Effect of intraperitoneal injection of sulodexide on peritoneal function and albumin leakage in continuous ambulatory peritoneal dialysis patients.

Peritoneal protein loss is one of the inevitable consequences during continuous ambulatory peritoneal dialysis (CAPD). Our objective was to study the effect of sulodexide on the protein loss and efficiency of dialysis. This study included six patients receiving CAPD treated with sulodexide at the dose of 600 IU/day given by intraperitoneal injection for 10 days. Clinical and biologic parameters were assessed before starting the treatment (D0 and after 10 days of treatment (D10. We also evaluated the benefit of therapy persisting 20 days after the end of treatment (D30. The sulodexide administration produced a significant improvement of the peritoneal function as determined by a significant increase in the following ratios measured at the 4 th h of dwell time on D0 and D30: dialysate-to plasma (D/P) creatinine from 0.63 ± 1.45 to 0.85 ± 0.073 (P = 0.028) and D/P urea from 0.63 ± 0.15 to 79 ± 0.2 (P = 0.048). A significant decrease of albumin leakage was observed, which was 0.90 ± 0.40 g/L at baseline, 0.67 ± 0.36 g/L on the 10 th day, and 0.43 ± 0.22g/L 20 days after the end of treatment. Within 10-day treatment period, use of sulodexide resulted in a reduction in the peritoneal loss of albumin, in addition to improvement of the quality of dialysis and the residual renal function among these patients.

Metabolic syndrome and chronic kidney disease.

To determine the prevalence of metabolic syndrome (MS) in chronic kidney disease (CKD) patients as well as its effects on the progression of CKD, we conducted a prospective, longitudinal study including 180 patients with chronic renal failure followed at the outpatient service of Nephrology at the Saloul's University Hospital of Sousse (Tunisia) over six months. Our study population consisted of 101 men and 79 women. Chronic glomerulonephritis (36.6%) was the most frequent nephropathy. The mean serum creatinine was 249 ± 200 mmol/L and the mean estimated glomerular filtration rate (eGFR) was 55.8 ± 49.2 mL/min. Cardiovascular (CV) impairment was found in 27.2% of the patients. The prevalence of MS was 42.2%. Women had significantly more abdominal obesity than men. Subjects with MS were significantly older and predominantly females who had higher blood pressure and body mass index (BMI). CV complications were more frequent among the MS subjects than among the controls. Glycemia, triglycerides, total cholesterol and low-density lipoprotein-cholesterol (LDL-c) were significantly higher in the group of CKD patients with MS. However, the occurrence of MS was not influenced by the nature of nephropathy, the degree of the CKD and the use of renin-angiotensin blockers or statins. In multivariate analysis, predictors of occurrence of MS in our series included older age, female gender and higher BMI and LDL-c levels. The prevalence of MS in patients with CKD is higher than the general population. These patients should receive special multidisciplinary care to limit CV complications.

Hemodialysis duration, human platelet antigen HPA-3 and IgA isotype of anti-ß2glycoprotein I antibodies are associated with native arteriovenous fistula failure in Tunisian hemodialysis patients.

INTRODUCTION: Arteriovenous fistula (AVF) failure is a major cause of morbidity and mortality in hemodialysis patients. We assessed the role of a large panel of acquired and inherited thrombophilic markers in cases of AVF thrombosis among 101 Tunisians on chronic hemodialysis, all with native AVF. MATERIALS AND METHODS: In this case-control study, we considered the levels of fibrinogen, factor II, factor VII, factor VIII, factor IX, factor X, factor XI, factor XII, von Willebrand factor, natural coagulation inhibitors, D-Dimer, homocysteine, IgG, IgM and IgA anticardiolipin and anti-ß2glycoprotein I (anti-ß2GPI), and anti-H/PF4 antibodies; the presence of Lupus Anticoagulant; and genetic markers (Factor V Leiden, prothrombin 20210G>A, MTHFR 677C>T and 1298A>C). RESULTS: Multivariate analysis indicated that dialysis for >69 months (OR=10.12; 95% CI, 2.53 to 40.52; p=0.001), HPA-3aa genotype (OR=3.58; 95% CI, 1.36 to 9.4; p=0.01) and anti-ß2GPI IgA isotype (OR=3.4; 95% CI, 1.21 to 9.55; p=0.02) were independent risk factors for AVF thrombosis in Tunisian hemodialysis patients. Kaplan-Meier analysis showed that AVF survival was significantly lower for patients with anti-ß2GPI IgA than for patients without this isotype (log-rank test, p=0.014). CONCLUSIONS: IgA anti-ß2GPI may be of clinical relevance among Tunisians. Further studies on the polymorphism of ß2GPI and HPA systems would be helpful for identifying patient groups at high risk of AVF failure.

