Altered Expression of EMT-Related Factors Snail, Wnt4, and Notch2 in the Short-Term Streptozotocin-Induced Diabetic Rat Kidneys.

Background: The aim of this study was to determine the expression of epithelial to mesenchymal transition (EMT)-related transcription factors Snail, Wnt4, and Notch2 with key roles in renal fibrosis, in different renal areas of diabetic rats: glomeruli (G), proximal and distal convoluted tubules (PCT; DCT). Methods: Male Sprague Dawley rats were instilled with 55 mg/kg streptozotocin (diabetes mellitus type I model, DM group) or citrate buffer (control group). Kidney samples were collected 2 weeks and 2 months after DM induction and processed for immunohistochemistry. Results: Diabetic animals showed higher Wnt4 kidney expression both 2 weeks and 2 months post-DM induction, while Snail expression significantly increased only 2 weeks after DM initiation (p < 0.0001). We determined significantly higher expression of examined EMT-related genes in different kidney regions in diabetic animals compared with controls. The most substantial differences were observed in tubular epithelial cells in the period of 2 weeks after induction, with higher Snail and Wnt4 expression in PCT and increased Snail and Notch2 expression in DCT of diabetic animals (p < 0.0001; p < 0.001). Conclusion: The obtained results point to the EMT-related factors Snail, Wnt4, and Notch2 as a potential contributor to diabetic nephropathy development and progression. Changes in their expression, especially in PCT and DCT, could serve as diagnostic biomarkers for the early stages of DM and might be a promising novel therapeutic target in this condition.

Expression of renal vitamin D receptors and metabolizing enzymes in IgA nephropathy.

AIM: One of the main causes of end-stage renal disease (ESRD) in the world is IgA nephropathy (IgAN). Since kidney is a key player in vitamin D metabolism, we investigated the expression of renal vitamin D receptors (VDR) and metabolizing enzymes in IgA nephropathy patients (IgAN-P). METHODS: The sample included twelve IgAN-P who underwent ultrasound-guided renal biopsies and five controls who underwent nephrectomy due to clear renal carcinoma. Immunofluorescent staining was used to determine the expression of VDR, 25-hydroxyvitamin D3 -alpha-hydroxylase (1alpha-OHase) and vitamin D3 24-hydroxylase (CYP24A1). RESULTS: Significant increase in expression of VDR, which was prominent in distal tubular cells (DTCs) in tissues from IgAN-P, was found in comparison to the controls (p = 0.0368). The expression of 1alpha-OHase, calcitriol synthesizing enzyme, was significantly lower in IgAN-P, in comparison with controls (p < 0.0001). The opposite, expression of CYP24A1 (vitamin D degrading enzyme), was significantly higher in IgAN-P in comparison with controls (p = 0.0003). Additionally, we found significant negative correlation between percentage of CYP24A1 immunoreactive nuclei in proximal tubular cells (PTCs) and estimated glomerular filtration rate (eGFR) in IgAN-P (r = -0.6139; p = 0.0337). CONCLUSIONS: Our research indicates substantially decreased renal calcitriol production and increased vitamin D degradation in kidneys of IgAN-P, but larger studies are needed to confirm our results.

Impact of hemodialysis on liver stiffness measured with real-time two-dimensional shear wave elastography.

BACKGROUND AND AIMS: The impact of hemodialysis on liver stiffness is still unclear. The aim of the study was to assess liver fibrosis by real-time two-dimensional shear wave elastography (RT 2D-SWE) and to quantify the influence of net fluid withdrawal on liver stiffness during one hemodialysis session. The second aim was to investigate the influence of systolic blood pressure and time spent on dialysis (in years) on liver stiffness measurements. METHODS: This before/after hemodialysis (HD) study in a group of end stage renal disease (ESRD) patients was carried out with patients on regular HD. Measurements of liver stiffness were done using RT 2D-SWE directly before and after a hemodialysis session. RESULTS: In this study 27 patients with mean age 69.4 ± 14.75 years were included. Mean net fluid withdrawal volume per session was 2874.07 ± 778.35 ml. Mean pre-HD and post-HD liver stiffness measurements were 8.15 kPa (95% confidence interval, CI 7.61-8.68) and 6.70 kPa (95% CI 6.10-7.30 kPa), respectively. Mean liver stiffness reduction was 1.448 ± 1.14 kPa. The amount of fluid removed correlated with the decline in liver stiffness values after HD (ρ = 0.523, P = 0.003). There was a positive but statistically not significant correlation between time spent in HD and liver stiffness (ρ = 0.151, P = 0.623) CONCLUSION: Liver stiffness significantly declined after one session of HD. The change in liver stiffness was strongly correlated with the amount of net fluid withdrawal. Random liver stiffness measurements (LSM) by RT 2D-SWE does not precisely show the degree of fibrosis, Furthermore, it is presumed that postdialysis liver stiffness values likely reflect the real degree of liver fibrosis.

