The dilemma of dual renin-angiotensin system blockade in chronic kidney disease: why beneficial in animal experiments but not in the clinic?

Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients.

Recent insights into the pathogenesis of nephrotic syndrome.

Nephrotic syndrome is characterized by heavy proteinuria followed by hypoproteinemia, hypercholestrolemia, lipiduria, and edema. The glomerular filtration barrier (GFB) consists of glomerular endothelial cells covered with glycocalyx, the basement membrane, subpodocyte space and podocytes with foot processes and slit membranes between them. The coordinated function of GFB has been considered to be the major barrier against filtration of plasma proteins to urine. However, new hypothesis suggesting more permeable GFB has emerged. According to this, proteinuria might be prevented by tubular protein reabsorbtion. Experiments and human studies have revealed numerous putative permeability factors in idiopathic nephrotic syndrome (minimal change disease/focal segmental glomerulosclerosis). New antigens and antibodies have been suggested in "idiopathic" membranous nephropathy as well. Formation of nephrotic edema, the role of oncotic pressure and of different sodium and water retaining hormones have been subject of intensive study. These findings should pave the way to new therapeutic modalities targeted more precisely to the pathogenic mechanisms.

[The role of arachidonic acid metabolites in the regulation of renal function and pathogenesis of hypertension]. / Uloha metabolitu kyseliny arachidonové v regulaci renálních funkcí a patogenezi hypertenze.

Eicosanoids are twenty-carbon compounds derived from arachidonic acid. Lipoxygenases, cyclooxygenases and cytochrome P-450 enzymes contribute to their synthesis. Our review is focused on prostaglandins, leucotrienes, lipoxins, hepoxilins, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids. Most of these compounds have multiple functions and they also participate in blood pressure regulation and excretion of water and solutes in the kidney. They have some roles in the patogenesis of kidney disease, too. Both experimental models (mainly geneticaly modified mice and rats) and human epidemiological and genetical studies are used in the investigation of eicosanoid physiological and patophysiological functions. New information about their enzymatic regulations and receptors have already resulted in the development of new drugs, mainly antiasthmatics, but further investigation should bring about new results in the treatment of hypertension and other cardiovascular and renal diseases.

Effects of sodium restriction and cyclooxygenase-2 inhibition on the course of hypertension, proteinuria and cardiac hypertrophy in Ren-2 transgenic rats.

The present study was performed to evaluate the effects of sodium intake and of chronic cyclooxygenase-2 (COX-2) inhibition on systolic blood pressure (SBP) in heterozygous male transgenic rats harboring the mouse Ren-2 renin gene (TGR) and in transgene-negative normotensive Hannover Sprague-Dawley (HanSD). Twenty-eight days old TGR and HanSD were randomly assigned to groups fed either normal salt (NS) or low sodium (LS) diets. COX-2 blockade was achieved with NS-398 (1 mg x kg(-1).day(-1) in drinking water). During an experimental period of 26 days, SBP was repeatedly measured by tail plethysmography in conscious animals. We found that the LS diet prevented the development of hypertension in TGR and did not change SBP in HanSD. Low sodium intake also prevented proteinuria and cardiac hypertrophy in TGR. On the other hand, irrespective of sodium intake chronic COX-2 inhibition did not alter the course of SBP in either TGR or HanSD. The present data indicate that TGR exhibit an important salt-sensitive component in the developmental phase of hypertension. They also suggest that systemic COX-2-derived prostaglandins do not act as vasodilatory counterregulatory agents in TGR in which an exaggerated vascular responsiveness to angiotensin II is assumed as the pathophysiological mechanism in the development of hypertension.

Soluble adhesion molecules and cytokines in patients with myasthenia gravis treated by plasma exchange.

Plasma exchange (PE) is an effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except for acetylcholine receptor antibodies (AChRAbs), some other inflammatory mediators possibly activated in MG may also be removed during PE. Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL-6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 MG patients assigned to treatment with PE. On the basis of the serum levels of AChRAb the patients were subdivided into 2 groups (8 patients with low AChRAb, 12 patients with high AChRAb). Soluble adhesion molecules and cytokines were measured before the first and last PE, at the end of the first PE and in the samples of plasma filtrate obtained during the first PE. Before the first PE patients with MG had higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both after the first PE and during the course of PE, a substantial decrease in serum levels of AChRAb, sICAM-1 and sVCAM-1 was recorded. However, serum levels of sIL-2R and sTNF-R II were not significantly influenced by either a single treatment or during the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrates too. Patients with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than patients with low AChRAb. Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in patients with MG suggest some systemic activation of the immune response which is more pronounced in patients with high circulating AChRAb. PE led to the decrease in serum AChRAb and soluble adhesion molecules due to their effective filtration but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with the synthetic membrane.

