Open prospective study to evaluate cardiovascular risk factors and renal function in 2 dosage regimens of tacrolimus combined with mycophenolate mofetil and steroids in renal transplant patients: 5-year results.

BACKGROUND: Cyclosporine and tacrolimus (TAC) are the most potent immunosuppressants. TAC is considered less nephrotoxic, but may be an important factor in chronic graft dysfunction. The aim of the study was to evaluate kidney function and cardiovascular risk profile in 2 groups of low immunological risk kidney allograft recipients receiving 2 TAC dosages. MATERIALS AND METHODS: Patients were randomly assigned to 2 TAC-based treatments (group I [n = 14], standard dose; group II [n = 15], reduced dose). Patient and graft survival, graft function, occurrence of cardiovascular events (cardiac death, myocardial infarction, stroke), incidence of new-onset diabetes mellitus after transplantation, and cardiovascular risk factors were assessed over a 5-year period. RESULTS: Patient demographics and transplant characteristics were not statistically different between groups. TAC trough levels were significantly higher in group I for 24 months post transplant. Patient survival did not differ, but there were more acute rejection episodes and graft losses in group II. There were no significant differences in the rate of cardiac events. Graft function measured as serum creatinine levels and calculated glomerular filtration rate did not differ between groups. The same applies to new-onset diabetes mellitus after transplantation incidence. Office blood pressures were numerically higher in group I up to 24 months but this difference did not reach significance at any time. Similar results were obtained for serum lipids. CONCLUSIONS: Immunosuppression based on low doses of tacrolimus seems to be safe in the group of low immunological risk patients but in the 60-month follow-up does not offer any clear benefits in terms of potential nephrotoxicity or cardiovascular risk.

Renal allograft protection with angiotensin II type 1 receptor antagonists.

The renal benefits of agents inhibiting the renin-angiotensin-aldosterone system in renal transplant recipients, i.e. preventing the development of chronic graft nephropathy, are supposed but not finally proven. In a double-blind, placebo-controlled, cross-over study, we evaluated the influence of losartan on surrogate markers of tubular injury, urine excretion of transforming growth factor beta-1 (TGF-beta1) and amino-terminal propeptide of type III procollagen (PIIINP) in 16 patients after transplantation. The patients received randomly either losartan (50-100 mg daily) or the beta-blocker carvedilol (12.5-25 mg) for 8 weeks, allowing a placebo washout between treatments. The target office through blood pressure (BP) was below 130/85 mmHg. The BP did not differ in the treatment periods. Losartan significantly decreased N-acetyl-beta-d-glucosaminidase and alfa-1 microglobulin excretion relative to placebo and carvedilol. Urine excretion of TGF-beta1 and PIIINP was significantly lower after losartan. In conclusion, losartan reduces urine excretion of proteins associated with tubular damage and graft fibrosis.

One-year observation of kidney allograft recipients converted from cyclosporine microemulsion to tacrolimus.

The results from previous trials suggested that tacrolimus-based treatment in kidney transplantation was associated with a significantly lower incidence of acute rejection, and that cyclosporine microemulsion (CsA-Me)-treated patients converted to tacrolimus had numerically better 6-year graft survival than those remaining on CsA-Me. Death with a functioning graft and chronic graft nephropathy are the leading causes of late allograft loss. While standard cardiovascular risk factors are relevant, renal function itself becomes an important risk factor for cardiovascular morbidity and mortality in kidney transplantation patients. Expected benefits of the conversion from CsA-Me to tacrolimus with respect to renal function and cardiovascular status were the rationale for this observational study. Twenty one patients underwent conversion due to nephrotoxicity of cyclosporine (n = 18) or side effects (n = 3). Two out of 21 patients did not complete the study. The patient survival after 1 year was 100% in this group of patients; graft survival 94.7%. No cases of de novo diabetes mellitus were identified. Mean serum creatinine fell from 2.13 +/- 0.4 to 1.84 +/- 0.3 mg/dL (P < .02) and calculated glomerular filtration rate increased from 49.6 +/- 14.4 to 56.2 +/- 15.5 mL/min (P < .01). Total cholesterol decreased from 229.4 +/- 50.1 to 195.9 +/- 28.5 mg/dL (P < .005) and, low-density lipoprotein cholesterol from 125.7 +/- 37.3 to 104.4 +/- 22.6 mg/dL (P < .02). No significant changes in mean systolic or diastolic pressure or blood glucose levels were observed. The results of this observational study showed that in a group of patients with raised creatinine levels at entry, conversion to tacrolimus resulted in improved graft function and a more favorable cardiovascular risk profile.

