The Effects of Two Kinds of Dietary Interventions on Serum Metabolic Profiles in Haemodialysis Patients.

The goal of this study was to evaluate the effects of two kinds of 24-week dietary interventions in haemodialysis patients, a traditional nutritional intervention without a meal before dialysis (HG1) and implementation of a nutritional intervention with a meal served just before dialysis (HG2), in terms of analysing the differences in the serum metabolic profiles and finding biomarkers of dietary efficacy. These studies were performed in two homogenous groups of patients (n = 35 in both groups). Among the metabolites with the highest statistical significance between HG1 and HG2 after the end of the study, 21 substances were putatively annotated, which had potential significance in both of the most relevant metabolic pathways and those related to diet. After the 24 weeks of the dietary intervention, the main differences between the metabolomic profiles in the HG2 vs. HG1 groups were related to the higher signal intensities from amino acid metabolites: indole-3-carboxaldehyde, 5-(hydroxymethyl-2-furoyl)glycine, homocitrulline, 4-(glutamylamino)butanoate, tryptophol, gamma-glutamylthreonine, and isovalerylglycine. These metabolites are intermediates in the metabolic pathways of the necessary amino acids (Trp, Tyr, Phe, Leu, Ile, Val, Liz, and amino acids of the urea cycle) and are also diet-related intermediates (4-guanidinobutanoic acid, indole-3-carboxyaldehyde, homocitrulline, and isovalerylglycine).

Effects of the Malnutrition-Eat Additional Meal (MEAM) Diet on the Serum Levels of Albumin and C-Reactive Protein in Hemodialysis Patients.

The main objective of this project was to evaluate the efficiency of two kinds of nutritional intervention implemented in hemodialysis patients for 24 weeks (traditional nutritional intervention without a meal served before dialysis for group HG1, and nutritional intervention involving a meal served before dialysis for group HG2), and their impact on nutritional status and serum concentrations of C-reactive protein (CRP). Nutritional status and serum biochemical parameters were analyzed in the control group (CG, n = 70) and in two homogeneous groups of patients, HG1 (n = 35) and HG2 (n = 35). There was an interesting trend in both groups of patients connected with increased intake, mainly of energy and protein. In HG1, the greatest increase in energy intake was observed on Sundays, and in HG2 on the days with dialysis. In HG2, after 24 weeks of the nutritional intervention, an increase in serum albumin (p = 0.0157) and a decrease in CRP concentration (p = 0.0306) were observed, whereas in HG1 there was a decrease in serum albumin concentration (p = 0.0043) with no significant change in CRP concentration. The nutritional intervention applied, called the Malnutrition-Eat Additional Meal (MEAM) diet with an easily digestible meal served before dialysis, was aimed at improving the patients' nutritional status and the obtained results indicate the need not only for substantial reeducation of hemodialysis patients in the area of their diet, but also for undertaking further research and discussions on the possibility of ensuring adequate meals for hemodialysis patients before the dialysis procedure.

Basic inflammatory indices and chosen neutrophil receptors expression in chronic haemodialysed patients.

AIM OF THE STUDY: End stage renal disease (ESRD) patients on chronic haemodialysis (HD) are immuno-compromised and prone to infection. Toll-like receptors (TLRs) play a role as both primary sensors of pathogen invasion and activators of inflammatory reaction. To test if the immune impairment in HD patients is connected with the defective expression of the neutrophil TLRs, we aimed to examine their expression and chosen inflammatory indices. MATERIAL AND METHODS: We tested CD14, TLR4, and TLR9 expressions on neutrophils using flow cytometry. Soluble CD14, C-reactive protein (CRP), and mannose-binding lectin (MBL) concentrations were tested using the ELISA method in 31 ESRD patients on chronic haemodialysis programs and in 17 healthy control subjects. RESULTS: Neutrophil TLR4 and TLR9 expressions did not differ significantly compared to the controls. The ESRD patients had markedly increased CRP and sCD14 levels alongside decreased MBL concentrations and neutrophil CD14 expression. The TLR4 expression correlated well with both TLR9 and CD14 neutrophil expressions; however, the increased CRP in the blood did not correlate with the MBL concentration or TLR expression. CONCLUSIONS: The chronic program of haemodialysis and biochemical disorders in ESRD patients result in a low-grade chronic inflammation with no significant impact on the expression of neutrophil TLR4 and TLR9.

