Andrzej Adamowicz

PARATHORMON, CALCIUM, PHOSPHORUS, AND LEFT VENTRICULAR STRUCTURE AND FUNCTION IN NORMOTENSIVE HEMODIALYSIS PATIENTS

Clinical and experimental data suggest that Parathormon (PTH), calcium, and phosphorus participate in left ventricular hypertrophy (LVH) and affect myocardial contractility in end-stage renal disease. Cellular calcium overload and interstitial fibrosis induced by PTH may lead to impairment of left ventricular diastolic function. Hyperphosphatemia is an independent risk of cardiovascular mortality in dialysis patients. The aim of the study was to estimate the influence of PTH and calcium-phosphorus metabolism on left ventricular structure and function in hemodialysis patients, without hypertension and antihypertensive drug therapy (SBP = 126.2 ± 11.1 DBP = 75.8 ± 6.5 mmHg). Echocardiographic findings in a group of 22 normotensive HD patients had been compared to 43 hypertensive HD patients. Relationships between PTH, calcium-phosphorus metabolism and echocardiography in normotensive group were then evaluated. Left ventricular mass index (LVMI) was lower in normotensive patients: 128.3 ± 46.2 versus 165.8 ± 46.7 (p < 0.01). The prevalence of LVH was 55% in normotensive HD patients compared to 86% in hypertensive group (p < 0.01). In normotensive group we found correlation between PTH and LVMI (r = 0.44; p < 0.05). There were also significant relationships between calcium and posterior wall thickness (r = −0.44; p < 0.05), phosphorus and LVMI (r = 0.47; p < 0.05). A significant correlation was observed between both phosphorus, calcium × phosphorus product and E/A ratio: r = −0.47 and r = −0.43, respectively (p < 0.05 both). Disturbances of calcium-phosphorus metabolism and secondary hyperparathyroidism contributes to left ventricular hypertrophy, and impaired left ventricular diastolic function in normotensive hemodialysis patients.

Selenium concentrations and glutathione peroxidase activities in blood of patients before and after allogenic kidney transplantation

In animals and humans, the highest level of selenium (Se) occurs in the kidney. This organ is also the major site of the synthesis of the selenoenzyme glutathione peroxidase (GSH-Px). Decreased Se levels and GSH-Px activities in blood are common symptoms in the advanced stage of chronic renal failure (CRF). Blood samples for Se levels and GSH-Px activities measurements from patients were collected just before transplantation and 3, 7, 14, 30, and 90 d posttransplant. The Se levels in whole blood and plasma of patients before transplantation (79.5 and 64.5 ng/mL, respectively) were lower by 23% and 21%, respectively, as compared with controls (p<0.0001), and 7 d after operation, it further decreased in both components (p<0.01). Fourteen days after surgery, the levels reached the initial values and increased slowly in the later period. Red blood cell GSH-Px activity in patients in the entire period of the study did not differ from the control group. Plasma GSH-Px of patients before the surgery was extremely low (76 U/L) as compared with controls (243 U/L; p<0.0001) but increased rapidly to 115 U/L after 3 d, to 164 U/L after 14 d, and to 208 U/L after 3 mo posttransplant. In CRF patients, after kidney transplantation, plasma GSH-Px activity increased rapidly, approaching, after 3 mo, the values that were close to the normal levels. A negative correlation between creatinine level and plasma GSH-Px activity is observed in patients after kidney transplantation. Monitoring of plasma GSH-Px activity may be a useful additional marker of the transplanted kidney function.

Selenium and glutathione levels, and glutathione peroxidase activities in blood components of uremic patients on hemodialysis supplemented with selenium and treated with erythropoietin.

