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).

Subclinical toxicity of calcineurin inhibitors in repeated protocol biopsies: an independent risk factor for chronic kidney allograft damage.

The purpose of the prospective study was to determine the prevalence of subclinical toxicity of calcineurin inhibitors (CI) in repeated protocol renal allograft biopsies and to assess its impact on the development of chronic graft changes. A total of 424 biopsies were conducted in a cohort of 158 patients; of these biopsies, 158 were in the third week, 142 were in the third month and 124 were in the first year after transplantation. Histological signs of toxicity occurred in the third week in 33 (20.1%) patients, with persistence after CI dose reduction in the third month in 27 (19.0%) and in the first year in 23 (18.5%) patients. Of the toxic changes, 52% were clinically silent. At the end of the one-year follow-up, both subclinical and clinically manifest toxicity resulted in a similar progression of chronic changes quantified by Banff chronicity score and they significantly differed from the control group (P < 0.05). Subclinical toxicity affects a significant percentage of grafts; it occurs independently of dosage, blood level and type of applied CI. It is associated with the progression of chronic changes as early as in the first year after transplantation and represents an independent risk factor for chronic allograft damage. We report here our clinical approach to toxicity.

Improvement of cardiovascular risk factors and cosmetic side effects in kidney transplant recipients after conversion to tacrolimus.

AIMS: Tacrolimus and Cyclosporine A (CyA) are cornerstones in immunosuppressive therapy. Cyclosporine side eff ects include hypertension and hypercholesterolemia both of which may increase the risk of cardiovascular mortality, gingival hyperplasia and hirsutism are known to reduce quality of life. The aim of this prospective study was to evaluate changes in cardiovascular risk profile and cosmetic side eff ects after conversion from CyA to tacrolimus. METHODS: 25 stable kidney transplant recipients (9 male, 16 female) were converted from a CyA to a tacrolimus--based regimen. Mean age was 45.7 +/- 13.5 years. Time to switch following transplantation was 4.7+/-1.7 years. Reasons for conversion were multiple: arterial hypertension (9), hypertrichosis (3), gingival hyperplasia (3), hyperlipidemia (14). RESULTS: 19/25 patients completed the one year study period. One patient died, two returned to hemodialysis, two were switched back to CyA and one patient was lost to follow-up. There were statistically significant changes (p = < 0.05) in systolic and diastolic pressure and antihypertensive medication could be reduced in 13 patients. The dose of lipid-lowering agents could be reduced in the majority of the recipients and a complete withdrawal was achieved in 7 patients. Hypertrichosis and gingival hyperplasia resolved in all patients. Further, there was a significant improvement (p = <0.05) in urea and serum creatinine levels. Adverse events were consistent with the established safety profile for tacrolimus. CONCLUSIONS: Conversion to a tacrolimus-based regimen led to an improvement in the cardiovascular risk profile. Further, cosmetic side eff ects which may lead to non-compliance, resolved after the switch.

Sonographic findings in borderline changes and subclinical acute renal allograft rejection.

PURPOSE: A clinically manifested acute rejection is associated with graft dysfunction and with some ultrasound findings. The aim of our study was to determine the potential of ultrasound evaluation in the detection of subclinical acute rejective changes diagnosed in stable grafts by protocol biopsy. METHODS: Gray-scale evaluation, color Doppler imaging (CDI) and power Doppler imaging (PDI) was performed before each of 184 protocol graft biopsies in 77 patients in the third week, third month and first year after transplantation. The group was divided into four subgroups-normal histological finding, borderline changes, subclinical acute rejection of IA grade, and a clinically manifested acute rejection of IA grade. The sonographic findings were compared with individual groups. RESULTS: Detection of parenchymal edema using gray-scale imaging significantly differentiated borderline changes and subclinical acute rejection of IA grade from normal histological findings in the third week and in the third month (P=0.013, P=0.002 and P=0.024, P<0.001), respectively. A similar finding could be recorded in the latter group in the first year after transplantation (P=0.024). The presence of edema and reduced peripheral parenchymal perfusion in PDI significantly more often indicated a clinically manifested acute IA rejection (P=0.019, P=0.004, P=0.044). Parenchymal CDI hyperperfusion had a high specificity (89.5%) but a low sensitivity (60%) in the detection of the subclinical form of acute IA rejection. CONCLUSION: A composite gray-scale, PDI and CDI evaluation provide a significant differentiation of groups with borderline changes and subclinical acute rejection and groups with normal histological finding and clinically manifested acute rejection.

