Milenka Sain

Kidney Transplantation Improves Cognitive and Psychomotor Functions in Adult Hemodialysis Patients

Background: Kidney failure is believed to have a negative impact on cognitive function, and cognitive impairment is common among maintenance hemodialysis (HD) patients. Previous studies have shown a beneficial effect of kidney transplantation in certain cognitive tests but not across all cognitive domains assessed. But, most of these studies performed a cross-sectional analysis, suffered from lack of standardization of adequate dialysis dose, hemoglobin level, and insufficient sensitivity of neuropsychological tests. The aim of this study was to evaluate the effect of successful kidney transplantation on cognitive and psychomotor function in adequately dialyzed HD patients without severe anemia, using sensitive neuropsychological tests. Methods: Twenty-one medically stable patients (aged 45.1 ± 7.9 years) on maintenance HD (7.6 ± 4.2 years) were investigated before and 20.5 ± 8.5 months after successful kidney transplantation using Complex Reactiometer Drenovac, a battery of computer-generated psychological tests which measure a simple visual discrimination of signal location, short-term memory, simple convergent visual orientation and convergent thinking. Results: Our findings indicated significantly better cognitive and psychomotor performance after transplantation on tests that assess processing speed, attention, short time memory, convergent thinking and executive functioning. Also, significant negative correlation between follow-up time after transplantation and cognitive and psychomotor performance in minimum time of solving test of convergent thinking was found. Conclusion: We conclude that cognitive and psychomotor functions are superior after successful kidney transplantation compared with HD, and that early beneficial effects of transplantation are not transient and cognitive and psychomotor performance might be even improved in time following successful transplantation.

Efficient Haemodialysis Improves the Response to Hepatitis B Virus Vaccination

Background: As patients on chronic haemodialysis (PCHD) elicit a weaker response to vaccination with recombinant hepatitis B virus surface antigen (HBsAg), we conducted this study to see how dialysis efficacy affects response to hepatitis B virus (HBV) vaccination. Methods: Study subjects consisted of 30 PCHD. All subjects were vaccinated with 4 × 40 µg HBsAg i.m. at 0, 1, 2, and 6 months. If a subject had an HBsAg antibody (HBsAb) level <10 IU/l after vaccination, he or she received a booster dose. Subjects were divided into groups according to the level of HBsAb: non-responders (<10 IU/l), weak responders (10–100 IU/l), and good responders (>100 IU/l). Results: The group of responders had a significantly more efficient dialysis (Kt/V) than the group of non-responders (p = 0.027). This difference was not observed between groups of non-responders and weak responders. The group of good responders had a significantly better Kt/V than the group of non-responders (p = 0.012). Good responders had a significantly better Kt/V than weak responders (p = 0.019). Kt/V values showed a significantly positive correlation with the HBsAb level (r = 0.47; p = 0.006). Conclusions: The HBV vaccination reaction was weaker in PCHD with inefficient dialysis. Efficient haemodialysis significantly improves the response to vaccination with recombinant HBsAg.

Is there differences in cognitive and motor functioning between hemodialysis and peritoneal dialysis patients

Objective: Change in cognitive function is one of the well-known consequences of the end-stage renal disease (ESRD). The aim of this study was to determine the effect of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) on cognitive and motor functions. Methods: In this cross-sectional study, cognitive and motor functions were investigated in a selected population of 42 patients with ESRD (22 patients on chronic HD and 20 patients on CAPD, aged 50.31 ± 11.07 years). Assessment of cognitive and motor functions was performed by Symbol Digit Modalities Test (SDMT) and Complex Reactiometer Drenovac (CRD-series), a battery of computer-generated psychological tests to measure simple visual discrimination of signal location, short-term memory, simple convergent visual orientation, and convergent thinking. Results: The statistically significant difference in cognitive–motor functions between HD and CAPD patients was not found in any of the time-related parameters in all CRD-series tests or SDMT score. Higher serum levels of albumin, creatinine, and calcium were correlated with better cognitive–motor performance among all patients regardless of dialysis modality. The significant correlation between ultrafiltration rate per HD and short-term memory actualization test score (CRD-324 MT) among HD patients was found (r = 0.434, p = 0.025). Conclusion: This study has demonstrated that well-nourished and medically stable HD and CAPD patients without clinical signs of dementia or cognitive impairment and without significant difference in age and level of education performed all tests of cognitive–motor abilities without statistically significant difference.

