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The aim of the study was to characterize by molecular profiling two glomerular diseases: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) and to identify potential molecular markers of IgAN and FSGS progression. The expressions of 90 immune-related genes were compared in biopsies of patients with IgAN (n=33), FSGS (n=17) and in controls (n=11) using RT-qPCR. To identify markers of disease progression, gene expression was compared between progressors and non-progressors in 1 year follow-up. The results were verified on validation cohort of patients with IgAN (n=8) and in controls (n=6) using laser-capture microdissection, that enables to analyze gene expression separately for glomeruli and interstitium. In comparison to controls, patients with both IgAN and FSGS, had lower expression of BAX (apoptotic molecule BCL2-associated protein) and HMOX-1 (heme oxygenase 1) and higher expression of SELP (selectin P). Furthermore, in IgAN higher expression of PTPRC (protein-tyrosine phosphatase, receptor-type C) and in FSGS higher expression of BCL2L1 (regulator of apoptosis BCL2-like 1) and IL18 compared to control was observed. Validation of differentially expressed genes between IgAN and controls on another cohort using laser-capture microdissection confirmed higher expression of PTPRC in glomeruli of patients with IgAN. The risk of progression in IgAN was associated with higher expression EDN1 (endothelin 1) (AUC=0.77) and FASLG (Fas ligand) (AUC=0.82) and lower expression of VEGF (vascular endothelial growth factor) (AUC=0.8) and in FSGS with lower expression of CCL19 (chemokine (C-C motif) ligand 19) (AUC=0.86). Higher expression of EDN1 and FASLG along with lower expression of VEGF in IgAN and lower expression of CCL19 in FSGS at the time of biopsy can help to identify patients at risk of future disease progression.

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder, leading to end stage renal failure and kidney transplantation in its most serious form. The severity of the disease’s manifestation depends on the genetic determination of ADPKD. The huge variability of different phenotypes (even within a single family) is not only modulated by the two main ADPKD genes (PKD1 and PKD2) but also by modifier genes and the whole genetic background. Case presentation This is a report of an ADPKD family with co-inheritance of PKD1 and PKD2 pathogenic variants. The proband, with an extremely serious manifestation of ADPKD (the man was diagnosed in early childhood, and with end stage renal disease aged 23), underwent genetic analysis of PKD1 and PKD2, which revealed the presence of pathogenic mutations in both of these genes. The missense PKD2 mutation p.Arg420Gly came from the proband’s father, with a mild ADPKD phenotype. The same mutation of the PKD2 gene and similar mild disease presentation were found in the proband’s aunt (father’s sister) and her son. The nonsense mutation p.Gln2196* within the PKD1 gene was probably inherited from the proband’s mother, who died at the age of 45. It was only discovered post mortem, that the real cause of her death was kidney failure as a consequence of untreated ADPKD. Unfortunately, neither the DNA of the proband’s mother nor the DNA of any other family members from this side of the pedigree were available for further examination. The proband underwent successful cadaveric kidney transplantation at the age of 24, and this replacement therapy lasted for the next 15 years. Conclusions Here, we present a first case of bilineal ADPKD inheritance in the Czech Republic. This report highlights the significant role of modifier genes in genetic determination of ADPKD, especially in connection with seriously deteriorated disease phenotypes. In our case, the modifying role is probably mediated by the PKD2 gene.

The complete renal artery embolization is an alternative to surgical nephrectomy in seriously ill patients. Iatrogenic embolization can be used in many different conditions. Refractory nephrotic syndrome represents a very rare indication for embolization. Complete renal artery embolization has usually been complicated by postembolization syndrome (PES) which is characterized by flank pain and fever. Possible immunologic contribution to the PES leads some authors to the administration of corticosteroids to the patients undergoing embolization. We report here a cohort of 13 patients undergoing complete embolization of total 21 kidneys due to refractory nephrotic syndrome non-responding to the various specific treatment regimes. We treated our patients undergoing renal artery embolization according to special protocol containing combination of antibiotic drugs and corticosteroids (CS) to diminish PES and evaluated its influence to the cytokine production. The incidence of PES was less frequent and milder in comparison with the historical group of patients. Significant decrease in plasma levels of tumor necrosis factor α during first post-embolization day (8.37 pre- vs. 5.74 pg/ml post-embolization, P=0.0002) could partially explain the reduction of PES symptoms. The procedure was not complicated by severe complications and represents an elegant alternative to surgical procedure. The accurate timing of the embolization remains a controversial point in this intervention.

