Tacrolimus Versus Cyclosporine for Adult Lung Transplant Recipients: A Meta-Analysis

Background

Tacrolimus and cyclosporine are the 2 major immunosuppressants for lung transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this meta-analysis of randomized controlled trials (RCTs) was to compare the beneficial and harmful effects of tacrolimus and cyclosporine as the primary immunosuppressant for lung transplant recipients.

Methods

We conducted searches of electronic databases and manual bibliographies. We performed a meta-analysis of all RCTs comparing tacrolimus with cyclosporine as primary immunosuppression for lung transplant recipients. Extracted, pooled data for mortality, acute rejection, withdrawals, and adverse events were analyzed using Mantel-Haenszel tests with a random effects model.

Results

Three RCTs including 297 patients were assessed in this study. Mortality at 1 year or more was comparable between lung recipients treated with tacrolimus and cyclosporine (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.42-2.10; P = .88). Tacrolimus-treated patients experienced fewer incidences of acute rejection (MD = −0.14; 95% CI, −0.28 to −0.01; P = .04). Pooled analysis showed a trend toward a lower risk of bronchiolitis obliterans syndrome (BOS) among tacrolimus-treated patients, although it did not reach significances (OR, 0.53; 95% CI, 0.25-1.12; P = .10). Fewer patients stopped tacrolimus than cyclosporine (OR, 0.12; 95% CI, 0.03-0.48; P = .003). The rate of new-onset diabetes was higher among the tacrolimus group (OR, 3.69; 95% CI, 1.17-11.62; P = .03). The incidence of hypertension and renal dysfunction were comparable in these 2 groups (OR, 0.24; 95% CI, 0.03-1.70; P = .15; and OR, 1.67; 95% CI, 0.70-3.96; P = .25, respectively). There was a trend toward lower risk of malignancy in tacrolimus-treated patients, although it did not reach significance either (OR, 0.19; 95% CI, 0.03-1.13; P = .07). The incidence of infection was comparable in these 2 groups (MD = −0.29, 95% CI, −0.68 to 0.11; P = .16).

Conclusion

Using tacrolimus as primary immunosuppressant for lung transplant recipient resulted in comparable survival and reduction in acute rejection episodes when compared with cyclosporine.     

Heat Shock Protein Polymorphism Predisposes to Urinary Tract Malformations and Renal Transplantation in Children

Background

Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases.

Objective

To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation.

Patients and Methods

Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children.

Results

Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms.

Conclusion

Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.     

Tolerance of enteric-coated mycophenolate sodium in combination with calcineurin inhibitor in kidney transplant recipients: Polish experience

Introduction

Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the incidence of gastrointestinal adverse effects. This multicenter observational study was designed to evaluate the safety profile and drug tolerance in kidney transplant recipients.

Methods

Three hundred adult kidney recipients (median age 48 years) were enrolled over 3 years to receive EC-MPS de novo (n = 175), as a switch from azathioprine (n = 62) or mycophenolate mofetil MMF (n = 63); in combination with calcineurin inhibitor. Drug doses, serum creatinine, estimated glomerular filtration rate (eGFR), as well as drug tolerance, patient and physician evaluation of therapy (on a 4-point scale) were recorded at enrollment and followed over 28 weeks. We modeled the probability of the highest level (ie, best result) of the categorical outcome variable.