Alterations in conformational state of albumin in plasma in chronic hemodialyzed patients.

OBJECTIVE: In chronic hemodialyzed (CH) patients the balance between production of reactive oxygen species and antioxidant defense system is disturbed and shifted towards oxidative conditions. The properties of albumin in CH patients were studied before hemodialysis (HD) and post-HD. METHODS: Two oxidants were applied, organic t-butyl hydroperoxide (t-BOOH) and inorganic hydroperoxide (H2O2), for oxidation of albumin molecules. By comparison, albumin from healthy donors was also modified by both oxidants. The thiol content in albumin was determined by the Ellman method. Albumin properties were evaluated with the spin labelling technique using two covalently bound spin labels, maleimide (MSL) and iodoacetamide (ISL), and fatty acid spin probe, 16-doxylstearic acid (16-DS). RESULTS: A decrease in thiols level in HD albumin was greater than in control albumin. The t-BOOH modified the microenvironment at the binding site of MSL and ISL in control albumin molecules to a greater extent than hydrogen peroxide. Control albumin treated with t-BOOH and H2O2 showed an increase in the mobility of 16-DS. However, no changes were observed in albumin from CH patients treated with either of the oxidizing agents. CONCLUSION: Both oxidants induced strong conformational changes in albumin from healthy volunteers, but were less effective or ineffective in modification of albumin derived from CH patients. These results show that albumin from CH patients is highly modified in vivo and is not vulnerable to oxidation in the same way as normal albumin.

Prevalence of arterial hypertension and the number and classes of antihypertensive drugs prescribed for patients late after kidney transplantation.

BACKGROUND: There are limitations of the use of several classes of antihypertensive drugs in patients after kidney transplantation (KTx), as well as contradictory opinions on their effects on progression of graft dysfunction. In this study we assessed the prevalence of arterial hypertension (HA) and the antihypertensive agents used by the patients long after KTx. MATERIAL/METHODS: This retrospective evaluation of the number and classes of antihypertensive drugs was based on medical records of 348 patients (140 F, 208 M; mean age 49 ± 13 years) late after KTx (mean time after KTx 78 ± 43 months). The data were related to graft function. RESULTS: Ninety-three percent of patients after KTx required antihypertensive therapy. Only 8.7% were treated with 1 agent (mean eGFR 65.1 ± 27.4 ml/min), 26.3% received 2 drugs (eGFR 60.0 ± 25.8 ml/min), 34.2% received 3 drugs (eGFR 55.5 ± 23.4 ml/min), 20.1% received 4 drugs (eGFR 54.9 ± 24.9 ml/min), and 10.5% received ≥ 5 drugs (eGFR 45.9 ± 22.0 ml/min). The number of antihypertensive medications increased along with the deterioration of graft function. Dihydropyridine calcium antagonists (CCB) were the most common class of drugs recommended to the patients after KTx (81%), followed by ß-adrenergic antagonists (74.4%); α-antagonists (40.2%), angiotensin-converting enzyme inhibitors (38.7%), diuretics (34.1%), clonidine (17.8%) and angiotensin II receptor blockers (9.5%). CONCLUSIONS: HA is highly prevalent in KTx patients. Multidrug therapy is usually required for the treatment of HA in this population. Dihydropyridine CCB is the most common class of antihypertensive drugs used by them. Graft function is a determining factor in the number of antihypertensive agents.

Similar prevalence but different characteristics of pain in kidney transplant recipients and chronic hemodialysis patients.