SATB1 and PTEN expression patterns in biopsy proven kidney diseases.

BACKGROUND: In present study we investigated expression pattern of the special tissue markers. SATB1 and PTEN to evaluate possible influence in pathophysiology and development of various biopsy proven kidney diseases. METHODS: The 32 kidney biopsy samples were analysed using light, immunofluorescence and electron microscopy. There were 19 samples in proliferative and 13 samples in non- proliferative group of renal diseases. As control group, 9 specimens of healthy kidney tissue taken after surgery of kidney tumour were used. SATB1 and PTEN markers were used for immunofluorescence staining. Analysed tissue structures were glomeruli, proximal convoluted tubules (PCT) and distal convoluted tubules (DCT). The number of SATB1 and PTEN cells were calculated and the data compared between kidney structures, disease groups and control specimens. RESULTS: Both markers were positive in all investigated kidney structures, with expression generally, more prominent in tubular epithelial cells than in glomeruli, with the highest staining intensity rate as well as highest rate of both markers in DCT of proliferative diseases group (SATB1 64.5 %, PTEN 52 %). There was statistically significant difference in SATB1 expression in all tissue structures of interest in proliferative as well as non- proliferative group compared to control group (p < 0.01-p < 0.0001). PTEN expression were found significantly decreased in PCT of both disease groups in regard to control (PTEN 25.3 % and 23.8 % vs. 41.1 % (p < 0.01 and p < 0.001 respectively). CONCLUSION: SATB1 and PTEN could be considered as markers influenced in kidney disease development. SATB1/PTEN expression should be further investigated as useful markers of kidney disease activity as well as potential therapeutic target.

Epidemiology of 10-year paediatric renal biopsies in the region of southern Croatia.

BACKGROUND: Information about renal diseases in children is available from national registries of renal biopsies. Aim of the study was to compare the clinical presentation of glomerular diseases and tubulointerstitial space diseases with pathohistological diagnosis of indicated renal biopsies from pediatric population in the Croatian region of Dalmatia. METHODS: Out of 231 pediatric patients with suspected glomerular and tubulointerstitial diseases, 54 underwent ultrasound-guided renal biopsy at University Hospital of Split. Kidney allograft biopsy, and re-biopsy were excluded. The biopsy sections were examined under light microscopy, immunofluorescence and electron microscopy. The data was reviewed to determine the pathohistological spectrum and clinicopathologic correlations. We retrospectively analyzed kidney biopsy data from 2008 to 2017 and compared them to that between 1995 and 2005. RESULTS: The mean age of patients was 9.84 ± 5.4 years. Male:female ratio was 1.2:1. The main indications for biopsy were pure nephrotic syndrome without hematuria (25.9%), non-nephrotic proteinuria with haematuria (22.2%), nephritic syndrome with nephrotic proteinuria (18.5%), and isolated hematuria (16.7%). The most common pathohistological findings were IgA nephropathy (IgAN, 24.1%), minimal change disease (MCD, 16.7%), Henoch-Schönlein purpura glomerulonephritis (HSPN, 14.8%), Alport syndrome and focal segmental glomerulosclerosis (AS and FSGS, 11.1% each), tubulointerstitial nephritis and membranous glomerulopathy (TIN and MGN, 3.7% each), while other cases were diagnosed rarely. CONCLUSIONS: Changes in epidemiology of renal diseases in children between the analyzed periods showed an increasing trend of IgAN, MCD, HSPN, AS and FSGS, while mesangioproliferative glomerulonephritis (MesPGN) and endoproliferative glomerulonephritis (EDGN) showed a decreasing trend that can be explained with the new pathohistological classification.

