Tomasz Hryszko

Risk Factors of Nontunneled Noncuffed Hemodialysis Catheter Malfunction

Background: The use of noncuffed nontunneled central venous catheters is a widely accepted method of gaining temporary vascular access for hemodialysis. Malfunction and bacteremia are the main factors limiting catheter survival. Methods: We followed up prospectively 73 hemodialysis catheters (HC) (40 internal jugular, 33 femoral) in order to establish factors influencing HC malfunction. HC malfunction was defined as a catheter that was unable to attain and maintain blood flows of at least 150 ml/min. 73 HC were used for a total 1,100 days. Results: HC malfunction occurred in 23 cases (31.51%) during the study period, giving an overall rate of 21 episodes per 1,000 catheter days at risk. An analysis revealed a higher risk of HC malfunction with the catheterization of the femoral vein compared to the internal jugular vein (hazard ratio (HR) 6.3; 95% confidence interval (CI) 5.3–7.3). After correction for confounding factors in multivariate Cox analysis, the site of the catheterization remained a statistically significant predictor of HC malfunction (HR 5.03, 95% CI 3.83–6.23). After the first week malfunction rate was 42 and 8% for femoral and internal jugular site, respectively (relative risk (RR) for malfunction 5.3 (95% CI, 2.5–8). After the second and third week, the incidence of malfunction was 51 and 14% for femoral and internal jugular vein, respectively (RR 3.6, 95% CI 2.2–5.1). Conclusions: Catheterization of the internal jugular vein is associated with longer catheter survival when compared to the femoral vein. Hemodialysis catheters should be placed, if possible, in internal jugular vein to prevent their premature malfunction.

Patients on Peritoneal Dialysis But Not on Hemodialysis Have Elevated Concentration and Activity of Thrombin-Activatable Fibrinolysis Inhibitor

Cardiovascular disease (CVD) is a leading cause of death in patients on dialysis. Increased concentration of fibrinogen, dyslipidemia and impaired fibrinolysis are regarded as important risk factors for CVD. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently discovered inhibitor of the fibrinolytic system. The aim of this study was to investigate whether peritoneal dialysis (PD) and hemodialysis (HD) patients differ with regard to TAFI concentration and/or its activity. We also measured albumin, cholesterol, triglycerides and fibrinogen. The study was performed on 35 chronically dialyzed patients (14 on PD and 21 on HD) and 18 healthy volunteers. TAFI antigen and its activity were measured with commercially available kits. Albumin, cholesterol, triglycerides and fibrinogen were measured using standard laboratory methods. Only PD patients had significantly elevated level of TAFI antigen and its activity compared to control subjects. Differences in TAFI concentration and its activity between PD and HD were at the level of statistical significance (P=.09 and P=.07, respectively). PD patients had significantly higher concentration of cholesterol and triglycerides than HD group. Fibrinogen was elevated significantly in PD patients compared to HD and controls. There was no difference in albumin concentration between PD and HD. Significant positive correlations were found between fibrinogen or triglycerides and TAFI activity only in PD patients. We conclude that the above phenomenon may predispose PD patients to suppression of fibrinolysis.

Low Molecular Weight Iron Dextran Increases Fibroblast Growth Factor-23 Concentration, Together With Parathyroid Hormone Decrease in Hemodialyzed Patients

