Can uric acid blood levels in renal transplant recipients predict allograft outcome?

BackgroundHyperuricemia is common after renal transplantation, especially in those receiving calcineurin inhibitors. Little, however, is known about the relationship between uric acid (UA) levels and allograft outcome.MethodsWe conducted a retrospective single-center analysis (N = 368) in order to assess UA blood levels post-transplant association with allograft outcome. For this study, a median serum UA level of all measured UA levels from 1 month to 1 year post renal transplantation was calculated.ResultsPatients were divided into 2 groups based on the median UA level measured between 1 and 12 months post-transplant. Those with median UA level ≥ 7 and ≥ 6 mg/dL (N = 164) versus median UA level < 7 and < 6 mg/dL for men and women respectively (N = 204) had lower GFR values at 1, 3 and 5 years posttransplant (mean GFR ± SD of 43.4 ± 20.6 and 58 ± 19.9 at 3 years post-transplant, p < 0.001). In multivariate models, UA levels were no longer significantly associated with renal allograft function. In a multivariate cox proportional hazard model, UA level was found to be independently associated with increased risk for death-censored graft loss (HR of 1.3, 95% CI 1.0–1.7, p < 0.05 for every increase of 1 mg/dL in UA level).ConclusionHyperuricemia was found to be associated with increased death- censored graft loss but not with allograft function. Increased UA levels were not found to be an independent predictor of long-term allograft function despite the known association of hyperuricemia with the progression of cardiovascular and renal disease.     

Sex and the pregnant kidney: does renal allograft gender influence gestational renal adaptation in renal transplant recipients?

BACKGROUND: Animal work indicates that ovarian hormones are important in initiating and maintaining enhanced renal function in pregnant rats and that a renal response resembling pregnancy can be provoked in male rats exposed to pregnancy hormones. Women becoming pregnant following renal transplantation provide an opportunity to compare the functional response of male and female allografts to the gestational endocrine environment. METHODS: This retrospective observational study included 20 renal allograft recipients (age 29.7 +/- 2.4 yrs) (mean +/- SE) who had 22 pregnancies beyond 24 weeks (gestation at delivery 35.5 +/- 0.6 weeks). Donor characteristics, transplant details, renal follow-up data, and information about pregnancy and allograft function were obtained from hospital notes. RESULTS: Thirteen women received male allografts (donor age 30.0 +/- 3.9 years) (mean +/- SEM) and 7 women, female allografts (donor age 45.1 +/- 6.0 years) (P = .04). There were no significant differences between the two groups in maternal recipient age, transplant to pregnancy interval, antenatal complications, pregnancy outcome, or postnatal graft function. Compared to prepregnancy values serum creatinine (SCr) decrements and augmented 24-hour creatinine clearance (CrCl) were observed over the first trimester in both male and female allografts: Delta CrCl from 106.8 +/- 13.2 mL/min to 114.4 +/- 11.4 mL/min (35.6% increase) and 71.8 +/- 7.4 to 89.5 +/- 11.3 mL/min (24.7% increase), respectively, and Delta SCr from 90.1 +/- 5.4 micromol/L to 73.6 +/- 6.6 micromol/L (17.8% decrease) and 99.8 +/- 9.7 micromol/L to 78.0 +/- 5.7 micromol/L (13.5% decrease), respectively. Differences between the two groups did not reach statistical significance. CONCLUSIONS: Donor gender and/or age do not appear to influence the gestational renal response in kidney transplant recipients.     

Is there any effect of compliance on clinical parameters of renal transplant recipients?

Noncompliance with regard to diet, medications and routine physician visits is frequently observed among some patient groups. This results in late graft dysfunction and behavior loss. In the present study, we defined compliance as attendance at 80% or more outpatient visits. The study included 63 cadaveric and 158 living-related renal transplant recipients namely, 150 men and 76 women of 8 to 70 years of age (median 38 +/- 12) who were operated between 1986 and 2001. Demographic data, number of visits attended per month, cigarette smoking, and alcohol intake were probed with a questionnaire that was delivered to the patients, 8 of whom died; hemophagocytic syndrome (n = 4), cardiovascular disease (n = 2), Kaposi' sarcoma (n = 1), and cerebrovascular bleeding (n = 1). Twenty-three patients had lost their graft. Compliance among men was lower than among women, a result that trended toward statistical significance (P =.087). Compliance was not related to marital status (P =.297), but tended to increase with educational background (P =.059). Graft loss (P =.546) and aging (P =.509) were not related to compliance. There was no relationship between compliance and mortality rate (P =.526). Interestingly, living-related kidney transplant recipients showed lower compliance than cadaveric kidney recipients, a result that was statistically significant (P =.04). Noncompliance was also related to cigarette smoking during the pre- and posttransplant periods (P =.008 and P =.03, respectively), as well as alcohol intake (P =.000). In conclusion, male gender and living-related donation are related to noncompliance, but (in contrast with literature) not young age, graft loss, or mortality. Compliance increases with educational status of the patients. Smoking and alcohol intake are closely related to noncompliance.     

