Study on the association of UGT1A9 gene c.98T>C polymorphism and mycophenolic acid plasma levels in renal transplant patients.

Mycophenolate mofetil (MMF) is a prodrug active only after its hydrolysis to mycophenolic acid (MPA). The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms (SNPs) in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MMF. Expression levels and the activity of UGT1A9 may depend on the presence of some SNPs located in the gene promoter region (-2152C>T and -275T>A), as well as changes in the coding region (c.98T>C). The objective of this study was to evaluate the effect of allelic variants of the UGT1A9 c.98T>C polymorphism (rs72551330; g. 87289T>C) on MMF metabolism in renal transplant patients. MPA and MPA 7-O glucuronide (MPAG) levels were determined on plasma samples of kidney transplant patients (N = 39) by high-performance liquid chromatography using ultraviolet detection. DNA was isolated from leukocytes and stored at -20°C. The presence of SNPs was investigated using polymerase chain reaction, followed by amplicon sequencing. The analysis of the UGT1A9 c.98T>C polymorphism revealed that all study patients presented the TT genotype. Diverse MPA and MPAG plasma concentrations were detected, including therapeutic, subtherapeutic, and toxic levels. A standardized molecular method permitted identification of UGT1A9 c.98T>C polymorphism genotypes in the examined renal transplant patients. All individuals of the study group presented the same genotype (c.98TT) for that polymorphism. Thereby, no association between the c.98T>C polymorphism and MPA and MPAG plasma levels could be evaluated, despite different levels of these compounds being observed.

Factors Associated With Delayed Graft Function and Their Influence on Outcomes of Kidney Transplantation.

BACKGROUND: One of the main postoperative complications of kidney transplant is delayed graft function (DGF), which means absence of graft function after transplant or the need for dialysis during the first week post procedure. The occurrence of DGF currently in our hospital is high and has been attributed to a combination of many factors. The aim of this study was to evaluate the factors associated to DGF and their influence in the outcome of kidney transplants. METHODS: Historical cohort of 150 patients transplanted with live or deceased donor kidneys from 2011 to 2013. RESULTS: DGF was associated to time in dialysis and the number of recipient pre-transplant transfusions, donors age, serum creatinine level, use of vasoactive drugs in the donor, distance from place of organ retrieval and transplant center, and duration of cold ischemia time. DGF influenced post-transplantation outcome in regard to length of stay in intensive care, length of hospital stay, acute rejection episodes, and higher creatinine levels at discharge. Patients and graft survival were shorter in the DGF group. CONCLUSIONS: There are multiple factors related to DGF, the most important being those related to donors, and organ storage. The most important factor related to the recipient was the dialysis vintage. We did not find a correlation between DGF and HLA-compatibility. DGF consequences are important, including worse graft function and survival, as well as impact in recipient morbidity and mortality.

Kidney Transplantation at a Southern Brazilian University Hospital: A 35-Year Practice Review.

BACKGROUND: The Nephrology Unit at São Lucas Hospital, a University Hospital in Southern Brazil, has recently reached 35 years since its first kidney transplant. Few centers in the area have made a longitudinal analysis of processes, problems, grafts, and patient survival changes along this time. METHODS: A single-center, retrospective study was performed. Data were separated into different eras, based on the nature of immunosuppression used: pre-cyclosporine (1978-1986), cyclosporine (1987-1997), mycophenolate introduction (1998-2002), new immunosuppressant drugs (2003-2007), and the current period (2008-2013). RESULTS: Between April 27, 1978, and April 30, 2013, 1231 transplants were performed. Significant differences were detected among different eras. The number of transplants has been progressively increasing, to include significantly older recipients (and donors), at a longer waiting list time, receiving organs that underwent longer cold ischemia time (P < .001). Yet, fewer acute rejection episodes and lower incidence of myocardial infarction and post-transplant diabetes mellitus (P < .001) were detected. In the present era, patient survival at 1, 3, and 5 years is 98.3%, 94.6%, and 90.5% respectively, for living donors, and 92.4%, 87.2%, and 80.7% for deceased donors, respectively. Living donor graft survival is 92.2%, 88.7%, and 82.4%, respectively, whereas deceased donor survival is 80.4%, 71.1%, and 63.7%, respectively. CONCLUSIONS: This retrospective analysis has significant historical value. It assembles and depicts a long follow-up period of a transplant series at a single Brazilian center. Throughout the eras, organ and patient survival increased, with fewer rejection episodes or complications, yet with overall decreased graft function.