Fibroblast growth factor (FGF)‐23 inhibits PTH production. Elevated FGF‐23 and parathyroid hormone (PTH) levels are characteristic of hemodialyzed patients. Iron polymaltose was shown to increase FGF‐23 concentration. The effect of intravenous low molecular weight iron dextran (LMID) on these hormones and bone metabolism has not been studied in hemodialysis (HD). Twelve HD patients were prospectively followed up for 3 weeks after a single infusion of LMID. Calcium, phosphate, FGF‐23, PTH, degradation products of C‐terminal telopeptides of type I collagen (CTX) and procollagen I N‐terminal propeptide (PINP) were measured prior to, and at week 1 and week 3 after the LMID administration. FGF‐23 increased significantly from 453.4 (68.6–3971.5) pg/mL at baseline to 971.8 (779.5–3361.4) pg/mL (P = 0.001) at week 1 and started to decrease toward the initial value at week 3. The changes were accompanied by a significant decline in PTH from 367.6 (21.4–1487.4) pg/mL at baseline to 315.7 (16.4–1339.8) pg/mL (P = 0.018) at week 1 and subsequently began to increase toward the initial values. Phosphate, calcium, CTX and PINP did not change over the study course. LMID causes an increase in FGF‐23 concentration together with a decrease in PTH. Our study highlights a pathophysiological element, which may connect suppression of parathyroid glands with intravenous iron supplementation.

Effects of Long-Term Treatment with Simvastatin on Some Hemostatic Parameters in Continuous Ambulatory Peritoneal Dialysis Patients

Background/Aim: Disturbances in serum lipids, hemostasis and platelet functions are frequent features in uremia and may contribute to the progression of atherosclerosis and its thrombotic complications. Recently, attention has been paid to beneficial effects of statins on serum lipids and hemostasis in uremic patients. Peritoneally dialyzed (continuous ambulatory peritoneal dialysis; CAPD) subjects are particularly prone to dyslipidemia and have a high risk of cardiovascular death. The purpose of this work was to assess platelet functions, some hemostatic parameters and serum lipids in 8 hyperlipidemic CAPD patients treated with simvastatin (Zocor, MSD) for 6 months. Methods: Platelet aggregation in whole blood and in platelet-rich plasma (PRP) induced by collagen (2 µg/ml for whole blood and PRP), arachidonic acid (0.75 mM for whole blood and PRP), ADP (10 µM for whole blood and 5 µM for PRP) and ristocetin (0.75 mg/ml for whole blood and 1.5 mg/ml for PRP) was studied before and after 1, 3 and 6 months of simvastatin (dose: 10 mg at bedtime) treatment. Results: Whole-blood platelet aggregation induced by collagen decreased significantly after 3 and 6 months of the therapy, whereas in PRP, platelet aggregation induced by collagen and ADP decreased significantly after 6 months. Ristocetin-induced platelet aggregation in PRP decreased significantly after 3 and 6 months of simvastatin therapy. P-selectin remained unaltered by 6 months of simvastatin therapy. The fibrinolytic activity index was significantly higher after 3 months of the therapy when compared to the baseline values. Thrombomodulin, a marker of endothelial cell injury, was significantly lower after 3 and 6 months of the therapy. Prothrombin fragments 1 + 2 did not change significantly during 6 months of simvastatin administration. Cholesterol and LDL fell significantly as early as after 1 month and remained lowered during further months of the therapy. Conclusion: Simvastatin is an effective hypolipemic agent and favorably affects platelet aggregation, endothelial function and fibrinolysis in CAPD patients.

Correlation between carotid intima-media thickness and hematocrit and hemoglobin values in renal transplant recipients

Background: Cardiovascular diseases are the main causes of morbidity and mortality in kidney transplant recipients. Blood viscosity plays an important role in the development of arteriosclerosis in the general population. Since hematocrit (Ht) and hemoglobin (Hb) values are determinants of blood viscosity, we decided to perform a study to check the possible relevance between these hemorheological factors and carotid intima–media thickness (IMT) in renal transplant recipients. 
Patients and methods: The study was performed on 33 clinically stable renal transplant recipients and 19 healthy persons. All subjects underwent ultrasonographic measurements of IMT. Analyzed clinical parameters included: age, sex, body mass index (BMI), mean arterial blood pressure (MAP), pulse pressure (PP) time from renal transplantation, and time on dialysis. The following biochemical parameters were assessed: Hb, Ht, fibrinogen (Fbg), and homocysteine (tHcy) concentrations (estimated by enzyme immunoassay). 
Results: The two analyzed groups did not differ in respect to age and BMI. Mean concentrations of Hb and Ht values were lower in the patients group. Mean carotid IMT, Fbg, tHcy, MAP, and PP were significantly higher in the renal transplant recipients group when compared to the control group. IMT was positively correlated with age (r=0.55; p=0.001), Hb (r=0.36; p=0.04), Ht (r=0.34; p<0.05), PP (r=0.35; p<0.05), Fbg (r=0.4; p=0.02), and time on dialysis prior to transplantation (r=0.50; p=0.003) in the patients group. Multiple regression analysis in renal transplant recipients showed that the IMT was independently related to age, Hb or Ht values, and Fbg. 
Conclusions: The results for the first time show positive association between IMT and Ht and Hb values in renal transplant recipients. The results may implicate the role of these rheological factors in progression and acceleration of arterial remodeling in renal transplant recipients.