Patients with chronic renal failure (CRF) often have reduced concentrations of selenium (Se) and lowered activities of glutathione peroxidase (GSH-Px) in blood components. The kidney is a major source of plasma GSH-Px. We measured Se and glutathione levels in blood components and red cell and plasma GSH-Px activities in 58 uremic patients on regular (3 times a week) hemodialysis (HD). The dialyzed patients were divided in 4 subgroups and were supplemented for 3 months with: 1) placebo (bakers yeast), 2) erythropoietin (EPO; 3 times a week with 2,000 U after each HD session), 3) Se-rich yeast (300 microg 3 times a week after each HD), and 4) Se-rich yeast plus EPO in doses as above. The results were compared with those for 25 healthy subjects. The Se concentrations and GSH-Px activities in the blood components of dialyzed uremic patients were significantly lower compared with the control group. Treatment of the HD patients with placebo and EPO only did not change the parameters studied. The treatment with Se as well as with Se and EPO caused an increase in Se levels and red cell GSH-Px activity. Plasma GSH-Px activity, however, increased only slowly or did not change after treatment with Se and with Se plus EPO. In the group treated with Se plus EPO the element concentration in blood components was higher compared with the group supplemented with Se alone. The weak or absence of response in plasma GSH-Px activity to Se supply indicates that the impaired kidney of uremic HD patients has reduced possibilities to synthesize this enzyme.

Selenium, glutathione peroxidases, and some other antioxidant parameters in blood of patients with chronic renal failure

In the present study several parameters associated with oxidative stress were examined in the blood of 25 chronic renal failure (CRF) patients and the results were compared with 18 healthy subjects. Mean creatinine concentration in patients was 1,216 +/- 292 micromol/l. Selenium (Se) concentration in red cells, whole blood and in plasma of CRF patients (106 +/- 32.5, 59.0 +/- 16.7 and 42.4 +/- 13.8 ng/ml, respectively) was significantly (0.0001 < P 0.01) lower (by 20-42%) compared with the controls. Red cell and plasma glutathione peroxidase (GSH-Px) activities (16.6 +/- 3.4 U/g Hb and 93.7 +/- 32.9 U/l plasma) were lower by 12 and 53% (P < 0.05 and < 0.0001, respectively) in patients than in healthy subjects. GSH concentration in red cells of patients (2.81 +/- 0.45 mmol/l) was significantly (P < 0.001) higher (by 20%) than in control group. Malonyldialdehyde (MDA) concentration (expressed as thiobarbituric acid-reactive substances) in red cells of patients (725 +/- 155 nmol/g Hb) was significantly (P < 0.001) higher (by 28%) than in control group. No significant difference was observed in the activity of superoxide dismutase in pLasma between the two groups. In conclusion, our results confirm that the aLterations in Se levels in blood components and in GSH-Px activity in plasma show that the kidney plays an important role in Se homeostasis and in plasma GSH-Px synthesis.

Effect of erythropoietin therapy and selenium supplementation on selected antioxidant parameters in blood of uremic patients on long-term hemodialysis.

BACKGROUND The kidney accumulates the highest level of selenium (Se) in the organism and is the major source of plasma glutathione peroxidase (GSH-Px). Se, as an integral part of the active site of GSH-Px, plays an important role in protecting cell membranes from oxidative damage. Decreased blood Se levels and GSH-Px activity are common in chronic renal failure (CRF) patients. Our study was an effort to evaluate the effect of erythropoietin (EPO) therapy and Se supplementation for CRF patients undergoing regular hemodialysis (HD) on blood Se, red cell glutathione (GSH), and blood lipid peroxidation product levels, and on blood activity levels of GSH-Px and blood superoxide dismutase (SOD). MATERIAL/METHODS Our subjects were divided into three groups: I - CRF patients on regular HD and EPO, II - HD patients receiving EPO and Se, and III - healthy controls. Se levels, SOD and GSH-Px activities were measured spectrofluorometrically, the GSH level by Beutlers colorimetric method, and lipid peroxidation products using TBARS. RESULTS EPO therapy with Se supplementation significantly increased whole blood and plasma Se in HD patients, and raised red cell GSH-Px activity, but plasma GSH-Px activity, plasma superoxide dismutase, and plasma and red cell TBARS did not respond to Se supplementation. EPO alone showed no effect on these parameters. CONCLUSIONS Treatment with EPO and supplementation with Se significantly increased the element concentration in whole blood and plasma, and GSH-Px activity in red cells. Plasma GSH-Px activity did not respond to Se.

Decreased plasma glutathione peroxidase activity in uraemic patients.

