The oxidative stress response via Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) interlinks inflammation- and metabolism-related pathways in chronic kidney disease. We assessed the association ...between polymorphisms in Nrf2, superoxide dismutase (SOD2), glutathione peroxidase (GPX1), and the risk of end-stage renal disease (ESRD). The modifying effect of these polymorphisms on both oxidative phenotype and ESRD prognosis, both independently and/or in combination with the glutathione S-transferase M1 (
) deletion polymorphism, was further analyzed. Polymorphisms in
(rs6721961),
(rs4880),
(rs1050450), and
were determined by PCR in 256 ESRD patients undergoing hemodialysis and 374 controls. Byproducts of oxidative stress were analyzed spectrophotometically or by ELISA. Time-to-event modeling was performed to evaluate overall survival and cardiovascular survival. The
/
genotype increased ESRD risk (OR = 2.01,
= 0.002), which was even higher in combination with the
genotype (OR = 3.27,
= 0.019). Polymorphism in
also showed an effect on oxidative phenotypes. Overall survival in ESRD patients was dependent on a combination of the
(
/
) and
/
genotypes in addition to a patients' age and
polymorphism. Similarly, the
/
genotype contributed to longer cardiovascular survival. Conclusions: Our results show that
,
, and
polymorphisms are associated with ESRD development and can predict survival.
Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and ...higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous
gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous
gene deletion.
genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with
genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined.
Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups.
Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.
Chronic kidney disease is described as a progressive and irreversible deterioration in kidney function. When there is less than 10% of nephron function pertained, patients face end-stage renal ...disease, where renal replacement therapy is needed. Data show that the most common method used to treat advanced and permanent kidney failure is hemodialysis. . Increased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. The role of genetic polymorphism of antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 in susceptibility towards end-stage renal disease development has become prominent recently. Furthermore, GST gene polymorphism may modulate the degree of oxidative stress byproducts in end-stage renal disease patients and, therefore, influence their overall and cause-specific cardiovascular mortality.
Abstract
Background and Aims
The use of biocompatible glucose solutions is associated with longer preservation of residual renal function and less frequent occurrence of complications in patients on ...peritoneal dialysis. The aim of this study was to examine the influence of conventional and biocompatible glucose solutions to laboratory parameters and clinical outcomes of PD patients during a four-year period at Zvezdara University Medical Center.
Method
This retrospective study included 25 incident patients treated with continuous ambulatory peritoneal dialysis (CAPD) during the follow up period from 2018 to 2022. During 2018/2019 these patients used conventional solutions (Dianeal PD4) containing lactate as a buffer, while due to the change in solution production technology in 2020/2021, all patients were transferred to a biocompatible solution (Physioneal 40) with lactate and bicarbonate as a buffer. Clinical outcomes were compared in relation to the administered solution: pain during infusion (measured by a Visual Analogue Scale—VAS), correction of anaemia and bicarbonate, average annual 24h diuresis and 24h ultrafiltration, occurrence of CAPD peritonitis. The statistical significance of the differences between the two periods was checked using the SPSS.
Results
The average age of 25 patients was 61 ± 14 years, of which 59.1% were male and 40.9% female. The average BMI was 28.5 ± 5.30 kg/m2, and the most common comorbidities were HTA and DM. No statistically significant difference was found for the values of Le, albumin, Hb, PTH, bicarbonate, and K (p ˃ 0.05). During the use of biocompatible solutions, patients had statistically significantly lower Na values (138.84 ± 2.63 vs 137.17 ± 2.41 mmol/l, p = 0.0116, 95% CI 137.15– 138.84) and lower CRP values (15.3 ± 3.3 mg/l vs 7.7 ± 3.2, p = 0.0003, 95% CI 18.60-4.50). Although the dialysis exposure was longer, the rate of peritonitis was lower during the use of biocompatible solutions, but without a statistically significant difference (0.40 episodes per patient-year, vs 0.31 episodes per patient-year, p ˃ 0.05). No statistical significance was found in 24h diuresis value (900 ml vs 750 ml, p = 0.167.95% CI 686.90–1203.31) but the value is expected to be lower due to dialysis duration.