Endogenous erythropoietin levels and anemia in long-term renal transplant recipients.

BACKGROUND/AIM: Although anemia is a common complication after renal transplantation (RT), data concerning endogenous erythropoietin (EPO) levels in long-term RT recipients are rare. The goal of this study was to evaluate the prevalence of anemia within 6 months to 5 years after RT and to assess the relationship between the serum concentrations of endogenous EPO, graft function and grade of improvement of anemia. METHODS: 140 patients who had undergone RT were included in the group: 89 males (63.6%) and 51 females (36.4%), with an average age 46.8 +/- 12.8 years. The serum concentrations of EPO and creatinine (Cr) were tested in all the individuals and the values of the red blood component of blood count, serum ferritin (SF), plasma iron concentration, plasma total iron-binding capacity (TIBC), transferrin saturation (TS), folic acid and vitamin B(12) levels in the serum were determined. A statistical analysis of the results was performed using the correlation analysis, Mann-Whitney U test and Duncan's multiple range test. RESULTS: Normal blood count values were found in 91 patients (65%), and a mild grade of anemia with a mean hemoglobin (Hb) 114.4 +/- 11.9 g/l was observed in 45 patients (32.1%), and 4 patients (2.9%) fulfilled the diagnostic criteria for post-transplantation erythrocytosis. Individuals with normal Hb values had a mean EPO serum concentration of 39.3 +/- 12.3 mU/ml (median 37.2) and the mean Cr was 133.8 +/- 36.9 micromol/l (median 122). Patients with anemia (Hb <120 g/l in females, Hb <130 g/l in males) had a mean EPO value of 47.0 +/- 26.6 mU/ml (median 36.0) and a mean Cr of 203.8 +/- 108.9 micromol/l (median 181). The difference in the Cr values was statistically significant (p < 0.0001), while the difference between the EPO concentrations was not significant. No relation of EPO serum concentration with regard to graft function was found in the analysis. A lack of storage iron (SF <10 microg/l in females, SF <22 microg/l in males) was found in 16 patients (11.4%), and a lack of functional iron (TS <20%) was found in 27 patients (19.3%). CONCLUSIONS: Theprevalence of anemia in patients after transplantation was 32.1%. The most common cause of anemia is insufficient graft function development. The achieved values of the red component of blood count have no relation to the endogenous EPO serum concentrations.

IgA nephropathy associated with psoriasis vulgaris: a contribution to the entity of 'psoriatic nephropathy'.

BACKGROUND: It is generally accepted that there is no higher prevalence of renal disease in psoriatic patients, except in the case of secondary renal amyloidosis in psoriatic arthropathy. Contrary to this, however, some authors suggest that kidney diseases in psoriasis vulgaris may be more common and they presume the existence of 'psoriatic nephropathy'. METHOD: We report a case of IgA nephropathy in a patient with psoriasis vulgaris as a contribution to the ongoing discussion concerning this entity of 'psoriatic nephropathy'. RESULT: A 62-year-old man with a history of psoriasis vulgaris, without evidence of psoriatic arthropathy, was admitted to hospital for nephrotic proteinuria 6.74 g/day and a moderate decrease of glomerular filtration rate with a serum creatinine level of 213 micromol/L and creatinine clearance of 0.95 ml/s. Kidney biopsy revealed IgA nephropathy with vascular nephrosclerosis and tubulointerstitial nephritis. After 1 month of treatment with prednisone 1 mg/kg/day, proteinuria decreased to 2.45 g/day, and skin lesions almost completely resolved. CONCLUSION: About 10 cases of IgA nephropathy associated with psoriasis are referred to in the literature. We report an-other interesting case of IgA nephropathy in a psoriatic patient, as a contribution to the discussion regarding the hypothetical conception of 'psoriatic nephropathy'. We recommend routine urinalysis, careful examination of kidney function and a wider application of renal biopsy in psoriatic patients.

Selected indicators of bone metabolism in patients after kidney transplant.

Bone metabolism defects and skeleton diseases, so called renal osteopathy (RO), represent very serious clinical problems in the care of patients with kidney dysfunction. Renal osteopathy is a complicated skeletal disorder with a very complicated pathogenesis and we can encounter its individual forms in kidney transplant patients.