Does pregnancy increase graft loss in female renal allograft recipients?

Background  

Although many transplanted women who were previously infertile can conceive during the posttransplant period, maternal and fetal complications are likely. We evaluated the effect of pregnancy after renal transplantation in this study.     

Is there additional effect of MTHFR C677T mutation on lipid abnormalities in renal allograft recipients?

BACKGROUND: The MTHFR C677T mutation and elevated atherogenic lipoprotein levels are known as cardiovascular risk factors in patients with renal transplantation treated with cyclosporine (CsA). The aim of the present study was to eveluate the contribution of MTHFR C677T mutation to the risk of dyslipidemia in renal transplant recipients. We also studied the effect of the MTHFR-C677 T genotype on transplant survival. METHODS: The study included 29 nondiabetic renal transplant recipients and 27 healthy controls. MTHFR C677T genotypes were determined by PCR and RFLP techniques. Biochemical parameters were measured in a computerized autoanalyzer. RESULTS: In the patient group, the distribution of the CC, CT, and TT genotypes was 44.8% (n = 13), 37.9% (n = 11), and 17.2% (n = 5), respectively. The frequencies of the C and T alleles were 0.64 and 0.36, respectively. Subjects with the T allele had the highest levels of TC (P <.05) and LDL-C (P <.05); subjects with the CC genotype had the lowest. CONCLUSIONS: We observed that the MTHFR T allele has an unfavorable effect on serum lipid profile, leading to a rise in the total and LDL cholesterol concentrations. Thus, we believe that MTHFR C allele has a protective effect and MTHFR T allele has a detrimental effect on the serum lipid profile.     

A role for chronic parvovirus B19 infection in liver dysfunction in renal transplant recipients?

BACKGROUND: Clinically, liver dysfunction in renal transplant recipients is related to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The contribution of parvovirus B19 (B19) to liver disease in renal transplant recipients has not been studied. Here we present the association of liver dysfunction with or without the coinfection of B19, HBV, and HCV after renal transplantation. METHODS: We used enzyme-linked immunosorbent assay to identify B19, HBV, and HCV infections in serum samples taken from 144 renal transplant recipients before transplantation and at 12 and 24 months after transplantation. After each patient had fasted for 12 hr, blood was taken for measurement of aspartate aminotransferase and alanine aminotransferase monthly for at least 6 months. RESULTS: Liver dysfunction developed at the significantly higher incidence of 47% in the anti-HCV(+) patients compared with 6% in the noninfected group (P<0.0001). HBV infection had no impact on the incidence of liver dysfunction in renal transplant recipients. A higher incidence of liver dysfunction was found in 42% of B19 IgG(+)IgM(-) group patients compared with 13% of the B19 IgG(+)IgM(+) group (P=0.0051) and 9.5% of the B19 IgG(-)IgM(-) group (P=0.0003). A B19 polymerase chain reaction (PCR) assay revealed significantly higher liver dysfunction in 29% of B19 PCR(+) group patients compared with 13.6% of B19 PCR(-) patients (P=0.0419). Patients who were anti-HCV(+) and B19 PCR(+) had a significantly higher incidence of liver dysfunction than B19 PCR(-) patients (P=0.002). CONCLUSIONS: Chronic B19 infection and HCV infection, both separately and in combination, increase the incidence of liver dysfunction in renal transplant recipients. HBV infection does not seem to be independently or synergistically associated with liver dysfunction.     

Does pretransplant obesity affect the outcome in kidney transplant recipients?

