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Background. The multifactor aetiology of adolescent idiopathic scoliosis is commonly acknowledged. Both multivariate analyses of large study groups and the search for causes of adolescent idiopathic scoliosis and its progression in individual patients indicate that the aetiopathogenesis of this disorder is remarkably complex. The discovery of novel bone turnover markers, such as Klotho protein and FGF-23, means that their role in this condition also has to be considered. The aim of this paper is to evaluate the FGF-23 and Klotho protein concentration profiles as new contributors to the regulation of calcium and phosphate metabolism in children with adolescent idiopathic scoliosis and compare them with the values seen in healthy children. Material and methods. The study assessed a total of 70 children, including 35 children treated at the postural defects clinic of the Health Care Facility in Oleśno following a diagnosis of adolescent idiopathic scoliosis and 35 healthy children who constituted a control group. The levels of classic bone turnover markers, such as calcium and phosphorus concentration, alkaline phosphatase, 25-OH-D, and parathyroid hormone (PTH) activity, and of newly discovered contributors to calcium and phosphate metabolism regulation, namely Klotho protein and FGF-23, were determined in both groups. Results. There were statistically significant differences in the levels of basic parameters of calcium and phosphate metabolism between children with scoliosis and the control group, with scoliotic patients showing elevated calcium and 25-OH-D levels and reduced parathyroid hormone levels. Klotho protein levels in children with scoliosis were significantly lower than in the control group. Moreover, the scoliotic patients showed a marked trend towards higher FGF-23 levels as compared to the control group. Conclusions. 1. Adolescent idiopathic scoliosis is characterised by multi-level abnormalities of calcium and phosphate metabolism. 2. The increased FGF-23 levels and reduced Klotho protein concentrations found in serum samples collected from children with ado­lescent idiopathic scoliosis may suggest that these hormones play a role in the aetiopathogenesis of the disorder.

Primary aldosteronism (PA) seems to be a pathogenetically heterogenous disease. It is suggested that approximately 30% of all hypertensive patients are affected by this disease. Autonomous hypersecretion of aldosterone, which is observed in this patient group, may be caused by an adrenal adenoma (aldosteronoma), hyperplasia of the zona glomerulosa, mutation of the KCNJ5 potassium channel, or other rare pathogenetic factors. Contrary to what was believed before, PA may be the cause of resistant hypertension rather than mild hypertension, while 70% of the patients have normal serum potassium levels rather than hypokalemia (previously believed to be a classical PA symptom). Hypertensive patients with normal or elevated aldosteronemia (A), suppressed plasma renin activity (PRA) and an elevated A/PRA ratio should undergo further diagnostic work‑up for PA. PA is suspected to be the continuum of low‑renin hypertension. First‑choice therapy of PA should be based on long‑term administration of low‑dose mineralocorticoid receptor antagonists (spironolactone, eplerenone) and, in the nearest future, probably also aldosterone synthase antagonists such as CLI699, regardless of the morphological type of PA. It is still unknown whether pharmacological treatment will totally replace surgical treatment in some types of PA. Long‑term administration of low‑dose aldosterone antagonists is an effective and often underscored antihypertensive treatment, which rarely causes serious hyperkalemia if the kidney function is not impaired.

INTRODUCTION Nitric oxide is an important factor in the pathogenesis of liver cirrhosis. Its synthesis depends on the availability of L‑arginine and is inhibited by asymmetric dimethylarginine (ADMA). Symmetric dimethylarginine (SDMA) seems to be a good marker of multiorgan failure, especially renal failure. OBJECTIVES The aim of the present study was to evaluate the diagnostic significance of dimethylarginines in patients after liver transplantation. PATIENTS AND METHODS The study included 30 cadaver liver donors and 30 recipients with liver cirrhosis. The following parameters were estimated in donors and in liver recipients before and at days 1 and 3 after transplantation: serum alanine transaminase (ALT), aspartate transaminase (AST), and γ‑glutamyltranspeptidase (GGT) activity, international normalized ratio (INR), concentrations of bilirubin, albumin, creatinine, electrolytes, ADMA, SDMA, and L‑arginine. RESULTS Before transplantation cirrhotic patients showed higher bilirubin concentrations, higher ALT and GGT activity, and lower sodium and albumin levels compared with donors. At day 3 after transplantation, we observed a significant increase in ALT, AST, creatinine, sodium, ADMA, SDMA, and L‑arginine, and a decrease in bilirubin levels. A significant positive correlation between SDMA and creatinine was found in donors (P

