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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.

Two different models (WBS FLAB, WaSiM-ETH) were used in the project HochNatur (flood preven- tion and nature conservation in the Weiseritz catchment in the Eastern Ore Mts. - Erzgebirge) to determine risk areas with quick runoff processes and to simulate the discharge. It was done in different scales, in the mesoscale Weiseritz catchment as well as two selected subcatchments with different natural and urban conditions, the Weisbach subcatchment with a well-structured landscape, the Hockenbach subcatchment with a greater part of arable land. On the basis of selected scenarios, the effect of land use changes on the runoff generation proc - esses of an area and on the hydrograph is described. Land use changes are able to reduce the portion of quick runoff components, the water erosion and the discharge. The effect occurs especially in smaller catchments and with short heavy rains (events with a frequency of occurrence of 5-50 years). Depending on the present situation the changes have to include areas of more than 25% of the catchments area to cause a significant ef - fect. It became apparent that nature conservation and flood prevention agree well in their requirements with the land use. A rich structured landscape proved to be extraordinarily positive for both, flood prevention and nature conservation.

This study aimed at describing and explaining chemistry learning problems viewed from conceptual change model and misconceptions of students. The study was qualitative research of case study type conducted in one class of SMAN 1 Singaraja. Subjects of the study were a chemistry teacher and students. Data were obtained through classroom observation, interviews, and conception tests. The chemistry learning problems were grouped based on aspects of necessity, intelligibility, plausibility, and fruitfulness. Data were analyzed descriptively. The results of the study showed that the chemistry learning problems related to the aspect of necessity were that the teacher did not carry out the laboratory work and did not discuss the properties of the buffer solution. The problems related to aspects of intelligibility were the teacher asked successive questions, answered her own questions, gave wrong information, made unclear and wrong analogies, and did not ask student reasons. The problems related to the plausibility aspects were that the teacher had less emphasis on the importance of context and neglected the students’ alternative conceptions. The problems related to the fruitfulness aspects were that the teacher was less likely to provide complex problems especially with regard to the application of the buffer solution in everyday life. Students experienced misconceptions on some concepts of buffer solution.

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder caused by mutation in either one of two genes, PKD1 and PKD2. High structural and sequence complexity of PKD genes makes the mutational diagnostics of ADPKD challenging. The present study is the first detailed analysis of both PKD genes in a cohort of Czech patients with ADPKD using High Resolution Melting analysis (HRM) and Multiplex Ligation-dependent Probe Amplification (MLPA). Methods The mutational analysis of PKD genes was performed in a set of 56 unrelated patients. For mutational screening of the PKD1 gene, the long-range PCR (LR-PCR) strategy followed by nested PCR was used. Resulting PCR fragments were analyzed by HRM; the positive cases were reanalyzed and confirmed by direct sequencing. Negative samples were further examined for sequence changes in the PKD2 gene by the method of HRM and for large rearrangements of both PKD1 and PKD2 genes by MLPA. Results Screening of the PKD1 gene revealed 36 different likely pathogenic germline sequence changes in 37 unrelated families/individuals. Twenty-five of these sequence changes were described for the first time. Moreover, a novel large deletion was found within the PKD1 gene in one patient. Via the mutational analysis of the PKD2 gene, two additional likely pathogenic mutations were detected. Conclusions Probable pathogenic mutation was detected in 71% of screened patients. Determination of PKD mutations and their type and localization within corresponding genes could help to assess clinical prognosis of ADPKD patients and has major benefit for prenatal and/or presymptomatic or preimplantational diagnostics in affected families as well.

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.

Flood prevention and nature conservation are often considered not to be compatible. The Weiseritz catchment (eastern Erzgebirge, Saxony, Germany) was heavily affected by floods in August 2002. In response to this event, the German Environmental Foundation (Deutsche Bundesstiftung Umwelt, DBU) funded the project ‘Flood Prevention and Nature Conservation in the Weiseritz Area’ (HochNatur) which aimed to design measurements integrating both flood prevention and nature conservation.