ANCA-associated vasculitides, including Wegener's granulomatosis and microscopic polyangiitis, are systemic autoimmune diseases with poor prognosis in untreated patients, which can be dramatically improved by current therapeutic modalities. The aim of multi-centre randomized trials of the European Vasculitis Study Group is to optimise and standardise treatment of these diseases. From 1995-2001 our department contributed a total of 40 patients to the trials CYCAZAREM (cyclophosphamide versus azathioprine during remission for generalised vasculitis), MEPEX (plasma exchange versus methylprednisolone for severe renal vasculitis) and CYCLOPS (daily oral versus pulse cyclophosphamide during induction phase for generalised vasculitis). In this paper, we report on the preliminary results of long-term follow up of our patients included in international trials. The mean time of follow-up of the patients was 55.7 months with the patient survival rate of 72% and renal survival rate of 65%. Remission was achieved in 82% of patients, out of which 42% suffered a relapse. In generalised forms of vasculitides, treatment with cyclophosphamide is nowadays established as the standard therapy. The aim, however, is to further minimise its toxic effects by choosing the optimal therapeutic strategies. Complete results of all trials have not yet been published; nevertheless, the preliminary available data have already revealed new potential therapeutic approaches.

Background: The objective of the study was to evaluate the severity of kidney damage retrospectively and to analyze prognostic factors following ethylene glycol (EG) poisonings. Methods: Data concerning the clinical course of patients with EG poisoning between 2000 and 2002 were analyzed. The χ2 test, Student’s t test, Fisher’s test and the calculation of linear correlation coefficients were used for statistical analysis. Results: Thirty-three discharge records were obtained. Three patients died, and 11 patients developed acute renal failure (mean maximum serum creatinine level 618 µmol/l). Upon discharge, serum creatinine levels were still elevated in 10 patients. In all but 1 patient, renal function completely normalized within 20 months after intoxication. Conclusion: Adult men are the most endangered segment of the population. The most important prognostic factors are the ingested dose and early antidotal treatment. EG toxic kidney damage is reversible.

The aim of the multicentric randomized trial CYCLOPS is to optimize the treatment of induction of remission in patients with generalized, but not immediately life-threatening ANCA (antineutrophil cytoplasmic antibodies) -associated vasculitis. This will be achieved by reducing the dose of cyclophosphamide by administering it as intermittent pulses. The lower cumulative dose will be very probably accompanied with lower toxicity, whereas the effectivity should be comparable. We have enrolled 28 patients to the study. At present, 18 of them are suitable for evaluation. Our preliminary results show that pulse intermittent administration of cyclophosphamide is safer from the point of morbidity and mortality due to infectious complications. In our hands, this treatment modality does not seem to be less effective than the conventional daily oral cyclophosphamide. However, unambiguous results and treatment recommendations will not be available until the final evaluation of all patients enrolled in the trial.