Pegylated interferon for treatment of chronic hepatitis C in hemodialysis patients in Croatia

Background and Aims: Hepatitis C virus (HCV) infection is a frequent complication among long-term dialysis patients. The aim of the present study was to evaluate the efficacy and side effects of pegylated interferon-α2a (PEG-IFN-α2a) treatment in hemodialysis patients. Methods: We retrospectively reviewed charts of 16 HCV-RNA-positive hemodialysis patients. Results: There were 11 male and 5 female patients treated with dialysis for 6–28 years. Twelve patients had HCV genotype 1b, 2 patients had 3a, and 1 patient had genotype 2a. Although only 10 out of 16 patients completed 48 weeks of treatment, early virological response and end-of-treatment virological response were achieved in 9 and 13 patients, respectively. Sustained virological response was recorded in 9 patients. The most common side effect was anemia. A flu-like syndrome was documented in 6, myalgia in 4, and arthralgia in 5 patients. Rectorrhagia, endocarditis and severe cough were recorded in 1 patient each. Nine patients received a renal transplant, and all 6 responders remained HCV-RNA-negative. Conclusions: PEG-IFN-α2a has limited efficacy in dialysis patients. A significant proportion of patients discontinued treatment because of side effects. Additional studies with long-term follow-up are needed to determine the optimal treatment of HCV infection in the dialysis population.

The individually optimized bolus dose of nadroparin is safe and effective in diabetic and nondiabetic patients with bleeding risk on hemodialysis

The risk of bleeding is a well‐known complication in patients on hemodialysis (HD). The aim of this prospective study was to determine the lowest single bolus dose of low–molecular‐weight heparin nadroparin for safe and effective HD in patients with a bleeding risk. Forty HD patients were divided into 4 subgroups with 10 participants (diabetics with and without a bleeding risk, nondiabetics with and without a bleeding risk). The actual starting bolus dose was decreased by 25% after the initial 4 weeks, further decreased by 25% of the starting dose after 4 weeks, and changed due to extracorporeal circuit clotting in the last 4 weeks. The parameters of coagulation were measured at the beginning, after 2 and 4 h of HD sessions. A significant reduction of nadroparin (first vs. last HD session) was observed in: diabetics with a bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P<0.001), diabetics without a bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P<0.001), and nondiabetics with a bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P<0.001). Altogether, the reduction of the nadroparin dose in these groups was 42.05%; 33.04%, and 46.19%, respectively. Although anti‐Xa at hour 4 at the end of the study was <0.4 IU/mL in our diabetic and nondiabetic patients without a risk of bleeding, serious clottings in the extracorporeal circuit and vascular access thromboses were not found. This study demonstrated for the first time that individually optimized doses of nadroparin are sufficient for safe and effective HD in patients with a bleeding risk.

Cognitive‐Psychomotor Functions and Nutritional Status in Maintenance Hemodialysis Patients: Are They Related?

Both cognitive impairment and malnutrition are common in hemodialysis patients and associated with adverse clinical outcome. The aim of the study was to investigate performance on a detailed cognitive and psychomotor battery in maintenance hemodialysis patients in correlation to nutritional status. A selected population of 65 adult (20 females and 45 males, aged 57.84 ± 12.28 years) hemodialysis (4.78 ± 3.62 years) patients were investigated. The total time of test solving was correlated with Dialysis Malnutrition Score (DMS) in tests of simple visual discrimination of signal location (r = 0.215, P = 0.042), simple convergent visual orientation (r = 0.262, P = 0.020), and convergent thinking (r = 0.244, P = 0.034). The minimum time of test solving was also correlated with DMS in the test of simple convergent visual orientation (r = 0.227, P = 0.038), and in the test of convergent thinking (r = 0.223, P = 0.048). Total ballast, as a descriptor of stability in reaction time, was correlated with DMS in the test of simple visual discrimination of signal location (r = 0.281, P = 0.012), and in a test of short term memory actualization (r = 0.239, P = 0.028). Furthermore, significant correlation was noted between body mass index, serum creatinine, total cholesterol and albumin level with cognitive–psychomotor performance. Hemodialysis patients with a poorer nutritional status performed worse on cognitive and psychomotor tests. Further research is needed to assess the effects of treating malnutrition on cognitive–psychomotor performance in these patients.