Leptin and Serum Erythropoietin in Hemodialyzed and Peritoneally Dialyzed Uremic Patients during rHuEPO Therapy

Leptin produced by fat cell has an unanticipated role in hematopoietic system development. We examined the relationships between leptinemia and requirements of erythropoietin (Epo), endogenous Epo levels as well as markers of inflammation: C-reactive protein, tumor necrosis factor α (TNFα) and interleukin-1 (IL-1) in rHuEPO-treated patients maintained on chronic hemodialyses or peritoneal dialyses. The studies were performed on 51 chronically hemodialyzed patients, 20 of them did not receive rHuEPO, 31 subjects received rHuEPO, and 22 patients on CAPD, 13 of them did not receive rHuEPO, 9 subjects were given rHuEPO. In hemodialyzed patients (Epo and Non-Epo group) leptin levels were significantly higher when compared to CAPD patients (Epo and Non-Epo group, respectively). Leptin in peritoneal fluid was significantly higher in the Non-Epo group. In ultrafiltrate, leptin levels were below the detection limit of 0.5 ng/ml. Epo levels in the HD + Epo group were significantly lower than in the HD + Non-Epo group and CAPD + Epo group. TNFα and IL-1 concentrations were significantly lower in both groups of CAPD patients when compared to respective HD groups. Treatment with rHuEPO resulted in nonsignificant decline in serum leptin (p = 0.07 in HD and p = 0.08 in CAPD) and significant leptin loss in peritoneal fluid. It may be of clinical relevance in dialyzed patients. In both groups of Epo-treated patients, positive physiological correlation between leptinemia and BMI disappeared. Leptin levels do not correlate with rHuEPO requirements and serum Epo in dialyzed patients.

Factors associated with early catheter-related complications in peritoneal dialysis

PURPOSE It is advocated to delay the start of peritoneal dialysis (PD) at least 10-14 days after insertion of peritoneal catheter. The aim of this study was to investigate factors associated with catheter-related complications (CRC) in patients starting PD early (1-13 days) (ES) and late (14 days or more) (LS) after catheter implantation. MATERIAL/METHODS Single center, retrospective analysis of CRC occurring within 14 days of follow up after peritoneal dialysis initiation in ES and LS group of patients. RESULTS A total of 97 patients were analyzed. Seventy percent of them were ES. There were significantly more CRC in ES vs. LS (31% vs. 3%, p=0.01). Significantly more mechanical CRC occurred in ES than in LS (21% vs. 0%, p=0.01). Occurrence of infectious CRC did not differ between the groups. In multivariate analysis the only predictor of CRC development was the time elapsed between catheter insertion and beginning of PD (Odds Ratio [OR] 0.80 95% Confidence Interval [95% CI] 0.70-0.91; p=0.001). CONCLUSIONS Each day of delay of PD initiation following peritoneal catheter insertion decreases the odds for development of mechanical CRC.