Retrospective study about results of treatment of patients (pts) with primary (AL) and secondary (AA) amyloidosis is given. 31 pts with systemic forms of amyloidosis have been treated and followed-up in our department since 1993.6 men and 11 women were in the AL group with the mean age of 59 years. Multiple myeloma was diagnosed in 9 pts, monoclonal gammapathy of undetermined significance (MGUS) was found in 8 pts. The kidneys were affected in all pts, heart in 59% of pts, liver, joints and skin in 26% of pts and polyneuropathy was detected only in 1 pt. Progression of renal insufficiency with decrease of glomerular filtration rate (GFR) was detected in the AL group at the end of follow-up period compared with the initial level (p0.05) despite the intensive treatment. The difference did not reach statistical significance in other investigated parameters. Median of survival was 13 months from the assessment of diagnosis. Partial remission of amyloidosis was achieved in 9 pts, stable disease was in 5 pts and in 3 pts the disease progressed. 4 men and 10 women were in the AA group with mean age of 58 years. Underlying disease was rheumatoid arthritis in 7 pts, ankylosing spondylitis in 2 pts, juvenile chronic arthritis in 1 pt, Crohn's disease in 2 pts, eosinophilic fasciitis in 1 pt and chronic abscesses in NK cell deficiency in 1 pt. The kidneys were affected in all pts, bowels and heart in 36% of pts. GFR (p0.05) and plasma creatinine (p0.01) significantly decreased at the end of follow-up period compared with initial levels. Median of survival was 30 months. Partial remission was achieved in 2 pts, stable disease was in 3 pts and progression was detected in 9 pts despite the use of various treatment regimens.Both forms of systemic amyloidosis represent severe disease with limited response to treatment. The use of new drugs is promising and could lead to better response to treatment.

The pathogenesis of arterial hypertension in autosomal dominant polycystic kidney disease (ADPKD) is complex and likely dependent on interaction of hemodynamic, endocrine and neurogenic factors. We decided to evaluate the role of endothelin (ET1) and nitric oxide (NO) in the regulation of arterial blood pressure (BP) and to determine plasma levels of ET1 and NO in the group of patients with ADPKD. The ADPKD group (18 patients, 6 men + 12 women, mean age 44.6+/-11.7 years, with creatinine clearancecorrig1.1 ml/s) was compared with a control group of 27 healthy volunteers of comparable age. Plasma levels of ET1 assessed by direct RIA determination in the group of ADPKD patients (11.03+/-1.8 fmol/ml) were significantly increased (p0.001) in comparison with the control group (2.66+/-0.58 fmol/ml), while no significant differences were observed between normotensive and hypertensive patients in the ADPKD group. Serum levels of NO were evaluated according to the determination of serum levels of their metabolites - nitrites/nitrates. Serum levels of NO in the group of ADPKD patients (39.85+/-.38 micro mol/l) were significantly higher (p0.05) in comparison with the control group (22.7+/-1.20 micro mol/l), whereas in the ADPKD group no significant differences were observed between normotensive and hypertensive patients. Thus, our study supports the concept of complex alteration of both vasoconstrictor and vasodilator systems in the pathogenesis of arterial hypertension in ADPKD.

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.

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).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).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.Occurrence of sleep disorders and their characteristics in patients on CAPD is similar to that in hemodialyzed patients.

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.

In patients with monoclonal gammapathy (MG), renal impairment becomes the frequent complication. At the same time, its exact pathogenetic mechanism remains to be identified. We tried to detect urinary acidification defect that may become the first sign of the kidney parenchymal injury. The goal of our work was to estimate the incidence of the acidification impairment, the contribution of proximal and distal types of renal tubular acidosis and the dependency of the defect on the type of light chain paraprotein.In the group of 21 patients aged 38 to 82 years (14 females and 7 males) with monoclonal gammapathy accompanied with creatinemia lower than 180 micromol/l, the short acidification test was performed (calcium chloride was administrated and the urinary acidity was monitored). Renal tubular acidosis was diagnosed in those patients whose urinary acidity after the CaCl2 administration did not reach pH 5.25 or less. The control group consisted of 19 volunteers (6 males and 13 females) with normal renal functions. Results of the tests in MG patients and in control persons were compared using the unpaired Student's t-test. In 11 patients (52.4%) the urinary acidification defect of the incomplete type was detected. Eight of these patients (38.1%) had the distal and three (14.3%) had the proximal type of impairment. Eight patients with the acidification defect had the paraproteinuria kappa and four of them had that of lambda type. In persons without the acidification impairment kappa chains were found in 5 persons, lambda chains in 4 of them.In our group of MG patients acidification defect occurred in more than half of them. Contrary to the assumed higher nephrotoxicity of the lambda chains, the disturbance was more frequently found in patients with paraproteinemia of the kappa type.