The effect of obesity on renal transplant outcome remains unclear due to conflicting published studies. The purpose of this study was to assess whether obesity affects the outcome in renal transplant patients. METHODS: We retrospectively analyzed 33 obese (BMI >30; mean = 34.1 +/- 3.68; group I) and 35 nonobese (BMI < or = 30; mean = 23.6 +/- 3.18; group II) renal transplants performed at our center between March 1999 to December 2002. These two groups were well matched with respect to age, sex, donor source, hypertension, diabetes, ischemic heart disease, hyperlipidemia, native kidney disease (PCKD, 6 vs 4; diabetic, 5 vs 4; glomerulonephritis, 6 vs 7; FSGS, 2 vs 2 and IgA, 2 vs 7), HLA mismatch and immunosuppressants medications (Neoral, 21 vs 25; tacrolimus, 11 vs 10; Cellcept, 28 vs 31; Prednisone, 33 vs 35; ATG, 7 vs 8; Basiliximab, 14 vs 13 and Rapamycin, 5 vs 2, groups I and II, respectively). Follow-up was from 7 months to 4.4 years. RESULTS: Significant differences were noted in operating time, wound infection, perinephric hematoma, lymphocele, and number of hospital days. There were no significant differences between the two groups in the incidence of wound dehiscence, deep vein thrombosis, pulmonary embolism, atelectasis, urine leak, delayed graft function, acute rejection rate, and the following posttransplant variables: diabetes mellitus, myocardial infarction, hyperlipidemia, hypertension, and incisional hernia. We conclude that obesity significantly increases operating time, wound complications, and hospitalizations.     

Does etiology of end-stage renal disease affect sleep quality in kidney transplant recipients?

BACKGROUND: That hypertension (HTN) as a leading cause of end-stage renal disease (ESRD) is linked to sleep disorders in the general population can be the basis of a hypothesis that HTN may be a contributing factor to the poor quality of sleep in some kidney transplant recipients. This study was designed to investigate the correlation between ESRD secondary to HTN and sleep quality among kidney transplant recipients. METHODS: In this case control study, 201 kidney transplant recipients were divided into group I (ESRD) secondary to HTN, (n=82) and group II (ESRD secondary to other causes, n=119). The groups were matched for medical comorbidities, demographic and clinical data, and symptoms of anxiety and depression. Sleep quality assessed by means of the Pittsburgh Sleep Quality Index (PSQI) was compared between the study groups. RESULTS: The mean (SD) of the total PSQI score was significantly high in group I compared with group II (7.42 +/- 2.36 vs 6.60 +/- 3.07, P=.042). Similar results were observed for the sleep duration scores in the groups (1.22 +/- 1.12 vs 0.86 +/- 1.12, P=.026). In group I, all the other PSQI components were higher than those in group II, difference that were statistically significant. CONCLUSION: Sleep quality and duration was poorer among our kidney transplant recipients with ESRD secondary to HTN compared with the controls. Further studies, however, are required to investigate whether HTN is responsible for the reported poor quality of sleep in some kidney transplant recipients.     

Do cyclosporin proffles provide useful information in the management of renal transplant recipients?

BACKGROUND.: This study investigated the relationships between cyclosporinA (CsA) blood levels and episodes of renal allograft rejectionand nephrotoxicity following renal transplantation, with theaim of establishing whether CsA profiles provided more usefulinformation than single CsA blood levels in respect of theserelationships. METHODS.: One hundred and sixty-two profiles were performed over 16 monthsin 40 patients and analysed retrospectively. Blood samples weretaken at 0, 2, 4, 6 and 8 h after the morning CsA dose. Rejectionepisodes were diagnosed by renal biopsy and CsA nephrotoxicityby a fall in serum creatinine 1 week after a cut in CsA dose. RESULTS.: The mean area under the curve (AUC) was lower for profiles performedat the time of rejection (3821 h.ng/ml) than that of a matchedgroup of non-rejecting profiles (5479 h.ng/ml; P0.02). An AUCabove 6400 h.ng/ml significantly discriminated rejection fromnon-rejection, whereas pre-dose and peak CsA concentrationsdid not have such discriminating cut-off values. A comparisonof CsA-toxic and non-toxic profiles showed that there were nosignificant differences between mean CsA concentrations norbetween the mean AUCs of these groups. CONCLUSION.: We conclude that basing CsA dosing on CsA profiles could helpto avoid some early episodes of rejection without increasingthe risk of nephrotoxicity.     

