[Cyclosporin A versus cyclophosphamide in the treatment of nephrotic syndrome in children]. / Cyklosporín A verzus cyklofosfamid v liecbe detí s nefrotickým syndrómom.

BACKGROUND: The majority of cases of nephrotic syndrome in children is corticosensitive, however in some individuals aggressive cytotoxic therapy is necessary. Cyclosporin A and cyclophosphamide are widely used; however their relative effectiveness in maintaining remission of childhood nephrotic syndrome remains controversial. METHODS AND RESULTS: Effectiveness of long-term cytotoxic therapy (mean follow-up 7.4 years) in 63 children (mean age 6.19 +/- 4.30 years) with nephrotic syndrome was retrospectively analyzed; 14 patients suffered from corticosensitive, 33 from corticodependent and 16 from corticoresistant nephrotic syndrome. Corticotherapy alone was used in 15 patients (23.8%), cyclophosphamide was added in 27 (42.9%) and cyclosporin A in 38 cases (60.3%), while 17 patients (27%) were on both immunosuppressive agents. 84% children relapsed within 24 months after cessation of cyclosporin A. In 8 corticoresistant nephrotic syndrome patients (61.5%) from 13 children treated with cyclosporin A no remission occurred, in 5 children (38.5%) was remission obtained within 10 weeks, however in 4 of them relapsed disease during cyclosporin A therapy. 19 (70.4%) of 27 patients on cyclophosphamide therapy were in remission, in 8 of them (42.1%) even 2 years after cyclophosphamide therapy. CONCLUSIONS: Cyclophosphamide therapy of childhood nephrotic syndrome is more effective in maintaining long-term remission than cyclosporin A treatment.

[Relation between metabolism of trace elements and the antioxidant defense system in chronic nephropathies]. / Vztah medzi metabolizmom stopových prvkov a obranným antioxidacným systémom pri chronických nefropatiách.

BACKGROUND: Trace elements--zinc, copper and selenium are part of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GHPx). In renal diseases changes in the trace element metabolism may influence the equilibrium in the antioxidant defence system and enhance the toxic effect of reactive oxygen molecules. METHODS AND RESULTS: The authors examined in 53 children with chronic neprophathies (34 with chronic glomerulonephritis, 11 with chronic renal failure and 8 children included in a chronic dialyzation programme) zinc and selenium in blood and urine and antioxidant enzymes SOD and GHPx in red blood cells. The lowest SOD activity (737 +/- 219 U/g Hb, p < 0.01) and serum zinc concentration (12.9 +/- 3.2, p < 0.05) were found in children in the terminal stage of uraemia, GHPx was as compared with the group of healthy children elevated in all groups of sick children. In dialysed children GHPx was highest (p < 0.01) and correlated with urinary selenium concentrations (r = -0.86, p < 0.05). The SOD activity depended on the serum copper concentrations (r = 0.78, p < 0.05). The highest renal zinc and selenium excretion was recorded in patients with glomerulonephritis (p < 0.05). CONCLUSIONS: The results support the hypothesis on a causal relationship between trace elements and antioxidant enzymes.

Enalapril treatment of proteinuria in normotensive children.

A retrospective study was performed in 48 normotensive proteinuric children to evaluate the effect of enalapril (n = 17), a combination of enalapril and prednisone (n = 11) and prednisone alone (n = 20) on urinary protein excretion and systemic blood pressure. Enalapril treatment was associated with significant and persistent diminution of proteinuria from 1.32 +/- 0.23 to 0.53 +/- 0.11 and 0.44 +/- 0.07 g/day on the 4th and 8th week of treatment, respectively. Combined therapy with enalapril and prednisone resulted in a comparable significant reduction of proteinuria from a pre-treatment value of 2.06 +/- 0.42 to 0.63 +/- 0.22 and 0.52 +/- 0.17 g/day on the 4th and 8th week of treatment, respectively. In contrast to this, in the group treated with prednisone alone, proteinuria decreased significantly only from the 6th week of therapy (p < 0.02). Consequently, these children had significantly higher urinary protein losses at the 4th week of treatment as compared to patients on enalapril treatment (given either alone or combined with prednisone) (p < 0.01 and p < 0.05, respectively). Importantly, the enalapril-induced reduction of proteinuria was unrelated to variations in arterial blood pressure and no significant changes in this parameter were observed. The results indicate that enalapril can be used safety and effectively for symptomatic treatment of proteinuria in normotensive children with preserved renal function. ACE inhibitor provides additive antiproteinuric effect to corticosteroids by accelerating the rate of diminution of proteinuria. Its combination with prednisone may be of particular importance in those cases, where the degree of hypoproteinemia is a concern. (Tab. 2, Fig. 1, Ref. 29.)