Results

Two hundred seventy-three patients completed the study (91%). In the pooled study group (1) best drug tolerance was expected more frequently with tacrolimus versus cyclosporine (odds ratio [OR] 2.12, P < .05); (2) best physician evaluation, with earlier EC-MPS introduction (OR for 4-week delay: 0.99, P < .03) and higher eGFR (OR for 5 mL/min increase: 1.21, P < .01). Among the EC-MPS de novo administrations group: (1) best drug tolerance was expected more frequently with coadministered tacrolimus versus cyclosporine (OR 3.14, P < .02); (2) best patient evaluation, with higher eGFR (OR for 1 mL/min increase: 1.04, P < .04); and (3) best physician evaluation, with higher eGFR (OR for 1 mL/min increase: 1.04, P < .001) and earlier EC-MPS introduction (OR for 4-week delay: 0.99, P < .03). In the conversion from MMF to EC-MPS group: (1) best drug tolerance was expected less frequently with coadministered cyclosporine versus tacrolimus (OR 0.05, P < .04) and more frequently with younger recipients (OR .001, P < .04); (2) best physician evaluation was expected more frequently with lower EC-MPS dose (OR for 360-mg dose increase: 0.4, P < .01) and with higher eGFR (OR for 5 mL/min increase: 1.42, P < .002). Adverse events were reported among 49/300 patients (16 serious adverse events).

Conclusions

EC-MPS was tolerated better by younger kidney recipients, when combined with tacrolimus versus cyclosporine, and when introduced earlier after transplantation. EC-MPS tolerance decreased gradually with renal function deterioration.     

Mycophenolate mofetil monotherapy in liver transplantation

Aim

Calcineurin inhibitors (CI) are associated with significant morbidity in transplant recipients. The aim of this study was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in liver transplantation (LT).

Methods

We analysed 32 patients (24 males, 8 female, of mean age 55.7 years) who underwent LT between 1994 and 2003. In 29 patients immunosuppressive therapy was cyclosporine; in three patients it was tacrolimus. Eleven patients were submitted for LT due to hepatitis B cirrhosis; eight for hepatitis C cirrhosis, six for alcoholic cirrhosis, and seven for other diseases. In these patients, MMF was added gradually, simultaneously reducing the dosage of CI up to complete withdrawal. We considered the efficacy (decrease in serum creatinine) and the incidence of complications (acute and chronic rejection, leukopenia, diarrhea).

Results

Patients were converted to MMF after a median of 50 months after LT. MMF monotherapy was started after a median of 9 months in association with CI. Indications for switch to MMF monotherapy were adverse effects of CI (renal disfunction in 30 patients) and de novo tumoral evidence after LT in two patients. Median dosage of MMF was 750 mg twice daily (500-1500 mg). There was a statistically significant decrease in serum creatinine levels (2.02-1.7 mg/dL; P = .0001). Side effects were: leukopenia in five of 32 patients (15.6%), diarrhea in four of 32 patients (12.5%), and one acute rejection.

Conclusion

MMF monotherapy improved renal function and was not associated with a significant risk of allograft rejection. Side effects were mild with dose regimens up to 750 mg twice daily.     

Disparity in limb-salvage surgery among sarcoma patients

Background

Recent studies have shown that aggressive preoperative radiation increases the likelihood of limb salvage in sarcoma patients.

Method

The Surveillance, Epidemiology and End Results database was used to run an adjusted logistic regression for the receipt of cancer-directed treatment modalities.

Results

Of patients with specific surgical procedures recorded (n = 2,104), 86.0% had undergone a limb-sparing procedure. On bivariate analysis, African American patients were less likely to receive a limb-sparing procedure than white patients (80.4% vs 86.9%; P = .02). On multivariate analysis, African Americans were significantly more likely to receive preoperative radiation (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.22-4.40; P = .011), yet this did not translate into an increase in limb salvage (OR, .67; 95% CI, .42-1.08; P = .10). Limb salvage significantly increased for all groups in 2001 and after (OR, 2.75; 95% CI, 1.55-4.88; P = .001) without a decrease in survival. For those with tumors greater than 4 cm, there was a trend away from limb salvage for African Americans (OR, .59; 95% CI, .32-1.07; P = .08).

Conclusions

Our results of an increase in limb-salvage surgeries after 2001 without a decrease in survival support previous studies. The trend away from limb salvage for African Americans cannot be answered by this study.     