INTRODUCTION The largest group of patients with secondary hypertension comprises individuals with renovascular hypertension resulting from renal artery stenosis that is a potentially removable condition. It is caused by atherosclerosis in 70-80% of patients. OBJECTIVES The aim of the study was to evaluate the influence of intravascular brachytherapy (IVBT) procedure performed after percutaneous transluminal renal angioplasty (PTRA) on left ventricular (LV) function, mass regression and type of hypertrophy (LVH) determined on echocardiography during long-term follow-up. PATIENTS AND METHODS Sixty-two patients with atherosclerotic renal artery stenosis complicated by severe hypertension were treated with PTRA and randomly assigned to group 1 (PTRA alone) or group 2 (PTRA followed by IVBT). Subsequent IVBT was performed with the PARIS catheter and the Microselectron HDR (Nucletron) system for peripheral arteries. Treatment outcomes during follow-up were assessed with quantitative coronary angiography. LV mass and mass index (LVM and LVMI) and functional parameters prior to PTRA and during follow-up were determined by echocardiography with regard to the type of procedure. RESULTS The degree of renal artery stenosis was significantly different in groups 1 and 2. In both groups elevated LVMI was observed (p = 0.94). There were no significant differences in interventricular septum (IVS) to LV posterior wall (LVPW) ratio, relative LV wall thickness, volumetric parameters and LV ejection fraction between both groups. During follow-up the values of LVMI and IVS to LVPW ratio were significantly lower (p = 0.021 and p = 0.004, respectively) in the PTRA + IVBT group compared to the PTRA group. Analysis of the LV geometry and type of hypertrophy revealed a marked reduction in concentric LVH in the IVBT group during long-term follow-up. CONCLUSIONS Echocardiographic evaluation comparing several LV parameters in the PTRA alone and PTRA + IVBT groups showed that PTRA with subsequent brachytherapy were associated with better control of blood pressure and greater LVM regression, especially concentric hypertrophy, during long-term follow-up.

The influence of hemoperfusion with a cellulose-acetate-coated charcoal column (Adsorba 300-C, Gambro, Lund, Sweden) on plasma concentrations of calcitonin, testosterone and cortisol was studied in five psoriatic patients during 12 treatment periods. Calcitonin, testosterone and cortisol were effectively removed from blood plasma by the charcoal column with average plasma clearances of 34.0, 14.5 and 27.6 ml/min, respectively, at 30 minutes of hemoperfusion, and 4.9, 15.4 and 24.4 ml/min, respectively, at 180 minutes of hemoperfusion. After three hours of hemoperfusion, significant decreases of testosterone and cortisol were found in peripheral venous blood, while calcitonin fell insignificantly. It remains to be elucidated whether long-term use of hemoperfusion would require a detailed control of possible effects on the endocrine status of patients.

Pharmacotherapy has progressed rapidly over the last 20 years with the result that general practioners more and more often use drugs which may influence potassium metabolism at the kidney or gastrointestinal level, or the transmembrane transport of potassium at the cellular level. Potassium abnormalities may result in life-theatening clinical conditions. Hypokalemia is most frequently caused by renal loss of this electrolyte (thiazide, thiazide-like and loop diuretics, glucocorticoids) and the gastrointestinal tract (laxatives, diarrhea, vomiting, external fistula), and may be the result of an increased intracellular potassium influx induced by sympathicomimetics used mostly by patients with asthma, or by insulin overdosage in diabetic subjects. The leading symptoms of hypokalemia are skeletal and smooth muscle weakness and cardiac arrhythmias. Hyperkalemia may be caused by acute or end-stage renal failure, impaired tubular excretion of potassium (blockers of the renin-angiotensin-aldosterone system, nonsteroidal anti-inflammatory drugs, cyclosporine, antifungal drugs, potassium sparing diuretics), acidemia, and severe cellular injury (tumor lysis syndrome). Hyperkalemia may be the cause of severe injury of both skeletal and smooth muscle cells. The specific treatment counteracting hyperkalemia is a bolus injection of calcium salts and, when necessary, hemodialysis.

Summary Existence of hyperendorphinism in patients with chronic renal failure is very likely. It seems to be caused not only by systemic effects of opioids retained because of the impaired excretory function of the kidneys, but also by the altered generation and function of these hormones in peripheral organs, altered effect of opioid receptors on target organs, and the altered function of opioid peptides as neurotransmitters in the central nervous system. Hyperendorphinism in uremic patients may be a primarily beneficial compensatory mechanism counteracting disturbances of the internal environment with secondary harmful side effects which may contribute to the uremic state.

Background: Blood pressure control is the main influential variable in reducing microalbuminuria in patients with type 2 diabetes. In this subanalysis of the Natrilix SR versus Enalapril Study in hypertensive Type 2 diabetics with micrOalbuminuRia (NESTOR) study, we have compared the effectiveness of indapamide sustained release (SR) and enalapril in reducing blood pressure and microalbuminuria in patients ≥65 years of age. Methods: Of the 570 hypertensive patients with type 2 diabetes and persistent microalbuminuria in the NESTOR study, 187 (33%) individuals ≥65 years of age were included in this analysis. Of these, 95 patients received indapamide SR 1.5 mg and 92 patients received enalapril 10 mg, taken once daily in both cases. Adjunctive amlodipine and/or atenolol was added if required. Results: The urinary albumin-to-creatinine ratio decreased by 46% in the indapamide SR group and 47% in the enalapril group. Noninferiority of indapamide SR over enalapril was demonstrated (P = .0236; 35% limit of noninferiority) with a ratio of 0.95 (95% CI: 0.68, 1.34). Mean arterial pressure decreased by 18 mm Hg and 15 mm Hg in the indapamide SR and the enalapril groups, respectively (P = .1136). The effects of both treatments seen in these elderly patients were similar to those observed in the main population, although the extent of the reduction in microalbuminuria was slightly higher. Both treatments were well tolerated, and no difference between groups was observed regarding glucose or lipid profiles. Conclusion: Indapamide SR is not less effective than enalapril in reducing microalbuminuria and blood pressure in patients aged >65 years of age with type 2 diabetes and hypertension. Am J Hypertens 2007;20: 90-97

