Histomorphometric diagnostics of renal osteopathy in chronic dialysis patients at high risk of cardiovascular disease.

UNLABELLED: Chronic kidney disease-mineral and bone disorder (CKD-MBD) ranks among clinically and pathogenetically significant complications in patients with CKD. Numerous factors are involved in its development, and histomorphometric analysis of the bone tissue is still necessary for accurate diagnosis. METHODS: The open, pilot, prospective study aimed at performing a comprehensive histomorphometric bone analysis in 26 dialysis patients and assessing the relationships of different types of CKD-MBD to selected parameters of calcium and phosphate metabolism, densitometry, activity of parathyroid glands, presence of diabetes mellitus, and duration of dialysis treatment. RESULTS: Comparison of the histomorphometric characteristics demonstrated statistically significant correlations between the volume of bone trabeculae and s-procollagen 1 (.754) as well as s-calcitonin (.856). Similarly, there was a positive correlation between the size of tetracycline lines and volume of bone trabeculae (.705) and a strong negative correlation with the thickness of trabeculae (-.442). When assessing the serum levels of s-osteoprotegerin and serum RANKL, there was a correlation with osteoid thickness and bone trabeculae thickness. In case of s-osteoprotegerin, a statistical power was demonstrated in relation to osteoid thickness (.880); in case of s-RANKL, a statistical power was demonstrated in relation to the thickness of trabeculae (.830). When assessing the influence of dialysis duration, relationships to the volume of trabecular bone (.665) and volume of bone trabeculae (.949) were demonstrated. Finally, a relationship between s-1,25-hydroxyvitamin D and s-osteoprotegerin was observed (.739); also the relationships demonstrated were significantly lower volume of bone trabeculae in men (p = 0.067) and lower values of s-osteocalcin and s-procollagen 1 in diabetic patients (p = 0.014). CONCLUSION: The results provide new noninvasive possibilities of CKD-MBD detection that are based on selected serum parameters of bone metabolism. Presented are possibilities of noninvasive assessment of different types of CKD-MBD using serum osteomarkers in relation to comprehensive CKD-MBD histomorphometry.

[An effect of continuous and intermittent renal replacement therapy on antibiotic treatment in critically ill patients with sepsis - a practice-based perspective of vancomycin and gentamycin therapies]. / Vliv kontinuální a intermitentní náhrady renálních funkcí na antibiotickou lécbu u kriticky nemocných v sepsi - praktický pohled na lécbu vankomycinem a gentamicinem.

Sepsis and septic shock are common cause of hospitalisation in intensive care unit. Acute kidney injury is an accompanying manifestation of sepsis/septic shock leading to worsening of morbidity and also mortality and requiring use of intermittent or continual renal replacement therapy. Life saving effect is attributed to early and effective antibiotic therapy. Therapeutic drug monitoring and do-sage adjustment is important for successful treatment. Despite therapeutic drug monitoring of both antibiotic agents vankomycin and gentamicin the treatment still rises many questions about the convenient use in septic patients due to their nephrotoxicity.

[Anemia in chronic renal insufficiency and chronic failure]. / Anémie u chronické renální insuficience a chronického selhání.

Complicated metabolic changes in chronic renal insufficiency interfere with the formation and survival of erythrocytes at many levels. Anaemia which thus develops influences in a significant way not only the quality of life but also the prognosis of nephrological patients. The confirmed relationship between cardiovascular morbidity and mortality must be the starting point for early diagnosis and treatment of this anaemia. Administration of recombinant human erythropoietin in the early stage of renal insufficiency can moreover probably retard its progression. European guidelines for the treatment of anaemia give clear instructions how to proceed in the treatment of anaemia. The results of current, so far not completed studies, may modify in future the demands on target haemoglobin values and may elucidate how normalization of the red haemogram can influence the survival of patients with impaired renal function.

[Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) leading to the diagnosis of Wilson's disease]. / Trombotická trombocytopenická purpura--hemolyticko-uremický syndrome (TTP-HUS) vedoucí k diagnóze Wilsonovy choroby.

Authors describe the case of a patient suffering from Thrombotic Thrombocytopenic Purpura--Hemolytic-Uremic syndromee. Any cause of the disease was not found, except signs of liver injury. The etiology of indefinite liver disease that had been diagnosed several years before was examined. Wilson's disease was considered as a final eventuality. The finding of 488 micrograms of copper in the dry liver tissue confirmed the diagnosis of Wilson's disease in the end.

Determination of total antioxidant capacity in plasma by cyclic voltammetry. Two case reports.

The cyclic voltammetry (CV) was used for the measurement of the plasma total antioxidant capacity from two types of patients. The first one consisted of 29 volunteers (men aged 18-21 years) who were administered placebo or silymarin at a dose of 858 mg/day. After two months of silymarine administration, CV revealed a statistically significant increase in total antioxidant capacity compared to placebo. No statistically significant changes in TBARS, SH-groups, creatininin, urea, and uric acid concentrations were found. The second group under study comprised 49 patients with chronic renal disease during dialysis therapy. After dialysis, CV revealed a decrease of total antioxidant capacity in the plasma, which was equivalent to a decrease in creatinine, urea and uric acid. CV was performed using a system consisting of a working glassy carbon electrode, an auxiliary platinum electrode, and a reference saturated calomel electrode; a linear change of voltage of 200 mV/s was applied. CV is a simple and relatively reliable method for assessment of body antioxidant status. It is also time and cost effective.

