Stabilization of oxidative stress 1 year after kidney transplantation: effect of calcineurin immunosuppressives.

Kidney transplantation (KT) is one of the best treatments for patients with chronic renal disease. It leads to improved kidney function, but the oxidative stress (OS) is only partially eliminated after KT. This study evaluated the effect of KT on outcomes, such as (a) specific kidney functions, (b) metabolic parameters, as well as (c) OS-related markers in 70 patients (46 males, 24 females; mean age = 54 ± 11) before and 1 year after KT. Post KT, the patients were divided into two groups: those receiving only cyclosporine A (N = 36) and those receiving only tacrolimus (N = 34). Improved kidney function (creatinine, urea, and glomerular filtration rate) and biochemical and hematological parameters were found 1 year after KT. OS-related markers (total antioxidant capacity, advanced oxidation protein, and lipid peroxidation products) decreased, but glutathione level increased after KT. Alterations in superoxide dismutase and catalase activities were also found. Glutathione peroxidase levels were unchanged. The level of oxidized low-density lipoprotein was surprisingly, not significantly increased. There was no significant difference between calcineurin inhibitors in any of the measured parameters. Improved renal function after KT is linked to reduction in OS but independent of immunosuppressive therapy.

In vivo oxidized low-density lipoprotein (ox-LDL) aopp and tas after kidney transplantation: a prospective, randomized one year study comparing cyclosporine A and tacrolimus based regiments.

AIMS: Restoration of renal function after kidney transplantation (KT) is expected to improve oxidative stress (OS). However, little is known about the influence of calcineurin inhibitors on oxidized low-density lipoproteins (ox-LDL) after KT. The aim of this study was to evaluate ox-LDLs and related markers of OS, advanced oxidation protein products (AOPP) and total antioxidant status (TAS) in patients after KT on either cyclosporin A (CyA) or tacrolimus (Tac) treatment. METHODS: This was a prospective, randomized, single-center 12 month study evaluating time-dependent changes in biomarkers of OS before and after KT. Twenty nine patients (mean age 54.4 ± 11.1; 55% male and 45% female) were treated with CyA (Group A) and twenty four patients (mean age 52.9 ± 9.9; 75% male and 25% female) were treated with Tac (Group B). The ox-LDL, AOPP, TAS, lipid metabolism parameters, creatinine and glomerular filtration were assessed on day 1 before KT and on days 1 and 7, and in months 1, 3, 6 and 12 after KT. RESULTS: Over the 12 months, the ox-LDL for group A changed from 69.2±32.9 to 65.1±17.1 U/L (P=0.665), while AOPP significantly decreased from 233.0±159.6 to 156.5±90.1 µmol/L (P=0.025) and TAS from 1.87±0.31 to 1.68±0.20 mmol/L (P=0.030). For group B the ox-LDL changed from 62.9±29.7 to ± 61.4±14.6 U/L (P=0.168) and TAS from 1.87±0.51 to 1.68±0.20 mmol/L (P=0.168), while AOPP significantly decreased from 180.5±90.0 to 123.9±37.7 µmol/L (P=0.019). CONCLUSION: AOPP is more sensitive than ox-LDL for assessing OS after KT. TAS values appear to be insufficiently sensitive for monitoring OS in patients after KT.

Time-course evaluation of oxidative stress-related biomarkers after renal transplantation.

Patients with chronic renal disease have a high prevalence of oxidative stress (OS), which is associated with the cardiovascular complications occurring in this population. The restoration of kidney function after kidney transplantation (KT) can lead to reduction in the metabolic abnormalities and elimination of the OS. Time-dependent changes in OS-related markers and specific kidney function and metabolic parameters were evaluated in patients (N = 39; 23 males; 16 females; mean age = 57 ± 10 years) before (day 0) and after KT (day 1, 7, 30, 90, and 180) to monitor the graft. In particular, total antioxidant capacity (TAC), levels of advanced oxidation protein products (AOPP), lipid peroxidation as thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH); activities of glutathione peroxidase, catalase, and superoxide dismutase; and kidney function markers were measured. AOPP, TAC, and TBARS were significantly decreased, whereas GSH was significantly increased after KT. Antioxidant enzyme activities were not significantly changed during the monitored period after KT. Apropos specific kidney function markers and glomerular filtration significantly increased and creatinine level significantly decreased after transplantation. Changes in high-density lipoprotein cholesterol were also found. Our results show that successful KT results in normalization of the antioxidant status and lipid metabolism that is connected with both improved renal function and reduced cardiovascular complications.

Effect of different calcineurin inhibitors on AOPP and TAS after kidney transplantation.

OBJECTIVES: Little is known about the influence of calcineurin inhibitors on advanced oxidation protein products (AOPP) and total antioxidant status (TAS) after renal transplantation. DESIGN AND METHODS: AOPP and TAS were evaluated in transplanted patients on different calcineurin inhibitors. Thirty-five patients were treated with cyclosporine A (group A) and 33 with tacrolimus (group B). RESULTS: Over 6 months, the mean levels of AOPP in group A decreased from 205.9+/-125.7 to 140.9+/-78.9 micromol/L and TAS from 1.89+/-0.30 to 1.75+/-0.27 mmol/L. In group B, the mean levels of AOPP decreased from 196.5+/-123.9 to 129.6+/-63.8 micromol/L and TAS from 1.80+/-0.39 to 1.78+/-0.23 mmol/L. CONCLUSION: No significant differences in AOPP and TAS were found with respect to treatment. The only exception was the higher mean concentration of AOPP at month 1 in group A (p=0.026).

Assessment of haemoglobin a1c evolution using two statistical approaches (survival analysis and linear regression) in persons with diabetes mellitus.

BACKGROUND: Intensive selfmonitoring is an important and cost-demanding part of diabetes treatment. Continuous glucose monitoring (CGM) using transcutaneous sensors offers "real time" information on glycemia. In the present study, we assessed the therapeutic efficacy of CGM on metabolic control using two different statistical methods: linear regression and "survival analysis". OBJECTIVES: (1) to assess the therapeutic efficacy of CGM on metabolic control using two different statistical methods: linear regression and survival analysis; (2) to demonstrate the particular advantages of each statistical method. METHODS: A total of 42 persons with diabetes mellitus treated by means of an insulin pump participated in this study. According to the means of selfmonitoring persons with diabetes were divided into two groups: 1. intervention group of 17 persons using CGM, 2. control group of 25 persons using a glucometer. Each person was followed for a period of three months. At the beginning of the study and at the end of each month HbA1c was determined. RESULTS: Both the regression analysis and survival analysis brought evidence of significant changes of the HbA1c in either of the groups. The method of linear regression enables to analyse the evolution of HbA1c in each individual person followed by comparison of the groups. The survival analysis demonstrated that the probability of HbA1c decrease to the predefined level as well as its further maintaining at this level was higher in the CGM group. The mean time interval necessary to HbA1c decrease was shorter in the CGM group. CONCLUSIONS: The efficacy of CGM was demonstrated. In addition to linear regression, survival analysis appears to be an useful complementary method in the statistical evaluation of the treatment efficacy.