Tinnitus in the elderly: Profile, correlates, and impact in the Nigerian Study of Ageing

Objective

To determine the prevalence and correlates of tinnitus among community elderly and its impact on their quality of life.

Study Design

Longitudinal cohort.

Setting

Yoruba-speaking communities in Nigeria.

Subjects and Methods

Face-to-face interviews of 1302 subjects 65 years or older selected by the use of a multistage stratified sampling of households. Subjects were assessed for subjective tinnitus, chronic health conditions, functional impairment, and quality of life by use of the brief version of the World Health Organization quality of life instrument.

Results

Tinnitus was reported in 184 (110 female and 74 male subjects), giving a prevalence of 14.1 percent (SE = 0.49). Gender, age, economic status, educational level, residence, smoking, and alcohol consumption were not significantly associated with tinnitus. Univariate analysis revealed a history of recurrent otitis media (odds ratio [OR] = 4.5, 95% confidence interval [95% CI] 3.1-6.6, P = 0.01), head injury (OR 3.4, 95% CI 2.1-5.6, P = 0.01), rhinosinusitis (OR 2.4, 95% CI 1.5-4.0, P = 0.01), dizziness (OR 2.1, 95% CI 1.4-3.1, P = 0.01), and hypertension (OR 1.7, 95% CI 1.0-2.7, P = 0.05) as significant correlates. However, in multivariate analysis, only a history of otitis media and of head injury remained significant. Compared with those without, persons with tinnitus had a more negative perception of their overall health and a poorer quality of life as well as twofold likelihood to experience impairment in both activities of daily living and instrumental activities of daily living.

Conclusion

Tinnitus is common among elderly Nigerians and is associated with treatable health conditions, such as otitis media, rhinosinusitis, head injury, and hypertension. Its association with functional impairment and reduced quality of life highlights the need for inclusion in any comprehensive health care for the elderly.     

Incidence and risk factors for posttransplant subcapsular cataract: a long-term retrospective cohort study

Background

The occurrence and risk factors for posterior subcapsular cataract (PSC) after renal transplantation have received little attention.

Objectives

To analyze the cumulative incidence of PSC after renal transplantation and identify risk factors for the development of PSC.

Methods

Retrospective review of the records of the patients who underwent kidney transplantation between May 1986 and December 2008.

Results

We included 94 renal transplant recipients who showed PSC incidence at 5, 10, and 15 years of 3.5%, 40.5%, and 50.1%, respectively. Cumulative incidence of PSC during the follow-up was 37.2%. On multivariate analysis, age, body mass index (BMI) and cumulative corticosteroid dose were significantly associated with PSC. Recipient age above 50 years (hazard ratio [HR] = 2.88, 95% confidence interval [CI]: 1.42-5.83; P = .003), BMI above 25 kg/m² (HR = 2.28, CI: 1.09-4.78; P = .029), and prednisolone dose above 3 mg/kg/mo (HR = 7.79, CI: 3.34-18.99; P < .001) were independent risk factors for PSC. Diabetes, renal diagnosis, duration, and type of dialysis and posttransplant immunosuppressive regimen did not influence the occurrence of PSC.

Conclusion

The risk of PSC was low during the first years after transplantation reaching a plateau at 15 years posttransplantation. Among the risk factors for PSC, cumulative corticosteroid dose and body weight were the only modifiable risk factors.     

Heart transplantation under cyclosporine or tacrolimus combined with mycophenolate mofetil or everolimus

Objective

In this study, we examined whether cyclosporine was effective when combined with everolimus in clinical heart transplantation (HT).

Patients and Methods

From August 2004 to July 2007, 108 adult patients underwent primary HT. The main exclusion criteria were: donors >60 years; cold ischemia times >6 hours; recipients of multiorgan transplantation or a previous transplantation; and panel-reactive antibodies ≥25%. The cyclosporine plus everolimus regimen (group CE, n = 32) was suggested first; upon refusal or if the recipient or donor was positive for hepatitis B surface antigen or PCR + hepatitis C infection, then patient was randomly assigned to success cyclosporine plus mycophenolate mofetil (MMF; group CM, n = 24) or tacrolimus plus MMF (group TM, n = 25). All patients underwent similar operative procedures and postoperative care with protocol endomyocardial biopsies.