Anemia Is Correlated with Malnutrition and Inflammation in Croatian Peritoneal Dialysis Patients: A Multicenter Nationwide Study.

Malnutrition, inflammation, and anemia are common in peritoneal dialysis (PD) patients. In this study, correlations between Malnutrition Inflammation Score (MIS), laboratory and anthropometric parameters, and anemia indices in Croatian PD patients were analyzed. One hundred and one PD patients (males/females 54/47, age 58.71 ± 14.68 years, mean PD duration 21.82 ± 21.71 months) were included. Clinical, laboratory, and anthropometric parameters were measured. Statistically significant correlations between MIS and erythropoietin weekly dose per kg of body weight (ESA weekly dose), hemoglobin (Hb), and erythrocytes were found (r = 0.439, p < 0.001; r = -0.032, p < 0.001; r = -0.435, p < 0.001), respectively. Also, statistically significant correlations were found between MIS and mean corpuscular volume (r = 0.344, p < 0.001), iron (r = -0.229, p = 0.021), and total iron binding capacity (TIBC) (r = -0.362, p < 0.001), respectively. Furthermore, statistically significant correlations between ESA weekly dose and serum albumin level and body mass index (BMI) were found (r = -0.272, p = 0.006; r = -0.269, p = 0.006), respectively. When we divided PD patients into 2 groups according Hb level (Hb ≥ 110 [N = 60, 59.41 %]) and Hb < 110 [N = 41, 40.59%]), statistically significant differences were found in MIS score (3.02 ± 2.54 vs 4.54 ± 3.54, p = 0.014), C-reactive protein (CRP) (3.52 ± 6.36 vs 7.85 ± 7.96, p = 0.005), and serum albumin level (44.22 ± 8.54 vs 39.94 ± 8.56, p = 0.003), respectively. Our findings suggest that anemia is correlated with malnutrition and inflammation in Croatian PD patients. Further studies are needed to assess whether modulating inflammatory or nutritional processes can improve anemia management in PD patients.

Seasonal Variations of Nutritional Status in Maintenance Hemodialysis Patients.

Nutritional status of hemodialysis (HD) patients is influenced by a multitude of factors and it strongly correlates with morbidity and mortality. The aim of this study was to investigate the influence of seasonal changes on nutritional status in maintenance HD patients. A selected population of 84 adult (40 females and 44 males, aged 68.98 ± 13.45 years) HD (5.94 ± 6.44 years) patients were investigated. Clinical, biochemical and nutritional parameters (BMI, creatinine, urea, serum albumin, total cholesterol and Dialysis Malnutrition Score (DMS) were measured in cold (January and December) and mild (June and September) months, altogether in 336 HD sessions. Statistically significant differences between cold and mild months were found in BMI (P = 0.046), creatinine before HD (P = 0.011), urea before HD (P ≤ 0.001), urea after HD (P ≤ 0.001) and glucose (P = 0.001). Differences between male and female patients in DMS, serum albumin and creatinine level in cold and mild months were found; where females altogether had higher DMS score and lower serum albumin and creatinine levels. These results suggest that seasonal variations of clinical and laboratory variables that reflect nutritional status occur commonly among maintenance HD patients and might lead to biases in the interpretation of results in clinical studies in which measurement schedules vary during the year. Also, results suggested that female HD patients may constitute an especially vulnerable population for seasonal oscillations of nutritional status. The reasons for most of these variations are not apparent and require further investigation.

[[GUIDELINES FOR THE PREVENTION, MONITORING AND THERAPY OF CHRONIC KIDNEY DISEASE-METABOLIC BONE DISEASE IN PATIENTS WITH CHRONIC KIDNEY DISEASE].]

