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Fahrudin Masnić

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Some of the conditions which occur in maintenance hemodialysis (MHD) patients with a high incidence resulting in a decline in their quality of life, include malnutrition, renal osteodystrophy, refractory hypertension and chronic systemic inflammation. In developing countries, due to the low level of economic development, low-flux dialysis is the main means of extracorporeal blood purification therapy. But it can hardly remove the middle and large molecule uremic toxins and protein-bound toxins; as a result, the patients suffer from long-term complications and poor quality of life. In this study, we attempted to investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve their uremic complications. A total of 54 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into two groups: Group 1 (27 patients) received combined treatment of HD with hemoperfusion (HP) in this regimen: HD 2 times a week with HD+HP once a week two times in a row, then after two weeks, and afterwards once a month as a maintenance treatment. Group 2 (27 patients) was only undergoing maintenance HD 3 times a week. The clinical and laboratory properties of both groups were followed up for 18 months, whereas the primary outcomes included normal clinical data, high sensitive C-reactive protein (hsCRP), immunoreactive parathyroid hormone (iPTH), phosphorus (P04), calcium (Ca), albumin, iron (Fe), total iron binding capacity (TIBC), hemoglobin, Epo doses and types of hypertensive drugs. At the end of the 18-month observation, the serum concentration of albumin, P04, hsCRP, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower with Group 1 than with Group 2 (p<0.05). Whereas, higher levels of iPTH were noticed in group 1, but when the laboratory and clinical data are analysed of the group 1 alone a statistically significant lower values after the observational period are noticed especially in the serum values of iPTH (p<0.05), P04 (p<0.001), CRP (p<0.011), SBP and DBP (p<0.05). HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body which is mostly shown through reducing the values of iPTH and hsCRP. These findings suggest a potential role for HD+HP in the treatment of inflammation and renal osteodystrophy as well, because lowering these values of iPTH leads to a normalization of other minerals which is expected and therefore leads to a stabilization of this long-term uremic complications, which can improve the overall general condition of the MHD patient.

Introduction: Calciphylaxis is a rare, but serious, kidney complication. Calciphylaxia is a vasculopathy of small blood vessels characterized by the deposition of calcium deposits in intimal arterioles with the consequent proliferation of intima, fibrosis and thrombosis. Aim: The aim was to show the significance of recognition of calciphylaxis relies on heightened clinical awareness of the presence of atypical skin nodules or ulcers that occur in patients with hemodialysis dependence and to characterize features of calciphylaxis or components of treatment that may lead to improved outcome. Case report: We present the case of 84-year-old woman with chronic kidney disease and diabetes mellitus as well as severely painful, firm, indurated plaques on the lower extremities. The plaques progressed to involve larger areas with associated local ulceration and necrosis. Laboratory testing revealed hyperparathyroidism and incisional skin biopsy confirmed calciphylaxis. Wound microbiology confirmed Staphylococcus aureus. Conclusion: The diagnosis can be based on clinical grounds, supported by histological analysis if possible. The laboratory workout must cover all the possible implications of chronic kidney disease with special attention to Ca+ and P+ values and evidence of skin or systemic infection. Calciphylaxis must be known by dermatologist as early diagnosis and proper management can be decisive for better prognosis.