Natural killer cell activity unaffected by ozonated autohemotherapy in patients with end-stage renal disease on maintenance renal replacement therapy.

Ozonotherapy is a complementary medical approach in the treatment of resistant infections, immune deficiency syndromes, orthopedic pathologies and vascular diseases. The criticism of this method is associated with potentially harmful effects of ozone on cells. The aim of this study was to investigate the influence of ozonated autohemotherapy (O3-AHT) on the cellular response of the immunologic system represented by cytotoxic activity of natural killer cells. 12 hemodialyzed patients (8 M, 4 F) aged 64.8 +/- 7.6 years with peripheral arterial disease as the main reason for the treatment with O3-AHT were examined in a prospective, placebo controlled, single blind study. They received 9 sessions of autohemotherapy without ozone exposure as a placebo-control and subsequent 9 sessions of O3-AHT. The procedures were performed 3 times a week, just before hemodialysis session. Ozone-oxygen gas mixture with ozone concentration of 50 microg/ml produced by ozone generator (ATO3, KrioMetrum, Poland) was used during O3-AHT Natural killer cell activity was measured using lactate dehydrogenase release assay There was no statistical difference between natural killer cell activity (%) at the baseline (16.78 +/- 8.07), after nine sessions of control autohemotherapy (15.98 +/- 6.67), and after nine sessions of O3-AHT (18.26 +/- 8.82). In conclusion, our findings showed that O3-AHT in a dose of 50 mg/mL does not have any significant influence on natural killer cell function in hemodialyzed patients.

Clinical efficacy of ozonated autohemotherapy in hemodialyzed patients with intermittent claudication: an oxygen-controlled study.

BACKGROUND: Hemodialyzed patients are particularly exposed to the development of peripheral arterial occlusive disease. Ozonotherapy is used as a therapeutic tool in the treatment of this atherosclerotic complication, but there are still no properly designed studies to show the clinical effectiveness of this approach. The aim of this study was to evaluate the influence of ozonated autohemotherapy on walking ability and the subjective clinical experience of hemodialyzed patients with peripheral arterial disease. METHODS: Ten subjects with intermittent claudication (Fontain II stage) received the cycle of ozonated autohemotherapy with ozone concentration of 50 microg/ml and the cycle of oxygen autohemotherapy as a control in a cross-over, single-blind manner. Pain-free distance and maximal walking distance were measured using a standardized march test on a treadmill. The efficacy of therapy was assessed subjectively by patients on a five-degree scale. RESULTS: Significant prolongation of maximal waking distance after ozonated autohemotherapy was found, as compared to the baseline (by 30.5%) and to the oxygen control (by 22.7%) (p<0.01 and p<0.03). There was also significant increase in pain-free distance after ozonated autohemotherapy, as compared to the baseline (by 71.7%) and to the oxygen control (by 62.8%) (p<0.02 and p<0.03 respectively). In a subjective assessment (questionnaires) 90% of patients reported clinical improvement relative to the baseline after ozonated autohemotherapy as compared to 40% after the oxygen-control treatment (p<0.025). CONCLUSION: We demonstrated that ozonated autohemotherapy might prolong walking ability and attenuate subjective clinical signs of ischemia in patients with peripheral arterial disease treated regularly with hemodialysis.

The influence of ozonated autohemotherapy on oxidative stress in hemodialyzed patients with atherosclerotic ischemia of lower limbs.

Ozonated autohemotherapy is used as a complementary medical approach in the treatment of vascular disorders. One of the greatest problems concerning an application of ozone in medicine is its induction of oxidative stress. The standards of ozonotherapy were elaborated recently making this treatment useful and probably non toxic. The aim of the present study was to investigate the influence of ozonated autohemotherapy on the oxidative stress extent in hemodialyzed patients, known to be particularly exposed to generation and deleterious effects of free radicals. Twelve continuously hemodialyzed subjects with atherosclerotic ischemia of the lower limbs were examined in a prospective, controlled, single blind study. Autohemotherapy with blood exposure to oxygen served as a control. The protein and lipid peroxidation products, the reduced glutathione level in red blood cells and free hemoglobin plasma concentration were measured. The study showed that ozonated autohemotherapy with ozone concentration 50 microg/ml per gram of blood induced a significant decrease in glutathione level after 9 sessions of this procedure. Therapy did not cause either the enhancement of protein and lipid peroxidation, or erythrocytes damage. It seems likely that the antioxidant defense system, part of which is glutathione, neutralizes oxidative properties of ozone in this concentration and protects against oxidative cell damage.

