BACKGROUND: The unphysiological composition of peritoneal dialysis (PD) fluids induces progressive peritoneal fibrosis, hypervascularization and vasculopathy. Information on these alterations after kidney transplantation (KTx) is scant. METHODS: Parietal peritoneal tissues were obtained from 81 pediatric patients with chronic kidney disease stage 5 (CKD5), 72 children on PD with low glucose degradation product (GDP) PD fluids, and from 20 children 4-8 weeks after KTx and preceding low-GDP PD. Tissues were analyzed by digital histomorphometry and quantitative immunohistochemistry. RESULTS: While chronic PD was associated with peritoneal hypervascularization, after KTx vascularization was comparable to CKD5 level. Submesothelial CD45 counts were 40% lower compared with PD, and in multivariable analyses independently associated with microvessel density. In contrast, peritoneal mesothelial denudation, submesothelial thickness and fibrin abundance, number of activated, submesothelial fibroblasts and of mesothelial-mesenchymal transitioned cells were similar after KTx. Diffuse peritoneal podoplanin positivity was present in 40% of the transplanted patients. In subgroups matched for age, PD vintage, dialytic glucose exposure and peritonitis incidence, submesothelial hypoxia-inducible factor 1-alpha abundance and angiopoietin 1/2 ratio were lower after KTx, reflecting vessel maturation, while arteriolar and microvessel p16 and cleaved Casp3 were higher. Submesothelial mast cell count and interleukin-6 were lower, whereas transforming growth factor-beta induced pSMAD2/3 was similar as compared with children on PD. CONCLUSIONS: Peritoneal membrane damage induced with chronic administration of low-GDP PD fluids was less severe after KTx. While peritoneal microvessel density, primarily defining PD transport and ultrafiltration capacity, was normal after KTx and peritoneal inflammation less pronounced, diffuse podoplanin positivity and profibrotic activity were prevalent.
- Klíčová slova
- chronic kidney disease, kidney transplantation, pediatric, peritoneal dialysis, peritoneal membrane,
- MeSH
- chronické selhání ledvin * chirurgie metabolismus MeSH
- dialýza ledvin MeSH
- dialyzační roztoky metabolismus MeSH
- dítě MeSH
- glukosa metabolismus MeSH
- lidé MeSH
- peritoneální dialýza * škodlivé účinky MeSH
- peritoneum metabolismus MeSH
- peritonitida * metabolismus MeSH
- transplantace ledvin * škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dialyzační roztoky MeSH
- glukosa MeSH
Brain tissue oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS) is lower in hemodialysis patients than in the healthy population and is associated with cognitive dysfunction. The involved mechanisms are not known. We conducted this study to identify the factors that influence the rSO2 values in end-stage renal disease (ESRD) patients and to describe rSO2 changes during hemodialysis. We included a cohort of ESRD patients hemodialyzed in our institution. We recorded rSO2 using INVOS 5100C oximetry system (Medtronic, Essex, U.K.) and analyzed changes in basic laboratory values and hemodynamic fluctuations. Baseline rSO2 was lower in patients with heart failure (45.2±8.3 % vs. 54.1±7.8 %, p=0.006) and was significantly linked to higher red cell distribution width (RDW) (r=-0.53, p?0.001) and higher BNP level (r=-0.45, p=0.01). The rSO(2) value decreased in first 15 min of hemodialysis, this decrease correlated with drop in white blood count during the same period (r=0.43, p=0.02 in 10 min, r=0.43, p=0.02 in 20 min). Lower rSO(2) values in patients with heart failure and higher RDW suggest that hemodynamic instability combined with vascular changes probably leads to worse cerebral oxygenation in these patients. Decrease of rSO(2) in 15th minute of hemodialysis accompanied with a significant drop in leukocyte count could be explained by complement activation.