KA administration given in addition to a low-protein diet leads to a reduction of PTH secretion followed by diminishing of osteofibrosis. Osteomalacia will also be reduced by a better control of the calcium-phosphate metabolism, an increase of 1,25-(OH)2-D levels, and a lower burden of aluminum. Therapeutic levels of 25-OH-D and calcitonin (caused by simultaneous administration of vitamin D) are probably necessary to achieve this effect. KA are not only the optimum form of substitution in the nutritional treatment of chronic renal failure, but they seem to be very effective in the treatment of renal osteodystrophy.

Aim: Malnutrition and inflammation are involved in the pathogenesis of atherosclerosis and increased risk of cardiovascular diseases in end-stage renal disease. The aim of this study was to assess the relationship between concentrations of plasma adiponectin, serum C-reactive protein (CRP), carotid intima-media thickness (IMT) and duration of haemodialysis (HD) treatment in prevalent HD patients. Methods: Plasma adiponectin and serum CRP concentrations were estimated in 80 HD patients and 22 healthy controls. Carotid IMT was measured by ultrasound technique. HD patients were followed up for 23 ± 16 months. During this period, 24 of them died. Results: In HD patients, plasma adiponectin concentration was over 3 times higher than in controls (29.0 ± 2.1 vs. 8.7 ± 2.6 µg/ml; p < 0.001). HD patients with serum CRP concentrations ≧5 mg/l were characterized by a lower plasma adiponectin concentration than HD patients with the CRP Conclusions: (1) Inflammatory processes are associated with an inadequate low plasma adiponetin concentration in HD patients, and (2) a lower plasma adiponectin concentration seems to be a new predictor of poor outcome in HD patients.

BACKGROUND Acute renal failure (ARF) is characterized by impaired excretory, endocrine, homeostatic and metabolic function of the kidneys. It is well-known that leptin is an adipose-derived polypeptide hormone which is predominantly biodegraded by the kidneys. Therefore, plasma leptin concentration is increased in chronic renal failure (CRF). However, its' concentrations in patients with ARF were not investigated until now. The aim of the present study was to evaluate plasma leptin concentration in patients with ARF. PATIENTS AND METHODS 27 patients with ARF (age 44 +/- 4 years, BMI 26.0 +/- 0.9 kg/m2, means +/- SEM, 17 patients 15 M, 2 F recovered kidney function and 10 patients 7 M, 3 F died during the anuric phase), 27 hemodialysis patients (22 M, 5 F; age 45 +/- 2 years; BMI 26.2 +/- 0.8 kg/m2) with chronic renal failure (CRF) and 27 healthy subjects (HS) (22 M, 5 F; age 42 +/- 3 years; BMI 25.9 +/- 0.6 kg/m2) were examined. In patients with ARF, blood samples for plasma leptin and routinely assessed biochemical parameters were withdrawn before the first HD session (I), and in patients who survived a second time 5 days later during the anuric/oliguric phase (II), and a third one during the polyuric phase before discharge of the patient from hospital (III). In patients with CRF all examined parameters were estimated only once before a subsequent HD session. RESULTS Patients with ARF (before the first HD session) and CRF did not differ significantly with respect to BMI, serum creatinine and blood hydrogen ion concentrations. Plasma leptin level in patients with ARF before the first HD session was similar to values obtained in HS, but significantly lower (p < 0.01) than in patients with CRF (2.5 (1.9 - 8.2) vs. 3.4 (2.5 - 8.3) vs. 8.4 (2.9 - 16.9) ng/ml in ARF, HS and CRF, respectively). There was no significant difference in leptinemia between patients with ARF who survived and who died. In patients with ARF who survived, improvement ofrenal function was accompanied by a slightly (not significant) declining tendency in plasma leptin concentration (5.6 +/- 2.2 vs. 4.8 +/- 1.7 vs. 4.5 +/- 1.3 ng/ml; I, II, III phases of ARF, respectively). CONCLUSIONS In contrast to hemodialysis patients with chronic renal failure, patients with acute renal failure are characterized by normal plasma leptin concentration. Thus, difference in leptinemia between patients with chronic and acute renal failure seems to be due to preservation of large amounts of active renal parenchyma in ARF patients.

