Galectin 3 (LGALS3) Gene Polymorphisms Are Associated with Biochemical Parameters and Primary Disease in Patients with End-Stage Renal Disease in Serbian Population.

Galectin 3 plays a significant role in the development of chronic renal failure, particularly end-stage renal disease (ESRD). The aim of our study was to investigate the association between Gal-3 and biochemical parameters and primary disease in ESRD patients, by exploring the polymorphisms LGALS3 rs4644, rs4652, and rs11125. A total of 108 ESRD patients and 38 healthy controls were enrolled in the study. Genotyping of LGALS3 gene rs4644, rs4652, and rs11125 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). By multivariate logistic regression analysis, we found that LGALS3 rs4644 CC and rs4652 AA genotypes were significantly associated with a higher risk for lower hemoglobin, higher level of parathyroid hormone, and also occurrence of diabetes mellitus and arterial hypertension. The CAA haplotype was significantly more common in patients with diabetes, low hemoglobin level, and normal PTH level. It has been observed as well that the ACT haplotype was more common in patients with low glomerular filtration, low PTH, and normal hemoglobin level. We found that the LGALS3 rs4644 and rs4652 gene polymorphism may be involved in the pathogenesis and appearance of complications in ESRD patients and thus could be considered a new genetic risk factor in this population.

Multisystem inflammatory syndrome in a young adult successfully treated with plasmapheresis, immunoglobulins, and corticosteroids: a case report.

A novel condition named multisystem inflammatory syndrome has raised the alarm worldwide and is leading to severe illness and long-term effects in the post-COVID era. This condition includes infection with fever, abdominal symptoms, acute cardiac injury, and shock. It has similarities with severe forms of Kawasaki disease (KD). In this study, we present a case of a 20-year-old male patient with multisystem inflammatory syndrome associated with COVID-19 infection who was successfully treated with plasmapheresis, immunoglobulins, and steroids for 4 h/day without heparinization or ultrafiltration. Plasmapheresis represents a therapeutic option for KD in patients with all other therapeutic strategies that have failed. However, there is no evidence from controlled clinical trials confirming this option. In our case, plasmapheresis was beneficial in stabilizing and improving the patient's clinical condition. Given the pathophysiological and therapeutic similarities between KD and multisystem inflammatory syndrome, it could be considered a therapeutic option.

Platinum, palladium, gold and ruthenium complexes as anticancer agents: Current clinical uses, cytotoxicity studies and future perspectives.

Metallodrugs offer potential for unique mechanism of drug action based on the choice of the metal, its oxidation state, the types and number of coordinated ligands and the coordination geometry. This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry as many new approaches to the design of innovative metal-based anticancer drugs are emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have different modes of action and on prodrug and targeting strategies in an effort to diminish the side-effects of cisplatin chemotherapy. Examples of metal compounds and chelating agents currently in clinical use, clinical trials or preclinical development are highlighted.

Association between Hemodialysis Patient Outcomes and Compliance with KDOQI and KDIGO Targets for Mineral and Bone Metabolism.

BACKGROUND: Increased mortality of hemodialysis (HD) patients is associated with chronic kidney disease-mineral and bone disorders (CKD-MBD), and therefore, their correction may improve patient survival. Differences in targets recommended by KDOQI and KDIGO CKD-MBD guidelines directed us to compare the relative numbers of patients achieving these targets and to examine possible associations between compliance with the targets and patient outcome. METHODS: A total of 1,744 patients (61.2% males, aged 58.7 ± 12.5 years) dialyzed in 20 HD centers in Serbia were monitored for 3 years. The number of participants achieving KDOQI/KDIGO guideline targets for serum phosphorus, calcium, and iPTH was determined. The Cox proportional hazards model was used to select variables significantly associated with risk of time to death. RESULTS: A majority of patients were dialyzed thrice weekly for 4 h; 86.3% of them used phosphate binders and 49.3% vitamin D3. Proportions of patients achieving KDOQI and KDIGO targets were 49.5 and 44.4% for phosphorus, 53.2 and 76.7% for calcium, 21 and 42.8% for iPTH. Multivariate Cox analysis selected serum phosphorus level outside the KDIGO target, as well as serum iPTH levels outside KDOQI and KDIGO targets as significant mortality predictors. Areas under the receiver operating characteristic curves showed that achievement of both guideline targets for iPTH had similar survival predictive values. CONCLUSION: Serum phosphorus levels outside KDIGO targets and iPTH levels outside both KDOQI and KDIGO targets were associated with a significantly higher risk of death. These findings may be useful in the management of CKD-MBD and for establishing local guidelines.

Achievement of guideline targets in elderly patients on hemodialysis: a multicenter study.