Leptin is a new hormone influencing food intake, energy expenditure and body weight. This protein is produced by adipocytes, exerts its effects on brain, endocrine pancreas and other organs by activating transmembrane receptors and is cleared from plasma mainly by the kidneys. The aim of our study was to compare plasma concentrations of leptin in our nephrological out-patients and controls.We examined 36 diabetic patients with various stages of nephropathy, 12 males with nephrotic syndrome due to membranous nephropathy, 15 dialysis patients and 11 controls. Leptin was assessed in plasma by ELISA. There was a significant difference between plasma levels of leptin in males and females (7.7 +/- 11.4 vs 17.6 +/- 17.3, p0.001) and in dialysis and non-dialysis patients (19.6 +/- 16.5 vs 10.7 +/- 14.5, p0.05). There was also a difference between dialysed and non-dialysed men (15.1 +/- 16.2 vs 5.9 +/- 9.2, p0.05). We found no difference between men with and without nephrotic syndrome and between BMI or age. There was a positive correlation of leptin with diabetic and non-diabetic women. There was positive correlation of P-leptin with serum creatinine in non-dialysed women (r = 0.68, p0.001) and a negative correlation with S-albumin in nephrotic men (r = -0.65, p0.05).Women have higher plasma leptin concentrations than men and dialysis patients have higher concentrations than non-dialysed patients. Apart from the positive correlation with S-creatinine in non-dialysed women. There was positive correlation with S-albumin in nephrotic men there were no correlations with renal function, BMI, age, S-cholesterol, S-triglycerides and S-albumin.

TNF-alpha, IGF-I and leptin are agents which influence insulin resistance, they play probably a part in the pathogenesis of diabetic nephropathy and influence mutually their production. The objective of the submitted investigation was to assess whether there exist relations between their concentrations in the plasma of diabetic patients.The authors examined 37 patients aged 18-67 years from a diabetic clinic, 10 with normal albuminuria and normal renal function, 12 with microalbuminuria and 15 with macroalbuminuria and/or reduced renal function. TNF alpha, IGF-I and leptin were assessed in plasma, using commercial kits, by the ELISA method. IgF-I in plasma correlated inversely with glycated haemoglobin (r = -0.20, p0.05). In women a correlation was found between IGF-I and TNF-alpha concentrations (r = 0.65, p0.01). No other mutual correlations were found between concentrations of the investigated substances and between cytokine concentrations and serum creatinine, glycated haemoglobin, the blood glucose level and body mass index.IGF-I plasma levels correlate inversely with glycated haemoglobin and in women with the TNF-alpha level. No other correlations were found between IGF-I. TNF-alpha and leptin plasma levels. The levels do not correlate with age, renal function and compensation of diabetes.

Renal amyloid involvement results either from primary or secondary amyloidosis. Extent of amyloid tissue deposition in kidneys and clinical course depends not only on the type of basic process but reflects also time of diagnosis and possibility to influence the basic process.We analyzed laboratory and clinical data of patients with bioptically proven renal amyloidosis. We found renal amyloidosis in 27 patients from an overall number of 750 renal biopsies (RB) performed in our department (i.e. 3.6%). AA amyloidosis was diagnosed in 16 pts, AL amyloidosis in 11 pts. About 50% of patients had laboratory signs of nephrotic syndrome, all patients had various degree of proteinuria. Impaired renal function were found in more than 50% of patients, in 6 of them we had to start renal replacement therapy. 8 pts died. Complications of severe nephrotic syndrome were the causes of death in majority of cases. We have started investigation of some amyloid precursors and cytokines in patients with AA and AL amyloidosis. We compared the results with group of patients with vasculitis. We investigated plasma and urinary levels of SAA (serum AA) and soluble receptor for interleukin 2 (sIL-2R).Clinical features and laboratory findings in our patients with renal amyloidosis approximately are in accordance with literary data. Plasmatic level of SAA was increased not only in the group of patients with AA amyloidosis, but also in the group of vasculitis. Urinary sIL-2R was significantly increased in patients with AA amyloidosis in comparison with healthy controls.