Results

No 30-day mortality was noted in any group. The efficacy failure rates were 3%, 25%, and 16% in groups CE, CM, and TM, respectively (P = .04 between groups CE and CM). The 1-year survivals were 96.7% ± 18.1%, 89.7% ± 29.8%, and 81.0% ± 35.5% for groups CE, CM, and TM, respectively (P = .04 between groups CE and TM). The 3-year survival rates were 91.9% ± 28.3%, 79.8% ± 46.0%, and 81.0% ± 35.5% in groups CE, CM, and TM, respectively.

Conclusions

The 3 immunosuppressive regimens offered good efficacy after HT. The cyclosporine plus everolimus regimen showed a significantly better result with less efficacy failure (compared with cyclosporine plus MMF: 3% vs 25%) and better 1-year survival compared with tacrolimus plus MMF: 96.7% vs 81.0%.     

The efficacy and safety of high-dose mizoribine in ABO-incompatible kidney transplantation using anti-CD20 and anti-CD25 antibody without splenectomy treatment

Background

Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy.

Methods

Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12).

Results

The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant).

Conclusions

We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.     

Improvement of Renal Function After Conversion to Mycophenolate Mofetil Combined With Low-Level Calcineurin Inhibitor in Liver Transplant Recipients With Chronic Renal Dysfunction

Introduction

Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non-nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction.

Patients and Methods

We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 ± 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4-1.7 mg/dL (group I; n = 41); 1.8-2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5-2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria.

Results

Creatinine values after conversion were 1.4 ± 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected.

Conclusion

Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results.     

Clinical variables and neuromonitoring information (intracranial pressure and brain tissue oxygenation) as predictors of brain-death development after severe traumatic brain injury

Background and purpose

The aim of this study was to ascertain the role of clinical variables and neuromonitoring data as predictors of brain death (BD) after severe traumatic brain injury (TBI).

Patients and methods

This prospective observational study involved severe TBI patients admitted to the intensive care unit between October 2009 and May 2011. The following variables were recorded: gender, age, reference Glasgow Coma Scale after resuscitation, pupillary reactivity, prehospital hypotension and desaturation, injury severity score, computed tomography (CT) findings, intracranial hypertension, and low brain tissue oxygenation (Pti02) levels (<16 mm Hg), as well as the final result of BD.

Results

Among 61 patients (86.9% males) who met the inclusion criteria, the average age was 37.69 ± 16.44 years. Traffic accidents were the main cause of TBI (62.3%). The patients at risk of progressing to BD (14.8% of the entire cohort) were those with a mass lesion on CT (odds ratio [OR] 33.6; 95% confidence interval [CI]: 3.75-300.30; P = .002), altered pupillary reaction at admission (OR 25.5; 95% CI: 2.27-285.65; P = .009), as well low Pti02 levels on admission (OR 20.41; 95% CI: 3.52-118.33; P < .001) and during the first 24 hours of neuromonitoring (OR 20; 95% CI: 2.90-137.83; P < .001). Multivariate logistic regression showed that a low Pti02 level on admission was the best independent predictor for BD (OR 20.41; 95% CI: 3.53-118.33; P = .001).

Conclusions

Clinical variables and neuromonitoring information may identify TBI patients at risk of deterioration to BD.     

Induction With and Without Antithymocyte Globulin Combined With Cyclosporine/Tacrolimus-Based Immunosuppression in Renal Transplantation: A Meta-analysis of Randomized Controlled Trials

Objective

The objective of this study was to conduct a meta-analysis of randomized controlled trials (RCT) to compare the effectiveness and safety of induction with and without antithymocyte globulin (ATG) combined with cyclosporine/tacrolimus-based immunosuppression in renal transplantation.