- MeSH
- chronické selhání ledvin epidemiologie metabolismus terapie MeSH
- dialýza ledvin škodlivé účinky trendy MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozková hypoxie epidemiologie metabolismus MeSH
- mozkový krevní oběh fyziologie MeSH
- oxymetrie trendy MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- surveillance populace * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Mutations in INF2 are frequently responsible for focal segmental glomerulosclerosis (FSGS), which is a common cause of end stage renal disease (ESRD); additionally, they are also connected with Charcot-Marie-Tooth neuropathy. INF2 encodes for inverted formin 2. This protein participates in regulation of the dynamics of the actin cytoskeleton, involving not only the polymerisation, but also the depolymerisation of filaments. The present study is the first mutational analysis of INF2 done in the Czech Republic. METHODS: Mutational analysis of INF2 was performed on 109 patients (mean age at onset 41.44 ± 18.91 years) with FSGS or minimal change disease (MCD); and also in 6 patients without renal biopsy who had already developed chronic kidney disease (CKD)/ESRD at the time of diagnosis. We used high resolution melting method (HRM), with subsequent Sanger sequencing, in suspect samples from HRM analysis. The HRM method is an effective method for the screening of large cohorts of patients. RESULTS: Two pathogenic mutations (p.Arg214His and p.Arg218Gln) were detected in INF2. The first (p.Arg214His) was identified in the FSGS patient with a positive family history. The second mutation (p.Arg218Gln) was found in two brothers with ESRD of unknown etiology. The most frequent sequence change was the substitution p.P35P, the incidence of which corresponded with the frequencies available in the ExAC Browser and gnomAD Browser databases. This analysis also detected different exonic and intronic changes that probably did not influence the phenotype of the included patients. CONCLUSIONS: The INF2 mutational screening is useful in familial FSGS cases as well as in patients with an unknown cause for their ESRD, but with a positive family history. INF2 seems to be not only the cause of FSGS, but also of ESRD of unknown etiology. Our study has confirmed that the HRM analysis is a very useful method for the identification of single nucleotide substitutions.
- Klíčová slova
- End stage renal disease, Focal segmental glomerulosclerosis, High resolution melting method, INF2, Minimal change disease,
- MeSH
- Charcotova-Marieova-Toothova nemoc genetika metabolismus MeSH
- chronické selhání ledvin genetika metabolismus MeSH
- dospělí MeSH
- exony genetika MeSH
- fenotyp MeSH
- fokálně segmentální glomeruloskleróza genetika metabolismus MeSH
- forminy MeSH
- introny genetika MeSH
- kohortové studie MeSH
- lidé MeSH
- mikrofilamentové proteiny genetika metabolismus MeSH
- mutace genetika MeSH
- mutační analýza DNA metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- forminy MeSH
- INF2 protein, human MeSH Prohlížeč
- mikrofilamentové proteiny MeSH
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.
- MeSH
- angiotensinogen krev metabolismus moč MeSH
- biologické markery krev moč MeSH
- chronické selhání ledvin diagnóza metabolismus MeSH
- dítě MeSH
- hemolyticko-uremický syndrom diagnóza metabolismus MeSH
- interleukin-18 krev metabolismus moč MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- angiotensinogen MeSH
- biologické markery MeSH
- IL18 protein, human MeSH Prohlížeč
- interleukin-18 MeSH
In last decades was confirmed remarkable increase in number of old patients with chronic kidney disease. Despide of developments in dialysis technology and kidney transplantation there is a growing number of old patients who are not suitable for these methods. Recently were published data showing long-term effect of protein restricted diet supplemented with keto amino acids in elderly. Based on our results obtained in re-analysis of 3 000 patients we can confirm also good compliance and low risk of malnutrition.Key words: chronic kidney disease - keto amino acids - old age - restricted diet.
