Mechanisms of chronic heart failure development in end-stage renal disease patients on chronic hemodialysis.

More than 50 % of end-stage renal disease (ESRD) patients treated by chronic hemodialysis die from cardiovascular diseases, including congestive heart failure (CHF). The incidence of CHF is rising in both general and ESRD population. However, the mechanisms, which lead to the development of CHF in dialyzed patients, differ considerably. First, there are several factors leading to increase of the left ventricular afterload: volume overload between dialyses, hypertension, increased arterial stiffness, anemia, vascular access flow (arteriovenous fistula) and sympathetic activation. Second, hypertension, left ventricular hypertrophy, anemia and frequently present coronary artery disease worsen myocardial oxygenation. The combination of these factors explains the high incidence of CHF in dialyzed patients and their roles are reviewed in this article.

Dyslipidemia and anemia in chronically hemodialyzed patients.

More than 50% of end-stage renal disease subjects treated by chronic hemodialysis die from cardiovascular events. Although there is some information regarding to anemia compensation and to the levels of biochemical risk factors of atherosclerosis in other countries, the data from the Czech Republic are missing. The aim of this study was to estimate mean cholesterol, triglyceride and hemoglobin levels in hemodialyzed subjects in the Czech Republic and to compare them with current guidelines. During the years 2001-2006, nephrologists of all subjects screened by duplex Doppler ultrasonography of our department were asked to fill in questionnaires with basic history and laboratory data. Hemoglobin concentration was calculated separately for years 2001-2004 and 2005-2006 because of the change of recommended target value from 105 to 110 g/l in 2004. A total of 258 subjects were included, aged 65 +/- 14 years, 93 of them males. Patients came from 46 different hemodialysis centers in the Czech Republic. The presence of hypertension and diabetes was in 72.5% and 39.5%, respectively. Only 13.2% of subjects had the smoking history, and another 10% currently smoked. The mean +/- SD laboratory results were as follows: total cholesterol 5.0 +/- 1.1 mmol/l, triglycerides (2.5 +/- 1.4 mmol/l). Hemoglobin concentration was 104.4 +/- 14.4 g/l (mean +/- SD) in years 2001-2004 and 110.1 +/- 16.2 g/l in years 2005-2006. Hemoglobin full blood concentration was lower than recommended 105 g/l in 55% of hemodialyzed subjects during years 2001-2004, and it was lower than 110 g/l during years 2005-2006 in 47% of patients. Hypercholesterolemia above recommended 5.17 mmol/l was present in 39% of subjects. Triglycerides were elevated above 1.69 mmol/l in 64% of patients. Only 10% of subjects were treated by lipid-lowering drugs. We can conclude that in the Czech Republic, patients treated by chronic hemodialysis frequently suffer from anemia, despite the growing evidence of erythrocyte stimulating agents treatment benefit. Similarly, considerable number of these subjects has hypercholesterolemia and hypertriglyceridemia, only rarely treated by lipid-lowering drugs. However, this therapy is still not adequately supported by clinical research evidence.

Pregnancy-associated plasma protein A during hemodialysis with polyamide and diacetate cellulosic membranes.

Pregnancy-associated plasma protein A (PAPP-A) is a new prognostic factor of acute coronary syndrome in the general population. It is elevated in hemodialysis (HD) patients and at baseline, it was shown to be related to inflammation and oxidative stress. The aim of the study was to examine the relationship of PAPP-A and oxidative stress and inflammatory markers to HD treatment. Studied parameters were determined in 10 chronic HD patients treated with low flux polyamide (1st session) and diacetate cellulosic membranes (2nd session) at the beginning, after 15 minutes and at the end of the dialysis session. TRACE method (Time Resolved Amplified Cryptate Emission) was used for PAPP-A assessment. Results were evaluated with ANOVA. PAPP-A levels did not depend on the type of HD membrane but changed significantly with the time of the HD session. They increased significantly from the beginning of HD to 15 min and then decreased to the end of the HD session - p<0.05 15 min of HD vs start, p<0.01 end vs start, p<0.0001 end vs 15 min of HD for polyamide membrane and p=0.05 15 min of HD vs start, p<0.01 end vs start, p<0.0001 end vs 15 min of HD for diacetate cellulosic membrane. Changes in other parameters and differences between membranes were only minimal. We can conclude that PAPP-A as a marker of cardiovascular damage shows significant changes during the HD session. Its initial increase might be ascribed to its release from complexes or storage. During dialysis, it might be destroyed or cleaved and removed as free fragments. Its levels both before and after the HD session are higher than in healthy subjects.