During the last four decades, the renin–angiotensin system (RAS) has emerged as an important endocrine factor in the chain of physiological blood pressure regulation and water–electrolyte balance, and as a substantial determinant of cardiovascular and renal remodelling. For >20 years it has been established that angiotensinogen is produced in the liver, and is in turn cleaved by the proteolytic enzyme reninreleasing angiotensin I, which is converted to angiotensin II by the converting enzyme (ACE) in the lung and other organs. It is well known that this circulating RAS is suppressed in patients with diabetic nephropathy [1]. A turning point in the research on the RAS was the finding of local tissue-specific RAS in several organs. Such local systems were found not only in glomerular and tubulointerstitial cells of the kidneys but in almost all organs of the human body. Micropuncture studies of the nephron revealed 1000 times higher concentrations of angiotensin II in proximal tubular and interstitial fluid than in systemic blood [2]. What is the role of this local renal RAS systems? Under physiological conditions, the glomerular RAS is a main player in the regulation of glomerular filtration by influencing the resistance predominantly of the vasa efferentia and to a less degree of the vasa afferentia, and by altering the effective filtration surface. The tubulointerstitial RAS is presumed to stimulate sodium and bicarbonate reabsorption in proximal tubules (by activation of the luminal Naþ/Hþ exchanger, basolateral Na/HCO3 – cotransporter and Naþ/Kþ ATPase). Both systems seem to play an important role in the compensatory mechanisms induced by nephron injury. Excessive local angiotensin II concentration increases glomerular permeability by a variety of mechanisms such as a high intraglomerular transmembrane pressure, suppressed synthesis of negatively charged proteoglycans and nephrin, and enhanced synthesis of extracellular matrix components [3]. In proximal renal tubules, exposed to a protein load, increased angiotensin II synthesis induces interstitial fibrosis. There are two main angiotensin II receptors (AT1 and AT2). Both have been cloned and well characterized [3]. Most biological effects of angiotensin II (Figure 1) are mediated by the AT1 receptor via intracellular activation of phospholipase, inhibition of adenylate cyclase and stimulation of tyrosine phosphorylation [4]. The physiological function of the AT2 receptor is not so well elucidated; however, it is generally presumed that its activation antagonizes the effects transduced by AT1 receptor stimulation (Figure 1). Moreover, the existence of a third type of angiotensin family receptor was recognized (AT4). Stimulation of that receptor by angiotensin IV results in increased plasminogen acivator inhibitor-1 (PAI-1) synthesis in proximal tubular and endothelial cells in the kidney [5,6]. The existence of other types of receptors is still postulated.

Adipocytes secrete several biologically active substances that are presumed to be involved in obesity-related hypertension. There are no reports that deal with the relationship between plasma adiponectin concentration and blood pressure (BP). To evaluate the role of adiponectin in essential hypertension 33 patients with essential hypertensive (EHP) (12 women, 21 men) and 33 body mass index-matched normotensive healthy subjects (NHS) (13 women, 20 men) were studied. In EHP plasma adiponectin concentration was significantly lower than in NHS (9.1 +/- 4.5 v 13.7 +/- 5.2 microg/mL, respectively). In all subjects a significant negative correlation was found between plasma adiponectin concentration and mean, systolic, and diastolic BP, suggesting that adiponectin contributes to the clinical course of essential hypertension.

BACKGROUND Females are characterized by significantly higher plasma leptin concentration than males. It seems likely that sex hormones influence leptinemia independently from differences in body composition. The aim of the present study was to analyze the contribution of plasma concentrations of testosterone and estradiol on leptinemia in hemodialyzed patients. METHODS 110 hemodialyzed patients--HD (60 M, 50 F) and 70 healthy subjects (HS) (30 M, 40 F) were enrolled in this study. Plasma leptin, testosterone or estradiol and CRP concentrations and body composition by dual-energy X-ray absorptiometry (DEXA) were assessed. RESULTS Total body fat was significantly higher in females than in males (27.5 +/- 1.5% vs. 17.2 +/- 1.0% of body weight in HD and 36.0 +/- 1.0% vs. 18.2 +/- 1.4% in HS, respectively). Plasma leptin concentrations were markedly higher in females than in males both in HD (27.9 +/- 5.4 ng/ml vs. 9.6 +/- 1.9 ng/ml) and HS (16.5 +/- 1.7 ng/ml vs.3.1 +/- 0.4 ng/ml). A highly significant, strong positive correlation was found between total fat mass (TFM) and leptinemia in all studied groups. No significant univaried correlation between plasma leptin and testosterone or estradiol concentrations respectively was found both in HD and HS. Multiple regression analyses showed that the main determinant of leptinemia is TFM (beta = 0.623 and 0.798 in HS females and males respectively, and beta = 1.058 and 0.797 in HD females and males respectively). Plasma concentration of testosterone (beta = -0.139 and beta = -0.075 in male HD and HS respectively) and estradiol (beta = 0.199 and beta = 0.046 in females HD and HS, respectively) contributed to leptinemia only in a minor degree. CONCLUSION Both testosterone and estradiol are minor contributors to leptinemia both in HS and HD patients. The main determinant of leptinemia in these subjects is total body fat mass.

UNLABELLED Leptin - produced predominantly by adipocytes - is presumably also involved in pathogenesis of essential hypertension (EH). In the present study, we addressed the question whether and to what extent antihypertensive monotherapy does influence leptinemia in patients with mild or moderate EH. Forty-two EH patients were enrolled in this randomized, open-labeled study. In all subjects, plasma concentrations of leptin, insulin, glucose, cholesterol, triglycerides and creatinine were estimated twice - before and one month after initiation of monotherapy with perindopril, pindolol or felodipin, respectively. Plasma leptin concentration, in the afternoon and midnight, was significantly higher in patients with essential hypertension than in normotensive healthy subjects (p < 0.01). Therapy with perindopril or felodipin did not influence the daily profile of leptinemia or insulinemia, respectively. However, pindolol monotherapy showed a marked (p < 0.01) suppressive effect on the daily profile of leptinemia, but did not influence insulinemia. CONCLUSIONS First, patients with essential hypertension are characterized by higher plasma leptin levels as compared with normotensive healthy subjects; second, suppressive effect of pindolol on leptinemia may be of pathophysiological relevance in the course of weight gain during beta-blocker therapy.

