Andrzej Więcek

Plasma Immunoreactive Leptin and Neuropeptide Y Levels in Kidney Transplant Patients

Leptin and neuropeptide Y (NPY) seem to play an important role in food intake and energy expenditure. Leptin is secreted by adipose tissue in proportion fo fat stores and is presumed to be an important anorectic hormone. NPY is produced by the hypothalamus, and in contrast to leptin, is one of the most potent appetite stimulants yet demonstrated. On the other hand, in most patients increased appetite is present after successful kidney transplantation. Finally, a stimulatory effect of glucocorticoids on leptin secretion was reported. The present study aimed to assess the relationship between plasma leptin and NPY levels and body mass index (BMI) in haemodialyzed patients (HDP) with chronic renal failure and in kidney transplant patients (KTP). In both groups, BMI was of the same magnitude as in healthy controls. Despite the presence of a normal BMI, leptin levels in KTP (25.2 ± 3.6 ng/ml) and in HDP with chronic renal failure (25.3 ± 4.2 ng/ml) were higher than in controls (11.7 ± 1.8 ng/ml). The mean plasma NPY level in KTP (168.0 ± 10.3 pg/ml) was significantly higher (p < 0.01) than in controls (70.7 ± 5.9 pg/ml) and in HDP (77.0 ± 5.7 pg/ml). In all examined groups, a significant positive correlation was found between leptinaemia and BMI. Conclusions: (1) KTP are characterized by significantly elevated leptinaemia in spite of a normal BMI. In KTP this increased leptinaemia does not seem to be dependent only upon the fat mass and the kind and dosis of immunosuppressive therapy. (2) Similarly to healthy subjects, female KTP and HDP show markedly higher leptinaemia than males. (3) In contrast to healthy subjects and HDP, KTP are characterized by significantly elevated plasma NPY levels.

Relationship between plasma renin profile and leptinaemia in patients with essential hypertension

Both leptin and the renin-angiotensin system (RAS) can influence the activity of the sympathetic nervous system, water and electrolyte metabolism as well as vascular remodelling, which are all involved in the regulation of arterial blood pressure. Thus leptin and the RAS may act together in the pathogenesis of essential hypertension. The present study aimed to answer the following question: does an interrelationship exist between leptinaemia and the plasma renin activity (PRA) profile in normotensive and hypertensive subjects? Forty-three patients with essential hypertension (EHP) (23 females, 20 males, mean age 39.0 ± 1.8 years, mean body mass index (BMI) 26.8 ± 0.6 kg/m2, mean arterial pressure (MAP) 123 ± 2 mm Hg) and 32 healthy subjects (NTS) (18 females, 14 males, mean age 38.6 ± 2.2 years, mean BMI 25.4 ± 0.5 kg/m2, MAP 95 ± 1 mm Hg) were examined. Plasma leptin levels were estimated once after the administration of a diet containing 100–120 mmol Na/day and after overnight 8-h recumbency. PRA was estimated twice: first after the administration of a diet containing 100–120 mmol Na day and overnight 8-h recumbency (PRA I), and a second time after 3 days of sodium restriction (20 mmol Na/day), and 3 h of upright position (PRA II). Antihypertensive drugs were withdrawn 7 days before the study. In EHP plasma leptin concentration was insignificantly higher than in NTS (14.0 ± 2.0 vs10.8 ± 1.5 ng/ml respectively). Only females with hypertension showed a significant positive correlation between plasma leptin concentrations (expressed as the logarithmic values) and PRA I. Using the multiple regression analysis, in all studied subjects (EHP and NTS together), logarithm (log) of plasma leptin concentrations was significantly related to gender, BMI and MAP. Multiple regression analysis performed separately for EHP or NTS revealed a significant relation of log plasma leptin concentrations with gender and BMI. A significant correlation was found between log leptinaemia values and BMI, mean and systolic blood pressure respectively if the whole group of subjects (EHP+NTS) or EHP and NTS separately were analysed. Especially in hypertensive women a highly significant correlation was found between log plasma leptin concentrations and MAP. We conclude that a significant relationship between leptinaemia and PRA does exist in females with EH and that participation of both PRA and leptin in the pathogenesis of EH in females seems to be likely.

Does leptin play a role in the pathogenesis of essential hypertension

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 (p<0.0001). A significant positive correlation (p<0.02) was found between leptinaemia and mean (MAP), systolic and diastolic blood pressures, if data were analyzed for all examined subjects or separately only for women. Such a correlation could not be confirmed for male NHS and EHP subjects. The plasma neuropeptide Y concentration was higher in EHP than in NHS (77.1±23.0 vs. 63.6±9.8pg/ml, p = 0.05). In contrast to neuropeptide Y plasma insulin, cortisol, and growth hormone concentrations were similar in EHP and in NHS. Conclusion: 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.

Characterization of insomnia in patients with essential hypertension.