[Disorders of urinary acidification in patients with monoclonal gammapathies]. / Poruchy acidifikace moci u nemocných s monoklonální gamapatií.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

[Renal impairment in monoclonal gammapathies. Clinical study]. / Postizení ledvin u monoklonálních gamapatií. Klinická studie.

BACKGROUND: Renal involvement is an important and frequent complication in patient with monoclonal gammapathy (MG), especially in multiple myeloma (MM). Light chain proteinuria produces many renal manifestations, the most serious form is acute renal failure, which occurs in 5-10% of patients with MM. The frequency and form of renal involvement was determined in a group of patients with MG. The disturbances observed were correlated with the concentration and type of paraprotein in serum and urine. METHODS AND RESULTS: We investigated 82 patients, 37 men and 45 women with an average age of 63.5 years. Apart from standard nephrologic tests the aminoaciduria/24 h and urine acidification capacity was determined. In some patients renal biopsy was performed. Proteinuria was observed in 66 cases (80.5%), in 54 of them of Bence-Jones type. Nephrotic syndrome developed in 4 patients, in all cases the renal amyloidosis was present. Renal insufficiency was diagnosed in 39 patients (47.5%), mostly in MM. In 14 cases was renal insufficiency reversible, in 14 remain stable and in 11 progressed during the course of disease. Irreversible progression developed in terminal phase of disease in most cases. Acute renal failure was observed in 6 patients, only in four of them further course of renal disease could be evaluated. In half of these 4 patients the renal failure was reversible. CONCLUSIONS: Higher frequency of proteinuria and renal insufficiency was detected in patients with light chain paraprotein of lambda type, or biclonal kappa+lambda type. Aminoaciduria was diagnosed in 40% of patients, we did not observe complete Fanconi's syndrome. Incompleted form of renal tubular acidosis we diagnosed in 52% of cases without other signs of renal involvement.

[Plasma volume in polycystic kidney disease]. / Plazmatický volum u polycystické choroby levin.

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

[Rapidly progressing glomerulonephritis with antibodies against cytoplasm of neutrophilic leukocytes]. / Rychle progredující glomerulonefritida s pozitivními protilátkami proti cytoplazme neutrofilních leukocytu (ANCA).

The authors describe the clinical, laboratory and morphological findings, the clinical course and response to treatment in three patients with rapidly progressing glomerulonephritis where positive antibodies against the cytoplasm of neutrophil granulocytes (ANCA) were found. The authors confront their own clinical experience with data in the literature. Examination of ANCA is not only a significant contribution towards a more accurate diagnosis of renal vasculitis, but also an indicator of the activity of the disease and thus of the effectiveness of immunosuppressive treatment.

[Distal renal tubular acidosis in patients with Wilson's disease]. / Distální renální tubulární acidóza u pacientu s Wilsonovou chorobou.

Renal affection is part of the clinical picture of developed Wilson's disease. The most frequent sign of affection of the distal nephron is distal tubular acidosis (DRTA), more frequently its latent form with a normal systemic pH, but inability to reduce the urinary pH below 5.5 after an acid load. More detailed assessment of the type of this disorder was not made so far. To elucidate in greater detail the pathogenesis of DRTA in Wilson's disease the authors examined renal acidification in 13 patients with bioptically verified Wilson's disease, using three acidification tests: 1) the test involving oral administration of calcium chloride (CaCl2), 2) the test involving infusion of sodium sulphate (Na2SO4) and 3) the test using an infusion of NaHCO3. In none of the examined patients with Wilson's disease manifest (complete) DRTA was found with systemic acidosis, however, in five patients latent (incomplete) DRTA was revealed, i.e. after administration of CaCl2 the pH of urine did not decline below 5.5. Patients with Wilson's disease and DRTA differed from patients with Wilson's disease and normal renal acidification by the age at the time of assessment of the diagnosis (30.4 +/- 3.6 vs. 20.75 +/- 2.14 years, p less than 0.02) and the duration of the disease (i.e. the time from assessment of the diagnosis to the acidification examination: 4.6 +/- 4.86 vs. 15.38 +/- 2.40 years, p less than 0.01). In three of four patients with Wilson's disease and DRTA who were given Na2SO4, after its administration the pH of urine did not decline below 5.2.(ABSTRACT TRUNCATED AT 250 WORDS)