OBJECTIVES: Advanced age is associated with shorter survival on dialysis. The aim of the present study was to compare the adherence with KDOQI guideline targets and the association between mortality and satisfying the guidelines targets between hemodialysis patients aged 65 years and over and those younger than 65 years. METHODS: Data were collected using a questionnaire sent to all 46 HD centers in Serbia with totally 3868 HD patients. The 24 centers responded and sent the data on all patients aged 18 years or older that were on regular HD for more than 3 months (2153 patients, 1320 males, aged 18-90 years). Data are presented in two groups: a group of patients younger than 65 years (1438, 66.8 %) and a group of patients aged 65 years and over (715, 33.2 %). The percentage of patients whose values failed to meet the targets recommended by KDOQI Clinical Practice Guidelines was calculated for dialysis dose (spKt/V), hemoglobin, serum phosphorus, serum calcium and plasma iPTH (150-300 pg/mL). Patients were followed from enrollment until their death, kidney transplantation, departure from the center or the end of the study. RESULTS: Elderly patients were more likely to have hypertension, significantly lower systolic and diastolic blood pressure and smaller dialysis vintage than younger patients. They were less frequently treated with high-flux membranes and hemodiafiltration and they had significantly lower number of dialysis hours per week and significantly lower interdialytic weight gain. They used ESA and phosphate binders less frequently than younger patients (p < 0.001 and p = 0.002). Older patients had similar Kt/V as younger ones but they had significantly more frequent Hb level outside the target range than younger patients. During the year follow-up period, by using a Cox proportional hazards model it has been confirmed that age, dialysis vintage, weekly dialysis time and target values for Kt/V were significant independent predictors of time to death for younger patients and gender, dialysis vintage and iPTH were independent predictor of time to death for older patients. CONCLUSION: Despite less favorable dialysis prescription, older patients had similar Kt/V and less frequent deviations from the target values proposed by KDOQI for serum phosphorus and iPTH but more frequent deviation for Hb value as compared with younger patients. Risk factors for mortality differ between older and younger patients; out of five KDOQI targets, only Kt/V proved to be a significant risk factor for mortality for younger and iPTH for older patients.

Compliance with guidelines and predictors of mortality in hemodialysis. Learning from Serbia patients.

OBJECTIVES: The aims of the study were to determine the percentage of patients on regular hemodialysis (HD) in Serbia failing to meet KDOQI guidelines targets and find out factors associated with the risk of time to death and the association between guidelines adherence and patient outcome. METHODS: A cohort of 2153 patients on regular HD in 24 centers (55.7% of overall HD population) in Serbia were followed from January 2010 to December 2012. The percentage of patients failing to meet KDOQI guidelines targets of dialysis dose (Kt/V>1.2), hemoglobin (>110g/L), serum phosphorus (1.1-1.8mmol/L), calcium (2.1-2.4mmol/L) and iPTH (150-300pg/mL) was determined. Cox proportional hazards analysis was used to select variables significantly associated with the risk of time to death. RESULTS: The patients were on regular HD for 5.3±5.3 years, dialyzed 11.8±1.9h/week. Kt/V<1.2 had 42.4% of patients, hemoglobin <110g/L had 66.1%, s-phosphorus <1.1mmol/L had 21.7% and >1.8mmol/L 28.6%, s-calcium <2.1mmol/L had 11.7% and >2.4mmol/L 25.3%, iPTH <150pg/mL had 40% and >300pg/mL 39.7% of patients. Using Cox model (adjustment for patient age, gender, duration of HD treatment) age, duration of HD treatment, hemoglobin, iPTH and diabetic nephropathy were selected as significant independent predictors of time to death. When targets of five examined parameters were included in Cox model, target for KtV, hemoglobin and iPTH were found to be significant independent predictors of time to death. CONCLUSION: Substantial proportion of patients examined failed to meet KDOQI guidelines targets. The relative risk of time to death was associated with being outside the targets for Kt/V, hemoglobin and iPTH.

Epidemiology of end-stage renal disease and hemodialysis treatment in Serbia at the turn of the millennium.