Plasma levels and urinary excretion of proinflammatory cytokines and soluble adhesion molecules may be useful parameters of the activity of ANCA-positive renal vasculitis and lupus nephritis.Plasma levels and urinary excretion of TNF alpha, IL-6, IL-8, ICAM-1 and VCAM-1 were measured by ELISA in 14 patients (pts) with ANCA-positive renal vasculitis (8 active-ANCA-A, 6 in remission ANCA-R), 6 pts with active lupus nephritis (L.N), 15 pts with IgA nephropathy (IgAN) 10 pts with autosomal dominant polycystic kidney disease and 9 healthy subjects (Co). Fractional excretion (FE) of selected cytokines and adhesion molecules was also calculated. Pts with LN had in comparison with controls increased plasma levels of ICAM-1, VCAM-1, IL-6, IL-8 and TNF alpha, increased urinary excretion of VCAM-1, IL-8 and TNF alpha and increased fractional excretion of VCAM-1 and IL-8. Patients with ANCA-A had in comparison with controls increased plasma concentrations of ICAM-1 and VCAM-1, increased urinary excretion of VCAM-1, IL-6 and TNF alpha and increased fractional excretion of VCAM-1, IL-6, IL-8 and TNF alpha. Patients with ANCA-R had in comparison with controls higher plasma levels of ICAM-1, VCAM-1, IL-6 and TNF alpha, increased urinary excretion of VCAM-1 and TNF alpha and increased fractional excretion of VCAM-1, IL-6 and TNF alpha.Patients with ANCA-positive renal vasculitis had in contradistinction to pts with active LN increased fractional excretion of IL-6 and TNF alpha. Both cytokines are probably produced in renal vasculitis locally in the kidney. Increased plasma levels of soluble adhesion molecules and increased plasma levels and fractional excretion of proinflammatory cytokines in patients with ANCA-positive renal vasculitis in clinical remission may explain the strong propensity of these patients to develop relapses of the diseases on withdrawal of immunosuppressive treatment.

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.

IgA nephropathy is the most common glomerulonephritis all over the world and a considerable proportion of the patients reaches end-stage renal failure. Yet the standard treatment for the patients with progressive course and/or great proteinuria is currently lacking. All suggested treatment protocols, including short-term treatment with cyclosporine A had equivocal results. Therefore we decided to try long-term cyclosporine treatment.We treated 6 patients (4 males, 2 females, age 21-31 years) with bioptically proven IgA nephropathy and proteinuria over 3.5 g/24 hrs with or without nephrotic syndrome non responding to corticosteroid therapy administered for at least 3 months. Patients with serum creatinine greater than 200 mumol/l and/or glomerulosclerosis in more than 50% of glomeruli in renal biopsy were excluded. Pts were given cyclosporine A in initial dose 5 mg/kg bw/day then titrated aiming to the serum concentration of 70-150 ng/ml. Prednisone 5-10 mg on alternate days was given with cyclosporine. Proteinuria decreased during first month of therapy from 4.66 +/- 0.43 g/day to 1.38 +/- 0.29 g/day (p0.01) and remained low after one year of treatment (0.59 +/- 0.14 g/day, p0.001). Glomerular filtration rate (creatinine clearance) did not change during first month of therapy (1.25 +/- 0.21 ml/s vs. 1.38 +/- 0.29 ml/s), but slightly decreased after one year of treatment (1.05 +/- 0.14 ml/s, p0.05). We also calculated ratio of proteinuria to glomerular filtration rate (g/l) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80.10(-3) +/- 15.20.10(-3) before cyclosporin therapy, it decreased significantly after one month (11.56.10(-3) +/- 3.24.10(-3), p0.05) and achieved the lowest value after one year of therapy (6.78.10(-3) +/- 4.25 .10(-3) +/- 4.25.10(-3), p0.01). Serum cholesterol also significantly decreased after 12 months of therapy (6.21 +/- 0.62 vs. 5.41 +/- 0.45 mmol/l, p0.05).CyA significantly lowered moderate to high proteinuria with much less decrease of glomerular filtration rate in 6 patients with IgA. Significant decrease of proteinuria/GFR ratio strongly suggests some non-hemodynamic mechanisms of cyclosporine action in these patients. Therapy was well tolerated and side-effects were not so severe to require cyclosporine withdrawal.

