Cardiovascular risk assessment and coronary artery calcification burden in asymptomatic patients in the initial years of hemodialysis.

The specific tool for cardiovascular risk assessment in hemodialysis population has not yet been proposed, despite high prevalence of cardiovascular morbidity, and mortality in clinically asymptomatic patients. Coronary artery calcium score (CACS), as a reliable predictor of future cardiovascular events, might be a valuable approach. We sought to evaluate coronary artery calcification burden and its association with clinical and laboratory parameters in asymptomatic patients who recently initiated hemodialysis. The cross-sectional study included 60 asymptomatic patients receiving chronic hemodialysis for no longer than 48 months. CACS was assessed by cardiac computed tomography. Intima-media thickness (IMT) of both common carotid and femoral arteries were measured using ultrasonography. The mean total CACS was 160.50 (443). Patients' age correlated significantly with CACS (σ = 0.367; P = 0.004), carotid (σ = 0.375; P = 0.004) and femoral IMT (σ = 0.323; P = 0.013). Patients with CACS = 0 were significantly younger than patients with CACS >400: 52.4 ± 7.91 vs. 63.88 ± 8.37 years old, respectively (P = 0.034). In patients receiving dialysis for longer than 24 months CACS, femoral and carotid IMT were higher than in those dialyzed for less than 24 months; however, none has reached significance. There was a significant positive correlation between CACS and right (σ = 0.312; P = 0.018) and left (σ = 0.521; P < 0.001) femoral IMT, while not with carotid. CACS showed significant negative correlation with the serum iron (σ = -0.351; P = 0.007). Calcification burden varies significantly in asymptomatic patients in early years of dialysis. It correlates with patients' age and tends to increase with dialysis vintage. Femoral IMT might be useful for cardiovascular risk stratification in asymptomatic patients who recently initiated hemodialysis.

Total serum and intraerythrocyte magnesium concentrations in hemodialysis patients using different dialysate solutions.

Beside routinely used 0.5 mmol/L dialysate-magnesium, higher dialysate-magnesium (1.0 mmol/L) was recently introduced. The aim of this study was to evaluate the impact of different dialysate-magnesium on serum and intraerythrocyte levels of magnesium (Mg) before and after dialysis. The study included 43 patients receiving chronic hemodialysis, divided into two groups based on dialysate-magnesium (0.5 or 1.0 mmol/L) used prior to study initiation and during 12 months of follow-up. Blood samples were taken at the mid-week dialysis; total serum Mg was measured colorimetrically and intraerythrocyte Mg by atomic absorption spectrophotometry. Hypermagnesiemia-associated complications were observed for 12 months. Total serum Mg was 1.14 ± 0.19 mmol/L before and 0.95 ± 0.16 mmol/L after dialysis in patients using lower dialysate-Mg (p < 0.001), whereas it was 1.47 ± 0.25 mmol/L before and 1.49 ± 0.18 mmol/L after dialysis in patients using higher dialysate-Mg (p = 0.926). Intraerythrocyte Mg was 1.98 ± 0.34 mmol/L before and 1.97 ± 0.28 mmol/L after dialysis in the lower dialysate-Mg group (p = 0.939), while it was 2.09 ± 0.37 mmol/L before and 2.19 ± 0.48 mmol/L after dialysis in the higher dialysate group (p = 0.067). After 12 months total serum Mg decreased in both the groups, remaining lower in 0.5 mmol/L dialysate-Mg group. No hypermagnesiemia-related symptoms occur during 12 months of follow-up in both the groups. In patients using lower dialysate-Mg total serum Mg remains within the reference range and shows postdialytic decline, while in higher dialysate-Mg group it exceeded reference range before and after dialysis without significant intradialytic change. The intraerythrocyte values remain within reference range with both dialysates used. No clinical signs and symptoms of hypermagnesiemia occur during longer administration of higher dialysate-magnesium despite high total serum Mg level.

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.

Association of GSTO1 and GSTO2 Polymorphism with Risk of End-Stage Renal Disease Development and Patient Survival.