Obesity is a challenging health problem in Western societies. It is a risk factor for cardiovascular morbidity and mortality. Recent studies showed that adipose tissue is not only a passive energy store, but also an active endocrine organ, the secretions of which influence the function of many systems. It has been well known for decades that obesity influences the main ‘players’ of blood pressure regulation, in other words, the heart (increased cardiac output, cardiomyocyte hypertrophy), blood vessels (atherosclerotic changes, increased vascular resistance secondary to hypertrophy of vascular myocytes, increased vascular tone induced by sympathetic activity, abnormal paracrineuautocrine function of the endothelial cells), kidneys (sodium retention, activation of the renal renin-angiotensin system, development of obesityrelated glomerulopathy), and the sympathetic nervous system (enhanced activity). In addition, obesity leads to endocrine, metabolic, haemostatic and haematological abnormalities.

Our aim was to investigate systemic nitric oxide (NO) production and its potential determinants such as insulin resistance, dyslipidemia, and circulating methylated analogs of L-arginine in uncomplicated essential hypertension (EH). Nineteen newly diagnosed, untreated male subjects with mild pure uncomplicated EH and 11 normotensive controls were studied at rest after an overnight fast. The groups had comparable age, body mass index, creatinine clearance, cholesterol, fasting glucose, and insulin. In hypertensives, the urinary excretion rate of nitrite plus nitrate (Unox), an index of endogenous NO production, was depressed (56+/-17 vs. 77+/-23 micromol/mmol creatinine; p0.05), whereas plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, were increased (2.4+/-1.1 vs. 1.1+/-0.7 microM; p0.005). Circulating concentrations of symmetric dimethylarginine were similar in both groups (1.4+/-1.3 vs. 1.5+/-1.1 microM; p = NS). The L-arginine-to-ADMA ratio was reduced in hypertension (3.3+/-0.5 vs. 4.5+/-0.8; p0.001 for In-transformed data). There was no correlation between Unox and either the magnitude of insulin resistance or dyslipidemia in EH. Thus in male subjects with EH, endogenous systemic NO formation appears depressed, which is unrelated to accompanying insulin resistance or dyslipidemia. Circulating ADMA levels are increased in uncomplicated EH, which may be of potential relevance.

Background: Leptin is produced and released by adipocytes in proportion to fat stores. Leptin as an anorectic hormone plays an important role in the regulation of food intake, energy expenditure, and insulin secretion. In contrast, neuropeptide Y, insulin, cortisol, and growth hormone are presumed to be appetite modulators. Leptin and neuropeptide Y are both involved in the activation of sympathetic tone. Increased body fat stores in obese patients are involved in the pathogenesis of some metabolic disorders (e.g., hyperinsulinaemia, glucose intolerance) and arterial hypertension. Methods and Results: Based on this pathophysiological background, we tried to assess the relationship between plasma leptin and blood pressure in 41 patients with essential hypertension (EHP; 20 females, 21 males, mean age 38.7±1.9 years, mean body mass index – BMI – 25.8±0.5 kg/m2) and in an appropriately sex– and BMI–matched control group of 27 normotensive healthy subjects (NHS; 11 females, 16 males, mean age 39.7±2.5 years, mean BMI 24.8±0.6 kg/m2). The plasma leptin concentration did not differ significantly between EHP and NHS (13.0±1.9 vs. 8.1±1.0 ng/ml, respectively). In both groups a significant positive correlation was found between BMI and plasma leptin concentration (pConclusion: Both EHP and NHS are characterized by a positive correlation between BMI and leptinaemia. Leptin may be indirectly involved in blood pressure regulation, especially in women of both NHS and EHP.

This paper is a summary of results obtained in our studies on leptinemia in patients with chronic renal failure treated with recombinant human erythropoietin (rHuEPO), in kidney transplant patients, in patients with essential hypertension, and in pregnant women with preeclampsia. In this study, we found that rHuEPO treatment has a suppressive effect on leptinemia in patients with endstage renal failure. These results suggest that the appetite stimulating effect of rHuEPO may be mediated by a reduction of leptin synthesis and release. At the early stage of successful kidney transplantation, a significant decline of leptinemia was noticed, which was not related either to the excretory function of the graft or the kind and dose of immunosuppressants. In kidney transplant patients with grafts functioning well for 2.5 years, significantly elevated leptinemia was found. From these results, we may conclude that factors other than the excretory function of the graft and the kind and dosage of immunosuppressants may be involved in the pathogenesis of abnormal leptinemia in these patients. Both in normotensive subjects and patients with essential hypertension, a positive correlation was found between leptinemia and mean blood pressure, suggesting that leptin may be involved in the regulation of blood pressure. Both healthy and preeclamptic pregnant women show higher leptinemia than nonpregnant women. In preeclamptic women, leptin levels in maternal vein blood, umbilical cord blood, and amniotic fluid were significantly higher than respective values found in healthy pregnant women. In contrast to healthy pregnant and nonpregnant women, in women with preeclampsia, no correlation was found between the body mass index (BMI) and leptinemia. In preeclamptic women the abnormally elevated leptinemia was not related to blood pressure. Finally, no correlation was found between leptinemia in maternal and umbilical cord blood. From these studies, it follows that the elucidation of abnormal leptin secretion in the pathogenesis of preeclampsia needs further study.