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.

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.

Molecular genetics are a fundamental turning point in the approach to autosomal dominant hereditary renal polycystosis of adults (ADPKD). DNA analysis makes diagnosis possible at in any ontogenic period, i.e. also during the prenatal period. The objective of the present study was to test the presymptomatic DNA diagnosis in a major group of patients with ADPKD and the possibility to detect the disease in the initial stage and influence its development by early treatment and advise the patients on parenthood.In 1990-1994 the authors contacted 157 patients with polycystic kidney disease, adult type (ADPKD). 87 families were examined by Southern's RFLP method (gene PKD1, 16p13.3, standard probe 3'HVR and restrictase Pvu II). Of 493 members of these families only 25 (5.1%) refused to be examined. So far 378 examinations were completed, 90 proceed. In 40 of 132 examined subjects with the risk of ADPKD transmission of the gene was proved. Of four examinations of the foetus with the risk of ADPKD twice transmission of the gene was proved and the pregnancy was terminated. In three families with three or more members suffering from ADPKD in some there was not agreement between the result of linkage analysis of DNA and the clinical finding. The authors analyzed whether the cause is recombination or ADKPD conditioned by mutation of gene PKD2 (4p13-23). Linkage analysis remains in ADPKD the basic examination as the sequence of gene PKD1 is not yet completed. Discovery of gene PKD2 the mutations of which condition as many as 15% of all cases of ADPKD has an impact on the evaluation of linkage analysis. The reliability of prediction rises with the number of examined subjects in the family. The examination revealed that patients are willing to have DNA examinations (as many as 98%); despite this the number of examined subjects is only a small fraction of the anticipated 10,000 people in the Czech Republic suffering from ADPKD:DNA analysis in patients with autosomal dominant polycystic kidney disease is the most important examination for its diagnosis. It makes the diagnosis possible in all stages of ontogenesis, incl. prenatal diagnosis. It is a highly valid parameter when these patients decide on parenthood. It makes early treatment possible which can influence the development of the disease and its complications.

Reactive oxygen species are generated physiologically in cells with a significant increase in certain pathological conditions, such as inflammation, cancer, aging, degenerative disease. If endogenous antioxidant systems, in our study represented by glutathione peroxidase, are exceeded by this oxidant flux, tissue injury may occur. Activity of glutathione peroxidase (GPx) was determined using Beutler's modified spectrophotometric assay in erythrocytes from autosomal dominant polycystic kidney disease patients. Activity of glutathione peroxidase was significantly (at p0.0001) lower there (17.75 +/- 3.69 U/g haemoglobin) compared to the control group (23.26 +/- .61 U/g Hb). Lower antioxidant enzyme defence system of ADPKD patients, here represented by GPx, can potentiate injury caused by free radicals and possibly play a role in the progression of autosomal dominant polycystic kidney disease.

