molecules, and plasma N-terminal prohormone of brain natriuretic peptide concentrations were also measured. Patients were divided into quartile subgroups based on RI value (Q1: RI≤0.68, Q2: RI=0.69–0.72, Q3: RI=0.73–0.76, and Q4: RI≥0.77). ResultsThe analyzed subgroups were comparable with respect to demographics (except age) and anthropometric parameters as well as comorbidities. The values of age, serum phosphate, pulse wave velocity, left ventricular mass (LVM), and LVM index (LVMI) increased in subsequent RI quartile subgroups. The strongest correlation was found between RI and age, LVM, LVMI, and plasma parathormone concentration and was negative with estimated glomerular filtration rate. In backward stepwise multivariate regression analysis, the RI variability was explained by age, LVMI, and serum phosphate concentration. ConclusionArterial stiffness and left ventricular hypertrophy may significantly influence the intrarenal vascular resistance measured using Doppler sonography in stable kidney transplant recipients.


http://journals.lww.com/transplantjournal/Fulltext/2013/08270/Extrarenal_Factors_Influencing_Resistance_Index_in.12.aspx

The Survival Benefit of Kidney Transplantation in Obese Patients.

AJT The Survival Benefit of Kidney Transplantation in Obese Patients.

• Gill JS, Lan J, Dong J, et al. 
• The Survival Benefit of Kidney Transplantation in Obese Patients. [JOURNAL ARTICLE]
• Am J Transplant 2013 Jul 25.

Obese patients have a decreased risk of death on dialysis but an increased risk of death after transplantation, and may derive a lower survival benefit from transplantation. Using data from the United States between 1995 and 2007 and multivariate non-proportional hazards analyses we determined the relative risk of death in transplant recipients grouped by body mass index (BMI) compared to wait-listed candidates with the same BMI (n = 208 498). One year after transplantation the survival benefit of transplantation varied by BMI: Standard criteria donor transplantation was associated with a 48% reduction in the risk of death in patients with BMI ≥ 40 kg/m(2) but a ≥66% reduction in patients with BMI < 40 kg/m(2) . Living donor transplantation was associated with ≥66% reduction in the risk of death in all BMI groups. In sub-group analyses, transplantation from any donor source was associated with a survival benefit in obese patients ≥50 years, and diabetic patients, but a survival benefit was not demonstrated in Black patients with BMI ≥ 40 kg/m(2) . Although most obese patients selected for transplantation derive a survival benefit, the benefit is lower when BMI is ≥40 kg/m(2) , and uncertain in Black patients with BMI ≥ 40 kg/m(2) .

http://www.unboundmedicine.com/medline/citation/23890325/The_Survival_Benefit_of_Kidney_Transplantation_in_Obese_Patients_

Abdominal tuberculosis following kidney transplantation: clinicopathologic features and follow-up in a unique case series

Clinical Transplantation Abdominal tuberculosis following kidney transplantation: clinicopathologic features and follow-up in a unique case series

Background Kidney transplant recipients are at a high risk of opportunistic infection. The aims of this study were to describe the epidemiology, clinical features, and prognosis of abdominal tuberculosis (TB) in kidney transplant recipients. Methods All cases of abdominal TB that occurred in kidney transplant recipients at our center between 1998 and 2010 were retrospectively reviewed. Detailed demographic data, clinical profile information, and the treatment response were recorded. Results Among the 7833 kidney transplantations performed during the study period, eight patients (0.1%) developed abdominal TB. There were four men and four women in this group. The mean age of the patients was 44 ± 12 yr. The time from kidney transplantation to TB was 6.7 ± 3.4 yr. The symptoms were weight loss (87.5%), diarrhea (87.5%), fever (75%), abdominal pain (62.5%), and lower gastrointestinal bleeding (37.5%). The delay between the identification of the clinical symptoms and the diagnosis was an average of six months. The diagnosis was confirmed histopathologically for most patients. The cecum and ascending colon were the most common sites involved. Two patients required surgical intervention. Five patients received a 4-drug regimen, and three had hepatotoxicity. The median length of antituberculous therapy was nine (6–12) months. Five patients lost their graft. Overall, the hospital mortality was 12.5%. Conclusions Kidney transplantation increases the risk of TB, particularly as an extrapulmonary disease. The symptoms of infection are often attenuated, leading to delayed diagnosis. Therefore, a careful approach to the patient and supportive data are necessary to make the final and timely diagnosis.