[Will administration of omega-3 unsaturated fatty acids reduce the use of nonsteroidal antirheumatic agents in children with chronic juvenile arthritis?]. / Môze podávanie omega-3 nenasýtených mastných kyselín znízit spotrebu nesteroidných antireumatík u detí s juvenilnou chronickou artritídou?

BACKGROUND: An increased intake of omega-3 polyunsaturated fatty acids (PUFA) in the diet of patients with rheumatoid arthritis has a favourable effect on the course of the disease. The objective of the present work was to assess the effect of such a diet on the daily consumption of non-steroid antirheumatic drugs in children with juvenile chronic arthritis. METHODS AND RESULTS: A group of 23 children with the diagnosis of chronic juvenile arthritis was divided by the method of random numbers into two groups. The first group received in addition to ibuprofen treatment a diet with an increased content of omega-3 PUFA. The second group served as control. In the first group (13 patients, mean age 11 years) in the course of five months treatment the original ibuprofen consumption declined by 17.3% (from a mean value of 28.4 mg/kg/day to 23.4 mg/kg/day), while in the control group (10 children, mean age 9.1 years) there was a decline of 6.5% (from a mean value of 23.7 mg/kg/day to 22.7 mg/kg/day). This difference was statistically significant at the level of 0.05 (P = 0.03). CONCLUSIONS: Despite the statistically significant difference in the decline of daily consumption of the non-steroid antirheumatic drug in the investigated groups of patients and the obvious favourable effect of omega-3 PUFA the mean consumption of the drug remained in the first group after five months of treatment higher (23.4 mg/kg/day) than in the control group (22.4 mg/kg/day).

[Antioxidant enzyme activity in erythrocytes in children with kidney diseases]. / Aktivita antioxidacných enzýmov v erytrocytoch u detí s oblickovými chorobami.

BACKGROUND: An important place is ascribed to the formation and action of free oxygen radicals in the pathogenesis of some kidney diseases. The objective of the present work was to examine the antioxidant enzyme defence mechanism in children with different nephropathies. METHODS AND RESULTS: In a group of 58 children (32 boys and 26 girls, mean age 13.9 years) with different renal diseases (35 children with chronic glomerulonephritis-GN, 8 children with a relapse of the nephrotic syndrome and 15 patients with chronic renal insufficiency-CHRI) the concentration of superoxide dismutase and catalase (KAT) was examined. The SOD and KAT activity in erythrocytes was assessed spectrophotometrically at 240 nm. In the whole group of patients the mean SOD values (632 +/- 102 U/g Hb) and KAT values (3.29 +/- 0.54 mukat/g Hb) were within the reference range. The highest mean SOD and KAT values were recorded in children with a relapse of nephrotic syndrome. In the group with chronic GN the SOD concentration in erythrocytes correlated significantly with total protein levels and serum creatinine resp. (r = 0.350, p < 0.05 and r = -0.458, p < 0.01 resp.). In the CHRI stage the authors revealed a significant relationship between the SOD activity and total protein levels (r = 0.550, p < 0.05). CONCLUSIONS: The activity of basic antioxidant enzymes SOD and KAT in erythrocytes of children with nephropathies is not significantly reduced. In patients with chronic GN there is a significant correlation between renal functions and SOD.

Changes of physico-chemical characteristics of red blood cells in children with nephrotic syndrome.

Changes of milieu interieur in nephrotic syndrome (NS) have many consequences in various organs. We have measured the electrical charge of erythrocytes (Ery) with binding of alcian blue (AB) in 18 children with relapse of NS (12 minimal changes, 3 membranous and 3 mesangioproliferative glomerulonephritis) and 15 healthy children. The most important finding was that the binding of AB to Ery in patients with minimal change nephrotic syndrome (MCNS) and other aetiologies of NS was significantly less than that in the control group (p < 0.05). In addition, we have studied the thermal denaturation of the Ery membranes by differential scanning microcalorimetry. In some children with NS we have seen the splitting of B transition. We suppose that these phenomena occur as the result of structural change, which may involve lipoprotein components of the cytoskeletal network.

Serum response of Escherichia coli strains causing dyspepsia and urinary tract infection: relation to alpha-hemolysin production and O type.

A total of 109 alpha-hemolytic and 104 nonhemolytic Escherichia coli isolates from children with dyspepsia and urinary tract infections were investigated for resistance to the bactericidal activity of human serum. A significantly higher proportion of serum resistance was found in alpha-hemolytic E. coli isolates than in nonhemolytic isolates (P < 0.01). An association between the titer of alpha-hemolysin produced and serum resistance was found.

