Marcin Adamczak

Decreased plasma adiponectin concentration in patients with essential hypertension

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.

Reversal of Glomerulosclerosis after High-Dose Enalapril Treatment in Subtotally Nephrectomized Rats

Interventions to block the renin-angiotensin system (RAS) halt the progression of renal lesions in renal damage models. It has recently also been reported that established glomerulosclerosis can be reversed by pharmacologic blockade of the RAS. It was the aim of this study to confirm that high doses of angiotensin-converting enzyme (ACE) inhibitors reverse established glomerulosclerosis and to extend the findings by providing quantitative information on glomerular geometry, podocytes and other glomerular cells, renal vessels and tubulointerstitial tissue. Male Sprague Dawley rats were subjected to subtotal surgical renal ablation (SNX) (n = 27) or sham operation (n = 31) and fed using a pair-feeding protocol. Eight weeks after surgery, rats were either sacrificed or allocated to two arms: enalapril treatment (48 mg/kg body wt per day administered in the drinking fluid for 4 wk) or no treatment. Renal morphology was evaluated after 8 or 12 wk, respectively, by stereology in tissue fixed by pressure-controlled perfusion. Both systolic BP and albumin excretion rate were significantly higher in SNX compared with sham-operated controls. They were significantly reduced in SNX after delayed enalapril treatment. The glomerulosclerosis (GSI), tubulointerstitial (TII), and vascular (VI) damage indices were significantly higher in all SNX groups than in sham-operated controls. At the end of the experiment (12 wk after SNX) GSI, TII, and VI were significantly lower in SNX with delayed enalapril treatment (0.77 +/- 0.18, 0.63 +/- 0.19 and 0.43 +/- 0.16, respectively) compared with untreated SNX (1.64 +/- 0.14, 1.16 +/- 0.34 and 0.67 +/- 0.29, respectively). GSI, TII, and VI were also significantly lower in SNX with delayed enalapril treatment compared with SNX sacrificed without treatment 8 wk after SNX. The same was true for glomerular volume. The number of podocytes was not affected by SNX, but podocyte volume was increased. Both indices remained unaffected by treatment. The numbers of cells within the mesangium and endothelial cells per glomerulus were significantly lower in SNX after delayed enalapril treatment compared with untreated SNX. These results strongly suggest regression of preexisting lesions, i.e., glomerular, tubular, and vascular remodeling as well as reversal of glomerular hypertrophy by ACE inhibitor treatment. The study confirms that high-dose ACE inhibitor treatment causes partial reversal of glomerular as well as interstitial lesions in subtotally nephrectomized rats.

Reversal of glomerular lesions involves coordinated restructuring of glomerular microvasculature.

There is increasing evidence from both human and experimental studies that at least partial reversal of glomerulosclerosis can be achieved by glomerular remodeling. This requires substantial changes in glomerular architecture, specifically of glomerular capillaries. It was the purpose of the present study to characterize the stereologic and topologic characteristics of glomerular capillaries when partial reversal of glomerular lesions is achieved by high-dose angiotensin-converting enzyme inhibitor treatment. Sham-operated male Sprague-Dawley rats were compared with subtotally nephrectomized (SNX) rats. The latter were kept untreated for 8 wk and subsequently randomly divided into one group that was continued without treatment and another group that was treated with enalapril (48 mg/kg body wt per d administered in the drinking fluid for 4 wk). Renal morphology was evaluated after 8 or 12 wk, respectively, by stereologic techniques after pressure-controlled perfusion fixation. In SNX rats at 8 and particularly at 12 wk, the glomerulosclerosis index was significantly higher than in sham-operated rats. At 12 wk, it was lower in rats that had been treated for 4 wk with enalapril compared with untreated SNX rats, suggesting partial reversal of glomerular lesions. This was associated with a decrease in mean glomerular volume and mean glomerular tuft volume, a reduced number of capillaries per glomerulus, and reduced total length of capillaries per glomerulus but without any significant change in the length of individual capillaries. The numerical capillary density (Euler number density) as an index of topologic complexity did not change. The total capillary surface area per glomerulus was strikingly increased after subtotal nephrectomy and partially reversed after enalapril. This was accounted for primarily by fewer capillaries without any change in diameter. In parallel, the number of endothelial cells per glomerulus was strikingly increased after subtotal nephrectomy and decreased with enalapril treatment, but endothelial cell volume remained elevated. The study shows harmonious coordinate remodeling of the entire glomerulus during regression of glomerular lesions after subtotal nephrectomy. Proportionate reduction of glomerular volume and capillary number without change of individual capillary length were found. The numerical capillary density of the tuft therefore remained unchanged.