AAV are a group of systemic immune-mediated diseases with a strong and highly specific association with ANCA. In recent years, there has been increasing evidence that ANCA might play a direct pathogenic role in triggering AAV. Nevertheless, effectors of cell-mediated immunity prevail in the inflammation sites in patients with AAV. Numerous studies found increased markers of T-cell activation in AAV. Moreover, this activation persisted even in remission and despite treatment. Finally, successful therapeutic attempts using T cell-directed treatment were also reported. There has therefore been substantial evidence that T cells are involved in the pathogenesis of AAV, even though the exact mechanisms are yet to be elucidated. In this review, recent findings on the contribution of T cells to the pathogenic processes in AAV will be briefly summarized. Special emphasis will be placed on the Th1/Th2 concept, the role of T-regulatory cells, and the role of effector memory T cells in the pathogenesis of AAV.

Background Clinical experience with mycophenolate mofetil (MMF) in glomerulonephritis still remains limited. Methods In order to assess the experience of one center with the efficacy and tolerability of MMF in patients with glomerulonephritis, we performed a retrospective 6-year analysis of 68 patients treated by MMF for glomerular disease, mainly anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV: n = 34) and systemic lupus erythematosus and lupus nephritis (SLE: n = 24). Indications were maintenance treatment in 40% of patients, induction treatment in patients not tolerating cyclophosphamide in 27%, and disease relapse in 33%. Mean treatment duration was 11.5 months. Results Efficacy endpoints were serum creatinine, urinary protein excretion, and steroid dose. In AAV patients, MMF was associated with significant improvement in 18%, partial improvement in 26%, stabilization in 29%, and disease progression in 12%; adverse event dropouts totalled 15%. In SLE, the respective figures were 30, 22, 9, and 22%, with 17% adverse event dropouts. The most frequent side effects were gastrointestinal events (n = 7) and infections (n = 3). None was life-threatening and there were no deaths. Conclusions MMF, in the relatively low doses used, was safe and effective, stabilizing or improving AAV in 73% of patients and SLE in 61%. Further prospective randomized controlled trials with MMF in renal vasculitis and lupus nephritis are clearly warranted.

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 pauciimmune small-vessel vasculitides are multisystem diseases with frequent renal involvement. They are strongly associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). In this review we have focused on the ethiopathogenesis and the role of ANCA, clinical presentation and histopathologic findings of different ANCA - associated vasculitides (AAV). Current treatment strategies and the overall and renal outcome of patients with AAV are also discussed.

In recent years much work has been done to find regularities in data streams. Normally streams are complete and well ordered. Major defects, such as incomplete or misleading events, occur in practice at least after some finite time. In this paper we describe a method developed for recognizing previously known patterns from a data stream. The solution is based on case based reasoning (CBR) with an extension to handle imperfect information. We also introduce a new idea to use two different case-bases instead of only one. The performance has been evaluated using simulated data and the obtained results are considered encouraging.

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.

We present a case of a 79-years old woman with acute anuric renal failure due to biopsy confirmed immunotactoid glomerulonephritis. Despite biclonal gammopathy IgG lambda, no hematologic or any other underlying malignancy was found. A possible association with viral hepatitis, cryoglobulinemia or autoimmune disease was also excluded. The patient was treated with pulse i.v. dexamethasone with very good results. Diuresis resumed and renal function gradually normalized. Our patient is one of the oldest patients with immunotactoid glomerulonephritis described. The presentation by acute renal failure with an improvement of renal function after therapy has not been previously published.

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.

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.

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.

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.

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.

