Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy, in the course of which some patients may develop chronic kidney disease (CKD). It is clinically important to investigate the markers of a poor prognosis. The levels of angiotensinogen (AGT) and interleukin-18 (IL-18) in serum and urine were evaluated. Study was conducted in 29 children with a history of HUS. Serum and urine AGT concentration was significantly higher in children after HUS as compared to the control group. No differences depending on the type of HUS and gender were noted. The serum concentration of IL-18 in children after HUS was significantly lower, whereas in urine did not differ significantly between the sick and healthy children. A negative correlation between the concentration of AGT in serum and albuminuria in patients after HUS was detected. The results indicate that the concentration of AGT in serum and urine in children after HUS increases, which may indicate the activation of the intrarenal renin-angiotensin-aldosterone system. The statement, that AGT may be a good biomarker of CKD after acute kidney injury due to HUS requires prospective studies with follow-up from the acute phase of the disease on a larger group of patients. Reduced IL-18 serum concentration in children after HUS with no difference in its urine concentration may indicate a loss of the protective effects of this cytokine on renal function due to previously occurred HUS., K. Lipiec, P. Adamczyk, E. Świętochowska, K. Ziora, M. Szczepańska., and Obsahuje bibliografii
Gum acacia (GA) is used in pharmaceutical, cosmetic and food industries as an emulsifier and stabilizer, and in some countries in the traditional treatment of patients with chronic kidney disease (CKD). We have previously found that GA ameliorates adenine -induced chronic renal failure (CRF) in rats. Different brands of GA are commercially available, but their comparative efficacy against adenine-induced CKD is unknown. Here, we explored the effects of three different brands of GA (Sudanese GA, SupergumTM and GA from BDH) on some physiological, biochemical, and histological effects of adenine-induced CRF in rats. Adenine (0.75 %, w/w in feed, four weeks) reduced body weight, and increased urine output. It also induced significant increases in blood pressure, and in creatinine, urea, several inflammatory cytokines in plasma, and indices of oxidative stress, and caused histological damage in kidneys. Treatment of rats concomitantly with any of the three GA brands, significantly, and to a broadly similar extent, mitigated all the signs of CRF. The results suggested equivalent efficacy of these brands in antagonizing the CRF in this animal model. However, to enable standardization of different brands between laboratories, the use of the chemically well-characterized GA preparation (such as SupergumTM) is recommended., B. H. Ali, ... [et al.]., and Obsahuje seznam literatury
Fibroblast growth factor 21 (FGF21) is one of the members of endocrine arm of FGF family. Its actions as a glucose and lipids metabolism regulator are widely known. Although the mechanism of FGF21 action in kidneys is still under investigation, FGF21 was considered as a marker of early kidney function decline. While many researchers focused on adult subjects in this matter, there are no data regarding children. Therefore, we have investigated the relationship between plasma or urine FGF21 levels and kidney function in a group of 42 pediatric patients with chronic kidney disease (CKD). Anthropometrical parameters and blood pressure were taken, routine biochemical tests were performed. The concentration of FGF21 in serum and urine was determined by enzyme immunoassay. The results revealed significantly higher serum FGF21 concentration among children from CKD group. However, serum FGF21 level was not related to gender, proteinuria, eGFR or renal replacement therapy. Urine FGF21 concentration correlated negatively with albuminuria and positively with eGFR. Documented negative correlation of FGF21 fractional excretion and eGFR is not enough to support the role of FGF21 as a biomarker for predicting kidney disease progression in children and adolescents. Other mechanisms including local kidney FGF21 production or enhanced excretion due to higher extrarenal production may result in higher urine FGF21 concentrations.
Vitamin D status and the relationship between serum 25(OH) vitamin D concentrations and the components of insulin resistance were examined in 120 patients with chronic kidney disease stage 2 and 3. Insulin sensitivity/resistance was calculated by the quantitative insulin sensitivity check index (QUICKI). In this analysis, the prevalence of insulin resistance was 42 %. Only 17 % of patients had serum 25(OH) vitamin D concentration in the recommended range ( ≥ 30 ng/ml), 42 % suffered from vitamin D insufficiency and 41 % had moderate vitamin D deficiency. Insulin resistance significantly correlated with serum 25(OH)D and 1,25(OH) 2 D concentrations, renal function and protein excretion rate. Our results support the increasing evidence that vitamin D deficiency may be one of the factors participating in the development of insulin resistance already in the early stages of chronic kidney disease. and K. Štefíková ... [et al.].