Methods

Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of RCTs, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality, and then extracted data. Data were extracted for patient and graft survival, acute rejection, the incidence of Banff, cytomegalovirus (CMV) infection, leukopenia, and thrombocytopenia. Dichotomous outcomes were reported as relative risk (RR) with 95% confidence intervals (CI).

Results

Four RCTs (892 patients) were identified. The data showed that induction with ATG was more beneficial than no induction with ATG to reduce the incidence of chronic rejection (RR 0.70; 95% CI, 0.57-0.84) and acute rejection within 6 months (RR 0.68; 95% CI, 0.49-0.96) and at 12 months (RR 0.67; 95% CI, 0.50-0.89) as well as Banff II episodes (RR 0.53; 95% CI, 0.30-0.91), but increased the incidences of CMV infection (RR 1.61; 95% CI, 1.27-2.04) and leukopenia (RR 3.88; 95% CI, 2.80-5.38) and thrombocytopenia (RR 2.92; 95% CI, 1.77-4.04). There was no statistical difference between patient or graft survival rates at 6 and 12 months, as well as the incidences of Banff III or Banff I after transplantation.

Conclusion

Based on available data induction with ATG was more efficient to reduce the rate of acute rejection episodes and chronic rejection responses after renal transplantation, but was associated with increased side effects, particularly CMV infections. It is important to provide the most benefit for an individual patient.     

Hepatitis C and the incidence of diabetes mellitus after renal transplant: influence of new immunosuppression protocols

Background

Hepatitis C has been associated with an increased incidence of diabetes mellitus (DM) following renal transplantation (RT).

Methods

Patients who underwent RT between 1985 and 2001 were excluded if they showed DM prior to RT, graft survival of less than 90 days, and unknown anti-HCV status (n = 15). Two groups (G1 and G2) were distinguished according to the immunosuppressive regimen: G1 (transplanted 1985-1996) received steroids, azathioprine, and cyclosporine (n = 330), whereas G2 (1997-2000) received new drugs in several combinations (MMF in 87% and/or tacrolimus in 35% [n = 240]). Patients with HCV antibodies pre- and/or post-RT were considered HCV-positive. Post-RT DM requiring prolonged treatment with oral antidiabetics or insulin (>1 month) was assessed using Kaplan-Meier curves and Cox analysis.

Results

G2 patients were significantly older, had a greater body mass index (BMI), and suffered significantly less from acute rejection episodes during the first year than G1 patients. Furthermore, fewer required maintenance steroids. HCV-positivity was more common in G1 than in G2 (n = 96, 29.1% vs n = 27, 11.3%). Six G2 patients were successfully treated with interferon pre-RT, achieving negative PCR-HCV status (maintained post-RT). DM incidence at 4 years was similar in G1 and G2 (8.8% and 8.2%). G1 HCV-positive patients showed a greater risk of developing DM than HCV-negative patients (28.0% vs 6.2% at 10 years; P = .001). In G1, multivariate analysis showed that age, BMI, and HCV-positivity were significant risk factors predicting DM (relative risk, 5.7; 95% confidence interval 2.7-12). In G2 patients, HCV was not associated with an increased risk of DM; in the multivariate analysis only age appeared to be a risk factor.

Conclusions

The reported relationship between hepatitis C and post-RT DM was not observed among patients receiving new immunosuppressive treatments. Confirmation of this finding requires extended follow up. The reduced use of steroids and effective pre-RT use of interferon may also be responsible for the benefit.     

Antioxidant enzymes, presbycusis, and ethnic variability

Objective

A proposed mechanism for presbycusis is a significant increase in oxidative stress in the cochlea. The enzymes glutathione S-transferase (GST) and N-acetyltransferase (NAT) are two classes of antioxidant enzymes active in the cochlea. In this work, we sought to investigate the association of different polymorphisms of GSTM1, GSTT1, and NAT2 and presbycusis and analyze whether ethnicity has an effect in the genotype-phenotype associations.