Does Thymoglobulin Induction Increase Susceptibility to Carbapenem-Resistant Acinetobacter baumannii Sepsis-related Death in Expanded Criteria Donors?

BACKGROUND: Solid organ transplant recipients are susceptible to antibiotic-resistant infections and carbapenem-resistant Acinetobacter baumannii (CRAB) has recently been recognized as a serious complication in solid organ recipients. High mortality rates have been described. METHODS: We retrospectively analyzed 807 transplantations and detected 10 patients who died 24 hours after the diagnosis of septicemia, all with CRAB-positive blood cultures. Recipients were followed up for at least 1 year and were stratified into the following groups: Group 1, patients alive; Group 2, patients that died due to other causes except Acinetobacter infection; and Group 3, patients who died within 24 hours of CRAB diagnosis. RESULTS: CRAB-positive patients died a median of 3.17 (range, 1.81-18.7) months after transplantation. In these patients, expanded criteria donors (ECDs) were more frequent (P < .001), as were the use of anti-thymocyte globulin (ATG) induction (P = .02) and delayed graft function (P = .01). For ECD recipients, death rate from any cause, whether induced with ATG or not, was 25% and 20.6%, respectively (odds ratio [OR], 1.28; confidence interval [CI] 95%, 0.56-2.91; P = .68). The death rate from CRAB-related sepsis was 10.3% and 0% whether receiving ATG or not, respectively (OR, 15.49; CI 95%, 0.87-277.16; P = .014). There was a 25.75-fold increase in the death rate in ECD kidney recipients induced with thymoglobulin and with CRAB-related sepsis. CONCLUSION: Transplants from ECDs and induced with thymoglobulin may be at increased risk of CRAB death in 24 hours when compared with patients with standard donors and induced with thymoglobulin.

Acute Graft Pyelonephritis Occurring up to 30 Days After Kidney Transplantation: Epidemiology, Risk Factors, and Survival.

Acute graft pyelonephritis is a very common infection in renal transplantation. The impact of acute graft pyelonephritis (AGPN) on graft and patient outcome has not yet been established. Eight hundred seventy kidney and kidney-pancreas transplants were retrospectively studied, over last 13 years, to verify occurrence of AGPN in the first 30 days post-transplantation. We found that 112 patients (15.8%) presented post-transplantatiom AGPN up to 30 days after a kidney transplantation. The occurrence was higher in older patients (P = .005) and in those with ureteral stents (P = .06). Escherichia coli was the most frequent microorganism in urine cultures (32%). Ureteral stent (relative risk = 1.7; confidence interval [CI], 1.1-2.5; P = .018) was a major risk factor for AGPN as well as older ages (RR = 1.02; CI 1.01-1.04; P = .001), length of hospitalization stay (RR = 1.01; CI, 1.01-1.02; P < .001), and anti-thymocyte globulin (ATG) induction (RR = 1.6; CI, 1.022-2.561; P = .04). Long-term graft and patient survival was significantly lower in patients with pyelonephritis in the first 30 days after transplantation (OR 1.43; 95% CI, 0.95-2.16; P = .024 and OR 1.77; 95% CI, 1.12-2.80; P = .006, respectively). Acute pyelonephritis in the first 30 days after transplantation is therefore associated with a lower long-term graft and patient survival.

Quality of life and sexuality in chronic dialysis female patients.

Patients in end-stage renal disease (ESRD) present reduced quality of life (QOL) and impaired sexual function. Previous studies have mostly addressed male sexual dysfunction. This was a cross-sectional controlled study that applied a general and the World Health Organization Quality of Life-bref questionnaires to assess demographic, marital, and sexual conditions, and QOL in 86 healthy women aged 18 or more years (Group 1), and 38 female ESRD patients on dialysis for at least 2 months (Group 2). The effect of several explanatory variables upon QOL components was estimated. Quality of life was lower in Group 2 -- overall, and on physical and environment domains. To undergo dialysis and to be poorly educated negatively affected the QOL. Yet age, a stable marital relationship or being sexually active had no effect. Female patients undergoing chronic dialysis had lower QOL and were significantly more sexually dysfunctional than comparable healthy women. Decline in sexual function had no effect on the QOL.

