Treatment of End-Stage Renal Disease in Central and Eastern Europe: Overview of Current Status and Future Needs

The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990–1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RTT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries.     

Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin

The role of autophagy, a process in which the cell self-digests its own components, was investigated in glioma cell death induced by the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase-inhibiting drug simvastatin. Induction of autophagy and activation of autophagy-regulating signalling pathways were analyzed by immunoblotting. Flow cytometry/fluorescent microscopy was used to assess autophagy-associated intracellular acidification and apoptotic markers (phosphatidylserine exposure, DNA fragmentation and caspase activation). Cell viability was determined by crystal violet, MTT or LDH release assay. Simvastatin treatment of U251 and C6 glioma cell lines caused the appearance of autophagolysosome-like intracytoplasmic acidic vesicles. The induction of autophagy in U251 cells was confirmed by the upregulation of autophagosome-associated LC3-II and pro-autophagic beclin-1, as well as by the downregulation of the selective autophagic target p62. Simvastatin induced the activation of AMP-activated protein kinase (AMPK) and its target Raptor, while simultaneously downregulating activation of Akt. Mammalian target of rapamycin (mTOR), a major AMPK/Akt downstream target and a major negative autophagy regulator, and its substrate p70 S6 kinase 1 were also inhibited by simvastatin. Mevalonate, the product of HMG-CoA reductase enzymatic activity, AMPK siRNA or pharmacological inactivation of AMPK with compound C suppressed, while the inhibitors of Akt (10-DEBC hydrochloride) and mTOR (rapamycin) mimicked autophagy induction by simvastatin. Inhibition of autophagy with bafilomycin A1, 3-methyladenine and LC3β shRNA, as well as AMPK inhibition with compound C or AMPK siRNA, markedly increased apoptotic death of simvastatin-treated U251 cells. These data suggest that inhibition of AMPK-dependent autophagic response might sensitize glioma cells to statin-induced apoptotic death.     

The quality of mother–child shared reading: its relations to child’s storytelling and home literacy environment

In the present study, we analysed the relations among the quality of mother–child shared reading, child’s storytelling and family literacy environment. The sample included 20 mother–child dyads, with 5-year-old children, who were recorded during shared reading. The quality of shared reading was assessed with the Scale for Observing Shared Reading while children’s storytelling was assessed with the textless book Frog Goes to Dinner. We found that the quality of mother–child shared reading was related to the coherence of children’s stories and to the factors of home literacy environment. Child’s age when parents started reading to him, the number of all books and children’s books in child’s home together explained 43.1% of the variance in the quality of shared reading. The findings give an insight into the process of the quality of the interactive reading between a child and an adult and emphasize the importance of shared reading for child’s storytelling.     

Multivariate analysis of preoperative and postoperative neutrophil-to-lymphocyte ratio as an indicator of head and neck squamous cell carcinoma outcome

Recent publications have highlighted a greater utility of routine blood tests in patients with various cancers than previously assumed. It appears that the neutrophil-to-lymphocyte ratio (NLR) may be a good predictive biomarker for overall survival (OS) and disease-free survival (DFS). Preoperative and postoperative NLR data for patients with head and neck cancers have yet to be established. The aim of this study was to evaluate the preoperative and postoperative NLR in 182 patients with head and neck squamous cell carcinoma and to determine the association of NLR with OS and DFS. The statistical analysis of OS and DFS and their predictors was performed using Kaplan–Meier survival analysis and multivariate Cox proportional hazards regression analysis, with factors including age, sex, alcohol and tobacco use, tumour location, treatment after surgery, and lymphocyte and neutrophil counts. Longer OS was significantly associated with not consuming alcohol, preoperative neutrophil and lymphocyte counts, preoperative NLR, and the difference between the preoperative and postoperative NLR (P = 0.016). Longer DFS was significantly associated with not consuming alcohol, preoperative neutrophil and lymphocyte counts, postoperative NLR, and the difference between preoperative and postoperative NLR (P = 0.028).     

Beneficial effect of a novel pentadecapeptide BPC 157 on gastric lesions induced by restraint stress,ethanol, indomethacin,and capsaicin neurotoxicity

Very recently, the integrity of capsaicin somatosensory neurons and their protection were suggested to be related to the activity in nociception of a newly discovered 15-amino acid peptide, BPC 157, shown to have strong beneficial effect on intestinal and liver lesions. Therefore, from this viewpoint, we have studied the gastroprotective effect of the pentadecapeptide BPC 157, on gastric lesions produced in rats by 96% ethanol, restraint stress, and indomethacin. The possible involvement of sensory neurons in the salutary actions of BPC 157 (10µg/kg, 10 ng/kg intraperitoneally) was studied with capsaicin, which has differential effects on sensory neurons: a high dose in adult (125 mg/kg subcutaneously, 3 months old) or administration (50 mg/kg subcutaneously) to neonatal animals (age of the 7 days) destroys sensory fibers, whereas a low dose (500µg/kg intraperitoneally) activates neurotransmitter release and protective effects on the mucosa. In the absence of capsaicin, BPC 157 protected gastric mucosa against ethanol, restraint, and indomethacin application. In the presence of neurotoxic doses of capsaicin, the negative influence of capsaicin on restraint, ethanol, or indomethacin lesions consistently affected salutary activity of BPC 157. However, BPC 157 protection was still evident in the capsaicin-treated rats (either treated as adults or as newborns) in all of these assays. Interestingly, after neonatal capsaicin treatment, a complete abolition of BPC gastroprotection was noted if BPC 157 was applied as a single nanogram-regimen, but the mucosal protection was fully reversed when the same dose was used daily. In line with the excitatory dose of capsaicin the beneficial effectiveness of BPC 157 appears to be increased as well. Taken together, these data provide evidence for complex synergistic interaction between the beneficial effectiveness of BPC 157 and peptidergic sensory afferent neuron activity.     

Health-Related Quality of Life,Treatment Efficacy,and Hemodialysis Patient Outcome

The aim of the study was to examine the influence of improved treatment of hemodialysis (HD) patients on their health-related quality of life (HrQoL) and to assess the predictive value of HrQoL dimensions on patient outcome. The prospective cohort study involved 102 HD patients, and their clinical and laboratory parameters and HD adequacy indices were followed from 2001 to 2007. HrQoL was measured using KDQOL-SF Version 1.3 in 2001, 2004, and 2007. During a six-year period, quality of HD and anemia treatment improved and resulted in significant increase of mean Kt/V (1.2–1.56) and hemoglobin levels (86.5–115.6 g/L). All four HrQoL dimensions (i.e., physical, mental health, kidney disease target issues, and patient satisfaction) remained unchanged, but significant improvement in several HrQoL physical health domains and the effects of kidney disease domain was found. Mortality rate decreased from 18.6% to 7.14% per year. Age was associated positively, but kidney disease target issue score negatively, with patient death. Improved HD adequacy and anemia treatment in HD patients were followed with maintenance of all four HrQoL dimensions unchanged over six years. Moreover, an improvement in several physical health domains and the effects of kidney disease domain was found. Age and kidney disease target issue appeared as significant predictors of patients' death.     

Urinary protein patterns in patients with Balkan endemic nephropathy

Purpose

Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls.

Methods

The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN.

Results

In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m² isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m², beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m² 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m² only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent.

Conclusion

Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m². IgG was increasingly found as eGFR decreased.