The application of presymptomatic diagnosis of polycystic kidney disease (PKD) relies on satisfactory collaboration between the affected families and the team of health workers. The objective of the present study was to assess the initial level of knowledge of the disease and its hereditary character, the attitudes of families with PKD to presymptomatic and prenatal testing focused on methods of molecular genetics as well as attitudes to induced abortion if the gene of PKD is detected in the foetus.In a group of 104 subjects who had genetic examinations on account of familial PKD by means of questionnaires knowledge of the diagnosis, clinical and genetic prognosis and attitudes to presymptomatic and prenatal genetic tests were investigated. About 75% of the members of the group had adequate knowledge of the name of the disease and description of the clinical picture, 96.1% were informed on the hereditary character of the disease but only 1.9% knew details about the heredity. The scope of genetic risk was mentioned by some 30%, 51% were unable to express their opinion on the risk. A positive attitude to testing for the presence of the PKD gene was recorded in almost 100% if they themselves were concerned, 94% when their offspring under age was concerned but only 19.2% when the foetus was concerned. Only 5.3% of the respondents would agree with induced abortion in case of positive prenatal evidence of the PKD gene in the foetus and a few more respondents (14%) were opposed to abortion and some 80% were unable or unwilling to express their opinion.In members of families with PKD an important role is played by knowledge of clinical and genetic aspects of the disease. Genetic counselling must be part of comprehensive care and should always precede indication of molecular genetic methods (DNA analyses).

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 (p0.05) 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, p0.05). 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.

The authors compare changes of intraocular pressure during haemodialysis and haemofiltration in six patients. The measurements were made with the patients in a sitting position, using an applanation tonometer according to Perkins, during both operations every hour. A rise to 25 torr was recorded in one patient repeatedly during haemofiltration in both eyes one hour after the blood pressure had risen to 220/120 and 210/110. In the other patients the variations of the intraocular pressure were within the physiological range. Based on data in the literature the authors recommend the use of haemofiltration in patients with glaucoma and after eye surgery.

The authors elaborated a method for assessment of the renal lithium clearance, CLr, the results of which correlate well with the plasmatic clearance (CLp] (r = 0.785, p less than 0.05). This correlation improved substantially after correction of CLr to the clearance of endogenous creatinine, CLcr (r = 0.945; p less than 0.05). The mean values of CLr of the investigated group--26.4 ml/min are in agreement with the results published by other authors. A significant correlation between CLr and CLcr (r = 0.826, p less than 0.05) along with comparison of the intraindividual variability of assessed results indicates that it is better to use as a parameter of sodium absorption from the proximal tubule the fractional lithium clearance rather than absolute values of CLr.

Using nephrological, genealogical and molecular genetic methods, the authors examined 85 members of 19 families with autosomal dominant polycystic kidney disease. With the aid of probe 3'HVR, alpha-globin and restriction endonuclease Pvu II, the families were found 95% informative. The rate of diagnostic reliability was also 95%. The authors verified the homogeneity of the disease in the Czech population and the applicability of the probe and endonuclease for molecular gene diagnostics in the population.

In patients with chronic kidney failure in the long-term dialysis programme multiple minute cysts frequently develop in the shrunken kidneys. In addition to the cysts, in 20% of patients there are also multiple kidney tumours causing severe complications. In most cases the clinical picture of the disease is insignificant, hematuria being the most frequent manifestation. The authors present their cohort of 21 patients with irreversible kidney failure, who have been examined by computer tomography in the 1986-1987 years. The mean period of dialysis programme was 5.7 years, chronic glomerulonephritis and interstitial nephritis being the basic disease. The patient were, according to the results of computer tomography, divided into four groups: 1. the presence of cysts or tumours was not demonstrated, 2. multiple cysts were found in bilateral localization, 3. less than 3 cysts were found, 4. there was a kidney tumour. A factor causing the development of the cysts has not yet been identified. It is presumed that the disease is caused by a biologically active substance which is not efficiently dialyzed. On the basis of the present work the authors recommend the aimed examination of the kidneys in patients at the stage of chronic kidney insufficiency and particularly in patients subjected to dialysis for long period of time. The recommended examination is by computer tomography and the attention should be centered to possible occurrence of acquired cystic disease of kidney tumours.

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.