[An overview of the results of renal transplantation in the Czech Republic]. / Piehled výsledku transplantací ledvin v Ceské republice.

Renal (kidney) transplantation is now a routine and the most successful form of renal replacement therapy. There is a long tradition of renal transplantation in the Czech Republic, The first was performed as early as 1961 in Hradec Kralove, and the programme as such was launched in 1966 with the first successful transplantation at the Institute of Experimental Surgery (later Institute for Clinical and Experimental Medicine, Prague). At present, transplantations are being performed at 7 transplantation centres (IKEM Prague, Centre for Cardiovascular and Transplantation Surgery Brno, Faculty Hospitals Hradec Kralove, Plzen, Olomouc and Ostrava and Faculty Hospital Motol for children). From the programme launch until the end of 2010, 8,761 renal transplantations were performed, 364 in 2010 alone. One-year patient and cadaver renal allograft survival, transplanted in the CR between 2000 and 2009, is around 95% and 92%, respectively, and 5-year survival is 87% and 81%, respectively. As of 31st December 2009, a total of 3,771 patients lived with functional renal allograft in the Czech Republic and the proportion of patients with irreversible renal failure treated with transplantation has recently been around 40%.

[Urinary tract infections and chronic renal failure]. / Infekce mocového traktu a chronické selhání ledvin.

The paper briefly summarizes issues related to urinary tract infections in adults: predispositions and risk factors, classification, assessment of pathogenicity of bacterial agents, the role of bacteriuria and leucocyturia, interpretation of findings, treatment principles and an association with chronic renal failure. Urinary tract infections are the second most frequent infectious disease in the population. They most often affect women of childbearing potential and then seniors of both sexes who have multiple risk factors. Escherichia coli and Staphylococcus saprophyticus are the most pathogenic towards urinary tract; they are responsible for 85% and 10-15% of cases of acute uncomplicated urinary infections, respectively. Chronic pyelonephritis, a chronic interstitial nephritis, is the fourth most frequent cause of chronic renal failure. Chronic renal failure is a risk factor for the development of urinary infections due to metabolic disorders resulting in secondary immunodeficiencywith a disorder of all components of immunity. In patients with chronic renal failure, urinary tract infections occur most frequently after kidney transplantation when graft pyelonephritis is a life-threatening complication. Therefore, urinary tract infection prevention with co-trimoxazole once daily over at least 6 months is recommended in renal allograft recipients.

[Mineral-bone disorder with chronic kidney disease]. / Minerálove-kostní porucha pri chronickém onemocnéní ledvin.

Mineral-bone disorder in chronic kidney disease is a clinical syndrome provoked by the combination of three factors: abnormal laboratory results, bone morphology disorder and extra-bone calcification. Its onset in adult age is linked with a decrease in glomerular filtration (GF < 1 ml/s). Fully developed forms occur in the course of regular dialysis treatment. The use of the traditional denomination "renal osteodystrophy" is currently restricted to the bone morphology finding. As there are two threshold types of bone turnover (low and high) and two degrees of mineralisation (low and normal), there is a total of four basic variants of mineral-bone disorder. The high turnover variants--secondary hyperparathyreosis and a combined disorder--are still the most frequent and are diagnosed in 70 to 80% of cases. Low turnover disorders include osteomalatia (OM) and adynamic bone disease (ABD). While OM is becoming increasingly rare, the occurrence of ABD is on the rise. The main reason for this may be the steady growth in the age of dialised patients and a number of risk factors, as well as treatment with inadequately high doses of vitamin D. Progressive chronic kidney disease may be linked with D-hormone deficit, negative calcium balance and with positive phosphate balance. Phosphates become a key factor in the development and progression of secondary hyperparathyreosis and extra-bone calcification in the case of D-hormone substitution. Therefore, maintaining a good phosphate balance by restricting their intake or by reducing their intestinal resorption through the use of phosphate binders is the most efficient therapeutic procedure. In patients with chronic kidney failure, adequate dialysis treatment is necessary. Hyperphosphatemia and extra-bone calcification are new independent risk factors of cardiovascular morbidity and mortality.

Neurohumoral activity, heart failure and prognosis in patients with end-stage renal disease treated by hemodialysis.