Accessible online at: www.karger.com/journals/nef Dear Sir, We read with great interest the paper by Roxborough et al. [1] on the reduction of the glutathione peroxidase (GSH-Px) activity in haemodialysis (HD) patients. The authors noted that in serum of patients with endstage chronic renal failure (CRF), the GSHPx activity was 2.65 times lower when compared to controls (106 vs. 281 U/l; p ! 0.001). Following HD, the GSH-Px activity rose by 38%, although remained below control values. We studied some antioxidant parameters in blood of patients in different stages of CRF. Several groups of patients were investigated: nondialyzed patients and several groups of patients on long-term regular HD: (1) supplemented with baker’s yeast (placebo), (2) supplemented with selenium (Se) in the form of Se-rich yeast (Y-Se; 300 Ìg Se given orally three times a week), (3) treated with erythropoietin at doses of 2,000 U three times a week, and (4) supplemented with YSe and erythropoietin (doses as above). Blood samples were drawn into heparinized vacutainer tubes, and plasma was removed by centrifugation. The plasma Se concentration was assayed fluorometrically [2], and the plasma GSH-Px activity was measured spectrophotometrically by the method of Paglia and Valentine [3] with t-butyl hydroperoxide as substrate. The results obtained were compared with healthy subjects (control group). In all groups of patients, at the beginning of the study, the plasma GSH-Px activity was 1.8 to 2.1 times lower (p ! 0.001) as compared with the control group. The plasma Se levels in nondialyzed and in dialyzed patients before HD, taking the group together (n = 44), were significantly lower (p ! 0.001 and p ! 0.05, respectively) than in healthy subjects. The patients, methods of treatment and plasma Se levels, and plasma GSH-Px activities obtained are shown in table 1. In two groups of HD patients who were regularly supplied with Se, 3 months after supplementation the Se concentration in plasma increased significantly (p ! 0.001), but the GSH-Px activity did not

The influence of calcineurin inhibitors on pulse wave velocity in renal transplant recipients.

Background. Pulse wave velocity (PWV) is a marker of the arterial wall stiffness and independent cardiovascular risk factor in hemodialysis patients. Cyclosporine A (CyA) and tacrolimus (TAC) are known to differ in the influence on cardiovascular risk factors in renal transplant recipients. Recent studies suggest that CyA may decrease arterial compliance. The aim of the study was to assess the influence of CyA and TAC on the PWV and arterial wall stiffness in renal transplant recipients. Methods. The study population consisted of two groups of cadaveric renal transplant recipients, 76 patients each, matched for age, sex, blood pressure, body mass index, and length of the post-transplant follow-up. PWV between carotid and femoral artery was measured using a Complior device. Fasting blood was sampled for serum creatinine, lipid profile, uric acid, glucose, and C-reactive protein. Results. Aortic pulse wave velocity—a marker of increased arterial stiffness—was significantly higher in CyA group compared with TAC group (9.33 ± 2.10 vs. 8.54 ± 1.35, respectively; p < 0.01). Uric acid, total cholesterol, triglycerides, and LDL-cholesterol concentrations were significantly higher in CyA group. Significant correlations were found between PWV and age, systolic and diastolic blood pressure, and fasting glucose in the CyA group, but only between PWV and age in TAC group. Conclusion. CyA-based immunosuppressive therapy is associated with an unfavorable profile of cardiovascular risk factors and increased arterial stiffness in renal transplant recipients.

Long graft cold ischemia time is associated with increased arterial stiffness in renal transplant recipients.