Lack of impact of donor age on patient survival for renal transplant recipients ≥60years

There has been an increase in the number of older patients on the transplant waiting list and acceptance of older donor kidneys. Although kidneys from older donors have been associated with poorer graft outcomes, whether there is a differential impact of donor age on outcomes in older recipients remains unclear. The aim of this study was to evaluate the effect of donor age on graft and patient survival in renal transplant (RT) recipients ≥60years. Using the Australia and New Zealand Dialysis and Transplant Registry, outcomes of 1,037 RT recipients ≥60years between 1995 and 2009 were analyzed. Donor age groups were categorized into 0-20, >20-40, >40-60, and >60years. Compared with recipients receiving donor kidneys >60years, those receiving donor kidneys >20-40years had lower risk of acute rejection (odds ratio 0.46, 95% CI 0.27, 0.79; P<0.01) and death-censored graft failure (HR 0.37, 95% CI 0.19, 0.72; P<0.01). There was no association between donor age groups and death. With a corresponding growth in the availability of older donor kidneys and the observed lack of association between donor age and patient survival in RT recipients ≥60years, preferential allocation of older donor kidneys to RT recipients ≥60years may not disadvantage the life expectancy of these patients.     

Variability of mycophenolic acid elimination in the renal transplant recipients – population pharmacokinetic approach

Abstract

The aim of this study was to develop a population pharmacokinetic (PK) model for clearance of mycophenolic acid (MPA) in adult renal transplant recipients, to quantify the PK parameters and the influence of covariates on the MPA pharmacokinetic parameters. Parameters associated with plasma concentrations of MPA at steady-state were analyzed in 70 renal transplant recipients (mean age 42.97 years; mean total body weight 75.33?kg) using nonlinear mixed-effect modeling (NONMEM). Characteristics of patients screened for influence on the pharmacokinetic parameters were gender, age, body weight, time after transplantation, whether the patient was diagnosed as having diabetes mellitus, organ source (living or deceased donor), biochemical parameters and co-therapy (tacrolimus, cyclosporine, prednisolone, omeprazole, bisoprolol, carvedilol, nifedipine). A validation set of 25 renal transplant recipients was used to estimate the predictive performance of population pharmacokinetic model. Typical mean value of MPA oral clearance, estimated by base model (without covariates) was 0.741?L?h^?1. During population modeling, the full model showed that clearance of the MPA was significantly influenced by age, total daily dose of MPA, creatinine clearance, albumin level, status and gender of a donor, and the nifedipine and tacrolimus co-therapy. In the final model, clearance of MPA was reported to be significantly influenced by age, total daily dose of MPA and thenifedipine co-therapy. The derived model describes adequately MPA clearance in terms of characteristics of our patients, offering basis for individual pharmacotherapy approach.     

Does renal function deteriorate more rapidly in diabetic cardiac transplant recipients?

BACKGROUND: Selection criteria for cardiac transplant candidates with diabetes mellitus (DM) have been liberalized resulting in increased numbers of diabetic patients receiving organs. Calcineurin inhibition results in nephrotoxicity. Whether this nephrotoxicity is accelerated in diabetic heart transplant recipients is unknown. METHODS: To investigate this question, we derived the glomerular filtration rate (GFR) at transplant and at multiple time intervals thereafter for adult heart transplants performed from January 1, 2000 to January 1, 2005. GFR was estimated using the Modification of Diet in Renal Disease Study equation (GFRMDRD) and the Cockcroft-Gault (GFRCG) formula. RESULTS: In all, 257 patients were nondiabetic and 102 patients were diabetic before and after transplant. The diabetic patients were older (57+/-8 vs. 53+/-13 years; P<0.01) and had greater body mass index (27.5+/-5.1 vs. 25.5+/-4.4 kg/m; P<0.01) than nondiabetic patients. Baseline renal function was significantly reduced in diabetic patients with higher serum creatinine (1.6+/-0.5 vs. 1.4+/-0.5 mg/dL), lower GFRCG (65+/-27 vs. 73+/-35 mL/min), and lower GFRMDRD (54+/-23 vs. 65+/-32 mL/min; all P<0.01) than nondiabetic patients. All patients were treated with cyclosporine or tacrolimus posttransplant. The change in the GFRMDRD in nondiabetic and diabetic patients was constant and comparable at 1, 2, and 3 years posttransplant. In normal subjects, GFRMDRD declined from baseline by 7+/-26, 5+/-23, and 7+/-23 mL/min(2) and in the diabetic patients was 13+/-22, 9+/-26, 10+/-22 ml/min(2) at 1, 2, and 3 years, respectively (P=NS). CONCLUSION: This data suggests that nephrotoxicity posttransplant is not accelerated in diabetic recipients.     