BACKGROUND: Chronic renal failure treated by regular hemodialysis is frequently accompanied by chronic heart failure; the mortality of both is high. AIM: To evaluate the role of markers of neurohumoral activation for the prognosis of patients treated with regular dialysis. PATIENTS: 99 patients with end-stage renal disease were followed up for 3 years. METHODS: Clinical evaluation, echocardiography, biochemistry including NT-proBNP and big endothelin (Big-ET). RESULTS: The incidence of heart failure was 97% and the 3-year mortality was 50%. The sensitivity of NT-proBNP and Big-ET level for the prediction of death was 0.712 and 0.824, respectively, and specificity 0.642 and 0.695, respectively. The cut-off points were NT-proBNP > or = 2,000 pg/ml and Big-ET > or = 1.55 pmol/l. Neither NT-proBNP nor Big-ET could be incorporated in the multivariate model for overall survival, which means that although both parameters significantly influenced overall survival as single risk factors, they were not effective in competition with the other significant predictors. CONCLUSION: Overall survival seems to be influenced namely by age, hemoglobin, left atrium diameter or pulmonary congestion class on chest X-ray, while probability of early risk was associated with Big-ET, history of diabetes mellitus, C-reactive protein, uric acid and hemoglobin. The only intersection of the models is hemoglobin as a thoroughly significant predictor.

[The importance of determination of Nt-proBNP and big endothelin in diagnosing chronic heart failure in patients on regular haemodialysis treatment]. / Význam stanovení Nt-proBNP a big endotelinu pro diagnostiku chronického srdecního selhání u nemorných v pravidelném hemodialyzacním programu.

We have followed 99 patients with end stage renal failure, treated by regular haemodialysis. Chronic renal failure is frequently accompanied by chronic heart failure (over 50%), especially by heart failure with preserved ejection fraction. Patients treated by regular haemodialysis had a tendency to cardiomegaly (51%), mild systolic dysfunction of the left ventricle (mean LVEF 53%) and diastolic dysfunction (88%) of the hypertrophic left ventricle. They had also activated endothelin and neurohumoral system. Only 3% of the patients had normal values of Nt-proBNP and big endothelin. The plasma level of Nt-proBNP in haemodialysed patients correlated with cardiothoracic ratio and with ejection fraction. The plasma level of big endothelin correlated only with cardiothoracic ratio.

Phagocyte-derived oxidants and plasma antioxidants in haemodialysed patients.

OBJECTIVE: Oxidative stress is one of the important complications occurring in haemodialysis. The aim of the study was to determine haemodialysis-induced changes in oxidative burst of phagocytes and the antioxidative properties of plasma. METHODS: Twenty-seven patients and 50 healthy controls were examined. Oxidative burst of phagocytes and plasma antioxidative potential were measured luminometrically. Concentrations of major plasma antioxidants (vitamin E, bilirubin and uric acid) were also determined. RESULTS: Phagocyte chemiluminescence was higher in patients before haemodialysis compared with that in controls and decreased after haemodialysis compared with predialysis status. A significant increase in plasma antioxidative potential and uric acid was found in patients before haemodialysis. These parameters decreased after haemodialysis compared with both predialysis and control values. CONCLUSIONS: The higher generation of phagocyte-derived oxidants and the decline in plasma antioxidative properties after haemodialysis confirm insufficient antioxidant defence in patients with chronic renal failure.

[Variability of plasmatic levels of big endothelin and NT-proBNP in patients with heart failure in a chronic haemodialysis programme]. / Variabilita plazmatických hladin big endotelinu a NT-proBNP u nemocných se srdecním selháním v chronickém hemodialyzacním programu.

Inter-dialysis variability in levels of big endothelin and NT-proBNP in plasma were studied in 22 patients with established systolic and/or diastolic dysfunction of the left cardiac ventricle assigned to a chronic haemodialysis programme. The plasmatic level of NT-proBNP in all patients was practically unchanged. There was a falling trended between haemodialysis treatments but this was not statistically significant and in absolute values clinically insignificant. Fluctuations were found between individuals but on average all values were stable and high in the pathological range. No significant changes in the plasmatic level of big endothelin were found either. The average levels were again stable and insignificant and the indicated trend did not achieve clinical or statistical significance. The values were once again high in the pathological range. Plasmatic levels of NT-proBNP and big endothelin do not vary according to the phase of the dialysis cycle and mainly reflect the long-term condition of endothelium failure and long-term stress in the left ventricle. Concentrations are not affected by changes in volume or uraemia between dialysis treatments and the suggested trend towards a fall in NT-proBNP and a rise in big endothelin does not have a clear explanation. In any case, this trend remained within the pathological range and is probably not clinically significant.

[Fibrillary immunotactoid glomerulonephritis--an unusual cause of irreversible kidney failure]. / Fibrilární-imunotaktoidní glomerulonefritida--neobvyklá prícina nezvratného selhání ledvin.