Introduction. Insomnia may increase risk of cardiovascular events. There is little data available reporting the prevalence and clinical relevance of insomnia in patients with essential hypertension. Therefore, the aim of the study was to investigate the relationship between insomnia and different clinical and biochemical parameters in essential hypertension patients. Methods. Four hundred and thirty‐two patients (mean age: 47±13 years; 253 male, 179 female) with essential hypertension were screened for insomnia using the Athens Insomnia Scale (AIS). Several variables including age, sex, known duration of hypertension, body mass index, creatinine, left ventricular mass index, coexisting disorders, smoking status and alcohol use were analysed. Twenty‐four‐hour ambulatory blood pressure measurements (ABPM) were performed. Results. Among patients included in the study, 207 subjects (mean age: 49±13 years; 47.9%) had an AIS score of 15 or higher and were identified as insomniacs. Insomnia was more frequent in women than in men (60.9% vs 38.7%, p<0.001) and was reported more frequently in patients with coronary artery disease. Subjects with insomnia were older and had longer duration of hypertension. There were no differences between insomniacs and non‐insomniacs in ABPM parameters. A relationship was found between the number of antihypertensive drugs and insomnia frequency. There were correlations between AIS score and age (r = 0.21; p<0.001) and duration of hypertension (r = 0.22; p<0.001). In the sub‐group of untreated essential hypertension patients, there were negative correlations between AIS score and night fall in systolic and diastolic blood pressure. Conclusion. Our results showed that insomnia is common in patients with essential hypertension and indicate an association between insomnia and gender, known duration of hypertension and number of antihypertensive drugs taken. Untreated essential hypertension insomniacs were characterized by less pronounced nocturnal fall in both systolic and diastolic blood pressure compared with non‐insomniacs.

Frequency of renal artery stenosis and variants of renal vascularization in hypertensive patients: analysis of 1550 angiographies in one centre.

Renal artery stenosis (RAS) is an important cause of arterial hypertension and chronic kidney disease. The aims of our study were to assess the prevalence of RAS and to examine the frequency of variants of renal vasculature, that is, multiple and/or accessory renal arteries in hypertensive patients referred to renal angiography. We evaluated retrospectively 1554 arteriographies of hypertensive patients. Angiograms were evaluated to find RAS, significant RAS (>60% stenosis of the lumen), radiological signs of atherosclerosis, aneurysms of the renal arteries or aorta and variants of kidney vascularization. The frequency of RAS including occlusions was 15.1% (21.3% of them were significant and suitable for revascularization). Variants of renal arterial vascularization were found in 26.5% of patients (multiple renal arteries—11.2% and accessory renal arteries—15.3%). Significant RAS was found more frequently in patients older than 60 years—OR 4.76 (2.08–10.86). Coronary artery disease, history of myocardial infarction or stroke significantly increased the chance of RAS detection. The frequency of renal accessory arteries was lower in patients older than 60 years and in patients with the radiological signs of atherosclerosis. Results of this study indicate that haemodynamically important RAS is found more frequently in hypertensive patients older than 60 years. Symptomatic atherosclerotic disease found in the peripheral and/or coronary arteries and diabetes mellitus increases the chance of RAS detection. Decreased occurrence of renal accessory arteries was found in hypertensive patients with radiological signs of atherosclerosis.

The influence of chronic periodontitis on serum TNF-α, IL-6 and hs-CRP concentrations, and function of graft and survival of kidney transplant recipients

Abstract:  Objective:  The aim of the study is to analyze whether chronic periodontitis (CP) influences serum tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and high‐sensitivity C‐reactive protein (hs‐CRP) concentrations in renal transplant recipients and patients or graft survival.

Endocrine Changes in Chronic Dialysis Patients

There are at least six reasons why endocrine abnormalities may be expected in patients with chronic renal failure (CRF).

Erythropoietin Secretion in Patients with Chronic Renal Failure after Pure Oxygen Breathing

The present study aimed to assess the relationship between erythropoietin (EPO) secretion and hyperoxemia in uremic patients. In 19 patients with chronic renal failure (10 were hemodialyzed and 9 were not dialyzed) and in 13 healthy subjects plasma erythropoietin levels were assessed during 6 h of air breathing and a second time during 2 h of pure oxygen breathing and during 4 h after discontinued oxygen breathing. Under basal conditions, uremic patients showed higher plasma erythropoietin levels (39.85 +/- 5.86 mU/ml in hemodialyzed and 29.05 +/- 4.94 mU/ml in nondialyzed patients) as compared with healthy controls (21.04 +/- 1.77 mU/ml). Pure oxygen breathing was followed by a significant decline of plasma EPO levels both in patients with chronic renal failure and in the control group. However, this decline was significantly less marked and of longer duration in chronic renal failure patients than in healthy controls.

Atrial natriuretic peptide and arginine-vasopressin secretion in patients with active renal stone disease.

The pathogenesis of active renal stone disease (ARSD) is still not fully elucidated. In the present study the role of atrial natriuretic peptide (ANP) and arginine-vasopressin (AVP) as potential pathogenetic factors in ARSD were examined. Thirty patients with ARSD and 21 healthy subjects (HS) were examined both under bed rest (BR) and head-out water immersion (WI) conditions. Serum concentrations of electrolytes (Na, Ca, Mg), ANP and AVP were assessed before (0′), and after 60 and 120 minutes of BR or WI, respectively. Urinary excretions of Na, Ca, Mg, and oxalates were also estimated during BR and WI.Patients with ARSD showed higher basal plasma levels of ANP and a greater response of ANP secretion, but a lower suppression of plasma AVP to WI induced hypervolaemia as compared with the controls. In addition, in patients with ARSD the physiological relationship between plasma AVP concentration and urinary excretion of Ca and Mg (positive correlation), between plasma ANP level and urinary excretion of Ca and Mg (negative correlation), and between plasma ANP and AVP concentration (negative correlation), respectively, were absent. In addition, patients with ARSD showed a positive correlation between plasma ANP and urinary oxalate excretion. From the results obtained in this study we conclude that both AVP and ANP may be involved in the pathogenesis of ARSD.

Plasma parathyroid hormone and erythropoietin levels in patients with noninflammatory acute renal failure

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.