Study Design

Case-control study of 134 DNA samples.

Setting

University-based tertiary care center.

Subjects and Methods

Clinical, audiometric, and DNA testing of 55 adults with presbycusis and 79 control patients with normal hearing.

Results

The GSTM1 null genotype was present in 77 percent of white Hispanics and 51 percent of white non-Hispanics (Fisher's exact test, 2-tail, P = 0.0262). The GSTT1 null genotype was present in 34 percent of control patients and in 60 percent of white presbycusis subjects (P = 0.0067, odds ratio [OR] = 2.843, 95% confidence interval [95% CI] = 1.379-5.860). The GSTM1 null genotype was more frequent in presbycusis subjects, i.e., 48 percent of control patients and 69 percent of white subjects carried this deletion (P = 0.0198, OR = 2.43, 95% CI = 1.163-5.067). The NAT2*6A mutant genotype was more frequent among subjects with presbycusis (60%) than in control patients (34%; P = 0.0086, OR = 2.88, 95% CI = 1.355-6.141).

Conclusion

We showed an increased risk of presbycusis among white subjects carrying the GSTM1 and the GSTT1 null genotype and the NAT*6A mutant allele. Subjects with the GSTT1 null genotypes are almost three times more likely to develop presbycusis than those with the wild type. The GSTM1 null genotype was more prevalent in white Hispanics than in white non-Hispanics, but the GSTT1 and NAT2 polymorphisms were equally represented in the two groups.     

Prospective Clinical Trial Comparing Two Immunosuppressive Regimens, Tacrolimus and Mycophenolate Mofetil Versus Everolimus and Low-Dose Cyclosporine, in De Novo Renal Transplant Recipients: Results at 6 Months Follow-up

Objective

The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus.

Patients and Methods

Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids.

Results

At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 ± 38 vs EVL 250 ± 55 mg/dL; P < .003).

Conclusions

This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.     

Nepalese patients' anxiety and concerns before surgery

Study Objective

To determine the changes in anxiety level and need for information at three different time points before surgery.

Design

Prospective observational study.

Setting

Ward (T₁), preoperative holding area (T₂), and operating room (T₃) of a university hospital.

Patients

201 adult, ASA physical status 1 and 2 patients scheduled for elective operations.

Measurements

Level of anxiety and need for information about surgery and/or anesthesia were assessed with the Amsterdam Preoperative Anxiety and Information Scale (APAIS) three times before the start of surgery: in the ward, the preoperative holding area, and the operating room.

Results

The psychometric characteristics of the APAIS were similar to its original Dutch version. The frequency of patients with high preoperative anxiety peaked at the preoperative holding area. The median score on need for information decreased from T₁ [4; interquartile range (IR) 2-5] to T₂ (3; IR 2-4) (P < 0.005) and T₃ (3; IR 2-4) (P < 0.01). While the mean anxiety scores for anesthesia were significantly (P < 0.001) higher than for the surgical procedure at all three time points, when patients were still in the ward their need for information about their surgical procedure was significantly (P < 0.05) greater than it was for the anesthesia. Patients who were more desirous of information also were more anxious (P < 0.001). Predictors of high anxiety were female gender [odds ratio (OR) 4; 95% confidence interval (CI) 1.09-14.94] and need for general anesthesia (OR 7.1; 95% CI 0.93-54.98). The characteristics, general anesthesia (OR 3.3; 95% CI 1.1-10.0), younger age (≤30 yrs; OR 2.9; 95% CI 1.3-6.4), education (>12 yrs; OR 2.6; 95% CI 1.2-5.4), and no previous surgery (OR 2.6; 95% CI 1.2-5.5), correlated with greater need for information.