Fibrillary-immunotactoid glomerulopathy (FITGP) is a rare cause of nephrotic syndrome. In this patient, male 65-years-old, respectively, fibrillary glomerulonefritis (FGN) was diagnosed by percutaneous renal biopsy. Clinically, the disease manifested with long term proteinuria and nephrotic syndrome without any associated systemic disorder. Histologically, glomeruli showed deposition of PAS+, fuchsinophilic and Orange G+ material in the mesangium and basal membranes. Strong granular immunofluorescent IgG, C3, kappa and lambda light chains deposition was present in the mesangium. Electronmicroscopically, depositions of fibrillary material in the expanded mesangium and in the peripheral basal membranes were found. Randomly distributed nonbranching fibrils measured 18-28 nm. After 18 months of follow-up, the therapy with corticosteroids and Cylosporin A was without effect, and the disease progressed into chronic renal failure, and after 24 months of biopsy the patient is undergoing hemodialysis now.

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

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

[Diagnosis of malacoplakia in a transplanted kidney by needle biopsy]. / Malakoplakie transplantované ledviny diagnostikovaná punkcní biopsií.

Malakoplakia is an uncommon inflammatory condition rarely involving parenchyma of transplanted kidney. We report a 44-year-old female recipient of a cadaveric renal allograft treated with cyclosporin A and prednisone. After transplantation, E. coli and Citrobacter bacteruria occurred and three years later decreased graft function developed. Percutaneous needle biopsy was performed and diagnosis of malakoplakia was established. Histologically, interstitial sheets of plasmocytes and histiocytes with periodic acid-Shiff positive cytoplasm containing Michaelis-Gutmann bodies were present. Ultrastructurally, phagolysosomes containing membrane fragments and various developmental stages of inclusions to fully developed Michaelis-Gutmann bodies were found. The patient was treated with co-piperacillin and subsequently pefloxacin and renal functions improved after six months follow-up. Our case suggests that malakoplakia represents an abnormal defective histiocytic response to the infection in the setting of immunosuppressive therapy.

[Hypertension in hemodialyzed uremic patients]. / Hypertenze u hemodialyzovaných uremiku.

The pathogenesis of hypertension in haemodialyzed uraemic patients is multifactorial. The following are involved: sodium and water retention as a result of the impaired excretory capacity of the kidneys, excessively increased activity of the RAAS and sympathetic nerve, increased levels of the vascular constrictor endothelin-1, cumulation of endogenous inhibitors of NO synthesis and reduced formation of vasodepressor factors. As to other factors in the development of hypertension raised intracellular calcium associated with hyperparathyroidism may participate, the stiffness of calcified arteries, erythropoietin treatment and preexisting essential hypertension. Treatment comprises salt restriction below 5 g/day, systematic control of the volume of extracellular fluid by ultrafiltration during every haemodialysis to the level of so-called dry weight and pharmacological treatment in patients where volume control dos not suffice. All drug groups are used. In their selection contraindications are taken into consideration as well as co-morbidity, the dialyzability of antihypertensive drugs and compelling evidence. In patients with a preserved residual diuresis furosemide is administered--125-750 mg/day. Beta-blockers are indicated in patients with IHD, in particular after IM. Calcium blockers are recommended in ventricular hypertrophy and diastolic dysfunction, when beta-blockers are contraindicated and in elderly patients. ACEI indicated in congestive heart failure and left ventricular hypertrophy with systolic dysfunction. Inhibitors of AT1 receptors are an alternative in case of undesirable effects od ACEI. Alpha-blockers and central alpha agonists are used mainly in combinations. In case of failure the haemodialyzation method can be altered or changing the patients to CAPD may be considered. The relationship between BP and the survival of haemodialyzed patients is bimodal. An adverse effect is exerted by a high as well as low BP and in particular by interdialyzation hypotension. The target BP for the haemodialyzed population has not been defined so far. There is, however, evidence that a high BP is independently associated with the de novo development of IHD and MAP above 106 mm Hg with de novo development of cardiac failure. MAP below 98 mm Hg minimalizes the development and progression of left ventricular hypertrophy and MAP below 106 mm Hg the development of heart failure. Long-term survival for 15 and more years is statistically significantly associated with MAP lower than 99 mm Hg.

[Hypertension after kidney transplantation]. / Hypertenze po transplantaci ledviny.