The study presents the epidemiological features of patients treated with renal replacement therapy (RRT) in Serbia from 1997 to 2009 and compares the results of hemodialysis treatment in 1999 and 2009. Epidemiological data were obtained from the National Registry of RRT patients and data on hemodialysis treatment from special surveys conducted in 1999 and 2009. Within the period 1997-2009 the incidence of patients on RRT increased from 108 to 179 per million population (pmp), prevalence rose from 435 to 699 pmp, while mortality rate fell from 20.7% to 16.7%. The frequency of patients with glomerulonephritis decreased, while that of patients with diabetes and hypertensive nephropathy increased. In late 2009 there were 5208 patients receiving RRT in Serbia. Within the examined period new hemodialysis and reverse osmosis equipment were purchased, high-flux dialyzers with synthetic membranes were increasingly used and the number of patients receiving hemodiafiltration increased to 17.6%. Kt/V greater than 1.2 was recorded in 16% of the patients in 1999 but 52% in 2009. Options for correction of anemia and mineral disorders have also improved. The percentage of patients with HbsAg (13.8% vs. 4.8%) as well as anti-hepatitis C virus antibodies positive patients (23.2% vs. 12.7%) was significantly lower in 2009 than in 1999. Both the incidence and prevalence of RRT patients in Serbia are rising continuously, while the mortality rate is falling. More favorable conditions for dialysis treatment have brought about significant improvement in the results over the last 10 years.

[Problem of creation of arteriovenous fistulae for hemodialysis in older patients].

INTRODUCTION: A significant problem in elderly on hemodialysis is vascular access creation. The aim of the study was to determine the factors of functionality of arteriovenous fistulas in elderly people. MATERIAL AND METHODS: Target groups in the four-year study were patients over 65 years of life. The authors analyzed the demographic structure, the etiology of kidney weakness, the type of anastomosis, arteriovenous fistula location, use of catheters from hemodialysis, blood pressure and size of the lumen of blood vessels used for anastomosis. Routine hematological and biochemical parameters were determined in all subjects. The study included 120 patients, 42 (35%) women and 78 (65%) men. RESULTS: Functional arteriovenous fistulae were found in 62 (51.70%) patients, aged 72.5 +/- 4.23 years and nonfunctional ones in 58 (48.3%) respondents aged 72 +/- 5.09 years. A significant difference between the studied groups was reached in relation to the type of anastomosis (p = 0.005) and sites of the located fistulas (p = 0.03). Hypertensive nephropathy occurs statistically significantly more frequently in patients with functional fistula (p = 0.03). Sedimentation (p = 0.01), hemoglobin (p = 0.04), platelets (p = 0.003), total cholesterol (p = 0.04) and low density lipoproteins (p = 0.03) had statistically higher values in patients with nonfunctional fistulae. CONCLUSION: Atherosclerosis and increased coagulation in the old people on hemodialysis represent an important cause of complications of arteriovenous fistulae.

Central venous catheters in hemodialysis: to accept recommendations or to stick to own experience.

BACKGROUND/AIM: Hemodialysis catheter, as an integral part of hemodialysis, is a catheter placed into the jugular, subclav ian and femoral vein. The most common catheter-related complications are infections and thrombosis. The aim of the study was to analyze the prevalence of complications associated with differently inserted central-vein catheters for hemodialysis. METHODS: The study was organized as a prospective examination during the period from December 2003 to No vember 2006, and included all patients who needed an active depuration by hemodialysis, hospitalized at the Clinical Center Kragujevac. The subject of the study were 464 central-vein catheters inserted during the mentioned period and there were recorded all complications related to the placement and usage of catheters. RESULTS: The largest percent of inserted catheters was into the femoral vein--403 (86.8%), significantly less into the jugular vein--42 (9.2%), while into the subclavian vein there were placed only 19 catheters (4%). The average of femoral catheter functioning was 17 catheter days, in jugular catheters it was 17.3 days while the subclavian catheters had an average rate of functioning of 25.9 catheter days; there was found a statistically significant difference re garding the duration of functioning (p = 0.03). By microbe colonization of smear culture of the skin at the catheter in sertion site, in clinically present suspicion of catheter infection, there was obtained a positive finding in 5.5% of catheters placed into the femoral vein and 7.1% of catheters instilled into the jugular vein, of which Staphylococcus aureus was the most important bacterial type, without statistically significant difference (p = 0.51). Haemoculture, done when there was a suspicion of bacteriemia, was positive in 3.7% of the patients with femoral and 4.8% with jugular catheters; Staphylococcus aureus was the most common bacteria type, but there was no statistically significant difference (p = 0.65). Colonizing the smears of the cut catheter tops, there was found a positive finding in 8.9% of femoral and 4.7% of jugular catheters in which the mentioned type of staphylococcal bacteria was prevalent, without statistically significant difference (p = 0.82). In 77% of femoral, 71.4% of jugular and 68.4% of subclavian catheters, there were no complications associated with insertion and manipulation of catheters for hemodialysis and the difference was at the limits of statistical significance (p = 0.06). CONCLUSION: Unconvincing rate of infections and a smaller percent of serious complications associated with the placement and use of central vein catheters instilled into the femoral vein, indicate that personal experience is sufficient recommendation to convince us that femoral vein does not represent a region with an increased risk for insertion of hemodialysis catheters.