Chronic kidney disease (CKD) is a systemic disease with numerous complications associated with increased morbidity and mortality. Chronic kidney disease-metabolic bone disease (CKD-MBD) starts at early stages of CKD with phosphorus accumulation and consequent initiation of numerous events that result with the development of secondary hyperparathyroidism with changes on bones and extraskeletal tissues. The most important and clinically most relevant consequences of CKD-MBD are vascular calcifications which contribute to cardiovascular mortality. Patients with the increased risk for the development of CKD-MBD should be recognized and treated. Prevention is the most important therapeutic option. The first step should be nutritional counseling with vitamin supplementation if necessary and correction of mineral status. Progression of CKD requires more intensive medicamentous treatment with the additional correction of metabolic acidosis and anemia. Renal replacement therapy should be timely initiated, with the adequate dose of dislaysis. Ideally, preemptive renal transplantion should be offered in individuals without contraindication for immunosuppressive therapy.

Depression and serum interleukin-6 levels in patients on dialysis.

BACKGROUND: Depression is a common psychiatric problem in patients undergoing dialysis. Several studies have been performed to validate the association between depression and inflammation in haemodialysis patients. The levels of proinflammatory cytokines are increased in chronic renal failure patients, as in depression. The objective of this study was to compare the incidence of depression in the patients on dialysis (on hemodialysis /HD/ and on continuous ambulatory peritoneal dialysis /CAPD/), and a relationship between depression and the presence of inflammation. SUBJECTS AND METHODS: 88 patients (52 on HD and 36 on CAPD) were enrolled in this study. Depressive symptoms were measured with the Beck Depression Inventory (BDI). The BDI is a 21-item self-report instrument, and the elevated symptoms of depression were defined as a BDI score ≥16. HD patients were treated with high-flux polysulphone biocompatible dialyzers and CAPD patients were treated with usual dwell time (4-6 hours during the day and 8-10 hours at night). The presence of an inflammatory state was assesded by determinations of plasma interleukin-6 (IL-6) levels. RESULTS: Depression (BDI ≥16) was present in 28.4% of dialysis patients, 35% of patients on hemodialysis (HD) and 18.1% of patients on continous ambulatory peritoneal dialysis (CAPD). The BDI score was significantly lower in CAPD patients comparing to HD patients, as well as the levels of albumin, C-reactive protein (CRP) and interleukin-6 (IL-6). IL-6 serum levels were similar in patients with depression and patients without depression in the whole group, as in HD patients. In CAPD patients without depression IL-6 levels were significantly lower. CONCLUSIONS: The prevalence of depression was higher in HD comparing to CAPD patients. Although IL-6 level was higher in HD compared to CAPD patients, the relationship between depression and presence of inflammation parametars were observed in CAPD, but not in HD patients.

Successful treatment of renal artery embolism even forty-eight hours after event.

Renal artery embolism is a disease that is easily missed due to its infrequent and nonspecific presentations. Although early diagnosis and optimal thrombolytic treatment can sometimes restore renal function, therapeutic guidelines have not yet been established. However, early anticoagulant therapy is beneficial and selective infusion of lytic agents into renal artery has been reported with increasing frequency and efficacy if used in the early stage. We report that intra-arterial thrombolytic therapy with low dose of 35 mg recombinant tissue plasminogen activator (t-PA) may be an effective and safe strategy for the treatment of renal artery embolism, despite the period of ischemia being longer than 48 hours.

[How to prevent protein-energy wasting in patients with chronic kidney disease--position statement of the Croatian Society of Nephrology, Dialysis and Transplantation]. / Kako prevenirati i lijeciti proteinsko-energetsku pothranjenost u bolesnika s kronicnom bolescu bubrega--osvrt hrvatskog drustva za nefrologiju, dijalizu i transplantaciju na preporuke medunarodnog drustva za prehranu bubreznih bolesnika.