[Optimal therapy with erythropoietin (EPO) in patients with renal anemia on hemodialysis therapy]. / Optimalizace lécby EPO u pacientu s renální anémií v pravidelném hemodialyzacním lécení.

Treatment of anaemia of renal origin by recombinant erythropoietin (EPO) is well established and is considered to be an integral part of therapy in patients with chronic renal failure. An open, non-controlled and multicenter study was designed with aim to verify the dosage of EPO, necessary to reach and maintain rational correction of renal anaemia in a representative group of patients in chronic haemodialysis (HD) treatment. Target range of haemoglobin (Hb) was defined to be 100-120 g/l in adult patient, length of maintenance phase of follow-up 6 months. 183 patients from z 8 HD centres were included to the study, in this number 83 (45.4%) men and 100 (54.6%) women, aged 59.8 +/- 14.4 years (min. 20 and max. 87 years). During the next 6 months haemoglobin levels raised from baseline value Hb0 100 g/l to Hb1 102.9, resp. Hb2-104.9, Hb3 106.1, Hb4 107.5, Hb5 108.2 and Hb6 108.1 g/l; while mean total weekly doses of EPO/kg (TWD/kg) in the respective period corresponded to TWD/kg0 62 IU, resp. TWD/kg1 66 IU, TWD/kg2 67 IU, TWD/kg3 62 IU, TWD/kg4 64 IU, TWD/kg5 60 IU, TWD/kg6 56 IU. Clinical complications (inflammatory state, bleeding...) that could in different extent reduce the effectivity of EPO treatment were observed in 50 cases. No serious clinical complications that could be attributed to EPO treatment were found. On basis of results of our study, it is justified to assume that target range of Hb between 100-120 g/l can be reached with relatively modest increase of EPO dosage in comparison to current praxis in HD centres in CR, and that following cautious dosing of EPO (comparable to the dosing schema in our study) the treatment should not be connected with the development of major clinical complications.

[Dual-photon bone densitometry in dialyzed patients]. / Dvoufotonová kostní denzitometrie u dialyzovaných nemocných.

In non-invasive diagnosis of renal osteodystrophy the levels of bone minerals and the extent of bone turnover are evaluated. The contents of bone minerals are assessed quantitatively by different modalities of bone densitometry, among which the most accurate one is double-energy bone densitometry. So far no standard examination method was defined nor the most suitable portion of the skeleton for densitometric examination. In order to find such an area and also to assess the prevalence of bone demineralization, its severity and regional differences the authors made a cross-sectional study of bone density in dialyzed patients. The group comprised 45 patients, 24 men and 21 women subjected to regular dialyzation treatment for 20-24 months. In a lambda whole body bone densitometry was performed with evaluation of regional densities of the trunk, upper and lower extremities. At the same time the state of bone turnover was assessed arbitrarily using values of serum concentrations of intact parathormone; parathormone concentrations below 50 pg/ml were considered low, above 200 pg/ml high and concentrations within the mentioned range as the normal bone turnover. In the group of patients 62% had a high, 22% a normal and 16% a low bone turnover. The study provided evidence of a significant reduction of bone density (Z score <-1) in 58% of patients. In 92% of patients demineralization affected most and first the extremities. In 69% it affected the lower extremities and in 23% the upper ones. 8% of the patients had the most severe affections in the area of the trunk. This order of affliction was not influenced by bone turnover, sex and in women by age. The diaphysis of long bones seems to be a representative examination area of the skeleton for densitometric measurements in patients with regular dialyzation treatment.

[Dyslipoproteinemia and chronic kidney failure]. / Dyslipoproteinémie a chronické selhání ledvin.

Lipoprotein abnormalities are a regular part of metabolic changes associated with chronic renal failure. The character of dyslipoproteinaemia changes with the severity of disorders of renal functions, from initial deviations in the composition and distribution of circulating lipoprotein particles (a decline of glomerular filtration to 0.7-0.8 ml/s) to differently expressed changes of plasma lipid concentrations in terminal renal failure. The basis of the pathogenetic mechanism of these lipid abnormalities is the negative effect of the uraemic environment on the formation and catabolism of triglyceride-risk lipoproteins and on the function of the reverse cholesterol transport. An important part is also played by the modification of lipoprotein particles by oxidation and glycation. To a different extent also the nutritional status is manifested via the unfavourable composition of dietary fats, reduced effectiveness of antioxidant factors and in some instances also carnitine deficiency. Haemodialysis treatment and in particular peritoneal dialysis modify these lipid abnormalities. From the quantitative aspect renal dyslipoproteinaemia is not very striking, despite this its quantitative changes are important. It may have a negative impact on the progression of renal disease by its participation in the development of glomerular sclerosis and tubulointerstitial fibrosis. As one of the important risk factors it participates also in the acceleration of atherosclerosis in patients with chronic renal failure and in their much higher cardiovascular mortality as compared with the general population. These factors justify efforts to influence uraemic dyslipoproteinaemia. Fibrates or statins are indicated in conjunction with the supporting effect of diet and modification of the dialysis regimen. In tables and figures some results assembled by the authors are presented obtained in a group of dialyzed patients (characteristic of the lipid profile under basal conditions on fasting and after an oral lipid load and experience with influencing dysliopoproteinaemia by fenofibrates and atorvastatin).