Conclusion
Our study showed that patients treated with the CAPD method while using a biocompatible solution have statistically significantly higher values of 24h ultrafiltration, lower Na and CRP values and less occurrence of pain during infusion, which significantly affects the quality of life. Although this may indicate better preservation of the peritoneal membrane, a prospective and randomized study is needed to clarify these potential differences.
Abstract
Background and Aims
Peritonitis is a common and severe complication in Continuous ambulatory peritoneal dialysis (CAPD). A high peritonitis rate affects PD patients’ technique survival and ...mortality. The aim of this retrospective study is to assess epidemiological aspects, microbiology presentation with antibiotic resistance and clinical outcomes for patients with acute CAPD peritonitis during 5-year period.
Method
The study included all patients treated by CAPD between the 1st of January 2017 and 1st of January 2022 in the Clinical Hospital Center Zvezdara. We included prevalent patients on CAPD, and analyzed demographic, clinical and microbiological data, and patient's outcomes during 5 year period. The data was collected from patient records, medical history and processed in SPSS.
Results
This study included 119 patients treated by PD of which 24 (8.13%) had one or more acute episodes of CAPD peritonitis in the designated period. The mean age of the population was 69±9 year, 54% were male, 20% had diabetes mellitus and 60% arterial hypertension as cause of end stage renal disease. During follow up it was diagnosed 41 episodes of CAPD peritonitis. The main characteristics of patients with peritonitis were turbid liquid (100 %), abdominal pain (73 %) and fever (43 %). Gram staining revealed that 53 % were gram-positive, and 10 % were gram-negative. The most frequent bacterial specimen was Staphylococcus epidermidis (11) followed by Streptococcus viridans (6), sterile culture (9), Staphylococcus aureus (3) and other organisms less than 2 episodes. The peritonitis rate was 1 episode per 27.36 patient-months, or 0.44 episodes per patient year. Resistance to Ampicillin and Penicillin occurred most often. In 2 patients, PD peritonitis was present once each, with multi-resistant bacteria: Klebsiella pneumoniae which was treated with parenteral administration of Tigacycline and Methicillin-resistant Staphylococcus aureus (MRSA) which was treated with parenteral administration of Moxifloxacin and Clindamycin. Out of 24 patients, 2 (8.33%) had 4 episodes of peritonitis, 3 (12.5%) had 3 episodes of peritonitis, 6 (25%) had 2 episodes of peritonitis, and the rest (54.16%) were had only one each. Only one patient had an episode of relapsing peritonitis. During 5-year period, 1 (4%) patient died of acute CAPD peritonitis caused by Proteus mirabilis, 7 (29%) died of other causes, 11 (46%) were transferred to hemodialysis and 5 (21%) are still receiving treatment by CAPD modality. CAPD peritonitis was the reason for technical failure in 20% patients.
Conclusion
PD-associated peritonitis is serious infective complication which could influence the outcome of PD patients, including technique survival. The rate and outcomes of peritonitis in our patients were slightly above of current recommendations.
Abstract
Background and Aims
Kidney disease is a common complication in patients with multiple myeloma and other plasma cell dyscrasias. This disease can be manifested by various kidney disorders, ...which can evolve as either an acute or chronic disorder. Cast nephropathy is the most common cause of severe acute kidney injury (AKI) in patients with multiple myeloma. Among newly diagnosed patients, 20 to 50 % have AKI or cronic kidney disease (CKD) at the time of diagnosis. Treatment of acute renal failure consists of good supportive care and anti-myeloma therapy. Introduction of novel agents has considerably improved outcome in patients with multiple myeloma and renal failure. The aim of this study was to identify the most common risk factors (RF) for mortality in patients with MM and renal failure.
Method
The study included 22 patients ( mean years 67 ± 12 years, 12 men). Who followed two years. We analyzed routine laboratory tests, Bence Jones protein, urinary protein excretion, and creatinine clearance. Plain radiography for the evaluation of skeleton lesions were performed for all patients.