Beneficial clinical effects of ozonated autohemotherapy in chronically dialysed patients with atherosclerotic ischemia of the lower limbs--pilot study.

Ozonated autohemotherapy is a controversial but successful method of treatment, used in particular in European countries. There are many fields in which medical ozone could be of value: treating different infections, immunodeficiency syndromes, neoplasms. Encouraging results have also been achieved in the treatment of atherosclerotic ischemia of the lower limbs. In this preliminary study, the influence of blood ozonation on the intensity of symptoms of ischemia of the lower extremities was analysed among dialysed patients with chronic renal failure. We examined 5 hemodialyzed patients and 7 patients treated with peritoneal dialysis immediately before and after 14 sessions of ozonated autohaemotherapy. Eleven patients (91.6%) reported a subjective decrease in perceived intensity of ischemic pains, or observed prolongation of intermittent claudication distance. During march tests performed on a treadmill, we found significant prolongation of intermittent claudication distance in all examined patients - 65.6% (mean value, p (< or =0.01). Patients treated with peritoneal dialysis achieved much greater improvement than did hemodialyzed patients (165% vs. 42%). We concluded that autohemotherapy with ozone, in a concentration of 34.4 mcg/ml of blood, is safe, easily applied and may be useful In the therapy of atherosclerotic ischemia of lower extremities among dialyzed patients. It could also be a complement to current treatment, especially in cases where the latter has failed.

[Evaluation of prophylaxis and actual prevalence of HBV infection in twelve hemodialysis centers of Northern Poland]. / Ocena profilaktyki i aktualnej sytuacji epidemiologicznej zakazenia HBV w dwunastu osrodkach hemodializy Polski pólnocnej.

The aim of the study was to estimate the HBV infection preventive measures used in the twelve dialysis centres in north Poland. In all of the centres hepatitis B vaccination and segregation of HBV infected patients (dedicated machines or separate rooms), which are the two basic HBV infection control methods, were introduced. Our results point out that in some of the centres certain modification of these methods would be possible, including universal predialysis vaccination programme, changes in hepatitis B vaccination schedules with most effective routes of vaccination only and dedication for HBV infected patients not only separate rooms but separate dialysis staff as well.

The relationship between insulin, glucose and serum uric acid and their contribution to the progression of renal damage in patients with primary glomerulonephritis.

It is known that some metabolic disturbances may modify the progression of renal disease including primary glomerulonephritis, but the role of purines in this process is still unknown. To investigate this, 13 untreated patients with primary glomerulonephritis were followed up for a mean of 17.6 months to analyze the changes in proteinuria and glomerular filtration rate. On entering the study, each patient was given an oral glucose tolerance test and an oral fructose load test. The areas under the glucose (PGA), insulin (PIA) and uric acid (PUAA, post-fructose) curves were calculated. Glomerulonephritic patients were found to have a statistically higher response to fructose than controls (782 +/- 219 vs 518 +/- 154, P < 0.005). Multiple regression analysis showed that PGA, PIA and PUAA were independently related to changes in proteinuria and glomerular filtration rate during the natural course of the disease. This preliminary study suggests that purine metabolism may modulate the progression of renal disease in proteinuric patients.

[Relationship between some parameters of carbohydrate metabolism, proteinuria and glomerular filtration rate in patients with primary glomerulonephritis]. / Zaleznosc pomiedzy niektórymi parametrami gospodarki weglowodanowej a bialkomoczem i filtracja klebuszkowa u chorych z pierwotnymi klebuszkowymi zapaleniami nerek.

It is very well known that carbohydrate metabolism disturbances may affect progression of renal disease in patients with moderate renal insufficiency. The aim of this study was to analyse the relationship between glucose, insulin and changes of creatinine clearance and proteinuria in patients with primary glomerulonephritis and normal renal function. Thirteen non-treated patients with primary glomerulonephritis, were given 75 g glucose orally and area under insulin and glucose curves were estimated. Afterwards all patients were followed-up for 17.6 +/- 3.1 months and none of them was subjected to any pharmacological intervention. At the end of the study neither proteinuria nor creatinine clearance changed significantly. But significant linear correlations were found between pre-follow-up glucose and insulin and changes of daily proteinuria (r = 0.632, p < 0.05; r = 0.538, 0.05 < p < 0.1) respectively. No correlations were found between insulin and glucose area and changes of creatinine clearance. Authors analyze the potential role of some factors linking the glucose metabolism and proteinuria.