Incidence of delayed graft function in cadaveric kidney transplants in Brazil: a multicenter analysis.

To evaluate the frequency of delayed graft function (DGF) in kidney transplant centers in Brazil, we sent a questionnaire requesting information on the number of cadaveric donor kidney transplants performed during the years 2000, 2001, and 2002, the number of early nonfunctioning grafts, and the number of patients on dialysis during the first posttransplant week with subsequent recovery. Among all centers performing more than 50 kidney transplants during the last year of evaluation, 6, performing 612 cadaveric kidney transplants during the study period, replied to the questionnaire. Sixty procedures (9.7%) resulted in nonfunctioning grafts, while 312 (55.6%) patients required dialysis during the first Ptx week: 216 (53.9%) in 2000, 189 (62.3%) in 2001, and 216 (51.6%) in 2002. The frequency of DGF during the study period was higher than that noted by several previous foreign studies. To better evaluate the possible causes of this finding, a more extensive and focused study is warranted.

Bag exchange in continuous ambulatory peritoneal dialysis without use of a face mask: experience of five years.

This article describes our five-year experience of continuous ambulatory peritoneal dialysis (CAPD) with bag exchanges performed without use of a face mask. The study took place in the renal unit at a university hospital. All patients admitted to the CAPD program from February 1995 to March 2000 were trained to perform bag exchanges without use of a face mask. Occurrence of peritonitis episodes was the outcome of interest. We evaluated 94 patients (52 women, 42 men) with a mean age of 48 +/- 21 years and a total follow-up of 50,502 patient-days. During that time, 79 episodes of peritonitis occurred in 46 patients, for a peritonitis rate of 0.57 episodes/year. The most frequently isolated micro-organisms were Staphylococcus epidermidis in 20 patients (25.3%) and S. aureus in 11 patients (13.9%). Renal transplantation was the major cause of drop-out [23 patients (43.4%)], followed by peritonitis [14 patients (26.4%)], death due to cardiovascular complications [9 patients (17.0%)], loss of ultrafiltration [2 patients (3.8%)], and other causes [5 patients (9.4%)]. The probability of being free of peritonitis at 12 months was 0.60, and at 60 months, 0.37. Peritonitis rates during the study period were not different from those reported by other centers, supporting the hypothesis that routine use of a face mask during CAPD bag exchange may be unnecessary.

Peritonitis prevention in CAPD: to mask or not?

OBJECTIVE: To assess the efficacy of wearing a face mask to prevent peritonitis during continuous ambulatory peritoneal dialysis (CAPD) bag exchange. SETTING: Renal unit at a university hospital. PATIENTS: Two groups of patients on CAPD were compared: those performing bag exchange with (n = 24) and those without a face mask (n = 40). OUTCOMES: Occurrence of first episode of peritonitis and total number of episodes. RESULTS: No difference was found between groups with respect to probability of developing the first episode of peritonitis (p = 0.757). Patients holding university degrees had evidence of protection, with borderline significance [relative risk (RR) 0.52; confidence interval (CI) 95%, 0.23 -1.18; p= 0.109]. Cox's proportional hazard regression analysis also demonstrated a significant protective factor for patients with university level education (RR 0.42; Cl 95%, 0.18 - 0.98; p = 0.04). Incidence of peritonitis was not significantly different between groups: with-mask group had 1.0 episode/year, and without-mask group had 0.94 episodes/year. Staphylococcus epidermidis was the most commonly identified agent. Staphylococcus aureus was found more frequently in the with-mask group (p = 0.003). Peritonitis due to Streptococcus viridans and Enterococci were detected only in the without-mask group. CONCLUSION: The current study suggests that routine use of face masks during CAPD bag exchanges may be unnecessary and could be discontinued.