Protein-energy wasting (PEW) is a frequent problem in patients with end-stage renal disease, which is associated with adverse outcome. Risk factors for development of PEW in dialysis patients include anorexia, limitations in food intake due to problems with mineral metabolism (hyperphosphatemia, hyperkalemia). Prevention of PEW in dialysis population demands different therapeutic measures to correct abnormalities and to prevent loss of energy and proteins. Therapeutic approach should be individualized based on the specific problems of each patient in order to correct metabolic problems and to optimize food intake. In patients with inability to maintain nutritional status with standard oral feeding, other measures which include oral nutrition supplements and intradialytic parenteral feeding should be applied. Anabolic steroids, growth hormone and adequate oral nutritional supplements, together with physical activity may prevent further catabolism and correct abnormalities. Appetite stimulators, antiinflammatory interventions and anabolic drugs seem promising; however, their efficacy should be investigated in future clinical trials.

[Treatment of anemia in chronic kidney disease--position statement of the Croatian Society for Nephrology, Dialysis and Transplantation and review of the KDIGO and ERPB guidelines]. / Lijecenje anemije u kronicnoj bubreznoj bolesti--stav hrvatskog drustva za nefrologiju, dijalizu i transplantaciju i osvrt na preporuke KDIGO i ERBP.

Renal anemia is the result of chronic kidney disease (CKD) and deteriorates with disease progression. Anemia may be the first sign of kidney disease. In all patients with anemia and CKD, diagnostic evaluation is required. Prior to diagnosing renal anemia, it is necessary to eliminate the other possible causes. Direct correlation between the concentration of hemoglobin and the stage of renal failure is well known. Early development of anemia is common in diabetic patients. Correction of anemia may slow the progression of CKD. Anemia is an independent risk factor for developing cardiovascular disease in patients with CKD. Treatment of anemia in patients with CKD is based on current guidelines. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anemia in CKD patients and ERBP (European Renal Best Practice) group its position statement and comments on the KDIGO guidelines. The Croatian Society of Nephrology, Dialysis and Transplantation (HDNDT) has already published its own guidelines based on the recommendations and positive experience of European and international professional societies, as well as on own experience. The latest version of Croatian guidelines was published in 2008. Since then, on the basis of research and clinical practice, there have been numerous changes in the modern understanding of the treatment of anemia in CKD. Consequently, HDNDT hereby publishes a review of the recent recommendations of international professional societies, expressing the attitude about treating anemia in CKD as a basis for new guidelines tailored to the present time.

BCM--body composition monitor: a new tool for the assessment of volume-dependent hypertension in patients on maintenance haemodialysis.

Hypertension is a common finding in end-stage renal disease patients with the prevalence between 20 to 85%. Although the etiology of arterial hypertension (AH) in this patient group is multifactorial, sodium and volume excess leading to extracellular volume overload are one of the most important and potentially adjustable causes. Control of volume status can either normalize the blood pressure (BP) or make the AH easier to control in the great majority of dialysis patients. Heavy reliance is placed on the dialysis procedure to gradually remove fluid over a period of days to weeks until a stable dry weight is achieved. Numerous attempts have been made to utilize alternative methods to more accurately assessment of dry weight, and the newest and most interesting method is multifrequency bioelectrical impedance spectroscopy (BIS). In this prospective study we used BIS in 65 haemodialysis (HD) patients in order to detect those with volume-dependent hypertension and to further investigate the role of dry weight management in BP control. Dry weight was corrected at the beginning, and after 1, and 3 months. Final data were collected after six months. Our data showed that assessment of fluid overload using BIS provides better management of fluid status and BP control in the patients on maintenance HD, and that dry weight correction can lead to significantly better control of volume-dependent hypertension in this patient group.

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.

Differences in epidermal thickness and expression of apoptosis regulatory proteins in the skin of patients with chronic renal failure and pruritus.

Chronic renal failure is often associated with skin itching (pruritus) in dialysis patients. In order to investigate the possible causes of pruritus, the epidermis of the thigh of 12 dialysis patients and 4 controls from patients without renal disease were examined. The sections of the epidermis were measured and immunohistochemically analyzed using antibodies to Bcl-2, Bax, caspase-3 proteins and TUNEL method. While the mean thickness of normal epidermis was 53 µm, in dialysis patients it ranged between 23 and 34 µm during the 3-5 year period on dialysis. Compared to normal skin, the fine balance between the Bcl-2 and Bax proteins did not greatly change in the epidermis of dialysis patients during the three years of dialysis. Following five-year dialysis, the epidermis displayed increased Bax and decreased Bcl-2 expression in the basal and intermediate epidermal layers, as well as the presence of apoptotic cells (TUNEL and caspase-3 positive) both in the superficial and intermediate epidermal layers. Our study demonstrated the predominant expression of cell death Bax proteins over cell survival Bcl-2 proteins, and apoptotic cells in the deeper layers of the epidermis in patients on long-term dialysis. We speculate that the thinning of the epidermis might be associated with the appearance of dead cells in the deeper epidermal layers, while the changed internal milieu of epidermal cells could possibly affect the intra-epidermal nerve endings thus leading to the sensation of pruritus.