Thrombin-activatable fibrinolysis inhibitor in kidney transplant recipient with dyslipidemia

Kidney transplant recipients are not only prone to dyslipidemia but also have a high risk of cardiovascular death. Impairment of the fibrinolytic system is thought to be one factor playing a role in development of thrombotic complications. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations and activities in renal transplant recipients stratified based upon serum cholesterol values above 220 mg/dL or below 200 mg/dL. The groups did not differ regarding age, creatinine clearance, BMI, time after transplantation, albumin, fibrinogen, thrombomodulin, or PAP. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex TAT, prothrombin fragments 1 + 2); TAFI activator; thrombomodulin (TM), catalyzer of TAFI activation; and the degree of plasmin generation (plasmin-antiplasmin complex PAP) using commercially available kits. In patients with hyperlipidemia significantly higher TAFI concentrations and activities may contribute to prolonged ECLT and lowered fibrinolytic activity index (FAI). Increased levels of F1 + 2 and TAT were observed in hypercholesterolemic patients, indicating enhanced thrombin generation. Elevated TAFI concentration, and activities and enhanced thrombin generation observed in hypercholesterolemic kidney transplant recipients may contribute to hypofibrinolysis and progression of atherosclerosis in this group of patients.

Renal Handling of Sclerostin in Response to Acute Glomerular Filtration Decline

Deterioration of glomerular filtration rate (GFR) is associated with alterations of bone metabolism. It translates clinically to bone fragility and increased fractures rate among patients with impaired GFR. Recently, sclerostin (SCL) gained much attention as an important factor in pathogenesis of mineral and bone disturbances in patients with renal diseases. There is no data about SCL behaviour in patients with acute GFR decline. The aim of this study was to evaluate the renal handling of SCL. This is a prospective, single-centre observational study in patients undergoing nephrectomy due to urological indications. Serum and urinary SCL levels were measured prior and after nephrectomy. 25 patients were enrolled. After surgery, eGFR significantly declined (from 87.4±19.7 to 67.7±25.7 ml/min/1.73 m(2), p<0.0001). Nephrectomy caused more than 20 times higher renal fractional excretion of SCL [0.15 (interquartile range, IQR 0.09-0.40) vs. 2.78 (IQR 1.51-4.02)%, p<0.001], while its serum level remained intact [0.69 (IQR 0.57-0.90 vs. 0.65 (IQR 0.53-0.88) ng/ml, p=0.4]. The magnitude of eGFR reduction was associated inversely with change in urinary SCL fractional excretion (r=-0.6, p=0.001) and with alteration in serum SCL level (r=-0.5, p=0.01). Our results suggest that increased serum SCL concentrations at moderately reduced GFR are not due to diminished renal clearance. At more severely decreased GFR, elevated SCL concentration results from both increased production and reduced renal elimination.

C-terminal and intact FGF23 in critical illness and their associations with acute kidney injury and in-hospital mortality

Background FGF23 proved its value in prognostication of cardiovascular events and mortality among renal patients and general population. Limited data exist whether FGF23 may have any use in prediction of negative outcomes among critically ill patients admitted to intensive care unit (ICU). Methods Single center cohort study performed among patients admitted to ICU. The primary exposure was FGF23 plasma concentration measured within 24 h of ICU admission. The primary outcome was incident Acute Kidney Injury (AKI) and in‐hospital mortality during the ICU stay. Results The study enrolled 79 patients admitted to ICU. C‐terminal FGF23 (cFGF23) but not intact FGF23 (iFGF23) concentration was significantly elevated in patients, who acquired AKI and non‐survivors (p < .001). ROC analysis of cFGF23 yielded an AUC of 0.81 and 0.85 for prediction of incident AKI and death during ICU stay, respectively. Multivariate analysis showed higher odds for AKI (OR 1.80; 95% CI 1.10–2.96) and in‐hospital mortality (OR 2.85; 95% CI 1.60–5.06) for one unit increase of log transformed cFGF23. Conclusions cFGF23 measurement may serve as a novel biomarker for incident AKI and death among critically ill patients.