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Nephrotic syndrome (NS) remains a serious clinical setting characterized by marked proteinuria, hypoproteinemia and hypercholesterolemia, usually accompanied by the presence of oedemas. It could be presumed, that the newly discovered hormone leptin plays an important role in the complex metabolic processes occurring in patients with NS, in which apart from the changes in the hydratation, and the protein and lipid spectre profile changes, the alteration of the metabolism of glycides elicited by the treatment with corticosteroids (CS) is often observed. The aim of the study was to investigate the plasma levels of leptin and its plasma soluble receptor (sLe-R) before and after the treatment with CS and to evaluate their relationship with albuminemia and/or proteinuria. The study group consisted of 15 men and 15 women (mean age 49 +/- 13.7 years) with newly diagnosed NS, verified by renal biopsy, in which subsequently CS treatment was started. Before the treatment (period 1) and further one month (period 2) and six months (period 3) after the start of the treatment the following parameters were measured: body mass index (BMI), serum levels of creatinine, albumin, cholesterol, triglyceride, cholinesterase, proteinuria/24 hour and plasma levels of leptin and sLe-R. In comparison to the relatively high values of BMI in the period 1 a decrease of BMI towards the physiologic range was observed during the treatment periods. Statistically significant changes were also observed in proteinuria (decrease) and in serum cholesterol and albumin levels of whereas in other biochemical parameters, including plasma leptin and sLe-R levels, statistically significant changes were not found. A trend to negative correlation with borderline statistical significance could be observed between leptin and sLe-R. The results of our relatively unique study on leptin--dealing with long-term follow-up of the patients with NS suggest that regardless prominent metabolic alterations present in NS the plasma levels of leptin and sLe-R remain relatively stable, and that of regulation of leptin in this setting is probably complex and multifactorial.

In normotensive patients (pts) with apparently inherited electrolyte disorder characterized by hypokalemia and with metabolic alkalosis the suspicion is usually pronounced on the diagnosis of Bartter syndrome or Gitelman syndrome. During the last two years three pts were admitted to our nephrologic unit of the 1st Internal Department of the 1st Medical School who presented with hypokalemia, metabolic alkalosis and alkalic urine and were followed previously under working diagnosis of (incomplete) renal tubular acidosis. In the article we give the description of the clinical picture in the three pts diagnosed as Bartter/Gitelman syndrome. In conclusion--the problems of differential diagnosis in pts with such a complex disorder of acidobase balance are discussed and new diagnostic approach with mutational studies is suggested.

An overview of fibrillary glomerulonephritis (GN) is given as well as the description of clinical course in four patients diagnosed and treated in our department. Fibrillary GN and immunotactoid glomerulopathy are entities, characterized by fibrillar and microtubular deposits in mesangium and the glomerular capillary loops. Decisive for diagnosis of fibrillary GN (resp. immunotactoid GN) remains the electron microscopy (EM) of the renal biopsy (RB) specimen. At the nephrologic division of 1st Internal Department of 1st Medical School of Charles University four cases of patients with fibrillary GN were diagnosed from the mid seventies (when both entities were newly described) by the end of the year 2001. In all patients the diagnosis was proven by EM. RB was indicated mainly for proteinuria, hematuria and decrease of renal function. On conclusion: though fibrillary GN/immunotactoid GN are relatively rare disorders, they represent entities, which should not be omitted in the differential diagnosis of nephrotic syndrome/renal insufficiency and which deserve further study.

An overview concerning different types of kidney involvement associated with monoclonal gammapathy (MG) is given, focused on light-chain deposition disease (LCDD). Pathophysiologic basis of LCDD remains in the light-chain tissue deposition (resp. in tissue deposition of immunoglobulin's stable domain). This mechanism is typical for monoclonal immunoglobulin's overproduction as found in MG. Clinical picture of LCDD reflects multiorgan character of disorder, while renal lesions rank among the most frequent, serious and best documented ones. Clinical data referring to a group of six patients, treated in our nephrologic department are presented. Diagnosis of LCDD was established on basis of the renal biopsy finding. Renal functions were decreased at the time of diagnosis in all patients, whereas haemodialysis treatment was started in one patient. On conclusion therapeutic possibilities of LCDD are discussed, in which number symptomatic therapy of renal failure is combined with corticosteroids therapy and cytostatic therapy; prognosis of most patients remains serious.

Leptin is a protein hormone produced by adipocytes. Its basic known function is its central hypothalamic action leading to reduction of food intake and augmentation of energy expenditure and thus to reduction of body weight. Various types of leptin receptors were found in other organs and tissues. The kidney is the main site, where leptin is eliminated from the body (probably by tubular degradation) under normal conditions and its blood concentrations increase significantly during renal failure. Leptin increases diuresis and natriuresis, increases sympathetic nerve activity in the kidney and participates in the elevation of blood pressure. It can also be involved in morphological changes in renal tissue, such as glomerulosclerosis, or stimulate growth and invasiveness of tumours.