The interstitial expression of alpha-smooth muscle actin in glomerulonephritis is associated with renal function.

BACKGROUND: In a healthy kidney, contractile protein alpha-smooth muscle actin (ASMA) is immunohistochemically strongly expressed only in the blood vessels, while in pathological conditions it can be visualized in glomerular mesangial cells and interstitial myofibroblasts. The aim of this study was to explore the possible correlation between expression of ASMA in glomerulonephritis (GN) and indicators of renal function. MATERIAL/METHODS: We analyzed expression of ASMA in percutaneous renal biopsy of 142 adult and pediatric patients with GN and its correlation with blood pressure, serum creatinine, creatinine clearance and 24-hour urine protein at the time of biopsy. Immunoexpression of ASMA was analyzed quantitatively using computer-assisted morphometric analysis. Relative surface of ASMA expression in all glomeruli and interstitium was calculated for each patient. RESULTS: In adults and children, greater expression of ASMA in interstitium was associated with higher serum creatinine and reduced creatinine clearance. Conversely, greater ASMA expression in glomeruli was associated with normal or decreased serum creatinine in adults and increased creatinine clearance in children. In children, correlation was found between high blood pressure and ASMA expression in interstitium. CONCLUSIONS: We confirmed that interstitial expression of ASMA is associated with reduced renal function at time of biopsy. The connection of ASMA expression in glomeruli with lower serum creatinine and normal or increased creatinine clearance suggests a favorable role of this phenotypic change in glomerular filtration rate; further investigation is needed.

Influence of local inflammation of the peritoneal membrane on diuresis and residual renal function in patients treated with peritoneal dialysis.

The aim of this study was to investigate the connection between local inflammation of the peritoneal membrane and diuresis, as well as the residual renal function (RRF) in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Twenty patients treated with CAPD participated in this cross-sectional study. To determine the influence of local inflammation of the peritoneal membrane, effluent interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels were measured. The level of IL-6, in the group as a whole, was significantly higher in effluent (7.87 pg/mL) than in serum (1.29 pg/mL). There was a significant correlation between effluent and serum IL-6 (r = 0.608; P = 0.002). There was also a significant relationship between effluent and serum IL-6 and duration of CAPD treatment, respectively (r = 0.577; P = 0.004; r = 0.528; P = 0.008). Further, there was a significant negative correlation between effluent IL-6 and daily diuresis (r = -0.533; P = 0.008), but there was no significant correlation between effluent IL-6 and RRF (r = -0.339, P = 0.072). On the other hand, the concentrations of effluent IL-6 were significantly higher in patients with RRF <2 mL/min than in those with RRF ≥2 mL/min (P = 0.039). In conclusion, local inflammation has a significant impact on the amount of diuresis and probably on RRF in patients on CAPD.

[Do we know all effects of heparins in hemodialyzed patients?]. / Znamo li sve o ucincima heparina u bolesnika lijecenih hemodijalizom?

Anticoagulation with heparins during hemodialysis (HD) is aimed at preventing the activation of coagulation in the extracorporeal circuit. As HD patients are exposed to unfractionated and low molecular weight heparins (LMWH) for years, non-hemorrhagic effects (osteoporosis, reduction of elevated blood pressure, with lesser intra- and interdialytic hypotensive episodes, effects on brain microvascular circulation and decreasing vascular dementia and Alzheimer's disease, and chronic and malignant diseases) require new trials with individualized doses of heparins.

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 ß protein (Aß) in the blood and on Aß 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.