BACKGROUND: Chronic pain is frequent in both hemodialysis (HD) patients and kidney transplant (KTx) recipients but its detailed characteristics have never been thoroughly investigated. AIM: To compare prevalence of pain, its locations and characteristics, and analgesics use in chronic HD and KTx patients. METHODS: A cross-sectional comparative study in 164 HD patients and 114 stable deceased donor KTx recipients. All participants completed the modified McGill Pain Questionnaire. RESULTS: Overall, 63% of HD patients and 62% of KTx patients reported pain. Fifty-four percent of HD patients and 67% of KTx patients indicated more than one location of pain. Severe pain was more common in HD patients, and prevalence of pain-associated symptoms from major body systems was higher in HD patients. Pain in both groups was mostly local, paroxysmal and/or chronic. Fifteen percent of HD patients and 37% of KTx patients with chronic pain were not receiving pain relief drugs. The general feeling of illness was lower in KTx than HD patients (4.54 ± 2.1 vs. 5.6 ± 0.7; p < 0.0001); however, in the former group, it was systematically increasing with the time after transplantation. CONCLUSIONS: A successful kidney transplantation does not lead to a significant reduction in the prevalence of pain when compared to chronic HD patients. Pain relief medications are underused in KTx patients.

The effect of selenium supplementation in the prevention of DNA damage in white blood cells of hemodialyzed patients: a pilot study.

Patients with chronic kidney disease (CKD) have an increased incidence of cancer. It is well known that long periods of hemodialysis (HD) treatment are linked to DNA damage due to oxidative stress. In this study, we examined the effect of selenium (Se) supplementation to CKD patients on HD on the prevention of oxidative DNA damage in white blood cells. Blood samples were drawn from 42 CKD patients on HD (at the beginning of the study and after 1 and 3 months) and from 30 healthy controls. Twenty-two patients were supplemented with 200 µg Se (as Se-rich yeast) per day and 20 with placebo (baker's yeast) for 3 months. Se concentration in plasma and DNA damage in white blood cells expressed as the tail moment, including single-strand breaks (SSB) and oxidative bases lesion in DNA, using formamidopyrimidine glycosylase (FPG), were measured. Se concentration in patients was significantly lower than in healthy subjects (P < 0.0001) and increased significantly after 3 months of Se supplementation (P < 0.0001). Tail moment (SSB) in patients before the study was three times higher than in healthy subjects (P < 0.01). After 3 months of Se supplementation, it decreased significantly (P < 0.01) and was about 16% lower than in healthy subjects. The oxidative bases lesion in DNA (tail moment, FPG) of HD patients at the beginning of the study was significantly higher (P < 0.01) compared with controls, and 3 months after Se supplementation it was 2.6 times lower than in controls (P < 0.01). No changes in tail moment was observed in the placebo group. In conclusion, our study shows that in CKD patients on HD, DNA damage in white blood cells is higher than in healthy controls, and Se supplementation prevents the damage of DNA.

Antibodies against N-homocysteinylated proteins and their determinants in patients on long-term hemodialysis.

INTRODUCTION: The factors that determine the level of antibodies against N-homocysteinylated (N-Hcy) proteins have not been established so far. The clinical significance of these antibodies and their effect on cardiovascular (CV) risk in patients with end-stage renal disease (ESRD) are still unknown. OBJECTIVES: The aim of this study was to identify the factors that determine the level of antibodies against N-Hcyalbumin and N-Hcy hemoglobin in patients on long-term hemodialysis (HD). PATIENTS AND METHODS: The study involved 247 subjects on long-term HD (110 women, 137 men; age range, 23-89 years) and 60 controls matched for age, sex, and CV risk factors (serum creatinine level <140 micromol/l). Serum antibodies against N-Hcyalbumin and N-Hcyhemoglobin were determined using an in-house enzyme-linked immunosorbent assay. Total homocysteine (tHcy), folate, and 8-isoprostaglandin F2alpha (8-iso-PGF(2alpha)) were also measured. RESULTS: Patients on HD had higher serum levels of anti-N-Hcy-albumin (absorbancy at 490 nm: 0.56 [0.49-0.623] vs. 0.259 [0.198-0.338], P <0.0001) and anti-N-Hcy-hemoglobin antibodies (0.659 [0.597-0.723] vs. 0.379 [0.289-0.442], P <0.0001) as compared with controls. The level of both antibodies correlated with tHcy (r = 0.56, P <0.0001 and r = 0.67, P <0.0001, respectively), 8-iso-PGF(2alpha) (r = 0.48, P <0.0001 and r = 0.63, P <0.0001, respectively), and folate (r = -0.18, P = 0.0054 and r = -0.38, P <0.0001, respectively), but not with HD duration, the initial cause of ESRD, and CV comorbidity. CONCLUSIONS: In HD patients, tHcy is an independent predictor of antibodies against N-Hcy proteins. Folate and 8-iso-PGF(2alpha) concentrations were not independently associated with the levels of both antibodies.