Hypertension is the most frequent non-rejection complication after transplantation of the kidney. It is encountered in 60 to more than 80% of recipients, depending on the investigated population and the definition of hypertension. It develops also in recipients who were normotensive before transplantation. While in dialyzed uraemic patients in the pathogenesis the most important part is played by hypervolaemia, after transplantation most frequently immunosuppressive treatment plays a part. The objective of our study was to assess the incidence of hypertension in the 1st and 2nd year after transplantation resp., the achieved blood pressure level (BP) the method of hypertension therapy in the group of recipients having immunosuppression treatment with corticoids, cyclosporin A (CyA) and mycophenolate mofetil (MFM). The group comprises 58 recipients of cadaverous renal grafts, 35 men (mean age 44.4 +/- 10.7 years and 23 women (mean age 44.8 +/- 12.6 years). 53 recipients (91.4%) had a graft for the first time, 5 recipients (8.6%) had already a second renal transplantation. Thirteen men (37%) and 8 women (35%) had a functioning graft for at least two years. The blood pressure was assessed by the auscultation method during every ambulatory control examination, with the patient sitting, on the upper extremity on the contralateral extremity with an arteriovenous fistula. The rate of ambulatory check-up examinations depended on the time after discharge from hospital following transplantation: in the first month 1x a week, in the second to third month 1x in two weeks, from the 4th month usually once a month. The BP reading at the end of the first and second year resp. after transplantation was obtained by calculating the mean value of three consecutive readings: from the ambulatory check-up at the end of the 1st and 2nd year resp. after transplantation and the preceding and subsequent check-up examination. Hypertension was defined as a BP exceeding 130/85 mm Hg or a median arterial pressure (MAP) higher than 100 mm Hg. MAP was calculated from the mean value of the SBP and DBP according to the formula: MAP = DBP + 1/3(SBP-DBP).

[Controlled clinical study of Consupren versus cyclophosphamide in chronic glomerulonephritis. II. Adverse effects]. / Kontrolovaná klinická studie Consupren versus cyklofosfamid u chronických glomerulonefritid. II. Nezádoucí úcinky.

BACKGROUND: The second part of the study was designed to assess Consupren side effects. METHODS AND RESULTS: The groups of patients studied were described in Part I. Side affects typical of Cy-A were evaluated only in the CS group. Gastrointestinal intolerance, only mild and temporary, was observed in 31%, neurotoxicity in 44%, hypertrichosis in 37%, nephrotoxicity in 25%, and gingival hypertrophy in 19%. Mean values of systolic and diastolic blood pressure did not change significantly in the course of treatment. When changes in blood pressure were individually investigated in particular patients, they were found in 31% in the CS group and in none in the K group. Mean values of uric acid non-significantly increased in the CS group and, on individual investigation, hyperuricaemia was observed in 31%. Mean values of serum potassium did not alter significantly. Signs of possible hepatotoxicity were found in 37% patients of the CS group. In this group, there was a significant decrease in haemoglobin mean values and a decrease in haemoglobin of more than 25 g/l was observed in 44% of CS group patients. In the K group significant decrease in mean leukocyte count was noted, but no patient developed real leukopenia. CONCLUSIONS: The occurrence of side effects was comparable to data known from the literature.

[A controlled clinical trial of Consupren versus cyclophosphamide in chronic glomerulonephritis]. / Kontrolovaná klinická studie Consupren versus Cyklofosfamid u chronických glomerulonefritid.

BACKGROUND: Experience gained from recent studies shows, that Cyclosporine-A (Cy-A) may decrease proteinuria (PU) in some forms of chronic glomerulonephritis (GN) with the nephrotic syndrome. The aim of this study was to test the efficacy of Czech-made Cy-A, Consupren. METHODS AND RESULTS: 30 patients with chronic GN, confirmed by biopsy and PU higher than 3 g/d, corticodependent or corticoresistant, were randomized according to the month of birth to either therapy with Consupren at an initial dose of 5 mg/kg/d (CS group, after dropout of 3 patients who did not finish the treatment, n = 16) or Cyclophosphamide at a dose of 1.5 mg/kg/d (K group, n = 11), and prednisone maintained at the original dose in both groups. The treatment was stopped after six months or after achieving remission. The main criterion of efficacy was PU. The decrease in mean values, statistically evaluated by Holm's procedure was highly significant in the CS group and non-significant in the K group. A similar evaluation of PU corrected by glomerular filtration rate was significant in both groups. Partial or complete remission was reached in 50% of CS group patients and in 34% of K group patients (NS). In the CS group a significant increase in the mean values of albumin and gama-globulin, and a decrease in cholesterol levels were observed. In the K group, these changes were non-significant. CONCLUSIONS: In patients with chronic GN and the nephrotic syndrome, the efficacy of Consupren treatment gives comparable, or even better results versus treatment with Cyclophosphamide.