The occurance of mid- and longterm uremic complications is related to the low clearance rate of middle and large molecule uremic toxins when hemodialysis (HD) alone is adopted. As the uremic toxins and their corresponding biological effects become increasingly clear, blood purification treatment that aims to remove these toxins, has developed from a stage of life-sustaining to improving the quality of life. The objective of this study was to evaluated demographic, clinical and laboratory data in patients who underwent the combination of maintenance hemodialysis with hemoperfusion (HP) and in those who recieved HD alone and to investigate whether this combination could improve the clearance rate of middle and large molecule uremic toxins. A total of 26 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into three groups: Group 1 (7 patients) received combined treatment of HD with HP biweekly (HD 2 times a week with HD+HP once a week), whereas Group 2 (10 patients) was given HD with high flux dialyzer and Group 3 (9 patients) was given HD with low flux dialyzer 3 times a week. This study was followed for 4 months. Before and after the observational period demographic and clinical data were taken from the medical history and blood samples were taken for hemoglobin (Hb), iron (Fe), total iron binding capacity (TIBC), albumin (Alb), calcium (Ca), phosphorus (P04) and parathyroid hormone (PTH). This study included 13 female and 13 male patients with a mean age of 41, 62 + 11.12 and a mean dialysis duration of 62, 78+53, 33 months. When it comes to baseline characteristics, patients of the group 3 were significantly older than patients in other groups (p=0.001). At the end of the four months observation period, the same difference according to age was noticed (p=0.01). Also, HD+HP group had significantly higher values of TIBC (p=0.006) and significantly lower serum levels of P04 (p=0.001). EPO doses were very similar in group 1 and 2, but in group 3 there were noticeably lower than in those two groups but without a significant difference. The serum levels of albumin were higher in group 3 compared to the other two groups but also without statistical difference. No statistical difference between groups after the follow up period was observed in terms of Hb, Fe, PTH, Ca, BMI, duration of dialysis treatment and vascular access. When groups are viewed individually, in the HD+HP group serum P04 levels were significantly lower after the 4 months off the follow up period than it was at the beginning (p=0.031) and also TIBC was significantly higher (p=0.018). In group 2 the values of TIBC were significantly lower after the follow up period than it was at the beginning (p=0.025). No significant difference was noticed in group 3 but serum PTH levels tends to decrease after 4 months compared to baseline measurement. This combination treatment of HD with HP was superior to HD in reducing levels of phosphorus. These findings suggests a potential role of reducing the risk of cardiovascular events in this population especially when it is known that hyperphosphatemia has been pointed out as the primary culprit in the process of cardiovascular calcification. Also, patients who underwent the combined treatment showed higher values of TIBC but unfortunately no difference was noticed between Hb levels and EPO doses. These results eventually demonstrates their role in the improvement of renal disease anemia, which opens up the possibility of further research on a larger sample and over a longer period of time.

Aneliya Parvanova, Matias Trillini, M. A. Podestà, I. Iliev, C. Aparicio, A. Perna, Francesco Peraro, N. Rubis, F. Gaspari et al.

Abstract Context Acetyl-l-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabolism, decreased systolic blood pressure (SBP), and ameliorated insulin sensitivity in hypertensive nondiabetic subjects at high cardiovascular risk. Objective To assess the effects of ALC on SBP and glycemic and lipid control in patients with hypertension, type 2 diabetes mellitus (T2D), and dyslipidemia on background statin therapy. Design After 4-week run-in period and stratification according to previous statin therapy, patients were randomized to 6-month, double-blind treatment with ALC or placebo added-on simvastatin. Setting Five diabetology units and one clinical research center in Italy. Patients Two hundred twenty-nine patients with hypertension and dyslipidemic T2D >40 years with stable background antihypertensive, hypoglycemic, and statin therapy and serum creatinine <1.5 mg/dL. Interventions Oral ALC 1000 mg or placebo twice daily on top of stable simvastatin therapy. Outcome and Measures Primary outcome was SBP. Secondary outcomes included lipid and glycemic profiles. Total-body glucose disposal rate and glomerular filtration rate were measured in subgroups by hyperinsulinemic–euglycemic clamp and iohexol plasma clearance, respectively. Results SBP did not significantly change after 6-month treatment with ALC compared with placebo (−2.09 mm Hg vs −3.57 mm Hg, P = 0.9539). Serum cholesterol, triglycerides, and lipoprotein(a), as well as blood glucose, glycated hemoglobin, fasting insulin levels, homeostatic model assessment of insulin resistance index, glucose disposal rate, and glomerular filtration rate did not significantly differ between treatments. Adverse events were comparable between groups. Conclusions Six-month oral ALC supplementation did not affect blood pressure, lipid and glycemic control, insulin sensitivity and kidney function in hypertensive normoalbuminuric and microalbuminuric T2D patients on background statin therapy.