A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB in patient with known malignancy and onset of renal failure was indicated with regard to an atypical picture of kidney involvement (non-enlarged kidneys, without any structural changes typical for tumour mass presence). Though spread of the primary tumour to the kidney is not uncommon, involvement severe enough to impair renal function is unusual and occurs primarily with rapidly growing haematologic malignancies; diagnosis is being established by renal biopsy only rarely.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary disease of kidney. The renal function is impaired by the development of the cysts. Patients with ADPKD have often affected other organs. Nowadays there is established linkage analysis of ADPKD using microsatellites in Czech Republic. Molecular analysis allows presymptomatic diagnosis in risk-individuals and prenatal diagnosis in affected families. The detection of mutations is performed supporting by the grant in Czech Republic. The detection of mutation will contribute to more precise diagnosis in controversial cases.

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.

Background: A lot of patients with end stage renal disease with the necessity of renal replacement therapy have some sleep problems. The aim of this study was to get basic information about the sleep of patients treated with continuous ambulatory peritoneal dialysis (CAPD), mainly their subjective view on their sleep, including comparison with hemodialyzed patients (HD)., Methods: All patients treated with continuous ambulatory peritoneal dialysis in two dialysis centres were given a simple questionnary containing 20 questions concerning sleep. It was filled in by all these patients--25 patients (mean age 58.1 years)--12 men and 13 women. Data obtained from 103 hemodialyzed patients from the same two-dialysis centres were used for comparison (mean age 60.4 years)--61 men and 42 women (the same questionnary)., Results: 40% of CAPD patients regard their sleep as bad. Thirty six percent of patients have problems with falling asleep, 32% awake three times or more during the night and 28% snore or have some breath problems. CAPD patients feel more frequently tired after the night (32% vs. 18.4% HD), more patients sleep during the day (64% vs. 5.15% HD) and fewer patients feel restlessness of legs (36% vs. 45.6% HD). These differences are not statistically significant., Conclusion: Occurrence of sleep disorders and their characteristics in patients on CAPD is similar to that in hemodialyzed patients.

The concentration of Cu, Se and Zn in whole human blood and plasma was analysed by inductively coupled plasma mass spectrometry. Method involved dilution of sample by diluted nitric acid and Triton X-100 and measurement of 65Cu, 77Se and 66Zn intensities. Calibration solutions were spiked by main interferents. In order to evaluate suitability of the method for recognition of alternation of trace elements concentration, the uncertainty of results was estimated. The major part of uncertainty was due to repeatability, the other source (calibration and interferences) were found to be of lesser importance. The resulting uncertainty of concentration of mentioned trace elements is low as compared to between individual variability. Short-term (within day) and long-term (between day) variability of trace elements concentration was investigated and compared with between individual variability too. The time variability was negligible except for Zn concentration. The alternations of trace elements concentration in patients with several renal diseases were investigated. Only in case of patients in end-stage renal disease: hemodialyzed patients and patient treated by continuous ambulatory peritoneal dialysis the significant alternations were proved.

An overview concerning principles and development of gene therapy from experimental models to first trials of application gene therapy in clinical medicine is provided. Increased attention is focused on specific methods of gene transfer into kidneys. Renal hereditary diseases represent an important subgroup of the diseases of the kidney, leading non rarely to chronic renal failure; (autosomal dominant) polycystic kidney disease remains to be one of the most frequent and clinically important. Preliminary conditions, including technical tools and pathophysiological insights to be fulfilled, as prerequisites for an application of gene therapy in polycystic kidney disease, are discussed.

The efficacy of recombinant human erythropoietin (r-HuEPO) in patients with multiple myeloma (MM) has been confirmed in several clinical trials. We report our experience of r-HuEPO treatment in 5 myeloma patients with renal failure. The therapy with r-HuEPO (Eprex, Janssen-Cilag or Recormon, Boehringer, Mannheim) was started after 4-8 months from diagnosis, the drug was administered intravenously (in one patient subcutaneously after cessation of hemodialysis treatment), two or three times weekly. The initial doses were 4-12,000 units/week (mean 8,400). In all patients good response during the first month of therapy was observed. Median Hb and hematocrit increased from 70 g/l and 20.8% to 87 g/l and 26% after 1 month and to 105 g/l and 30.3% after 4-6 months, respectively. The need for blood transfusion decreased significantly--from 2.72 TU/month to 0.13 TU/month. WHO performance status and patients self-assessment of quality of live improved substantially after r-HuEPO. No serious adverse events, including hypertension and/or thromboembolic events were observed. In accordance with some previous reports we conclude r-HuEPO is effective and safe treatment in patients with MM and renal failure. Moreover, lower doses of growth factor could be effective in this particular group of patients.