Protective effect of recombinant human erythropoeitin against cisplatin cytotoxicity and genotoxicity in cultured Vero cells.

Cisplatin is an effective agent against various solid tumors. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity. Therefore, strategies for minimising the toxicity of cisplatin are of a clinical interest. The aim of this study was to investigate the protective effect of recombinant human erythropoietin (rhEPO) against the cytotoxicity and apoptosis induced by cisplatin in cultured Vero cells. Three types of treatments were performed: (i) cells were treated with rhEPO 24 h before exposure to cisplatin (pre-treatment), (ii) cells were treated with rhEPO and cisplatin simultaneously (co-treatment), (iii) cells were treated with rhEPO 24 h after exposure to cisplatin (post-treatment). Our results showed that rhEPO reduced cisplatin-induced cell mortality. Besides, rhEPO administration prevented cisplatin-induced DNA damage. Furthermore, rhEPO decreased the caspase-3 activity and pro-apoptotic factors levels (p53 and Bax) induced by cisplatin. It increased also the expression of the anti-apoptotic factor Bcl2 in Vero cells. Altogether, our results suggest a protective action of rhEPO against cisplatin cytotoxicity and genotoxicity via an anti-apoptotic process. The most protective effect was observed with rhEPO when it was administrated 24 h before cisplatin treatment.

Induction of DNA fragmentation, chromosome aberrations and micronuclei by cisplatin in rat bone-marrow cells: protective effect of recombinant human erythropoietin.

Cisplatin (Cisp) is one of the most effective chemotherapeutic agents. However, at higher doses several side effects may occur. Recombinant human erythropoietin (rhEPO), a glycoprotein regulating haematopoiesis, has recently been shown to exert an important cyto-protective effects in many tissues. The purpose of this study was to explore whether rhEPO protects against Cisp-induced genotoxicity in rat bone-marrow cells. Adult male Wistar rats were divided into six groups of 18 animals each: control group, rhEPO-alone group, Cisp-alone group and three rhEPO+Cisp-groups (pre-, co- and post-treatment condition, respectively). Our results show that Cisp induced a noticeable genotoxic effect in rat bone-marrow cells. In all types of treatment, rhEPO significantly decreased the frequency of micronuclei, the percentage of chromosome aberrations and the level of DNA damage. The protective effect of rhEPO was more efficient when it was administrated 24h before exposure to Cisp.

Recombinant human erythropoietin prevents cisplatin-induced genotoxicity in rat liver and heart tissues via an antioxidant process.

Cisplatin (Cisp) is one of the most effective chemotherapeutic agents. However, at higher doses, liver and heart injuries may occur. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in many tissues. For that reason, we tried to check the protective effect of rhEPO against Cisp-induced genotoxicity and oxidative stress in liver and heart tissues. Our experiments were performed using six groups of adult male Wistar rats. The control group was treated only with saline solution. The rhEPO group was given a single dose of rhEPO. The Cisp group was given a single injection of Cisp. The rhEPO+Cisp groups were given rhEPO simultaneously, 24 hours before, and 5 days after Cisp injection. Our results clearly showed that Cisp induced noticeable DNA damage in the liver and heart, accompanied by a significant increase in protein carbonyl level, reduced glutathione (GSH) depletion, and a decrease in catalase activity. Rats treated with rhEPO, simultaneously, before, or after Cisp injection, remarkably decreased DNA damage. It decreased also the protein carbonyl level, restored GSH depletion, and enhanced catalase activity. Our results highlight an interesting cytoprotective strategy using rhEPO against Cisp-induced liver and heart injuries.