[Does erythropoietin treatment influence the lipid status of patients on maintenance hemodialysis?]. / Czy leczenie erytropoetyna wplywa na zmiany podstawowych wskazników gospodarki lipidowej u chorych przewlekle dializowanych?

UNLABELLED: Plasma lipid disturbances are common among patients on maintenance haemodialysis and it seems to be important to evalate lipid status on r-Epo since this treatment of anemia is becoming substantial and so often used in that population. It appears more valuable because there are controversial data in the literature concerning this problem. The aim of the present study was to measure changes in serum lipid concentration in two comparable groups: I--11 patients (7f, 4m) aged 47 +/- 8 years receiving r-Epo s.c. during at least 6 months before HD and 2 years of HD with initial dose 3 x 50 u/kg b.w. and II--18 patients (7f, 11m) aged 45 +/- 8 years without r-Epo in that period of time. Following parameters were estimated every two months: total cholesterol (CH-C), HDL cholesterol (HDL-CH), LDL cholesterol (LDL-CH), triglycerides (TG), apolipoprotein B (Apo B). CONCLUSIONS: 1. Subcutaneous therapy with r-Epo is an effective method of treatment of anemia in dialysis patients. 2. Long-term r-Epo treatment does not permanently influence the blood lipid profile in hemodialysed patients.

[A case of spontaneous non-traumatic rupture of the kidney during renal vessel thrombosis]. / Przypadek samoistnego nieurazowego pekniecia nerki w przebiegu zakrzepicy naczyn nerkowych.

We present a case of spontaneous non-traumatic rupture of kidney in a 78-year old patient, probably caused by renal vessel thrombosis. In spite of the relatively good prognosis in early diagnosis, the outcome of presented case was fatal because of late surgical complications.

[Effect of human recombinant erythropoietin (r-EPO) on behavior of iron status parameters in patients with chronic renal failure treated with dialysis]. / Wplyw rekombinowanej ludzkiej erytropoetyny (r-EPO) na zachowanie sie parametrów gospodarki zelazem u chorych z przewlekla niewydolnoscia nerek leczonych hemodializami.

For proper erythropoietic response to r-Epo iron, folic acid and B12 vitamin are needed. Iron deficiency is the most common in uremic patients treated with r-Epo. So the aim of presented study was to measure hematological and iron status changes. Studies were carried out in 23 anemic, uremic, hemodialysis patients. They were divided into two groups, the first HDa--5 people (3W, 2M) aged 23-49 (mean 34 +/- 12) years and the second HDb 18 patients (11W, 7M) aged 21-56 (mean 38 +/- 12) years. Mean hemoglobin (HGB) before r-Epo was 6.9 +/- 1.0 g/dl in HDa, and 6.7 +/- 1.1 g/dl in HDb. r-Epo in HDa group was given during 12 weeks i.v. and afterwards s.c. for other 4 weeks with initial dose 3 x 50 u/kg b.w. (mean during 4 months 65 +/- 24 u/kg m.c. 3 times weekly). Patients from HDb group received r-Epo during 12 months only s.c. with initial dose 2000 u three times per week (mean during 12 months 26 +/- 4 u/kg m.c. 3 times weekly). Dose of r-Epo was changed accordingly to HGB concentration to keep it between 10-12 g/dl. Blood morphological parameters were monitored weekly using hematological autoanalyser Technicon H1, simultaneously an iron status indicators as iron, transferrin and ferritin were measured. An increase of HGB concentration, erythrocytes count and Ht value was observed in all patients (I-HGB 10.1 +/- 2.9, II-HGB 9.2 +/- 1.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of iron status monitoring during erythropoietin treatment in uremic predialysis patients.

Since recombinant human erythropoietin (r-Hu EPO) has been introduced to the treatment of anemia in uremic patients the issue of optimal therapy appeared. For proper erythropoiesis not only erythropoietin but also iron, folic acid and B12 vitamin are needed. Iron deficiency is one of the most common factors causing resistance to r-Hu EPO in uremic patients, so its recognition and eventual supplementation is required for optimal hemopoietic response. The aim of presented study, besides monitoring hematological changes, was to measure iron status parameters such as iron, transferrin, ferritin and percentage of hypochromic erythrocytes and estimation of their usefulness in monitoring iron deficiency during r-Hu EPO treatment.