An overview of constantly enlarging spectrum of renal lesions in monoclonal gammapathies and new insights in possible pathogenesis of renal disturbances is given. Between the different types of renal affections a predominant role is played by the "myeloma kidney", induced by the presence of casts, primary amyloidosis with light chains deposition and tubular dysfunctions. Case stories of 3 patients, affected by myeloma kidney (with acute and chronic renal failure) and primary amyloidosis (with pronounced nephrotic syndrome) in context of monoclonal gammapathy are presented. Clinical problems of patients necessitating intensive hematologic and nephrologic care are highlighted, as well as need of early diagnosis and complex care.

Backgrounds: Hyperlipidemia is a common and serious complication in patients with chronic nephrotic syndrome which unremitted may result in accelerated atherosclerosis. Accumulation of lipids in glomeruli may moreover contribute to the progression of renal insufficiency in these patients., Methods: Total cholesterol, HDL-cholesterol and its HDL2 a HDL3 subfractions, LDL-cholesterol, triglycerides, free fatty acids, apoprotein B, apoprotein A1 and lipoprotein (a) were determined before any immunosuppressive and/or hypolipidemic therapy in 15 patients (pts) with nephrotic syndrome (8 pts with proteinuria higher than 10 g/24 hrs-NS-A, 7 with proteinuria between 5 and 10 g/24 hrs-NS-B), 7 pts with glomerulonephritis with low proteinuria (GN) and 6 pts with autosomal dominant polycystic kidney disease (PKD). All pts had normal glomerular filtration rate., Results: Plasma cholesterol (10.26 +/- 2.22 vs. 4.75 +/- 0.66 mmol/1, p < 0.001), plasma triglycerides (4.03 +/- 1.64 vs. 2.17 +/- 0.12 mmol/1, p < 0.05), LDL-cholesterol (7.16 +/- 1.55 vs. 2.62 +/- 0.67 mmol/1, p < 0.001) and apoprotein B (1.92 +/- 0.47 vs. 1.11 +/- 0.31 g/1, p < 0.01) were significantly higher in NS-A than in PKD. There was no difference in total HDL-cholesterol and the ratio HDL2/HDL3 between investigated groups of pts. Lipoprotein (a) was higher in NS-A than in other investigated groups of pts. The differences between NS-B and PKD were less significant., Conclusions: Disorder of lipid metabolism is more serious in patients with more severe nephrotic syndrome than in nephrotic patients with milder proteinuria. Hypercholesterolemia is complicated in these subjects by hypertriglyceridemia and by the increase of apoprotein B and A1 and lipoprotein (a). Metabolic and renal consequences of these disorders depend undoubtedly on their duration and probably also on other factors (e.g. age, hypertension, long-term therapy with corticosteroids., etc.).

An overview of new insights in pathogenesis of intracranial manifestations-especially concerning intracranial aneurysms (ICA) and subarachnoid hemorrhage-in autosomal dominant polycystic kidney disease (ADPKD) is given. Results of CT examinations of 65 patients with ADPKD are presented: they disclosed findings suspects of intracranial aneurysms in 4 patients, other vessel abnormalities and malformations in 6 patients and cystic dilatations in cisterna magna-of arachnoid cyst type in 6 patients. A case story of a patient successfully treated for subarachnoid hemorrhage due to aneurysm rupture is presented. Indications and screening methods in ADPKD patients with ICA are discussed. Brain abnormalities in ADPKD-especially ICA-suggest the complex nature of this genetic disorder, and regarding to the possible clinical impact, should be adequately managed.

An overview of actually accepted hypothesis of etiology and pathogenesis as well as overview of experimentally induced models of autosomal dominant polycystic kidney disease (ADPKD) is presented. Though chemically induced renal cysts in rats and other small laboratory animals fed by antioxidants (diphenylamine and s.o.) represent the commonest experimental model, strains of animals with inherited cystic kidney disease were inbred too. Experimental works on tissue cultures derived from patients with ADPKD, which are aimed especially on study of epithelial changes (epithelial hyperplasia and s.o.), deserved special attention. On conclusion, advantages of the different models and next steps necessary to accomplish for understanding etiology and pathogenesis of ADPKD are indicated.