[The influence of Helicobacter pylori infection on the occurance of gastroesophageal reflux in patients with renal insufficiency].

INTRODUCTION/AIM: Gastric acid is a key factor in the pathophysiology of gastroesophageal reflux disease. A plausible mechanism by which the Helicobacter pylori infection might protect against reflux disease is by its propensity to produce atrophic gastritis. The aim of the study was to establish the influence of Helicobacter pylori infection on the occurrence of gastroesophageal reflux in patients with different stages of renal insufficiency. METHODS: The examination was organized as a prospective, clinical study and involved 68 patients--33 patients with preterminal stage of renal failure and 35 patients with terminal renal insufficiency. Due to dyspeptic difficulties, in all the patients there was preformed upper esophagogastroscopy and Helicobacter pylori infection was found by ureasa test. RESULTS: The patients with preterminal renal insufficiency were significantly younger than patients with terminal renal failure (53.4 +/- 11.1 vs. 65.4 +/- 12.3 years; p = 0.014). There was found a statistically significant difference between the groups in Helicobacter pylori infection (p = 0.03), hiatal hernia (p = 0.008), gastroesophageal reflux disease (p = 0.007), and duodenal ulcer (p = 0.002). Using the multiple non-parametric correlative analysis there was confirmed a negative correlation between Helicobacter pylori infection and gastro-esophageal reflux disease (Kendal tauB = -0.523; p = 0.003) and hiatal hernia (Kendal tauB = 0.403; p = 0.021), while there was found a positive correlation between gastro-esophageal reflux disease and hiatal hernia (Kendal tauB = 0.350; p = 0.044). CONCLUSION: Helicobacter pylori infection is a significant protective parameter of the incidence of gastro-esophageal reflux disease in patients with both pre-terminal and terminal renal insufficiency.

Parametres of clinical and biohumoral status of pruritus in patients on chronic haemodialysis.

Pruritus is one of the commonest symptoms of dermatologic appearances in uraemic syndrome and it occurs in 90% of patients on dialysis with different etiology and pathophysiology. The aim of the study was to estimate the frequency of uraemic pruritus and the comparison with clinical and biochemical parameters in 124 patients treated by chronic haemodialysis at Department of Haemodialysis, Clinical Centre in Kragujevac. The routine laboratory analyses were carried out in the examined patients and the concentration of parathyroid hormone was determined. The study was based on data from history of disease and questionnaire taken out in all patients. Of 124 patients 46.8% had symptoms of uraemic pruritus. Concentration of urea, albumin concentration, iron, parameters UIBC, as well as hyperglycemia and time on dialysis are the significant are significantly correlated with uraemic pruritus. 27.6% of the examined patients had itching of all the body. Between the patients with localized itching and patients with generalized itching, there are statistically significant differences in the following parameters: erythrocyte count, hemoglobin concentration, hematocrit and TIBC, as well as glycemia concentration.

[Chronic inflammation, oxidative stress and effects of erythropoetin in end-stage renal disease patients].

INTRODUCTION: A few small-scale studies have shown that high levels of various parameters of inflammation were associated with a less efficient response to erythropoetin. The responsiveness to EPO in haemodialysis (HD) patients with relative risk of cardiovascular disease (CVD) remains undetermined. In a retrospective study of HD patients, we compared causes of CV morbidity and mortality in relation to various weekly EPO doses needed for stable hemoglobin (Hb) levels, according to the definition currently suggested by international guidelines. MATERIAL AND METHODS: On the basis of distribution of the weekly EPO doses (lower or higher than the minimally recommended), eighteen HD patients, aged 55.8+/-14.8 years, were divided into two groups with higher (A) and lower (B) EPO doses. We correlated EPO doses with positive (C reactive protein-CRP, fibrinogen, feritin) and negative (albumin, LDL, TIBC) acute phase reactans, BMI, the quality (Kt/V) and duration of HD. RESULTS: We also found a significantly positive corelation between CRP levels on the start of EPO therapy and weekly EPO dose in the univariate linear regression analysis (p-0.290). Higher EPO doses were associated with a lower levels of Kt/V, BMI, residual diuresis and higher levels of CRP, LDL, feritin, age and duration of HD. CRP levels were decreasing in the group with higher EPO doses. This important result can be explained the know EPO effect of endothelial cells apoptosis and inhibiting inflammation induced by HD. CONCLUSION: Chronic inflammation is a common cause of CVD, hyporesponsiveness to EPO and endothelial dysfuncton in HD patients. Our results suggest a new protective function of EPO.