Outcomes of atherosclerotic renal artery stenosis managed without revascularization.

OBJECTIVE: To determine how often patients with renal artery stenosis (RAS) managed without revascularization progress to accelerated hypertension and/or renal failure. PATIENTS AND METHODS: We examined the outcomes of 68 patients (mean +/- SEM age, 71.8 +/- 0.9 years) with high-grade (>70%) RAS identified between 1989 and 1993 who were treated without renal revascularization for at least 6 months after angiography. The time to last follow-up averaged 38.9 +/- 2.8 months. Other vascular beds were affected in 66 of the 68 patients. End points were revascularization, nephrectomy, dialysis, or death. RESULTS: The mean +/- SEM serum creatinine level rose from 1.4 +/- 0.1 to 2.0 +/- 0.2 mg/dL (P<.001). Mean +/- SEM blood pressure did not change (157 +/- 3/83+/-2 vs 155 +/- 3/79 +/- 2 mm Hg), but the need (mean +/- SEM) for medication increased from 1.6+/-0.1 to 1.9+/-0.1 drugs (P=.02). Four patients (5.8%) eventually underwent renal revascularization for refractory hypertension (1 patient), for progressive stenosis (1 patient), and during aortic reconstruction (2 patients). One additional patient underwent nephrectomy to improve blood pressure control. Five others (7.4%) developed end-stage renal disease (ESRD) for reasons other than progressive vascular disease, namely, diabetes (3 patients), atheroemboli (1 patient), and contrast toxicity without RAS progression (1 patient). In 1 further case, the reason for ESRD was unknown, and it may have been caused by vascular occlusion. During follow-up, 19 patients died of unrelated causes, including myocardial infarction and stroke. CONCLUSIONS: These data indicate that antihypertensive medication requirements increased and renal function deteriorated modestly in a subset of patients with atherosclerotic RAS managed initially without vascular intervention. Many achieved stable blood pressure for many years. Deterioration of renal function and mortality risk were greatest in patients with bilateral stenosis or stenosis to a solitary functioning kidney. These results reinforce the need for meticulous follow-up for disease progression but underscore the role of competing risks and high mortality from other cardiovascular diseases, which primarily determine the outcomes in patients with RAS and widespread atherosclerotic disease.

Long term treatment of IgA nephropathy with cyclosporine A.

20-50% of patients with IgA nephropathy (IgAN) reach end-stage renal failure. Yet a standard treatment for those with progressive course and/or great proteinuria is lacking. We treated 6 patients with biopsy proven IgAN, proteinuria over 3.5 g/24 h and S-creatinine less than 200 micromol/L non-responding to corticosteroids administered for 3 months. They were given cyclosporine A (CsA) 5 mg/kg bw/day then titrated aiming at a serum concentration of 70-150 ng/mL for one year tapered to discontinuation in 9 months. Prednisone 5-10 mg on alternate days was given with CsA. Proteinuria (g/day) decreased from 4.66 +/- 0.43 to 1.38 +/- 0.29 (p < 0.01) after 1 month and to 0.59 +/- 0.14 (p < 0.001) after 1 year of treatment and remained lower than baseline 2 years from the beginning (1.44 +/- 0.27, p < 0.001). GFR (creatinine clearance) did not change during the first month (1.25 +/- 0.21 mL/s vs 1.38 +/- 0.29 mL/s), but decreased after 1 year (1.05 +/- 0.14 mL/s, p < 0.05). After two years it increased to 1.17 +/- 0.16, NS from baseline. We also calculated the ratio of proteinuria to the GFR (mg/L) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80 + 6.47 before therapy, it decreased after 1 month (11.56 +/- 1.7, p < 0.05) and further after 1 year (6.78 + 1.45, p < 0.01). Three months after discontinuation it was still 14.32 +/- 1.00, p < 0.05 from baseline. In conclusion, CsA significantly lowered moderate to high proteinuria in 6 patients with IgAN. Significant decrease of the proteinuria/GFR ratio suggests some non-hemodynamic mechanism of CsA action. The therapy was well tolerated and side-effects were not so severe as to require CsA withdrawal.

[Pathophysiology of diabetic nephropathy]. / Patofyziologie diabetické nefropatie.

The epidemic increase of diabetic nephropathy stimulated also the interest in pathophysiological mechanisms that lead to the development of the disease. The main interest is concentrated on the glycosylation of proteins and lipids, activation of intracellular enzyme cascades (protein kinase C, aldosoreductase) and the effect of vasoactive compounds (NO, prostanoids, angiotensin II) and growth factors. Cytokines are also of great importance. Every new piece of information is used in search for new modes of therapy, but most of them remain at the stage of experiments.

[Plasma leptin levels in patients with kidney diseases of various etiologies]. / Plazmatické hladiny leptinu u pacientu s ledvinovým onemocnením ruzné etiologie.