Background. Patients with renal failure are characterized by impaired insulin-mediated glucose uptake. Insulin plays a major role in the maintenance of phosphate homeostasis but it remains to be determined Introduction whether in uraemia insulin-dependent renal and extrarenal phosphate disposal is also aVected. Insulin resistance is defined as a subnormal response Methods. The eVect of hyperinsulinaemia on serum to a given concentration of insulin, but although insulin concentrations of phosphate, ionized calcium and exerts multiple actions on target tissues and organs, intact PTH as well as renal excretion of calcium and the term ‘insulin resistance’ typically refers only to its phosphate was studied under euglycaemic conditions action on glucose homeostasis [1]. The actions of (glucose clamp technique) in patients with advanced insulin on carbohydrate, protein, lipid and mineral renal failure and in healthy subjects. Fifteen patients metabolism are initiated by its interaction with a with renal failure (mean serum creatinine 917 mmol/ l) specific receptor protein, which triggers a cascade of and 12 control subjects were included. All subjects intracellular events [2]. The action of insulin on mineral underwent a 3-h euglycaemic clamp with constant homeostasis is not limited to the liver, muscle, and fat infusion of insulin (50 mU/m2/min) following a prim- but insulin regulates tubular transport of all major ing bolus. The urine was collected for 3 h before and ions in the kidney [3]. The regulation of mineral throughout the clamp. homeostasis by insulin has been far less well studied Results. The tissue insulin sensitivity (M/I ) was lower than its eVects on glucose metabolism and in particular in patients with renal failure than in control subjects it remains to be clarified whether in a broad spectrum (5.3±2.4 vs 6.7±1.8 mg/kg/min per mU/ml, P= of insulin resistant states the action of insulin on renal 0.001) but the phosphate lowering action of insulin and extrarenal mineral metabolism is impaired. was larger in patients with renal failure than in control Insulin resistance in uraemia is a well established subjects. Urinary calcium excretion increased (P

BACKGROUND In patients with chronic renal failure, rHuEpo therapy ameliorates anaemia and improves wellbeing, exercise tolerance, and appetite. Both leptin and neuropeptide Y play an important role in regulation of appetite and energy balance in humans. METHODS The present study aimed to assess the influence of 12 months rHuEpo therapy on plasma leptin and neuropeptide Y concentrations in 15 haemodialysed patients (HDP) (6F, 9M; mean age 40.8+/-2.9 years; mean BMI 23.6+/-1.1 kg/m2; mean duration of HD 3.3+/-0.6 months) (Epo group). A second group (No-Epo group) consisted of 17 HDP (9F, 8M; mean age 44+/-3.2 years; mean BMI 24.3+/-1.0 kg/m2; mean duration of HD 2.5+/-0.4 months) not treated with rHuEpo for 12 months. Basal plasma leptin and neuropeptide Y concentrations were estimated by RIA at the beginning and after 3, 6, 9 and 12 months of rHuEpo therapy (Epo group) or clinical observation (No-Epo group). The control group consisted of 30 healthy subjects (15 females, 15 males, mean age=38.2+/-1.7 years, mean BMI 24.5+/-0.7 kg/m2). RESULTS Baseline plasma leptin concentrations in HDP were higher, although statistically not significant than leptinaemia in healthy subjects. After 3, 6, and 12 months of rHuEpo therapy plasma leptin concentrations were significantly lower than at the beginning of the study. Baseline plasma neuropeptide Y concentrations in HDP did not differ significantly from controls. After 3 and 6 months of the study period plasma neuropeptide Y concentrations increased significantly in patients of both the Epo and No-Epo group. This increase was, however, significantly higher in rHuEpo-treated than in untreated patients. CONCLUSIONS (1) rHuEpo treatment in haemodialysed patients with chronic renal failure is followed by a significant decline of leptinaemia and disappearance of the physiological positive BMI/leptinaemia relationship. (2) Suppression of leptinaemia induced by rHuEpo may be of clinical relevance in haemodialysed patients with chronic renal failure.

Of patients with acute myocardial infarction eligible for the International Study of Infarct Survival-4, randomized to captopril (n = 30) or placebo (n = 33), the captopril group had a significant decrease in blood adrenaline on day 3 compared with baseline values. Results suggest that suppression of sympathetic activity contributes to the beneficial effects of treatment with angiotensin-converting enzyme inhibitors in the early phase of acute myocardial infarction.