Single photon bone densitometry in hemodialysis patients.

Renal osteodystrophy is a common finding in patients with renal insufficiency. The maximum of its intensity is found in hemodialysis patients. Bone densitometry is so far the best method for non-invasive assessment of the extent of the illness. Some densitometric studies in hemodialysis patients have already been published but their results differ in prevalence and intensity of renal osteodystrophy. They also demonstrated a slight relationship between intensity of renal osteodystrophy and duration of the dialysis treatment. Opinions vary on the relationship between bone mineral density and markers of bone turnover. This cross-sectional study found high prevalence of renal osteodystrophy (Z-score below -1 in 57% of patients) as well as high a number of severely damaged patients (T-score below -2.5 in 40% of patients). It also showed some correlation between bone demineralisation and the duration of dialysis. None from evaluated markers of bone turnover correlated with bone mineral density.

[Endogenous erythropoietin in patients on regular dialysis therapy]. / Endogenní erytropoetin u nemocných v pravidelném dialyzacním lécení.

In a group of 66 patients with chronic renal failure having regular dialyzation treatment the serum concentration of endogenous erythropoietin (EPO), haemoglobin levels (Hb), haematocrit (Ht) and serum creatinine (Cr) were assessed. The examined subjects were never treated with recombinant erythropoietin and deficiency of iron, folic acid and vitamin B12 was ruled out. Endogenous EPO was assessed by the authors own RIA method, normal values being 24-42 mU/ml. The mean EPO concentration in the whole group of patients was 37.4 +/- 15.3 mU/ml, whereby 12 patients had an EPO serum concentration higher than the upper range of normal values. Between EPO concentrations and Hb values a certain positive correlation was found (r = 0.42). A similar relationship was revealed also between EPO concentrations and Ht values (r = 0.41). Patients with EPO values higher than 42 mU/ml had, as compared with the other patients, significantly higher values of erythrocytes (p .001). Statistical analysis did not reveal any relationship between EPO and Cr concentrations (r = -0.04). A low negative correlation was found between Cr and Hb values (r = -0.31) and between Cr and Ht values (r = -0.25). In the discussion the authors analyze the contemporary state of the problem of anaemia in chronic renal failure. Based on hitherto assembled knowledge they formulated the hypothesis ascribing considerable pathogenetic importance in the development of anemia to reduced sensitivity of bone marrow to EPO, probably as a result of retention of uraemic toxins and inhibitors of erythropoiesis. Inadequate EPO formation could be only a factor which makes it impossible for the developing anaemia to compensate and is due to an animpaired feedback at the level of recognition of the hypoxic signal.

[Erythropoietin and erythropoiesis after kidney transplantation]. / Erytropoetin a erytropoéza po transplantaci ledviny.

In a group of 15 patients after the first transplantation of a cadaverous kidney the authors monitored for the period of one month the serum erythropoietin concentration (Epo), haemoglobin levels (Hb), the haematocrit (Ht) and serum creatinine (Cr). The objective of the investigation was to evaluate in relation to serum concentrations of Epo and the function of the graft. Erythropoietin was examined by the authors own method before and after transplantation during the first 10 days daily and then on the 12th, 15th, 20th, 25th and 30th day. Normal values are 22-44 mU/ml. The mean Epo value before transplantation was 41.9 +/- 18.8 mU/ml. After transplantation the highest mean value of Epo was recorded on the second day when it reached a value of 102.8 +/- 144 mU/ml. The mean Epo serum concentration at the end of the study was 45.9 +/- 20.9 mU/ml and did not differ significantly from values recorded before transplantation. Between Hb and Ht values and Epo serum concentrations no correlation was revealed. Conversely, statistical analysis revealed a close inverse relationship between the drop of creatininaemia and the rise of Hb and Ht values. From the results of the investigation ensues that the decisive condition for the onset of the erythropoietic response after renal transplantation is adjustment of the milieu interiéur, induced by the restored excretory function of the graft which creates prerequisites for a normal response of the bone marrow to Epo.

Clinicopathological aspects of Richter's syndrome.

Richter's syndrome represents an acute transformation of chronic lymphocytic leukaemia or other type of low-grade malignant non-Hodgkin lymphoma to highly malignant anaplastic large-cell lymphoma. The prognosis of this complication is highly unfavourable. The authors report on eight cases of Richter's syndrome observed in a series of 198 patients with the clinical diagnosis of chronic lymphocytic leukaemia and evaluate some clinicopathological and immunological peculiarities of this disease.