BACKGROUND: 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. METHODS AND RESULTS: 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, p < 0.001) and in dialysis and non-dialysis patients (19.6 +/- 16.5 vs 10.7 +/- 14.5, p < 0.05). There was also a difference between dialysed and non-dialysed men (15.1 +/- 16.2 vs 5.9 +/- 9.2, p < 0.05). 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, p < 0.001) and a negative correlation with S-albumin in nephrotic men (r = -0.65, p < 0.05). CONCLUSIONS: 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.

[Relation between plasma levels of IGF-I, leptin and TNF-alpha in diabetics]. / Vztah plazmatických hladin IGF-I, leptinu a TNF-alfa u diabetiku.

BACKGROUND: 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. METHODS AND RESULTS: 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, p < 0.05). In women a correlation was found between IGF-I and TNF-alpha concentrations (r = 0.65, p < 0.01). 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. CONCLUSIONS: 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.

[Soluble cytokinin receptors in renal vasculitis and lupus nephritis]. / Solubilní receptory pro cytokiny u renální vaskulitidy a lupoidní nefritidy.

BACKGROUND: Activation of various cytokines, e.g. TNF alpha, IL-1 and/or IL-6 may play important role in the pathogenesis of renal vasculitis and lupus nephritis (LN). Systemic effects of these cytokines may be modulated by their circulating soluble receptors. Plasma levels of cytokine receptors may thus be also markers of the activation of these cytokines. METHODS AND RESULTS: Plasma levels of TNF alpha, its soluble receptor p75 (sTNF-RII), IL-6 and soluble IL-6 receptor (sIL-6R) were measured using ELISA in 17 pts with ANCA-positive renal vasculitis (12 active-ANCA-A, 7 in remission ANCA-R), 9 pts with active lupus nephritis (LN) and 5 healthy subjects. Pts with LN had in comparison with controls increased plasma levels of TNF alpha, sTNF-RII, IL-6 and sIL-6R. Pts with ANCA-A had also in comparison with controls increased plasma levels of TNF alpha, sTNF-RII and sIL-6R, but plasma levels of IL-6 were not significantly increased dut to great standard deviation. Pts with ANCA-R had in comparison with controls increased plasma levels of sTNF-RII, but plasma levels of TNF alpha were in ANCA-R significantly lower than in ANCA-A. While the ratio TNF alpha/sTNF-RII was significantly lower in all groups of pts than in controls, the ratio IL-6R/sIL-6R was in comparison with controls significantly increased only in LN. CONCLUSIONS: While increased plasma levels of TNF alpha may be nonspecific marker of the activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are increased also in pts with ANCA-positive renal vasculitis in remission. Increased plasma levels of sTNF-RII may interfere with systemic effects of TNF alpha, but may also prolong the lifetime of its active form. Plasma levels of sIL-6R are increased both in ANCA-A and in LN, but their increase is, however, much less pronounced than that of sTNF-RII and cannot effectively block systemic effects of IL-6.

[Soluble adhesive molecules and cytokines in patients with myasthenia gravis treated with plasmapheresis]. / Solubilní adhezní molekuly a cytokiny u nemocných s myasthenia gravis lécených plazmaferézou.

BACKGROUND: Plasma exchange (PE) is effective therapeutic method used in patients with myasthenia gravis (MG) refractory to common therapy and/or with life-threatening respiratory complications. Except from acetylcholine receptor antibodies (AChRAb) some other inflammatory mediators possibly activated in MG may be also removed during PE. METHODS AND RESULTS: Serum levels of soluble adhesion molecules (sICAM-1 and sVCAM-1), IL-6 and soluble receptors for IL-2 (sIL-2R), IL6 (sIL-6R) and TNF alpha (sTNF-R II) were measured in 20 patients (pts) with MG indicated to the treatment with PE. Pts were subdivided on the basis of the serum levels of AChRAb into 2 groups (8 pts with low AChRAb, 12 pts with high AChRAb). Soluble adhesion molecules and cytokines were measured before the 1st and last PE, at the end of the 1st PE and in the samples of plasma filtrate obtained during the 1st PE. Pts with MG had before the 1st PE higher serum levels of sICAM-1, sVCAM-1, sIL-2R and sTNF-R II than controls. Both the first PE and the course of PE led to the substantial decrease of serum levels of AChRAb, sICAM-1 and sVCAN-1, serum levels of sIL-2R and sTNF-R II were not, however, significantly influenced by both the single and the course of PE. There were high levels of AChRAb, soluble adhesion molecules and soluble cytokine receptors in plasma filtrate, too. Pts with high circulating AChRAb had higher serum levels of sICAM-1 and sVCAM-1 than pts with low AChRAb. CONCLUSIONS: Increased serum levels of soluble adhesion molecules and soluble cytokine receptors in pts with MG indicated to the treatment by PE suggest some systemic activation of immune response which is more pronounced in pts with high circulating AChRAb. PE led to the decrease of serum AChRAb and soluble adhesion molecules due to their effective filtration, but, on the other hand, serum levels of soluble cytokine receptors were not influenced by PE, in spite of their effective filtration which is probably counteracted by their increased production, possibly stimulated by the contact of the blood with synthetic membrane.