Selenium supplementation to chronic kidney disease patients on hemodialysis does not induce the synthesis of plasma glutathione peroxidase.

BACKGROUND: Numerous authors have shown that selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity in plasma of chronic kidney disease (CKD) patients are lower than in healthy subjects, but there are only few publications on the level of GSH-Px protein in those patients and no reports on the effect of Se supplementation to HD patients on the level of this enzyme. SUBJECTS AND METHODS: Se concentration and GSH-Px protein level in plasma were measured in a group of 30 CKD patients on hemodialysis (HD) supplemented with 200 microg Se/day for 3 months, and 28 patients on HD administered with placebo. Se concentration was measured by graphite furnace atomic absorption spectrometry and plasma GSH-Px protein level by the sandwich ELISA method using polyclonal antibody specific for human plasma GSH-Px. RESULTS: Se concentration in patients on placebo did not change throughout the 3-month study period, but increased significantly in Se supplemented group. Se supplementation to CKD patients on HD had no effect on the level of GSH-Px protein. CONCLUSIONS: The lack of GSH-Px protein in CKD patients on HD is not linked to Se deficiency since the level of this element increased after Se supplementation while enzyme protein level did not change. The damaged kidney of HD patients is unable to synthesize GSH-Px, even after induction with selenium.

[Blood serum osteocalcin and beta-crosslaps concentrations in patients after renal transplantation]. / Stezenie osteokalcyny i beta-crosslaps w surowicy krwi u pacjentów po zabiegu przeszczepienia nerki--obserwacja wstepna.

In 16 patients (7 males, 9 females), aged 47.2 +/- 15.9 years, blood serum concentrations of osteocalcin, beta-crosslaps, parathormone, calcium, phosphate, creatinine and urea were determined before renal transplantation and 3 and 6 months following the procedure. Three as well as six months following renal transplantation significant decrease in blood serum concentration of osteocalcin and beta-crosslaps are found. A significant positive correlation between osteocalcin and beta-crosslaps concentration was found in each investigated period. Six-months observation revealed only partial correction of bone metabolism following renal transplantation.

The blood platelet proteome is changed in UREMIC patients.

Comparative analysis of the protein profile of blood platelets isolated from nondialyzed and hemodialyzed uremic patients and healthy controls has been performed. These preliminary results indicate markedly changed expression of several proteins in blood platelets from both groups of patients compared with controls, with dramatic changes in hemodialyzed patients in the over-expression of low molecular peptides with a very wide range of pI values.

NT-proBNP plasma levels and echocardiographic assessment of cardiac function in patients after renal transplantation.