Hypertension is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD), occurring early in the course of the disease. Disorders of tubular transport of sodium and increased plasma and blood volume (PV and BV), as a consequence, are thought to be involved in the pathogenesis of hypertension in ADPKD. In order to evaluate PV and BV in early stage of ADPKD, PV and BV were measured with radioactive serum albumin dilution technique. Three groups of subjects with normal glomerular filtration rate were studied: ADPKD hypertensive (ADPKD H, n = 10, age: 36.2 +/- 8.7 y), ADPKD normotensive (ADPKD N, n = 15, age: 33.4 +/- 7.4 y), and healthy volunteers (C, m = 8, age: 32.6 +/- 6.8 y). PV and BV expressed per kilogram of body weight did not differ among the 3 groups. When PV and BV were expressed per meter square of body surface area, diminished BV in the group ADPKD H in comparison to ADPKD N and group c (p < 0.05) was found, other parameters did not differ between the 3 groups. In conclusion--our results do not support the hypothesis of a significantly increased PV and BV of patients with ADPKD prior to the onset of hypertension.

Disorders of tubular transport of sodium are thought to be involved in pathogenesis of cyst formation and development of hypertension in autosomal dominant polycystic kidney disease (ADPKD). Recently lithium has been proposed as a quantitative marker of proximal tubular reabsorption of sodium and lithium clearance as a method to analyze tubular sodium handling. To evaluate tubular sodium handling in early stage of ADPKD, lithium clearance (600 mg of Lithium carbonicum p.o.) was performed in a control group of pts. with ADPKD and normal glomerular filtration rate (n = 28), age 19.9 +/- 8.8 years) and in a control group of healthy volunteers (n = 43), age 30.3 +/- 9.0 years). Both groups did not differ in plasma or urine concentrations of electrolytes; plasma creatinine levels were slightly higher in ADPKD group than in controls (83.4 +/0 18.0 mumol/l vs. 93.4 +/- 24.2 mumol/l, p < 0.05). We did not demonstrate any statistically significant difference between the group of ADPKD and control group in lithium clearance and in fraction excretion of lithium (23.6 +/- 14.5 vs. 19.5 +/- 8.7 ml/min, resp. 15.3 +/- 8.8 vs 13.8 +/- 7.8%). Nor proximal tubular resorption of sodium, neither distal tubular resorption of sodium did differ between the group of ADPKD and control group (86.18 +/- 2.2 vs 84.7 +/- 1.80% resp. 94.7 +/- 2.6 vs. 94.5 +/- 3.6%). When comparing parameters of sodium handling between pts. with ADPKD and hypertension (6/28) and pts. with ADPKD without hypertension no difference was found. In conclusion, we could not demonstrate any statistically significant difference in tubular handling of sodium, when based on lithium clearance between the groups of ADPKD with normal glomerular filtration rate and control group.

Arterial hypertension is found in as many as 75% patients with autosomal dominant polycystic kidneys with normal renal function, its pathogenesis is however not quite clear so far. The authors examined 16 patients with polycystic kidneys with normal or only slightly reduced renal function (plasma creatinine lower than 140 umol/l), 8 of these patients were normotonic (N) and 8 hypertonic (H). In all examined subjects right-sided cardiac catheterization was performed with assessment of the minute cardiac volume by thermodilution. To all patients in the course of one hour 1500 ml saline per 70 kg body weight were administered and the haemodynamic examinations were repeated after termination of the infusion. In all subjects before and after expansion the plasma renin activity was assessed (PRA), as well as plasma aldosterone (PA), plasma catecholamines (PC) and the atrial natriuretic factor (ANF), the renal blood flow and glomerular filtration by means of clearance and extraction of PAH and inulin clearance. The authors did not find differences in plasma concentrations, cardiac output and splanchnic and renal ANF extraction in groups N and H, nor in PRA, PA and PC. Volume expansion led in both groups to a comparable rise of ANF and suppression of PRA and PA. Group H did not differ from group N in any of the investigated haemodynamic and renal parameters except for systemic vascular resistance. In hypertensive patients before expansion a close correlation was found between pressure in the pulmonary artery in a wedged position and diuresis (r = 0.935, p less than 0.01) and natriuresis (r = 0.895, p less than 0.01). The volume expansion was in both groups associated with a comparable rise of diuresis, the haemodynamic response of patients N and H was however quite different. While in patients of group N a decline of the systemic vascular resistance occurred as well as an increase of the minute volume without a change of the renal flow and glomerular filtration, in hypertonic patients the systemic vascular resistance and minute volume did not change but there was a significant rise of the renal flow and glomerular filtration. The relationship of diuresis and natriuresis of hypertensive patients with polycystic kidneys to volume parameters and the rise of the renal perfusion pressure during volume expansion indicates the importance of pressure natriuresis for ensuring the sodium and volume homeostasis in these patients.