[Present possibilities of improving the diagnosis of glomerular erythrocyturia]. / Súcasné moznosti zlepsenia diagnostiky glomerulovej erytrocytúrie.

Examination of glomerular erythrocyturia which proved useful in the differential diagnosis of haematuria faces in practice two serious problems--the necessity to examine fresh urine and differences as regards the interpretation of criteria of glomerular erythrocyturia (from 10 to 80%). The authors examined therefore the morphology of erythrocytes in urine of 65 children with different causes of haematuria, incl. 35 patients with different forms of glomerulonephritis. They found that adding 25 mg thimerasol to 10 ml urine preserves urinary elements, incl. morphologically altered red cells for a period of 72 hours or longer. This makes it possible to examine the red cells under a phase microscope after dealing with ambulatory patients. Among various morphological forms of red cells in urine of 31 patients with glomerulonephritis in urine acanthocytes were found in a concentration above 5%, and in the majority above 20%. Acanthocyturia above 5% was not present only in 4 patients with glomerulonephritis, whereby all four suffered from mild erythrocyturia. The authors consider therefore acanthocyturia above 5% as the most reliable evidence of glomerulonephritis, in case of erythrocyturia above 10 Ery in the visual field. The criteria of acanthocyturia in children are thus lower than in adults.

[Renal venous thrombosis in neonates]. / Renálna venózna trombóza u novorodenca.

The authors present an account on a neonate with dextro-lateral renal venous thrombosis. They focus attention on the diagnostic and therapeutic procedure and compare it with available data from the literature. Contrary to data in the literature, they did not observe in the acute stage of renal venous thrombosis signs of disseminated intravascular coagulation in peripheral blood. It did not prove possible to elucidate the action of any of the factors leading to the development of renal venous thrombosis. After evidence of permanent functional loss of the right kidney nephrectomy was performed. Histopathological examination provided evidence of obliterating thrombosis of the renal veins with partial recanalization and calcifications. The authors emphasize the necessity of early diagnosis of renal venous thrombosis and adequate treatment based on the revealed findings.

[Hyperinsulinism--a new pathogenic cause of cardiovascular diseases]. / Hyperinzulinizmus--nová patogenetická cesta kardiovaskulárnych chorôb?

Authors call attention to the insulin-resistance and following hyperinsulinism, as important and may be also the basic factor, which is determining for high cardiovascular morbidity and mortality. Authors analyze the pathogenesis of the Reaven's syndrome X, syndrome 5H and their symptoms--insulin-resistance, hyperinsulinism, hyperlipemia with obesity, hypertension and eventually hirsutism. Authors analyze the congenital and acquired factors, which influence its manifestation and so occurrence of the cardiovascular diseases in the adulthood. In the past paediatricians gave little attention to this problem because they supposed the problem as the problem of the adult medicine. We can see that full 5H syndrome is only the top of the iceberg with basis in childhood. In the prevention of the cardiovascular diseases the task of the paediatricians is therefore not substitutable and in future they need to give to the X syndrome extraordinary attention.

[ACE inhibitors--a potential new group of drugs for treatment of kidney diseases]. / Inhibitory ACE--nová perspektivna skupina liekov v terapii oblickových chorôb.

ACE inhibitors, which till recently were used almost exclusively for treatment of cardiovascular diseases, are becoming a perspective group of drugs also in the treatment of nephropathies. It was found that they are effective in particular in the treatment of proteinuria of varying origin and have also a marked renoprotective effect and are therefore recommended to retard progression of renal failure. They reduce intraglomerular hypertension, increase glomerular filtration and the renal blood flow, and it is assumed that they can retard progression of chronic glomerulonephritis and diabetic nephropathy. We may expect already in the near future that their therapeutic application will be substantially extended also in clinical nephrology.

[ACE inhibitors--a prospective new group of drugs for the treatment of kidney diseases]. / Inhibitory ACE--nová perspektivna skupina liekov v terapii oblickových chorb.

ACE inhibitors which till recently were used only in the treatment of cardiovascular diseases are becoming a perspective group of drugs also in the treatment of chronic nephropathies. It was revealed that they are effective in particular in the treatment of proteinuria of different etiology and have also a marked renoprotective effect and are therefore recommended to slow down the progression of renal failure. They reduce intraglomerular hypertension, increase glomerular filtration and the renal blood flow, and it is assumed that they can retard the progression of chronic glomerulonephritis and diabetic nephropathy. It may be excepted that their therapeutic application will in the near future be extended also to clinical nephrology.