Conclusion

The frequency of anxious patients is variable at different time points before surgery. The factors correlating with anxiety before surgery are nonmodifiable. Providing information to those individuals is the only modifiable option.     

Association of the metabolic syndrome and long-term renal function in kidney donors

Background

Metabolic syndrome (MetS) may represent risk factor for long-term renal function of kidneys from living donors. The aim of this study was to evaluate the impact of MetS on renal function in donors.

Methods

Data regarding the presence or absence of MetS and renal function, as assessed by estimated glomerular filtration rate (eGFR) were obtained from 140 kidney donors before nephrectomy (BN) and at follow-up (AF). Donors were divided into those with (group 1; n =28) versus without MetS (group 2; n = 112).

Results

Comparing the groups, we observed a significantly greater reduction in eGFR among the group with MetS BN versus AF 27.5% (19.3-33.0) versus 21.4% (9.6-34.1 P = .02) respectively using a Cox regression model, including age, gender, serum uric acid, body mass index (BMI), and basal eGFR, MetS BN (hazard ratio = 2.2; 95% confidence interval [CI], 1.21-4.01; p = .01) was an independent factor associated with a greater risk of a-eGFR <70 mL/min/1.73 m² at follow-up (P < .001). Additionally, age (hazard ratio = 1.03%; 95% CI, 1.01-1.06; P < .001), and female gender (hazard ratio = 1.86; 95% CI, 1.03-3.36; P = .03) were associated with a greater decrease in eGFR. Individuals with MetS BN showed a GFR <70 mL/min/1.73 m² at significantly shorter follow-up time (5.6 ± 0.8 years) versus persons without MetS (12.8 ± 1.0 years; P = .001)

Conclusion

Kidney donors with MetS BN experiment a significantly greater decrease in eGFR at follow-up.     

Inflammation, metalloproteinases, and growth factors in the development of carotid atherosclerosis in renal transplant patients

Background

Cardiovascular disease is the leading cause of death in renal transplant (RT) patients. Both traditional and emerging risk factors, some of which are controversial, have been described in the pathogenesis of cardiovascular disease. Carotid ultrasound (CUS) is considered to be an excellent diagnostic tool for subclinical atherosclerosis.

Objective

To evaluate the relationship between biomarkers of inflammation, growth factors, metalloproteinases, and the development of subclinical atherosclerosis diagnosed by using CUS.

Methods

We studied 93 RT patients (aged 54 ± 12 years; 67.9% men; 13.5% with pre-RT diabetes mellitus). The following biomarkers were determined in the patients' blood hours before RT: C-reactive protein (CRP) and serum amyloid A using nephelometry; interleukin (IL) 2, 6, 8, and 10 and soluble IL-2 receptor, tumor necrosis factor (TNF) α, vascular endothelial growth factor (VEGF), epidermal growth factor, and monocyte chemotactic peptide using chemoluminescence; and pregnancy-associated plasma protein (PAPP)A using ELISA. A CUS was carried out during the first month after RT.

Results

Carotid intima-media thickness (IMT) was elevated in 51% of the patients, and 50.5% of the patients had atherosclerotic plaque. Both plaque (P = .004) and IMT (P = .001) correlated with age, and the increase of IMT was progressive, on both the left and the right side. Pre-RT CRP, IL-8, TNF-α, VEGF, MCP-1, and PAPP-A were significantly more elevated in patients with plaque. In the multivariate analysis adjusted for clinical variables, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.10; P = .04), CRP (OR, 7.5; 95% CI, 2.05-27.3; P = .002), IL-8 (OR, 4.73; 95% CI, 1.27-17.6; P = .02), and PAPP-A (OR, 4.45; 95% CI, 1.22-16.2; P = .023) were independent markers of the presence of plaque.

Conclusions

Age, CRP, IL-8, and PAPP-A, and not growth factors, are markers of carotid atheromatous plaque in RT patients.