[Clinical spectrum of the antiphospholipid syndrome]. / Klinické spektrum antifosfolipidového syndromu.

Antiphospholipid syndrome (APS) is characterized by multiple arterial and venous thromboses, repeated spontaneous abortions and thrombocytopenia, together with the presence of antiphospholipid antibodies in serum. We present three patients, two men and a woman, at the age of 43, 24 and 23 years respectively. The younger man and the woman had secondary APS and systemic lupus erythematosus, the older man had primary APS. The symptoms and course of the disease were different. The older man lives 17 years after the onset of first symptoms with multiple neurologic disorders, the younger man is symptomless. The woman died several months after the acute onset of the disease.

[Diabetic nephropathy]. / Diabetická nefropatie.

Diabetic nephropathy is one of the microvascular complications of diabetes. Its incidence is decreasing in insulin dependent patients, but extremely increasing in non-insulin dependent patients in developed countries. The development of nephropathy in an individual patient cannot be predicted in spite of new information about genetics and pathophysiology of the disease. Clinical course progresses from microalbuminuria to overt proteinuria and than to renal failure. The disease cannot be cured, but can be prevented or limited in progression. The most important measures are maintaining of normoglycaemia and blood pressure in low-normal values (best using ACE inhibitors), treatment of hypercholesterolaemia and protein restriction. Renal replacement therapy is available for all diabetic patients in our country without restriction, the best method is kidney transplantation if not contraindicated.

[Long-term administration of cyclosporine A in patients with IgA nephropathy]. / Dlouhodobé podávání cyklosporinu A u pacientu s IgA nefropatií.

BACKGROUND: 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. METHODS AND RESULTS: 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 (p < 0.01) and remained low after one year of treatment (0.59 +/- 0.14 g/day, p < 0.001). 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, p < 0.05). 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), p < 0.05) and achieved the lowest value after one year of therapy (6.78.10(-3) +/- 4.25 .10(-3) +/- 4.25.10(-3), p < 0.01). Serum cholesterol also significantly decreased after 12 months of therapy (6.21 +/- 0.62 vs. 5.41 +/- 0.45 mmol/l, p < 0.05). CONCLUSIONS: 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.

[Thromboembolic complications in nephrotic syndrome]. / Tromboembolické komplikace nefrotického syndromu.

Thromboembolic complications of nephrotic syndrome are very frequent. They can occur in the arterial or venous circulation. Venous thromboses are frequently asymptomatic and are manifested only by pulmonary embolism. Thrombosis of the renal vein may be dramatic and include renal failure. For the diagnosis various isotope, X-ray and ultrasound methods are used. Anticoagulation or thrombolytic treatment is used; in some instances also thrombectomy may be used. In patients with albumin levels lower than 20-25 g/l prophylactic administration of acetylsalicylic acid is useful. The clinical picture and therapeutic procedure are demonstrated on three brief case-histories.

[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.

[Rhabdomyolysis and acute renal failure]. / Rabdomyolýza a akutní renální selhání.

Rhabdomyolysis is damage of the skeletal muscles due to different causes which leads to the release of the contents of muscle cells into the blood stream and conversely to the penetration of water and other substances into muscles via the damaged membrane. This initiates many processes which damage the organism: hypovolaemia, hypocalcaemia, hyperkalaemia, hyperuricaemia, disseminated intravascular coagulation, renal failure. Renal failure in particular is a frequent and very serious complication. However, when correct treatment is provided, it is usually reversible. The diagnosis and differential diagnosis is not difficult if the possible presence of rhabdomyolysis is considered. Therapy involves in particular supplementation of the vascular volume and forced diuresis.

[Acute kidney failure associated with rhabdomyolysis]. / Akutní selhání ledvin na podklade rabdomyolýzy.

The authors describe three cases of rhabdomyolysis and acute renal failure. In all patients rhabdomyolysis developed in conjunction with ingestion of alcohol, in two moreover in combination with compression of an extremity by body weight during prolonged immobility. One patient was hospitalized on the day when rhabdomyolysis developed, the second one more than 24 hours after and the third one only several days after development of the condition. In none of them the diagnosis was established before the development of renal failure. All were subjected repeatedly to haemodialysis. One patient died from a complication--embolism of the brain--the remaining two patients recovered without sequelae. In the discussion the authors deal with reasons of late diagnosis of the disease.