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

The possible role of NF-κB1 Rs28362491 polymorphism in male fertility of Egyptian population

Male reproductive impairment is responsible for at least 50% of cases of couple infertility. Nuclear factor-kappa B (NF-κB) has been functionally linked to germ cell apoptosis, which may affect human fertility. The aim of this study was to determine the association between the rs28362491 SNP of the NF-κB1 gene and infertility in Egyptian men. In this case–control study, semen and blood samples of 247 infertile men, constituting the case group, and of 113 fertile healthy men as the control group were analysed. All study participants were genotyped for polymorphism of the NF-κB1 gene (rs28362491) by the polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) technique. Heterozygous I/D genotype of the NF-κB1 rs28362491 polymorphism was associated with a significantly lower risk of poor semen quality, including asthenozoospermia, astheno–teratozoospermia, and oligo–astheno–teratozoospermia, when compared to I/I genotype (odds ratio = 0.25, 0.26, 0.18, p < .0005, <.0005, <.0005) respectively. Overall, the presence of the D allele was associated with a significantly decreased risk of poor sperm quality as compared to the I allele (odds ratio = 0.56, 0.64, 0.49, p = .050, .038, .001). In conclusion, these results suggest that heterozygosity of the NF-κB1 gene may play a protecting role against male infertility in Egyptians.     

The BK virus in renal transplant recipients��review of pathogenesis, diagnosis, and treatment

The BK virus, a DNA virus from the Polyomavirus group, represents an opportunistic infection of immunosuppressed transplant recipients. Though the virus was discovered approximately 40 years ago, the emergence of BK virus nephropathy since 1995 onwards, with associated high graft loss rates, has revolutionized renal transplantation medicine. Kidney transplant professionals realized that the consequences of over-immunosuppression were as severe as the consequences of under-immunosuppression and we entered the era of immunosuppressive minimization. Despite this recognition, the optimal testing type for BK virus infections and frequency of testing are hotly debated. Similarly, optimal treatment strategies remain sources of intense controversy. The authors review the current strategies of screening, diagnosis, and possible treatment, and also review the amount and quality of evidence in favor or against. Similarities and differences between cytomegalovirus, Epstein-Barr virus, and BV virus, the three major viral infections in kidney transplantation, are highlighted.     

The burden of anti-HCV genotye-4 positivity in renal transplant recipients: 8 years follow-up

Whether renal transplant recipients with anti-HCV antibodies positivity and normal liver function tests within the first year after transplantation have different morbidity and mortality and graft failure compared to anti-HCV-negative recipients remains controversial. In this retrospective study, on 411 renal transplant recipients, we analyzed grafts morbidity, survival, and liver function tests over a period of 8 years. Patients were stratified according to their anti-HCV antibody status 1 year after transplantation into anti-HCV-positive and HCV-negative patients. The presence of normal liver function tests was mandatory at inclusion. All patients received the same immunosuppressive protocol consisting of cyclosporine A, mycophenolate mofetil and steroids. One year after transplantation, 137 patients were anti-HCV negative (33 %) while the rest 274 (67 %) were positive. At 5 years of follow-up, the study population consisted of 205 patients (71 patients, 35 % with anti-HCV negativity, and 134, 65 % with positivity). At the end of the study, only 144 patients were followed up (43 patients, 30 % with negative anti-HCV and 101 patients, 70 %, with positivity). We found that graft survival was not different between both groups. Moreover, serum creatinine showed a trend to be lower in HCV-positive patients compared to negative group although difference was not statistically significant. The number of graft loss was not different between both groups. Moreover, there was no difference between both groups as regards prevalence of acute rejection, diabetes mellitus, hypertension, CMV disease and proteinuria. We can conclude that anti-HCV positivity for 8 years in patients with normal liver function tests at 1 year does not impact graft morbidity and patient survival.