http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12210

Overall and Cause-Specific Mortality in Transplant Recipients with a Pretransplantation Cancer History

Transplantation - Current Issue Overall and Cause-Specific Mortality in Transplant Recipients with a Pretransplantation Cancer History

Background: It is unclear to what extent cancer history affects posttransplantation mortality in solid organ transplant recipients. Methods: We identified a Swedish population-based cohort of solid organ transplant recipients in the National Patient Register 1970 to 2008 and linked it to the Cancer and Cause-of-Death Register. Overall and cause-specific mortality was estimated using Cox regression. Results: Of 10,448 eligible recipients, 416 (4%) had a prior malignancy unrelated to the indication for transplantation diagnosed 2 months or more before surgery (median, 5.7 years). Mortality among cancer history recipients was 30% increased after transplantation, compared with other recipients (adjusted hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1–1.5; P<0.001), driven by cancer-specific death with no increase in cardiovascular, infectious, or other noncancer mortality. An increased rate of death due to cancer history was primarily observed among nonkidney recipients (adjusted HRnonkidney, 1.8; 95% CI, 1.3–2.5; HRkidney, 1.2; 95% CI, 1.0–1.4). Rates were greatest for patients with waiting times of 5 years or less but persisted with waiting times more than 10 years among kidney and nonkidney recipients with prior aggressive cancer types (gastrointestinal, breast, kidney/urothelial, and hematologic malignancies). Conclusion: We conclude that organ transplant recipients with cancer history are at a moderately increased rate of death after transplantation, driven primarily by death due to cancer recurrence.


http://journals.lww.com/transplantjournal/Fulltext/2013/08150/Overall_and_Cause_Specific_Mortality_in_Transplant.13.aspx

Comparison of Kidney Function Between Donation After Cardiac Death and Donation After Brain Death Kidney Transplantation

Transplantation - Current Issue Comparison of Kidney Function Between Donation After Cardiac Death and Donation After Brain Death Kidney Transplantation

Backgroud: Kidney graft survival is comparable between donation after cardiac death (DCD) and donation after brain death (DBD) kidney transplantation. However, data concerning kidney function after DCD kidney transplantation are lacking. Methods: We retrospectively compared kidney function between 64 DCD and 248 DBD kidney transplant recipients. Graft function was assessed using iothalamate glomerular filtration rate at 1, 4, and 12 months, then annually. The primary endpoint was the composite of death-censored graft loss or two consecutive iothalamate glomerular filtration rates less than 50 mL/min/1.73 m2 occurring within 5 years from transplantation. Secondary endpoints included death and graft loss or death. Results: Of the 312 patients, 102 (33%) experienced the primary endpoint, 78 (25%) experienced graft loss or death, and 44 (14%) died. In multivariable Cox regression analysis, there was no difference between DCD and DBD recipients regarding the primary endpoint (relative risk [RR], 1.16; P=0.59), death (RR, 0.97; P=0.94), or graft loss or death (RR, 1.09; P=0.79). In the subgroup of 64 DCD recipients, each 10-year increase in donor age was associated with increased risk of the primary endpoint (RR, 1.51; P=0.027) with the highest risk observed for donors older than 45 years (RR, 4.81; P=0.001). Delayed graft function affected 45% of the DCD recipients but had no impact on kidney function, graft survival, or patient survival. Conclusions: Posttransplantation kidney function is comparable between DCD and DBD kidney transplantations. In the subgroup of DCD recipients, kidneys from donors older than 45 years may be associated with a higher risk of poor kidney function; however, this finding requires validation in a larger patient group.


http://journals.lww.com/transplantjournal/Fulltext/2013/08150/Comparison_of_Kidney_Function_Between_Donation.10.aspx