BACKGROUND: Cardiovascular diseases are the most important causes of death in patients with chronic renal disease (CRD). Successful renal transplantation (RTx) corrects water and electrolyte disturbances and decreases or eliminates anaemia. It favourably influences cardiac haemodynamics and reduces risk of cardiovascular events. NT-proBNP plasma concentration is one of the prognostic and risk factors in such cases, whereas echocardiography that enables evaluation of the left atrium and ventricle allows detailed analysis of haemodynamic condition of the heart. AIM: To analyse NT-proBNP plasma concentration and selected echocardiographic parameters in patients after RTx at various time intervals after the procedure. METHODS: Seventeen patients after RTx were included in the study (age 46.5+/-16 years, 7 men and 10 women). NT-proBNP plasma level measurements and echocardiography were performed immediately before and at 3 and 6 months after RTx. Additionally, these parameters were assessed in patients receiving cyclosporine A (CsA) and tacrolimus (TAC). RESULTS: NT-proBNP plasma level decreases significantly after RTx (initially 4369+/-2420, at 3 months 2056+/-576, at 6 months 1580+/-572 pg/ml). In the TAC group, a significant reduction was observed at 3 months (from 13291+/-3563 to 1845+/-1022 pg/ml). In patients treated with CsA reduction occurred at 6 months after RTx (from 9447+/-3369 to 1246+/-436 pg/ml). At six-month follow-up significant changes in ejection fraction were not found. However, a significant increase in LV mass in CsA patients was observed. CONCLUSIONS: Reduction of NT-proBNP levels seems to be more the result of transplanted kidney function than of an improvement in circulation. Significant LV mass increase in CsA patients may be a result of higher blood pressure levels observed before and after RTx.

Red blood cell and plasma glutathione peroxidase activities and selenium concentration in patients with chronic kidney disease: a review.

The metabolism of oxygen in aerobic organisms leads to generation of reactive oxygen species (ROS). These entities are able to oxidize almost all classes of macromolecules, including proteins, lipids and nucleic acids. The physiological level of ROS is usually regulated by antioxidant defense mechanisms. There are at least three groups of antioxidant enzymes: superoxide dismutases, catalases and glutathione peroxidases (GSH-Pxs) which neutralize ROS. The trace elements (copper, zinc and selenium) bound to the active sites of the above listed enzymes play an important role in the antioxidant defense system. In mammals, a major function of selenium (Se) and Se-dependent GSH-Pxs is to protect cells from oxidative stress. Selenium concentrations and GSH-Px activities are altered in blood components of chronic kidney disease (CKD) patients. The Se level is frequently lower than in healthy subjects and the concentration very often decreases gradually with advancing stage of the disease. Studies on red cell GSH-Px activity in CKD patients reported its values significantly lower, significantly higher and lower or higher, but not significantly as compared with healthy subjects. On the other hand, all authors who studied plasma GSH-Px activity have shown significantly lower values than in healthy subjects. The degree of the reduction decreases gradually with the progression of the disease. High inverse correlations were seen between plasma GSH-Px activity and creatinine level. A gradual decrease in plasma GSH-Px activity in CKD patients is due to the fact that this enzyme is synthesized predominantly in the kidney and thus the impairment of this organ is the cause of the enzyme's lower activity. Se supplementation to CKD patients has a slightly positive effect in the incipient stage of the disease, but usually no effect was observed in end-stage CKD. Presently, kidney transplantation is the only treatment that may restore plasma Se level and GSH-Px activity in patients suffering from end-stage CKD. A few studies have shown that in kidney recipients, plasma Se concentration and GSH-Px activity are restored to normal values within a period of 2 weeks to 3 months following surgery and thus it can be acknowledged that Se supplementation to those patients has a positive effect on plasma GSH-Px activity.

[Severe exacerbation of chronic renal failure in the course of asymptomatic cystolithiasis]. / Ciezkie zaostrzenie przewleklej niewydolnosci nerek w przebiegu bezobjawowej kamicy pecherza moczowego.

There has been reported a case of severe exacerbation of chronic renal failure with bilateral hydronephrosis and urosepsis, which was caused by asymptomatic large urinary bladder stone. Life-threatening symptoms of uraemic syndrome were found, which required temporary hemodialysis treatment. Following removal of the calculus and controlling of severe urinary tract infection the patient was discharged with stable blood serum creatinine concentration 3.8 mg/dl.