Dialysis related amyloidosis (DRA) is a severe complication of the long-term dialysis treatment. beta 2 microglobulin and probably other factors influence the development of amyloid deposits. We investigated some of these factors during hemodialysis session.We investigated 20 patients undergoing regular hemodialysis treatment. Patients were divided into AMYL group (with histologically proven DRA) and NE-AMYL group (without signs of DRA). Plasma levels of following factors were investigated using standard ELISA kits: serum amyloid A (SAA), interleukin-6 (IL-6), macrophage-colony stimulating factor (M-CSF). In addition plasma concentrations of C-reactive protein (CRP) and beta 2 microglobulin (beta 2M) were investigated in the AMYL group. All these parameters were studied during different time periods of the hemodialysis session. Plasma levels of SAA and IL-6 did not increase during hemodialysis session and we did not find any difference in plasma levels of these factors between the group of patients with AMYLand NE-AMYL. Plasma levels of M-CSF increased during hemodialysis and its levels in AMYL group were significantly higher in comparison with NE-AMYL group at the end of hemodialysis session (5345.10 +/- 340.42 vs. 3458.45 +/- 332.15 pg/ml, p = 0.0011). A linear correlation was found between plasma levels of SAA and CRP during hemodialysis whereas no correlation was found between plasma levels of beta 2M and other factors.Our study suggests that plasma levels of M-CSF are increased in patients with chronic renal failure. Significant increase of M-CSF levels in the AMYL group could lead to greater activation of monocyte-macrophage system and could serve as factor supporting amyloid deposition process.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disease caused by mutations in at least three different loci. Mutations in the PKD2 gene are responsible for approximately 15% of the cases of the disease. We have screened 14 Czech families for mutation in the PKD2 gene. Clear evidence against linkage to the PKD1 gene was established by CA-repeat markers in five families. The disease could be linked to both genes according to linkage analysis in nine families but we have chosen these families because of the mild clinical course. An affected member from each family was analyzed by heteroduplex analysis (HA) and single strand conformation polymorphism (SSCP) for all 15 coding regions. Samples exhibiting shifted bands on HA or SSCP gels were sequenced. We detected five mutations (four new, and one which was previously described) and two polymorphisms. The four new mutations include one insertion, one deletion, one substitution (leading to premature translation stop), one amino acid substitution. Our results confirm that different point or small changes distributed throughout the PKD2 gene without clustering are responsible for the disease.

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.

Many controversial studies concerning relation between angiotensin converting enzyme polymorphism and renal and cardiovascular disease have been published during the last years. Most of the papers have suggested that the DD genotype plays an important negative role in the progression of some renal diseases (e.g. IgA nephropathy, diabetic nepropathy). The D allele may be an independent risk factor for development of the target organ damage in essential hypertension. The therapeutic response on inhibitors of angiotensin converting enzyme depends on insertion-deletion polymorphism. It probably also depends on the gender. The pathological mechanisms of insertion-deletion polymorphism have not yet been clearly identified.

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.

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.

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.

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.

The author describes some differences in the course of treatment of urinary pathway infections in prolonged reduced renal function. He emphasizes changes from the aspect of the clinical course of urinary infections and changes in the pharmacokinetics and pharmacodynamics of antibiotics and principles for selection of therapy are outlined.