Spleen rupture associated with septic emboli and endocarditis in a hemodialysis patient.

We present an uremic patient on chronic hemodialysis with splenic septic emboli associated with active infective endocarditis and anaerobic bacteremia complicated by ruptured spleen. A 62-year-old female patient was admitted because of fever and pain in the left upper abdomen and swelling and hematoma around the left brachiocephalic arteriovenous fistula. Transthoracic echocardiography revealed mobile hyperechoic mass (vegetation) on the anterior mitral valve. Abdominal ultrasound scan showed multiple hypoechoic lesions of the enlarged spleen, described as possible necroses or abscesses, and computed tomography showed low-density inhomogeneous lesions in the enlarged spleen with large perisplenic hematoma, with spleen rupture. Blood culture revealed anaerobic Gram-negative bacilli (Bacteroides spp.), ampicillin resistant. This is the first report of splenic rupture associated with anaerobic bacteremia and splenic septic emboli in a uremic patient on chronic hemodialysis. Splenic septic emboli with abscess/infarction in hemodialysis patients are a rare disorder but could be a consequence of dialysis access site infection and might predispose to splenic rupture. Ultrasound scan of abdomen is fast, inexpensive and easy to perform. As mortality is high, early surgical intervention on vascular access is mandatory.

Potential beneficial effects of low molecular weight heparin on cognitive impairment in elderly patients on haemodialysis

Vascular cognitive impairment or mixed vascular cognitive impairment and Alzheimer’s disease (AD) appear to be much more common in elderly patients than AD alone. Furthermore, vascular dementia (VaD) and AD are more prevalent in elderly patients receiving haemodialysis (HD), leading to a loss of independence and a poor quality of life. Hypotensive episodes in patients receiving HD contribute to vascular changes in the brain, with consequent progression of VaD and AD.The use of the lowest individually optimized bolus dose of low molecular weight heparin (LMWH) during HD, with fewer hypotensive episodes during and between HD procedures, may exert a sparing effect on changes in microvascular circulation and decrease the incidence of VaD and AD. We believe that long-term use of LMWH, with its direct effect on amyloid β protein (Aβ) in the blood and on Aβ accumulation in the brain and indirect effects on prevention of complement activation, may delay the progression of cognitive impairment in patients receiving HD.There is a need for a robustly designed, prospective trial to evaluate the effects of long-term treatment with LMWH on mild cognitive impairment, VaD and AD in elderly patients receiving maintenance HD.

What Are the Lowest Doses of Low Molecular Weight Heparin for Effective and Safe Hemodialysis in Different Subgroups of Patients