[Kidney transplantation at the Brno Transplantation Center]. / Transplantace ledvin v transplantacním centru Brno.

The transplantation activity in the Brno TC has increased significantly since 1994 and there are now 30 transplantations per 1 million population of the catchment area per year. It is, however, necessary to get more organ donors to attain the national average of 40 renal transplantations per 1 million inhabitants per year, which is also the average value in advanced European countries. With the use of immunosuppression with cyclosporin A the one, five and ten-year survival of grafts increased by 20, 35 and 15% resp., as compared with the period of conventional immunosuppression. The greatest losses of grafts were recorded in the Brno TC during the first year after transplantation and they accounted roughly for 25% during immunosuppression without and immunosuppression with cyclosporin A. The graft losses due to rejection declined from 63 to 21%. However, there was no decline of graft losses for non-immune reasons which accounted during all investigated time intervals for cca 20%. The ratio of graft losses on surgical--urological grounds did not change (before cyclosporin A, 5.9%, and with immunosuppression with cyclosporin A 6.6%). Also graft losses due to the recipient's death declined only insignificantly (14.4% before CyA and 8.4% with CYA). The most frequent causes of death of recipients were infections (40%), followed by cardiac deaths and haemorrhagic conditions (17% in both instances). The high rate of infections is due to aggressive immunosuppressive regimes and large doses of corticoids. Revision of immunosuppressive regimes and protective procedures is necessary. Haemorrhagic conditions such as disseminated coagulopathies remain unexplained so far. The cardiac deaths are associated above all with the rising age of renal transplant recipients and in the majority these deaths could not be prevented (acute myocardial infarctions and sudden deaths at home).

[Arthropathy and para-arthropathy in uremic patients on regular hemodialysis]. / Artropatie a paraartropatie u pravidelne hemodialyzovaných uremiku.

Arthropathies and para-arthropathies occur in two thirds of regularly haemodialyzed uraemic subjects. The incidence does not depend on age but the period of haemodialyzation treatment. After five years of treatment the articular apparatus is affected in 100%. In women, as compared with men, the joints of the upper extremities, in particular the small joints of the hands are significantly more frequently affected.

Changes in the T-lymphocyte subpopulation (CD+/CD8+) in the blood of patients following kidney transplant and during the acute rejection episode.

A study was made of changes in the ratio of CD4+/CD8+ in patients who had received cadaverous kidneys and who were under treatment with a combination of cyclosporin A + azathioprine + cor ticosteroids. The results showed that one month after the transparent there was a significant drop (P less than 0.05) in the immunoregulation index compared with the pretransplantation values. Throughout the whole period a correlation (r = -0.65, P less than 0.05) was found between the CD4+/CD8+ ratio and serum, creatinine. In recipients with acute rejection episode no significant difference was found between the CD4+/CD8+ values before the rejection episode (7 +/- 1 days and 3 +/- 1 days) and after it was diagnosed. The introduction of monoclonal antibodies specific for determinants in T-lymphocyte transplantation. Many authors have investigated changes in the CD4+ (helper inducer) to subpopulations (1) made possible immunological monitoring following the organ CDB+ (cytotoxic suppressor) ratio following the organ transplant (2, 3, 4, 5). Some reports (6, 7) have indicated that during rejection of a transplanted kidney there is a rise in the immunoregulation index (CD4+/CD8+), while other works (8, 9) failed to confirm this. Our work presents the dynamics of changes in the CD4+/CD8+ ratio in peripheral blood of recipients of cadaverous kidney transplants, and points to changes in the immunoregulation index before and during acute rejection episodes.

A T-helper/suppressor ratio in renal allograft recipients after various long-term immunosuppressive regimens.

The response of T-helper and T-suppressor cells to various immunosuppressive regimens was studied in long surviving cadaveric renal allograft recipients. Eight patients were immunosuppressed with Azathioprine and corticosteroids, 12 recipients were treated with a combination of Cyclosporin A, corticosteroids and Azathioprine for 1 year. Both regimens decreased the Th/Ts ratio significantly as compared with healthy controls (p less than 0.05). No correlation between the Th/Ts ratio and the serum creatinine concentration was found. Likewise, the Th/Ts ratio did not correlate with Cyclosporin A blood levels.