- MeSH
- adherence pacienta MeSH
- aminokyseliny MeSH
- chronická renální insuficience dietoterapie MeSH
- chronické selhání ledvin dietoterapie metabolismus MeSH
- dialýza ledvin MeSH
- ketokyseliny MeSH
- lidé MeSH
- nízkoproteinová dieta * MeSH
- potravní doplňky MeSH
- senioři MeSH
- transplantace ledvin MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aminokyseliny MeSH
- ketokyseliny MeSH
Pathogenesis of adenine-induced chronic renal failure may involve inflammatory, immunological and/or oxidant mechanisms. Gum arabic (GA) is a complex polysaccharide that acts as an anti-oxidant which can modulate inflammatory and/or immunological processes. Therefore, we tested here the effect of GA treatment (15 % in the drinking water for 4 weeks) in plasma and urine of rats, on a novel cytokine that has been shown to be pro-inflammatory, viz, DNA-binding high-mobility group box-1 protein (HMGB1). Adenine (0.75 % in the feed, 4 weeks) significantly increased indoxyl sulphate, urea and creatinine concentrations in plasma, and significantly decreased the creatinine clearance. GA significantly abated these effects. The concentrations of HMGB1 in urine before the start of the experiment were similar in all four groups. However, 24 h after the last treatment, adenine treatment increased significantly the concentration of HMGB1 when compared with the control. GA treatment did not affect the HMGB1 concentration in urine. Moreover, the concentration of HMGB1 in plasma obtained 24 h after the last treatment in rats treated with adenine was drastically reduced compared with the control group. This may explain its significant rise in urine. In conclusion, HMGB1 can be considered a potentially useful biomarker in adenine induced CRF and its treatment.
- MeSH
- adenin * MeSH
- arabská guma farmakologie MeSH
- biologické markery krev moč MeSH
- časové faktory MeSH
- chronické selhání ledvin chemicky indukované farmakoterapie metabolismus patofyziologie MeSH
- indican krev MeSH
- kreatinin krev MeSH
- ledviny účinky léků metabolismus patofyziologie MeSH
- mediátory zánětu krev metabolismus moč MeSH
- močovina krev MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- protein HMGB1 krev metabolismus moč MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenin * MeSH
- arabská guma MeSH
- biologické markery MeSH
- Hbp1 protein, rat MeSH Prohlížeč
- indican MeSH
- kreatinin MeSH
- mediátory zánětu MeSH
- močovina MeSH
- protein HMGB1 MeSH
Chronic kidney disease (CKD), and chronic renal failure in particular, is associated with vitamin D deficiency and with a disorder of all metabolic processes that are associated with vitamin D. Calcidiol levels are often low. At present, efforts are made to test and to pharmacologically modulate its levels and thus to contribute to greater availability of the substrate for external calcitriol production. Calcitriol production is reduced in CKD patients not only as a consequence of diminishing functional renal parenchyma but also as a consequence of 1-α-hydroxylase inhibition by FGF-23 and other factors. On the other hand, although parathormone (PTH) increases renal production of calcitriol, it also causes secondary hyperparathyroidism. Synthetic calcitriol (or α-calcidiol) supresses PTH production and is used to treat secondary hyperparathyroidism. This approach is often associated with adverse increase in calcaemia and phosphataemia as the effect on parathyroid glands is associated with an effect on the gastrointestinal tract where calcium and phosphor absorption is increased by calcitriol. Synthetic analogues of vitamin D inhibit parathyroid gland but have significantly lower effect on gastrointestinal tract. Paricalcitol is a selective VDR (vitamin D receptor) activator, used for targeted suppression of parathyroid glands. Vitamin D deficiency in general population is associated, at least in epidemiological studies, with a range of medical complications and the same also applies to patients with renal disease. Although randomised studies are not available, clinical observational studies repeatedly showed treatment with VDR activators to be associated with better prognosis. As other fields of medicine, nephrology currently pays a great attention to vitamin D and vitamin D receptor activation.
- MeSH
- chronická renální insuficience metabolismus MeSH
- chronické selhání ledvin metabolismus MeSH
- ergokalciferoly terapeutické užití MeSH
- fibroblastový růstový faktor 23 MeSH
- kalcitriol metabolismus terapeutické užití MeSH
- lidé MeSH
- protein vázající vitamin D metabolismus MeSH
- receptory kalcitriolu metabolismus MeSH
- sekundární hyperparatyreóza farmakoterapie etiologie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ergokalciferoly MeSH
- FGF23 protein, human MeSH Prohlížeč
- fibroblastový růstový faktor 23 MeSH
- kalcitriol MeSH
- paricalcitol MeSH Prohlížeč
- protein vázající vitamin D MeSH
- receptory kalcitriolu MeSH
Hemodialysis and peritoneal dialysis are methods of blood purification, which partially replaced excretory renal function in patients with chronic renal failure, which was depleted regime, dietary and pharmaco-therapeutic remedy, and who are not eligible for kidney transplantation. Both two methods are accompanied by increased oxidative stress. In peritoneal dialysis particularly the composition of dialysis solution contributes to oxidative stress. In extracorporeal hemodialysis the oxidative stress is associated with the character of hemodialysis membranes, non-specific loss of low molecular weight antioxidants, activation of leukocytes (oxidative burst), feroteraphy, supplementation with low molecular weight antioxidants and other factors. To improve and maintain the quality of life of dialysis patients, the continuous monitoring of oxidative stress-related parameters as non-traditional risk factors for cardiovascular complications development is suitable.