Dear Editor, Patients on hemodialysis (HD) are prone to two opposing hemostatic processes: a bleeding tendency and a hypercoagulable state. Bleeding episodes in patients on HD are common due to their underlying uremic state, age and concomitant diseases (diabetes, bleeding disorder, vascular diseases) (1). They may benefit from the possibility of using less systemic anticoagulation during HD (2,3). Regional anticoagulation with citrate has been developed for use as an alternative to unfractionated heparin, particularly in patients with a high risk of bleeding. But, for HD patients not at risk of bleeding, low molecular weight heparin (LMWH) provides a simple anticoagulation regimen. Prolonged use of citrate anticoagulation is complicated by concerns with calcium homeostasis and the development of metabolic alkalosis (4). A dialysate using low-dose citric acid instead of acetic acid as the acidifying agent may allow a heparin-free or reduced heparin dose dialysis. An improvement in the efficiency of dialysis, as demonstrated by a significantly higher eKt/V urea, was an unanticipated side benefit and might be explained by less dialyzer clotting from the dual anticoagulation effects of Ca chelation by citrate and heparin. The much higher cost of citrate dialysate currently makes this an unattractive option for regular use (5). The aim of our study was to find out what are the lowest single bolus doses of LMWH nadroparin calcium (Fraxiparine, Glaxo Welcome Production, Notre Dame de Bondeville, France) for the safe and effective HD in different subgroups of patients due to age, gender, diabetes and bleeding risk. The actual starting bolus dose of nadroparin (HD1 nadroparin), which was used in our Center for a minimum of 2 months according to the manufacturer’s recommendation (with only some “minor” bleedings from vascular access after HD, and very rare “major”gastrointestinal bleedings), was decreased twice by 25%: after the initial 4 weeks (HD2 nadroparin), and again after an additional 4 weeks (HD3 nadroparin). The maintenance period was 4 weeks (HD4 nadroparin) during which time this dose was adjusted due to clotting of the extracorporeal circuit. All 40 patients (age 64.93 ± 12.34 years) on intermittent HD for 61.63 ± 53.97 months, were included in this 12-week long study, 38 patients completed the study, two were transplanted, and none died. The nadroparin doses at the beginning and at the end of the study (HD1 vs. HD4) were: 53.19 ± 15.18 vs. 33.84 ± 12.64 IU/kg/HD; P < 0.001 (the reduction 36%). We investigated two subgroups of patients due to age: 25 patients >65 (mean 72.88 ± 5.26 years); and 15 patients <65 (mean 51.67 ± 8.68 years) undergoing intermittent HD for 52.60 ± 51.50, and 76.67 ± 56.39 months (respectively).The doses of nadroparin (HD1 vs. HD4) in patients >65 years were: 48.60 ± 10.45 vs. 31.34 ± 12.02 IU/kg/HD; P < 0.005, and patients <65 years: 60.84 ± 18.82 vs. 38.64 ± 12.88 IU/kg/HD; P < 0.001 (the reductions were 35.52% and 36.49%, respectively). Due to gender, we investigated subgroups of 22 male (mean age 63.36 ± 12.06 years) and 18 female patients (mean age 66.83 ± 12.75 years) undergoing intermittent HD for 53.82 ± 52.70, and 71.17 ± 55.48 months (respectively). The individually optimized bolus doses of nadroparin (HD1 vs. HD4) in male patients were: 53.04 ± 15.60 vs. 34.50 ± 12.80 IU/kg/ HD; P < 0.005, and in female patients were: 51.67 ± 14.70 vs. 32.93 ± 12.78 IU/kg/HD; P < 0.005 (the reductions were 35% and 36.27%, respectively). We also investigated four subgroups with 10 patients due to diabetes and bleeding risk (Table 1). A safe and significant reduction of nadroparin (HD1 vs. HD4) was observed in: diabetics with bleeding risk (49.66 ± 12.33 vs. 28.78 ± 9.60 IU/kg/HD; P < 0.001), diabetics without bleeding risk (50.70 ± 15.23 vs. 33.95 ± 16.97 IU/kg/HD; P < 0.001), and non-diabetics with bleeding risk (61.25 ± 18.68 vs. 32.96 ± 10.06 IU/kg/HD; P < 0.001). All together, the reductions of nadroparin dose in these groups were: 42.05%; 33.04% and 46.19%, respectively. The lowest reduction was in non-diabetics without bleeding risk: 12.03% (47.45 ± 10.87 vs. 41.75 ± 10.91 IU/kg/HD; P = 0.484) (6,7). bs_bs_banner

The Influence of Decreased Low-Molecular-Weight Heparin Nadroparin Dose on Diastolic Blood Pressure in Patients on Hemodialysis

The aim of present study was to assess the impact of decreasing single bolus dose of nadroparin on blood pressure in patients on hemodialysis (HD). Forty HD patients were included in this study. The bolus dose of nadroparin was decreased twice by 25%; this lower dose was maintained for last 4 weeks, during which the dose was adjusted. There were no significant differences between the first and the last predialysis: systolic blood pressure ([pre-SBP]; 131.05 ± 25.58 vs 125.92 ± 25.49 mm Hg; P = .133), diastolic blood pressure ([pre-DBP]; 73.82 ± 11.82 vs 72.89 ± 9.13 mm Hg; P = .653), and pulse pressure ([pre-PP]; 57.24 ± 20.39 vs 53.03 ± 21.20 mm Hg; P = .121). We found correlation between delta nadroparin and pre-DBP in the last HD (rho = 0.310; P = .031) but not between delta nadroparin and pre-SBP and pre-PP values. This is the first report of influence of nadroparin dose lowering on pre-DBP in HD patients.