Bence-Jones nephropathy, the most serious form of which is renal failure, is one of the frequent complications in multiple myeloma (MM). Precise pathogenetic mechanism of renal injury remains unclear. Experimental study points to the possible role of some cytokines in the development of this type of nephropathy. We have investigated the levels of interleukin-6 (IL-6), tumour nekrosis factor alpha (TNF-alpha) and their soluble receptors in patients with plasmocytoma.The group comprised 49 patients with plasmocytoma, mostly with MM. Significantly higher levels of IL-6 were found in patients with irreversible renal insufficiency and/or failure (group A-median 13.3 pg/ml, range 3.6-33.3) comparing patients with reversible impairment (group B-median 3.1-range 1.8-38.4) (p0.01) and those with normal renal functions (group C-median 2.3-range 0.97-7.41) (p0.01). Significant difference was also found between the groups B and C (p0.05). Analysis of variance with the use of various factors showed that the correlation between IL-6 and prognosis of renal disease was stronger (p0.001) than the correlation between cytokine levels and the clinical phase of MM (p0.05). The difference of IL-6 levels between various clinical stages of MM was not significant. The levels of sIL-6R were significantly increased in patients with both reversible and irreversible renal insufficiency comparing the group with unaffected renal functions (p0.05 and p0.01 respectively). TNF-alpha levels did not differ between all 3 groups of patients, however, significantly increased values of sTNF-R II were observed in group A vs B and group B vs C (p0.05).We conclude, that some cytokines, especially IL-6/sIL-6R, could play an important role in development of renal insufficiency in MM or other monoclonal gammapathies. We suggest that IL-6 levels could be predictive factor for renal insufficiency recovery.

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.

Renal affections are a frequent and clinically important complication of monoclonal gammapathies (MG), in particular of multiple myeloma (MM). The main pathogenetic factor in its development is most probably, despite the participation of other nephrotoxic factors, the action of Bence-Jones protein on the renal parenchyma. Mechanisms of renal affection differ - paraprotein (pp) interferes with tubular functions, precipitates in the cells of the tubular epithelium or in the tubular lumen, is deposited in renal tissue in the form of deposits. The main clinical manifestations include proteinuria, impaired tubular functions and reduced filtration capacity of the kidneys. In 5-10% patients renal failure develops, formerly associated with the unequivocally adverse prognosis of the disease. The change of the therapeutic approach which combines haematological and symptomatic treatment, incl. methods of extracorporeal treatment of the blood, however leads in half the patients to improvement or complete restitution of renal functions. The development of the disease is therefore to a considerable extent determined by the activity of the basic disease and its response to chemotherapy.

Reactive oxygen species and other free radicals are known to be the mediators of phenotypic and genotypic changes that lead from mutation to neoplasia. The imbalance in tumor cell antioxidant defense mechanism can influence also the sensitivity to cytoreductive therapy. In erythrocytes it can results to hemolysis which is one of pathogenetic mechanisms of anemia in cancer patients.We investigated the parameters of lipid peroxidation (malondialdehyde-MDA) and antioxidant enzymes here represented by superoxide dismutase (SOD) and glutathione peroxidase (GPx) in multiple myeloma. Nine patients of various clinical stage and activity of disease were studied. A significant higher concentration of total MDA in plasma (1.20 +/- 0.24 mumol/l v.s. 0.64 +/- 0.22 mumol/l, p0.0001) as well as in erythrocytes (2.72 +/- 0.81 mumol/l v.s. 1.03 +/- 0.44 mumol/l, p0.0001) was found comparing to the control group. The levels of free MDA in plasma (0.31 +/- 0.09 mumol/l v.s. 0.49 +/- 0.17 mumol/l, p0.05) and in erythrocytes (0.29 +/- 0.20 mumol/l v.s. 0.59 +/- 0.22 mumol/l, p0.001) were decreased in myeloma patients. A significantly lower activity of GPx (19.17 +/- 4.07 U/g v.s. 23.26 +/- 3.61 U/g Hb, p0.05) and SOD (1882.46 +/- 181.73 U/g v.s. 2347.13 +/- 502.51 U/g Hb, p0.05) in erythrocytes were found.We didn't observe evident relationship between the concentration of MDA or activities of SOD and GPx and either the stage of disease or level and type of paraprotein. We can conclude, that higher concentration of total MDA as a parameter of lipid peroxidation, is significantly increased in patients with multiple myeloma. It could be consequence of impaired antioxidant defence. These results propose possible role of free radicals with reduced antioxidant activity of SOD and GPx in multiple myeloma. As we can consider the role of free radicals in pathogenesis of malignant proliferation, prognostic value and the change during the course of therapy should by studied.

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.