A total of 19 patients with active nephrolithiasis, 14 patients with non-active nephrolithiasis and 17 healthy subjects were examined under standardized intake of calcium, phosphorus, purine and protein. In patients with both active and non-active renal stone disease the following abnormalities were found: elevated plasma levels of PTH and osteocalcin, increased activity of the bone isozyme of alkaline phosphatase, low plasma levels of phosphate and increased urinary excretion of calcium and oxalic acid. These abnormalities were more marked in patients with active than non-active nephrolithiasis. No correlation was found between plasma PTH levels and parameters of bone turnover as well as calciuria and oxaluria. Results presented in this paper suggest that (a) Smith's criteria of active renal stone disease are of minor pathogenetic and therapeutic value and (b) patients with active nephrolithiasis differ from non-active renal stone formers by more elevated oxaluria and markers of bone turnover and more marked abnormalities in calcium-phosphate metabolism related parameters.

The present study aimed to assess the influence of acetate (AC) and bicarbonate (BI) hemodialysis with a cuprophane membrane on plasma erythropoietin (EPO) levels in 30 patients with chronic renal failure (CRF). Fifteen patients were severely anemic with an Hct below 30%, while 13 were moderately anemic with an Hct equal to or more than 30%. None had received rHuEPO or ACE inhibitors before the study. Blood samples for EPO and pO2 estimation were withdrawn before and after 1, 2 and 5 h of AC dialysis. In 11 of the patients with an Hct < 30% the same protocol was repeated during BI dialysis. In spite of a significant decrease in pO2 during the first hour of AC dialysis, the plasma EPO concentration decreased significnatly in both severely and moderately anemic CRF patients from 35.4 ± 2.6 to 23.6 ± 3.5 mU/ml after 5 h of hemodialysis (p = 0.0001 by paired t-test) and from 39.5 ± 8.6 to 27.5 ± 8.9 mil/ml (p < 0.01) respectively. In contrast to AC dialysis, Bi dialysis failed to change the plasma EPO concentration (from 32.3 ± 4.1 to 30.3 ± 4.7mil/ml after 5 h of hemodialysis). Conclusions AC but not BI hemodialysis shows a significant suppressive effect on plasma EPO levels in anemic CRF patients in spite of a significant decline in pO2. Factors other than pO2 seem to be involved in the regulation of EPO secretion in CRF patients during AC dialysis.

The present study aimed to assess the function of proximal and distal tubules in patients with simple renal cysts. Thirty-one patients with simple renal cysts and 10 healthy subjects were examined. Based on the cyst fluid/plasma sodium ratio, 25 cysts were found to be of proximal origin and 6 of undetermined origin. In all patients cyst fluid and plasma concentrations of beta-2-microglobulin (beta-2-MG), sodium, potassium, calcium, phosphorus and total protein were assessed. Urinary excretions of sodium, potassium, calcium, phosphorus, beta-2-MG and Tamm-Horsfall protein (THP) were also estimated. Fractional excretion of beta-2-MG was calculated. The concentrations of beta-2-MG in fluid obtained from cysts of proximal origin were significantly higher than in fluid from cysts of undetermined origin (2.26 +/- 0 36 vs. 0.65 +/- 0.13 mg/l, p = 0.0004). Concentrations of THP (6.85 +/- 1.21 vs. 3.14 +/- 1.06 micrograms/ml, p0.05), and potassium (4.39 +/- 0.07 vs. 3.13 +/- 0.44 mmol/l, p0.05) were also higher in fluid from proximal cysts than in fluid from cysts of undetermined origin. Plasma beta-2-MG concentration was significantly higher in patients with proximal and undetermined cysts than in the control group (4.35 +/- 0.34 and 4.11 +/- 0.74 vs. 1.89 +/- 0.1 mg/l, p0.001). Urinary beta-2-MG excretion was also significantly higher in both groups of patients than in healthy subjects (474.8 +/- 165.9 and 346 +/- 94 vs. 100.2 +/- 19.6 micrograms/24 h, p0.05). Urinary THP excretion was significantly higher in patients with proximal cysts than in healthy subjects (31.0 +/- 5.1 vs. 16.3 +/- 2.5 mg/24 h, p0.05). From the results obtained in this study it seems that patients with simple renal cysts of proximal origin are characterized by abnormal tubular handling of beta-2-MG, and calcium and THP excretion. Thus, in patients with proximal cysts presence of a latent renal tubulopathy seems to be likely.

Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in hemodialyzed patients. Two groups of hemodialyzed patients, each of which comprised 17 subjects, were examined. The first group was treated by EPO (EPO group) while the second one did not receive this hormone (No-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9, and 12 month points of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex- and age-matched healthy subjects. After EPO therapy, an increase of the hematocrit value from 21.8 ± 0.9 to 32.6 ± 0.9% was observed, which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the No-EPO group, a significant although less marked rise of the hematocrit value (21.4 ± 0.4 to 24.2 ± 0.6%) was also noticed. EPO therapy did not change plasma levels of electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose, and alkaline phosphatase as well as plasma concentrations of calcium-related hormones (PTH, calcitonin, 1,25[OH]2D3), vasopressin, and triiodothyronine. EPO treatment induced a significant decrease in somatotropin, prolactin, follitropin, lutropin, ACTH, cortisol, plasma renin activity, aldosterone, noradrenaline, adrenaline, dopamine, glucagon, pancreatic polypeptide, and gastrin plasma levels and an increase in plasma insulin, estradiol, testosterone, atrial natriuretic peptide, thyrotropin, and thyroxine. These EPO-induced endocrine alterations were restricted mostly to the first 6 months of EPO administration. In patients of the No-EPO group, a significant decrease in the plasma levels of prolactin, noradrenaline, and dopamine and an increase of estradiol plasma levels were also noticed during the 1-year study period. Therefore, long-term treatment by EPO shows profound effects on the function of several endocrine organs. These effects are transitory and predominantly restricted to the first 6 months of EPO therapy. Not all endocrine alterations observed in EPO-treated patients seem to be due to the administration of this hormone.