Results
Overall two years mortality of patients with MM was 38.1% with no significant difference regard to patients' age and gender. About 33% of patients required renal replacement therapy and 19% remained on a chronic dialysis treatment program. Renal biopsy was performed in 9.1% of patients (1 - FSGS, 1 - LCCD, light chain deposition disease). Bone marrow transplant (stem cell transplant) was performed in 9.1% of patients. Of the associated comorbidities, 19% had DM, 81% had hypertension, CVD 52.4%. Osteolytic changes at the time of diagnosis were present in 52.4%. In older patients, kappa chains have been identified to a much more extent. Survival is significantly lower in dialysis dependent patients with a two-year survival of 30%. Binary logistic regression revealed that platelet decrease (OR = 0.982< CI 0.961–1.003< p = 0.09) and increase of IgA significantly influenced mortality (OR = 103,867< CI 0.459–23567.201< p = 0.09) can be considered as potential predictors of mortality. Comorbidity DM, HTA, CVD were not the predictors for mortality in patients with MM
Conclusion
Multiple myeloma associated with high mortality rate and kidney disease. High percentage of patients required renal replacement therapy (33%) and 19% remained on a chronic dialysis treatment program. Among the estimated parameters, the risk factors for mortality were significant decrease of platelet (p = 0.09) and increase IgA (p = 0.09). Survival is significantly lower in in dialysis dependent patients with a two-year survival of 30%.
Abstract
Background and Aims
In recent years, obesity has reached epidemic proportions, and it's a great challenge to choose an adequate treatment for obese ESRD patients. The aim of the study was to ...analyze the outcome in patients with peritoneal dialysis with different degrees of nutrition expressed through body mass index at the beginning of treatment.
Method
The prospective clinical study included 53 incidental patients, who started peritoneal dialysis between June 2006 and August 2015. According to BMI on the beginning of treatment, patients were divided into three groups: normal weight: BMI of 18.5 - 24.9 kg/m2, n=17, overweight: BMI of 25 - 29.9 kg/m2, n=25, obese: BMI> 30.0 kg/m2. n=11. Mechanical and infective complications, technique survival and patients survival were analyzed over 48 - months period.
Results
In terms of mechanical complications, there was no difference between the groups- malposition of the catheter (p = 0.769), leakage of dialysate (p = 0.462), hernia (p = 0.381). Exit sitе infection were most prevalent in group 3 - 1 episode/22 patient months vs 1 episode/30 patient months in groups 1 and 2, but without statistical significance (p = 0.272). However, the lowest incidence of peritonitis was in the group 3 - 1 episode/40 patient months vs 1 episode/30 patient months in group 2, and 1 episode/33 patient months in group 1, but even here the difference did not reach statistical significance (p = 0.624). Cardiovascular events – myocardial infarction, stroke and peripheral vascular disease were rare in all groups, with no statistical significance between groups. The incidence of hospitalizations was highest in the obese group – 1 episode/22 patient months vs 1 episode/27 patient months in group 2, and 1 episode/25 patient months in group 1 (p = 0.735). Kaplan Meier's analysis showed the worst, but not significant, survival of the technique in a group of obese patients (group 1 vs. group 2; p = 0.536; group 1 vs. group 3 - p= 0.662; group 2 vs. group 3 - p = 0.357). Also, overall patient survival was not differed between the groups (group 1 vs group 2 - p = 0.387; group 1 vs group 3 - p= 0.885; group 2 vs group 3 - p = 0.375). According to Cox's analysis, only values of total cholesterol at the end of the follow-up period (p = 0.027) and diastolic blood pressure (p = 0.013) were significantly associated with overall survival obese patients.
Conclusion
In the present study the degree of nutrition at the beginning of treatment had no significant effect on the outcome of peritoneal dialysis treatment. Therefore, patients should not be discouraged for peritoneal dialysis on the basis of BMI.
Abstract
Background and Aims
Peritoneal dialysis is an important form of treatment for patients with end stage chronic kidney failure requiring renal replacement therapy but its use may be limitted ...by growing number of elderly and disabled patients. Often, they choose an assisted peritoneal dialysis (assCAPD) as first option, that can be performed by relative or a nurs. The aim of this research was to analyse differences between two groups of patients (CAPD vs. assCAPD) in order to establish if two variants are comparable in regard of patients outcome.