Protective effect of erythropoietin against cisplatin-induced nephrotoxicity in rats: antigenotoxic and antiapoptotic effect.

Cisplatin (Cisp) is an active cytotoxic agent that was found efficient in the treatment of various types of solid tumors. Its nephrotoxic effect has been very well documented in clinical oncology. Erythropoietin (EPO), a renal cytokine-regulating hematopoiesis, has recently been shown to exert important cytoprotective effects in many experimental injuries. The aim of this study was to explore whether EPO would protect against Cisp-induced apoptosis in rat kidney. Adult Wistar rats were treated with saline solution as the control group, Cisp alone, EPO alone, or EPO with Cisp in different treatments: 1) EPO and Cisp simultaneously administrated to animals as a cotreatment; 2) EPO administered 24 hours before Cisp as a pretreatment; and 3) EPO administered 5 days after Cisp injection as a post-treatment. Our results have shown that Cisp induced renal failure, characterized with a significant increase in serum creatinine and blood urea nitrogen (BUN) concentrations. Cisp promoted kidney DNA fragmentation and apoptotic cell death. Apoptosis was revealed by an enhancement of proapoptotic protein (e.g., p53 and Bax) levels, decrease in antiapoptotic proteins (e.g., Bcl2 and Hsp27), and increase in caspase-3 activity. Treatments with EPO restored creatinine and BUN levels and inhibited Cisp-induced DNA damage in the kidney. Apoptosis was also reduced by the upregulation of antiapoptotic protein expressions, downregulation of proapoptotic protein levels, and reduction of caspase-3 activity.

Protective effect of recombinant human erythropoietin against cisplatin-induced oxidative stress and nephrotoxicity in rat kidney.

Cisplatin (Cisp) is one of the most widely used chemotherapeutic agents for the treatment of several human malignancies. The efficacy of Cisp is dose dependent and at higher doses serious kidney injury may occur. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present study was to explore whether rhEPO administration is protective against Cisp-induced oxidative damage and renal injury. Our results showed that Cisp induced a marked oxidative stress and renal failure. Administration of rhEPO (pre-, co- or postadministration with regard to Cisp) decreased oxidative damage induced by Cisp. Recombinant human EPO reduced malondialdehyde and protein carbonyl levels. Recombinant human EPO also prevented glutathione depletion and ameliorated the increased catalase activity induced by Cisp treatment. Furthermore, rhEPO restored creatinine and blood urea nitrogen levels increased by Cisp. We concluded that rhEPO administration especially in pretreatment condition protected rats against Cisp-induced renal oxidative stress and nephrotoxicity.

Epidemiology of hypertension among a population of school children in Sousse, Tunisia.

BACKGROUND: Pediatric hypertension is a field of increasing interest and importance. Early identification of children at risk for hypertension is important to prevent the serious, long-term complications associated with the condition. In Tunisia, there are no data available on the cardiovascular disease risk profile, such as hypertension, in the population of children. OBJECTIVE: To establish the prevalence of hypertension, the percentile distribution of blood pressure and the inter-relationships between hypertension and other cardiovascular disease risk factors among school children. METHODS: An epidemiological survey was conducted based on a representative sample of 1569 urban school children in Sousse, Tunisia. RESULTS: The prevalence of arterial hypertension was 9.6%, with no significant difference between boys (9.2%) and girls (9.9%). The prevalence of systolic and diastolic hypertension was 6.4% and 4.5%, respectively. In both boys and girls, systolic pressure had a highly significant positive correlation with height (boys: r=0.33, P<0.001; girls: r=0.08, P=0.02), weight (boys: r=0.47, P < or = 0.001; girls: r=0.35, P<0.001) and triglyceride concentrations (boys: r=0.13, P<0.001; girls: r=0.10, P=0.006). Among boys, a positive correlation was found between systolic blood pressure and age (r=0.12, P=0.001) and, among girls, a negative correlation was found (r=-0.12, P=0.001). CONCLUSION: This information will be used to help launch a regional program of heart health promotion in schools.