[Are dietetic and non-immunologic therapies becoming deciding factors in the treatment of autoimmune diseases?]. / Stáva sa diétna a neimunologická liecba rozhodujúcim faktorom v terapii autoimúnnych chorôb?

Authors call attention to non-immunological therapy and its determining role for fate and final prognosis in patients with autoimmune diseases. A stress importance of the timely and rigorous antihypertensive and antiinfectious treatment. From the dietary measures is best known favourable effect of the low protein diet and pharmacological limitation of the phosphorus supply. A new therapeutical aspect is the influence of the lipids on the autoimmune diseases activity and efficiency of the omega-3 unsaturated fatty acids. Non-immunological methods of the treatment are particularly valuable for the general practitioners and pediatricians, because enable them essentially to influence the course of the autoimmune diseases.

[New views on the pathophysiology of the nephrotic syndrome]. / Nové pohl'ady na patofyziológiu nefrotického syndrómu.

The authors draw attention to new pathophysiological aspects of some symptoms of the nephrotic syndrome (NS), in particular proteinuria, hypoalbuminaemia and oedema. In proteinuria they focus attention on the formation of a new population of heteropores in severe morphological forms of NS with penetration of high molecular proteins into urine. In hypoalbuminaemia the authors emphasize the importance of an inadequately increased albumin synthesis in the liver. In case of oedema in the majority of patients hypovolaemia is not present, as was assumed so far. In the pathogenesis of oedema primary Na retention in the kidneys is important caused by the glomerulonephritic process. New findings in the pathophysiology of NS lead to changes of several clinical approaches. The authors draw attention e.g. to the need of dietary protein restriction in NS, on altered effects of drugs in NS, new approaches to diuretic treatment etc.

[Personal experience with the use of human recombinant erythropoietin in the treatment of anemia in children with chronic renal insufficiency]. / Nase skúsenosti s pouzitím l'udského rekombinantného erytropoetínu v liecbe anémie u detí s CHRI.

The authors analyze the course of treatment with human recombinant erythropoietin (rHuEPO) in five children in the preterminal stage of chronic renal insufficiency and one premature infant with a low birth weight and anaemia and acute renal insufficiency. rHuEPO was administered, 50-100 u./kg, by the s.c. route 2-3X per week. During the first month of treatment the haemoglobin rose from 7.0 dag/l to 8.2 dag/l and persisted at this level approximately to the third month of treatment. The haematocrit reached values of 0.30 during the 4th month of therapy when the authors observed also the maximum increase of reticulocytes (20%). The authors did not find a marked decline of iron and ferritin concentrations. In the child with a low birth weight treatment with rHuEPO was started at the age of six weeks and the age haemogram was favourably influenced already after four weeks of treatment with rHuEPO.

[Recombinant erythropoietin--a fundamental change in the treatment of anemia?]. / Rekombinantný erytropoetín (rHuEPO)--zásadný obrat v liecbe anémií?

The authors summarize in the submitted review recent findings on erythropoietin (EPO) and recombinant EPO (rHuEPO), a new therapeutic preparation which changed fundamentally the clinical picture of many diseases associated with anaemia. The authors discuss the physiology of EPO, regulation of its secretion, mechanism of action on bone marrow and its importance in the pathogenesis of polycythaemia and in particular anaemia. They emphasize in particular the use of rHuEPO in the treatment of different forms of anaemia. They analyze the pathogenesis of renal anaemia and the importance of treatment with rHuEPO for improvement of the haemogram as well as the general condition of the patients, their adaptability, improved psychic condition and reduced need of transfusions. The authors draw attention to the great importance of treatment with rHuEPO in the treatment of anaemias associated with inflammatory diseases (rheumatoid arthritis, AIDS, Crohn's disease and others), anaemia associated with malignancies, in the treatment of surgical diseases and in autotransfusions, in anaemias of premature infants and in some congenital heart diseases. The introduction of rHuEPO into the treatment of anaemia is a great advance of modern pharmacotherapy, which moreover opened new vistas on the role of anaemia in the clinical picture of many diseases.

The importance of immunohistochemical examination of glomerulonephritis.

There were 942 cases of glomerulonephritis classified according to WHO out of 1499 renal biopsies. Immunoglobulins IgG, IgA, IgM, C3 and fibrinogen were examined immunohistochemically in a standard way and IgD, IgE, albumin, C4 and HBsAg in a non-standard way. The results were compared with a control group. The results show that the excluding value of the negative immunohistochemical examination in glomerulonephritis is higher than the proving value of the positive examination.