BACKGROUND Increased pulse wave velocity (PWV), an indicator of arterial stiffness, is associated with greater cardiovascular risk among renal transplant recipients. PWV depends on recipient-related factors and, as shown in recent studies, also on donor age. There is a lack of information whether graft-related factors influence arterial function in recipients. Graft cold ischemia time (CIT) significantly influences renal transplant outcomes. It was shown in an experimental model of aortic grafting that increased CIT promoted arteriosclerosis. The aim of the present study was to evaluate the relationship between renal graft CIT and PWV. METHODS Carotid-femoral PWV were measured in 103 cadaveric kidney recipients of mean age 45 +/- 12 years. We analyzed clinical data of recipient and donor ages, genders, body mass index, blood pressure, CIT, delayed graft function, and type of immunosuppressive therapy to compare patients with CIT < 24 (n = 24) versus CIT > or = 24 hours (n = 79). RESULTS PWV was lower among patients with shorter CIT (8.3 +/- 1.6 vs 9.2 +/- 2.0 respectively; P < .05). No significant differences were observed between the groups regarding donor and recipient ages, blood pressure, glomerular filtration rate, or immunosuppressive and cardiovascular therapy. A significant positive correlation was noted between PWV and CIT (r = .23; P = .019). Multiple regression analysis demonstrated that recipient age, therapy with cyclosporine, fasting glucose, systolic blood pressure, and CIT were independently associated with PWV. CONCLUSIONS Long CIT was associated with increased arterial stiffness. Further studies are necessary to understand the cause effect relationship of this finding.

Diffusion-weighted MR imaging of transplanted kidneys: Preliminary report.

Summary Background An aim of this study was to assess the feasibility of DWI in the early period after kidney transplantation. We also aimed to compare ADC and eADC values in the cortex and medulla of the kidney, to estimate image noise and variability of measurements, and to verify possible relation between selected labolatory results and diffusion parameters in the transplanted kidney. Material/Methods Examinations were performed using a 1.5 T MR unit. DWI (SE/EPI) was performed in the axial plane using b-values of 600 and 1000. ADC and eADC measurements were performed in four regions of interest within the renal cortex and in three regions within the medulla. Relative variability of results and signal-to-noise ratio (SNR) were calculated. Results The analysis included 15 patients (mean age 52 years). The mean variability of ADC was significantly lower than that of eADC (6.8% vs. 10.8%, respectively; p<0.0001). The mean variability of measurements performed in the cortex was significantly lower than that in the medulla (6.2% vs. 11.5%, respectively; p<0.005). The mean SNR was higher in the measurements using b600 than b1000, it was higher in ADC maps than in the eADC maps, and it was higher in the cortex than in the medulla. ADC and eADC measured at b1000 in the cortex were higher in the group of the patients with eGFR ≤30 ml/min./1.73 m2 as compared to patients with eGFR >30 ml/min./1.73 m2 (p<0.05). Conclusions Diffusion-weighted imaging of transplanted kidneys is technically challenging, especially in patients in the early period after transplantation. From a technical point of view, the best quality parameters offer quality ADC measurement in the renal cortex using b1000. ADC and eADC values in the renal cortex measured at b1000 present a relationship with eGFR.

Coronary artery calcification and large artery stiffness in renal transplant recipients

PURPOSE Coronary artery calcification (CAC) is an independent predictor of cardiovascular (CV) events in renal transplant recipients (RTR). Carotid-femoral pulse wave velocity (PWV), a non-invasive measure of large artery stiffness, also predicts CV events in RTR. The study investigated the relationship between CAC and PWV in RTR and assessed the performance of PWV measurement in predicting CAC. PATIENTS/METHODS The study was performed as cross-sectional analysis in 104 RTR. CAC was determined as total calcium score (CS) and calcium mass (CM). Carotid-femoral PWV was also measured. Sensitivity, specificity and receiver operating characteristic (ROC) curve were used to assess the performance of PWV as diagnostic test for presence of CAC. RESULTS CAC was found in 69% of participants. PWV was higher in RTR with CAC than in RTR without CAC (10.2±2.2 vs. 8.6±15; p<0.001). In univariate analysis CS was significantly correlated with age, duration of hypertension, waist circumference, PWV, hemoglobin concentration, and serum glucose. In multiple linear regression analysis CS was independently associated with age only, but not with PWV. Sensitivity and specificity of PWV>7.6m/s as cut-off for detecting CAC>0 was 0.889 and 0.406, respectively. Sensitivity and specificity of PWV>10.2m/s as cut-off for detecting severe CAC (CS>400) was 0.319 and 0.969, respectively. CONCLUSIONS The study confirmed high prevalence of coronary artery calcification in renal transplant recipients. The study does not support the hypothesis that aortic stiffness is independently associated with coronary artery calcification in RTR. PWV measurement may be useful in excluding severe CAC in RTR.