BACKGROUND: Oxidative stress in patients with end-stage renal disease (ESRD) is associated with long-term cardiovascular complications. The cytosolic family of glutathione S-transferases (GSTs) is involved in the detoxication of various toxic compounds and antioxidant protection. GST omega class members, GSTO1 and GSTO2 possess, unlike other GSTs, dehydroascorbate reductase and deglutathionylation activities. The aim of this study was to clarify the role of genetic polymorphisms of GSTO1 (rs4925) and GSTO2 (rs156697) as risk determinants for ESRD development, as well as in the survival of these patients. METHODS: A total of 199 patients and 199 healthy subjects were included in the study and genotyped for both GSTO1 and GSTO2 polymorphism. Protein thiol and carbonyl groups as markers of protein oxidative damage were determined spectrophotometrically. Cox proportional hazard model and Kaplan-Meier analysis were performed to investigate the role of GSTO1 and GSTO2 genetic polymorphism on mortality of ESRD patients during the follow-up period (36 month). RESULTS: Individuals carrying the variant GSTO2 GG genotype were at 2.45-fold higher risk of ESRD development compared to the wild type GSTO2 AA genotype (OR=2.45; 95%CI=1.18-5.07; p=0.016). The results of GSTO1/GSTO2 haplotype analysis showed that the haplotype combination of GSTO1 (*A)/GSTO2 (*A) (GSTO1 variant/GSTO2 wild type allele) was protective for ESRD (OR=0.23 95%CI=0.12-0.44, p=0.001). Patients carrying at least one GSTO1 reference allele have shorter mean overall (Log rank=2.844, p =0.241) and cardiovascular survival probability (Log rank=4.211, p=0.122). CONCLUSIONS: GSTO polymorphisms have been shown to act as significant markers in assessing the risk of ESRD development and patients' survival.

Fondaparinux monitoring in a patient with heparin-induced thrombocytopenia on hemodialysis.

Introduction: Heparin-induced thrombocytopenia associated to hemodialysis is rare. In case when citrate dialysis and/or non-heparin anticoagulants are not available, only possible medication to use for anticoagulation during hemodialysis is fondaparinux. However, laboratory monitoring of fondaparinux based on anti-Xa activity in dialysis patients has not been sufficiently documented yet. Case Outline: We created a local anti-factor Xa assay for measuring fondaparinux plasma concentration and efficacy in a patient with heparin-induced thrombocytopenia during hemodialysis. Fondaparinux given subcutaneously increases risk of adverse events due to its extended release and prolonged maintenance of toxic levels. When used intravenously fondaparinux remains safe, with reached steady-state level within dialysis and low risk of toxicity afterwards. Conclusion: Fondaparinux may be used as an alternative anticoagulant medication during hemodialysis in patients who develop heparin-induced thrombocytopenia. Adequate dose must be adjusted to patients' dry weight (0.03 mg/kg intravenously) and fondaparinux anti-coagulation monitoring must be provided.

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.

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.

"Watermelon stomach" in patients on chronic hemodialysis.

"Watermelon stomach" is a common name for gastric antral vascular ectasia (GAVE syndrome). This endoscopic finding is characterized by the appearance of parallel longitudinal red columns along mucosal folds, along with capillars dilatation and hemorrhagy. Finding reliable method for its recognition is of paramount importance. Patient B.D., a 54-year-old woman, developed renal failure, which led to hemodialysis treatment, on the basis of pyelonephritis chronica. As a consequence of the gastrointestinal bleeding, the patient had black stools and developed severe anemia. The endoscopic finding showed the existence of visible columns of vessels transversing the antrum in longitudinal folds and converging in the pylorus, with clear red spots and surrounding hyperemy covered by drops of fresh blood. The diagnosis of "watermelon stomach" was confirmed after the pathohistological examination of the tissue taken at the biopsy, followed by total gastrectomy. Postoperative status was normal, without gastrointestinal hemorrhagia, and she went on with hemodialysis. Before the surgery she received 105 blood transfusions, and after surgical treatment she has received only 18 so far. At the moment she is in good health condition, and on hemodialysis. The reason we have reported this case of "watermelon stomach" syndrome in patient with chronic renal failure is to indicate that this rare anomaly of gastric blood vessels can lead to gastrointestinal blood loss in these patients. Since it is often the reason for many wrong diagnoses, it should be also taken into consideration in cases like these.