Recent data indicated the importance of urinary losses of erythropoietin (Epo) in the pathogenesis of anaemia in patients with nephrotic syndrome. In the present study we aimed to investigate plasma and urinary Epo levels and their renal handling in relation to beta 2-microglobulin (beta 2m), sodium metabolism and the renin-angiotensin-aldosterone system (RAAS), respectively, in patients with sub-nephrotic range proteinuria (SNP), microalbuminuric diabetics and hypertensives, and in healthy subjects studied on a standardized diet containing 120 mmol sodium and 70 g protein per day. We found that patients with SNP were characterized by lower plasma levels of Epo than healthy subjects but no differences were found in urinary excretion of Epo, endogenous Epo clearance and its fractional excretion (FEEpo). There were no differences between groups in FE beta 2m and FENa and plasma aldosterone levels but plasma renin activity was higher in patients with SNP than in the controls. No relationships were found between Epo levels and activity of the RAAS and sodium metabolism, respectively. Our data suggest that lower levels of plasma Epo in patients with SNP and normal renal excretory function are not due to urinary losses of Epo but rather to the decreased production/degradation ratio.

The coincidence of increased red blood cell mass with obesity and hypertension has been confirmed in a number of studies. Since erythropoietin (EPO) induces hypertonic effect, we aimed to study the possible involvement of endogenous EPO in the pathogenesis of obesity-related hypertension (ORH). Seventy-two non-obese (body mass index-BMI 30kg/m2) patients with essential hypertension, and 32 non-obese normotensive control subjects were studied on 120mmol Na/24h diets for 3 days and 30mmol Na/24h diets for the following 3 days. Serum EPO levels, plasma renin activity (PRA), aldosterone (PAC) and urinary sodium and potassium excretion were estimated under both conditions. Hematocrit, hemoglobin and serum iron, ferritin and TIBC were measured in basal conditions. Patients with ORH showed significantly higher hematocrit values, hemoglobin levels and erythrocyte counts (p

PTH is incriminated as an uraemic toxin involved in the pathogenesis of anaemia in chronic renal failure. This fact was the background of our present studies performed in 14 patients with noninflammatory acute renal failure (NARF). Plasma levels of erythropoietin (EPO) and parathyroid hormone (PTH) were estimated in the anuric/oliguric (a/o) and polyuric (p) phase of NARF. In the a/o phase plasma EPO levels were predominantly normal, although inappropriately low to the degree of anaemia. In 50% of patients with NARF episodic short-term increases of plasma EPO levels were noticed which were not caused by worsening of anaemia. In the p phase plasma EPO concentrations were in the normal range (17.9 +/- 3.3 mU/ml) in spite of the same degree of anaemia as in the a/o phase. Plasma PTH levels were significantly elevated during the a/o phase (1.14 +/- 0.1 ng/ml), with a tendency to decline in the p phase (0.87 +/- 0.2 ng/ml). No correlation was found between plasma EPO and PTH concentrations. Results presented in this study suggest presence of relative EPO deficiency both during the a/o and p phases of NARF. As plasma PTH levels were not significantly correlated with serum EPO concentrations, its role in the pathogenesis of suppressed EPO levels seems unproven. Results presented in this study suggest deterioration of the physiological feedback between EPO secretion and the magnitude of erythropoiesis in NARF.

Scarce data exist concerning the long-term effect of percutaneous transluminal renal angioplasty (PTRA) enhanced with intravascular gamma brachytherapy (IVBT) in patients with renovascular hypertension.Seventy one patients aged 52 +/- 8 years with refractory renovascular hypertension were randomized to Group I (PTRA + IVBT) or Group II (PTRA). For the IVBT procedure, the PARIS catheter and Microselectron HDR (Nucletron) system was employed. Both baseline and 9-month follow-up quantitative computerized angiography (QCA) and ambulatory blood pressure monitoring analysis was performed to assess luminal parameters of restenosis and the effect of treatment on blood pressure.Thirty three patients from Group I and 29 patients from Group II underwent successful procedure. During nine months of follow-up, three patients died; including two patients in Group I (cardiac causes) and one patient in Group II (stroke). The follow-up lumen diameter stenosis was 30.6 +/- 13.7% and 40.4 +/- 11% in Groups I and II, respectively (p = 0.004). Late lumen loss in quantitative computerized angiography was 1.2 +/- 0.7 mm and 1.7 +/- 0.7 mm in Groups I and II, respectively (p = 0.004).Intravascular gamma brachytherapy using self-centering source performed after balloon angioplasty is a safe and effective method of prevention of restenosis after PTRA in patients with renovascular hypertension.