Regression of glomerulosclerosis in subtotally nephrectomized rats: effects of monotherapy with losartan, spironolactone, and their combination

Angiotensin II accelerates and renin-angiotensin system blockade halts progression; blockade with high doses even reverses established glomerulosclerosis. Aldosterone also accelerates progression of glomerulosclerosis, partially independently of angiotensin II. The purpose of this study was to assess the relative ability of an angiotensin receptor type 1 (AT1) blocker, a mineralocorticoid receptor blocker, and their combination to reverse glomerulosclerosis. Sprague-Dawley rats were subjected to subtotal renal ablation (SNX) or sham operation. Eight weeks after surgery, they were either euthanized or allocated to treatment with vehicle, losartan, spironolactone, their combination, or unspecific antihypertensive treatment (dihydralazine) for 4 wk. Renal morphology was evaluated by stereology in tissues obtained using pressure-controlled perfusion fixation. Systolic blood pressure was significantly higher in SNX compared with sham-operated animals and decreased in all treatment groups. Compared with wk 8 after SNX, the glomerulosclerosis index (GSI) had increased further by week 12 in the vehicle- and dihydralazine-treated groups but was significantly lowered in the SNX+losartan as well as in the SNX+losartan+spironolactone groups and had not progressed further in the SNX+spironolactone group. The study confirms the partial regression of established glomerulosclerosis in subtotally nephrectomized rats after high-dose AT1 receptor blockade. Nonhyperkalemic doses of spironolactone prevented the increase but failed to decrease the GSI below the 8-wk level and preserved podocyte numbers. Combining the AT1 blocker with mineralocorticoid receptor blockade failed to further increase the regression of glomerulosclerosis.

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.

Kidney and Hypertension—Causes

Abstract.Renal disease is closely associated with hypertension. On the one hand, kidney disease provokes hypertension. On the other hand, hypertension aggravates the progression of renal dysfunction.The pathomechanisms through which the kidney raises blood pressure have been considerably clarified in recent years. In experimental and clinical studies, it could be shown that ”hypertension goes with the kidney”. This suggests that some renal abnormalies predispose to hypertension. Recently, it could be shown that the kidneys of individuals with so-called essential hypertension have less glomeruli than the kidneys of control individuals.In renal patients the kidney raises blood pressure through several mechanisms. First, the pressure-natriuresis relationship is shifted to the right, i. e., sodium excretion requires higher renal perfusion pressures. Second, there is inappropriate activation of the renin-angiotensin system. Third, as only recently documented in detail, renal injury raises the sympathetic tone, even when whole kidney glomerular filtration rate (GFR) is unchanged. This results from stimulating afferent signals emanating from the kidney. Fourth, there is evidence of impaired endothelial celldependent vasodilatation even in very early stages of renal dysfunction. Fifth, the pulse pressure profile is altered as a consequence of premature and accelerated aging causing stiffening of the aorta.Knowledge of these pathomechanisms is important for selection of appropriate antihypertensive treatment.Zusammenfassung.Nierenerkrankungen sind mit Hypertonie vergesellschaftet. Einerseits lösen Nierenkrankheiten eine Hypertonie aus. Andererseits beschleunigt jedoch die Hypertonie den Nierenfunktionsverlust.Die Pathomechanismen, wodurch die Niere zur Blutdruckerhöhung führt, wurden intensiv beforscht. In experimentellen und klinischen Studien zur Nierentransplantation wurde gezeigt, dass der Blutdruck der Niere folgt („hypertension goes with the kidney“), was nahe legt, dass bei Patienten mit essentieller Hypertonie intrinsische Anomalien der Nieren vorliegen. Beispielsweise konnte gezeigt werden, dass Nieren von Patienten mit essentieller Hypertonie weniger Glomeruli aufweisen als Nieren von Kontrollindividuen. Bei Patienten mit primärer Nierenerkrankung sind mehrere Pathomechanismen für den Blutdruckanstieg verantwortlich. Zum Ersten ist die Blutdruck-Natriurese-Kurve nach rechts verschoben, d. h., zur Ausscheidung von Natrium werden höhere renale Perfusionsdrücke benötigt. Zum Zweiten ist die Aktivität des Renin- Angiotensin-Systems inadäquat hoch. Zum Dritten konnte gezeigt werden, dass bei Nierenschädigung der Sympathikotonus ansteigt infolge stimulatorischer Signale aus der Niere, welche zentral den Sympathikotonus steigern. Zum Vierten ist selbst bei frühen Stadien der Nierenerkrankung die endothelzellabhängige Vasodilatation beeinträchtigt. Schließlich führen Nierenerkrankungen zu vorzeitigem und beschleunigtem Altern durch Aortenversteifung und abnormes Pulsdruckprofil.Die Kenntnis dieser Pathomechanismen ist wichtig für die rationale Auswahl der Antihypertensiva bei Nierenpatienten.

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 Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics

Background: Lactobacillus plantarum 299v (LP299v) has been used in order to reduce gastrointestinal symptoms during antibiotic exposure. However, it remains controversial whether or not probiotics are effective in the prevention of Clostridium difficile infections (CDI) among patients receiving antibiotics. The aim of this study was to analyze the CDI among patients receiving antibiotics and hospitalized in the period before and after starting routine use of LP299v as a prevention of this infection. Methods: Among 3533 patients hospitalized in the nephrology and transplantation ward during a two-year period, 23 patients with CDI were diagnosed and enrolled in this retrospective study. Since November 2013, prevention of CDI with oral use of LP299v was performed in all patients treated with antibiotics and who were at a high risk of developing CDI. The observation period was divided into two twelve-month intervals before and after initiation of the use of LP299v as a prophylactic against CDI. Results: A significant (p = 0.0001) reduction of the number of cases of CDI was found after routinely using LP299v (n = 2; 0.11% of all hospitalized patients) compared with the previous twelve-month period of observation (n = 21; 1.21% of all hospitalized patients). Conclusions: Routine use of LP299v during treatment with antibiotics may prevent C. difficile infection in the nephrology and transplantation ward.