Abstract Introduction. Cardiovascular diseases are the leading cause of death in hemodialysis patients. The decline of residual renal function increases the prevalence and severity of risk factors of cardiovascular morbidity and mortality in these patients. Hypertension is common in dialysis patients and represents an important independent factor of survival in these patients. Methods. The study included 77 patients who are on chronic HD for longer than 3 months. Depending on the measured residual diuresis patients were divided into two groups. The study group consisted of patients with residual diuresis >250 ml/day, while patients from control group had residual diuresis <250 ml/day. All patients had their blood pressure measured before 10 consecutive hemodialysis treatments. Collected data were statistically analyzed using SPSS 16.0. Results. The study included 77 hemodialysis patients, mean age of 56.56±14.6 years and mean duration of hemodialysis treatment of 24.0 months. Of the total number of patients, 39(50.6%) had preserved residual renal function. Hypertension was more common in the group of patients who did not have preserved residual renal function (68.4% vs 25.6%). There was statistically significant negative linear correlation between the volume of residual urine output and the residual clearance of urea and values of systolic blood pressure [(rho=−0.388; p<0.0001); (rho=−0.392; p<0.0005)], values of mean arterial pressure [(rho =−0.272; p<0.05); (rho=−0.261; p=0.023; p<0.05)] and values of pulse pressure in hemodialysis patients [(rho =−0.387; p<0.001); (rho=−0.400; p<0.0005)]. Conclusions. Residual renal function plays an important role in controlling blood pressure in patients on hemodialysis. More attention should be directed to preserve residual renal function, and after the start of hemodialysis by avoiding intensive ultrafiltration with optimal antihypertensive therapy.

Introduction: Increased levels of C-Reactive Protein are found in 30-60% on hemodialysis patients and it is closely associated with the progression of atherosclerosis, cardiovascular morbidity and mortality. Non enzymatic antioxidants are antioxidants which primarily retain potentially dangerous ions of iron and copper in their inactive form and thereby prevent its participation in the production of free radicals. Aim: The aim of the study was to examine the relationship of CRP and non enzymatic antioxidants (albumin, ferritin, uric acid and bilirubin) i.e. examine the importance of CRP as a serum biomarker in assessing the condition of inflammation and its relationship to antioxidant protection in patients on hemodialysis. Methods: The study was cross-sectional, clinical, comparative and descriptive. The study involved 100 patients (non diabetic) on chronic hemodialysis. The control group consisted of 50 subjects without subjective and objective indicators of chronic renal disease. In all patients, the concentration of CRP as well as concentrations of non enzymatic antioxidants were determined. Results: In the group of hemodialysis patients 60% were men and 40% women. The average age of hemodialysis patients was 54.13 ± 11.8 years and the average age of the control group 41.72 ± 9.8 years. The average duration of hemodialysis treatment was 91.42 ± 76.2 months. In the group of hemodialysis patients statistically significant, negative linear correlation was determined between the concentration of CRP in and albumin concentration (rho = -0.251, p = 0.012) as well as negative, statistics insignificant, linear correlation between serum CRP and the concentration of uric acid (r = -0.077, p = 0.448). Furthermore, the positive, linear correlation was determined between serum CRP and ferritin (r = 0.159, p = 0.114) and positive linear correlation between CRP and total serum bilirubin (r = 0.121, p = 0.230). In the control group was determined a statistically significant, positive, linear correlation between serum CRP and uric acid concentration (rho = 0.438, p = 0.001) and statistically significant, positive, linear correlation between serum CRP and total serum bilirubin (rho = 0.510, p = 0.0001) A statistically significant, negative linear correlation was determined between CRP and albumin concentration (rho= -0.393, p = 0.005) as well as statistically significant, negative linear correlation between serum CRP and ferritin control group (rho = -0.391, p = 0.005). Conclusion: Elevated CRP level is a strong and independent predictor of low levels of serum albumin, which indicates that the hypoalbuminemia in hemodialysis patients could be more due to inflammation than malnutrition. There was no statistically significant correlation between CRP and other non enzymatic antioxidants (uric acid, ferritin, bilirubin), which shows that indicators of antioxidant defense in hemodialysis patients must be individually measured to determine their actual stocks and activity.

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