Patients with chronic kidney disease are exposed to oxidative stress (OS) that contributes to deterioration of health. Decrease in renal excretory capacity contributes to the accumulation of pro-oxidative substances that are detrimental not only to kidney but to the whole organism including the cardiovascular system. Components of antioxidant system play an important role in the elimination of the OS. The monitoring of antioxidant levels and products of oxidative damage in these patients and the correct interpretation of relationship between these markers and the function of kidney and other organs may contribute to the more effective treatment and health improvement of the patients.
- MeSH
- antioxidancia metabolismus MeSH
- chronické selhání ledvin komplikace metabolismus MeSH
- kardiovaskulární nemoci etiologie MeSH
- lidé MeSH
- oxidační stres * MeSH
- peroxidace lipidů MeSH
- volné radikály metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antioxidancia MeSH
- volné radikály MeSH
1. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effects. 2. Because this notion has recently been questioned, in the present study we compared the effects of a RAS-dependent antihypertensive therapy (a combination of trandolapril, an angiotensin-converting enzyme inhibitor (ACEI) and losartan, an angiotensin-II (AngII) receptor subtype 1A receptor antagonist) with a 'RAS-independent' antihypertensive therapy (a combination of labetalol, an alfa- and beta-adrenoreceptor antagonist with the diuretics, hydrochlorothiazide and furosemide) on the progression of CKD after 5/6 renal ablation (5/6 NX) in Ren-2 renin transgenic rats (TGR), a model of AngII-dependent hypertension. Normotensive transgene-negative Hannover Sprague-Dawley (HanSD) rats after 5/6 NX served as controls. 3. RAS-dependent and -independent antihypertensive therapies normalized BP and survival rate, and prevented the development of cardiac hypertrophy and glomerulosclerosis to the same degree in 5/6 NX HanSD rats and in 5/6 NX TGR. The present findings show that renoprotection, at least in rats after 5/6 NX, is predominantly BP-dependent. When equal lowering of BP was achieved, leading to normotension, cardio- and renoprotective effects were equivalent irrespective of the type of antihypertensive therapy. 4. These findings should be taken into consideration in attempts to develop new therapeutic approaches and strategies aimed to prevent the progression of CKD and to lower the incidence of ESRD.
- MeSH
- aldosteron moč MeSH
- angiotensin II krev metabolismus MeSH
- antihypertenziva farmakologie MeSH
- blokátory receptoru 1 pro angiotenzin II farmakologie MeSH
- chronické selhání ledvin farmakoterapie metabolismus prevence a kontrola MeSH
- diabetické nefropatie farmakoterapie prevence a kontrola MeSH
- diuretika farmakologie MeSH
- furosemid farmakologie MeSH
- hydrochlorthiazid farmakologie MeSH
- hypertenze farmakoterapie metabolismus MeSH
- indoly farmakologie MeSH
- inhibitory ACE farmakologie MeSH
- kardiomegalie farmakoterapie prevence a kontrola MeSH
- kombinovaná farmakoterapie MeSH
- kreatinin krev metabolismus moč MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- labetalol farmakologie MeSH
- losartan farmakologie MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- proteinurie krev metabolismus moč MeSH
- renin-angiotensin systém účinky léků MeSH
- renin metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aldosteron MeSH
- angiotensin II MeSH
- antihypertenziva MeSH
- blokátory receptoru 1 pro angiotenzin II MeSH
- diuretika MeSH
- furosemid MeSH
- hydrochlorthiazid MeSH
- indoly MeSH
- inhibitory ACE MeSH
- kreatinin MeSH
- labetalol MeSH
- losartan MeSH
- renin MeSH
- trandolapril MeSH Prohlížeč