The skeleton shows an unconventional role in the physiology and pathophysiology of the human organism, not only as the target tissue for a number of systemic hormones, but also as endocrine tissue modulating some skeletal and extraskeletal systems. From this point of view, the principal cells in the skeleton are osteocytes. These cells primarily work as mechano-sensors and modulate bone remodeling. Mechanically unloaded osteocytes synthetize sclerostin, the strong inhibitor of bone formation and RANKL, the strong activator of bone resorption. Osteocytes also express hormonally active vitamin D (1,25(OH)2D) and phosphatonins, such as FGF23. Both 1,25(OH)2D and FGF23 have been identified as powerful regulators of the phosphate metabolism, including in chronic kidney disease. Further endocrine cells of the skeleton involved in bone remodeling are osteoblasts. While FGF23 targets the kidney and parathyroid glands to control metabolism of vitamin D and phosphates, osteoblasts express osteocalcin, which through GPRC6A receptors modulates beta cells of the pancreatic islets, muscle, adipose tissue, brain and testes. This article reviews some knowledge concerning the interaction between the bone hormonal network and phosphate or energy homeostasis and/or male reproduction., I. Zofkova., and Obsahuje bibliografii
Five-sixths nephrectomy is a widely used experimental model of chronic kidney disease (CKD) that is associated with severe mitochondrial dysfunction of the remnant tissue. In this study, we assessed the effect of CKD on mitochondrial respiration separately in the rat kidney cortex and medulla 10 weeks after induction of CKD by subtotal 5/6 nephrectomy (SNX). Mitochondrial oxygen consumption was evaluated on mechanically permeabilized samples of kidney cortex and medulla using high-resolution respirometry and expressed per mg of tissue wet weight or IU citrate synthase (CS) activity. Mitochondrial respiration in the renal cortex of SNX rats was significantly reduced in all measured respiratory states if expressed per unit wet weight and remained lower if recalculated per IU citrate synthase activity, i.e. per mitochondrial mass. In contrast, the profound decrease in the activity of CS in SNX medulla resulted in significantly elevated respiratory states expressing the OXPHOS capacity when Complexes I and II or II only are provided with electrons, LEAK respiration after oligomycin injection, and Complex IV-linked oxygen consumption per unit CS activity suggesting compensatory hypermetabolic state in remaining functional mitochondria that is not sufficient to fully compensate for respiratory deficit expressed per tissue mass. The results document that CKD induced by 5/6 nephrectomy in the rat is likely to cause not only mitochondrial respiratory dysfunction (in the kidney cortex), but also adaptive changes in the medulla that tend to at least partially compensate for mitochondria loss.
Chronic kidney disease (CKD) is associated with increased concentration of intracellular calcium, which is pathological and may lead to irreversible damage of cell functions and structures. The aim of our study was to investigate the impact of 6 months vitamin D3 supplementation (14 000 IU/week) on free cytosolic calcium concentration ([Ca2+]i) and on the plasma membrane calcium ATPase (PMCA) activity of patients with CKD stage 2-3. PMCA activity of patients was also compared to that of healthy volunteers. Vitamin D3 supplementation of CKD patients resulted in the decrease of [Ca2+]i (119.79±5.87 nmol/l vs. 105.36± 3.59 nmol/l, n=14, P<0.001), whereas PMCA activity of CKD patients (38.75±22.89 nmol Pi/mg/h) remained unchanged after vitamin D3 supplementation (40.96±17.74 nmol Pi/mg/h, n=14). PMCA activity of early stage CKD patients before supplementation of vitamin D3, was reduced by 34 % (42.01±20.64 nmol Pi/mg/h) in comparison to healthy volunteers (63.68±20.32 nmol Pi/mg/h, n=28, P<0.001). These results indicate that vitamin D3 supplementation had a lowering effect on [Ca2+]i and negligible effect on PMCA activity in CKD patients., M. Morvová Jr., I. Lajdová, V. Spustová, M. Zvarík, L. Šikurová., and Obsahuje bibliografii
Adenine-induced model of chronic kidney disease (CKD) is a widely used model especially in studies testing novel nephroprotective agents. We investigated the effects of adenineinduced CKD in rats on the activities of some xenobiotic metabolizing enzymes in liver and kidneys, and on some in vivo indicators of drug metabolism (viz pentobarbitone sleeping time, and plasma concentration of theophylline 90 min post administration). CKD was induced by orally feeding adenine (0.25 % w/w) for 35 days. Adenine induced all the characteristics of CKD, which was confirmed by biochemical and histological findings. Glutathione concentration and activities of some enzymes involved in its metabolism were reduced in kidneys and livers of rats with CKD. Renal CYP450 1A1 activity was significantly inhibited by adenine, but other measured isoenzymes (1A2, 3A4 and 2E1) were not significantly affected. Adenine significantly prolonged pentobarbitone-sleeping time and increased plasma theophylline concentration 90 min post administration. Adenine also induced a moderate degree of hepatic damages as indicated histologically and by significant elevations in some plasma enzymes. The results suggest that adenine-induced CKD is associated with significant in vivo inhibitory activities on some drug-metabolizing enzymes, with most of the effect on the kidneys rather than the liver., M. Al Za’abi, A. Shalaby, P. Manoj, B. H. Ali., and Obsahuje bibliografii