Method
We analysed 61 patient divided into two groups (ass CAPD, N= 16 and CAPD, N= 45) who were dialysed in Zvezdara University hospital for more than 3 months and correlated number of peritonitis, exit site infections and overall mortality rates between two groups during the period of 60 months. Assistance was provided on the volontary basis by family member.
Results
Patients in assCAPD group were unsignificantly older (68+11vs. 60 + 12 years) and had higher comorbidity score. The groups were homogeneous according the presence of diabetes mellitus, CRP and PTH levels. There were no significant difference between the two of groups in the number of peritonitis (p=0,77), exit site infections (p=0,37) and overall survival (p= 0,74, Figure 1.).
Conclusion
Family member provides very good assistance in peritoneal dialysis giving the results that are comparable to that of self-performing CAPD patients. This is therefore very successful treatmen option for a special population of ESRD patients who can not performe CAPD on their own.
Figure:
The mechanisms for vascular calcification and its associated cardiovascular mortality in patients with ESRD are not completely understood. Dialysis patients exhibit profound vitamin K deficiency, ...which may impair carboxylation of the calcification inhibitor matrix gla protein (MGP). Here, we tested whether distinct circulating inactive vitamin K-dependent proteins associate with all-cause or cardiovascular mortality. We observed higher levels of both desphospho-uncarboxylated MGP (dp-ucMGP) and desphospho-carboxylated MGP (dp-cMGP) among 188 hemodialysis patients compared with 98 age-matched subjects with normal renal function. Levels of dp-ucMGP correlated with those of protein induced by vitamin K absence II (PIVKA-II; r = 0.62, P < 0.0001). We found increased PIVKA-II levels in 121 (64%) dialysis patients, indicating pronounced vitamin K deficiency. Kaplan-Meier analysis showed that patients with low levels of dp-cMGP had an increased risk for all-cause and cardiovascular mortality. Multivariable Cox regression confirmed that low levels of dp-cMGP increase mortality risk (all-cause: HR, 2.2; 95% CI, 1.1 to 4.3; cardiovascular: HR, 2.7; 95% CI, 1.2 to 6.2). Furthermore, patients with higher vascular calcification scores showed lower levels of dp-cMGP. In 17 hemodialysis patients, daily supplementation with vitamin K2 for 6 weeks reduced dp-ucMGP levels by 27% (P = 0.003) but did not affect dp-cMGP levels. In conclusion, the majority of dialysis patients exhibit pronounced vitamin K deficiency. Lower levels of circulating dp-cMGP may serve as a predictor of mortality in dialysis patients. Whether vitamin K supplementation improves outcomes requires further study.
Increased oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione S-transferases (GST) are involved in the detoxification of xenobiotics and protection of oxidative damage. We ...hypothesized that genetic polymorphism in antioxidant enzymes GSTA1, GSTM1, GSTP1 and GSTT1 is more frequent in ESRD and modulates the degree of oxidative stress in these patients.
GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 ESRD patients and 199 age- and gender-matched controls. Markers of protein and lipid oxidative damage thiol groups, carbonyl groups, advanced oxidative protein products, nitrotyrosine, malondialdehyde (MDA) and MDA adducts, together with total oxidant status and pro-oxidant-antioxidant balance were determined.
Individual GST polymorphisms influence vulnerability to both protein and lipid oxidation, with GSTM1-null gene variant having the most pronounced effect. Furthermore, a strong combined effect of null/low-activity GSTM1, GSTT1, GSTA1 and GSTP1 genotypes in terms of susceptibility towards oxidative and carbonyl stress was found in ESRD patients. When patients were stratified according to GSTM1 and GSTT1, the highest oxidant damage was noted in those with the GSTM1-null/GSTT1-null genotype. The observed effect was even stronger in patients with the third low-activity GSTP1 or GSTA1 genotype. Finally, the level of oxidative and carbonyl stress was most pronounced in the subgroup of patients with all four null or low-activity GSTM1, GSTT1, GSTP1 and GSTA1 genotypes.
According to the GST genotype, ESRD patients may be stratified in terms of the level of oxidative and carbonyl stress that might influence cardiovascular prognosis, but could also improve efforts towards individualization of antioxidant treatment.
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