Effects of Ramipril on Biomarkers of Endothelial Dysfunction and Inflammation in Hypertensive Children on Maintenance Hemodialysis: the SEARCH Randomized Placebo-Controlled Trial.

BACKGROUND: Hypertension, endothelial dysfunction, and inflammation are associated with increased cardiovascular mortality in end-stage kidney disease. We evaluated the effects of ACE (angiotensin-converting enzyme) inhibition on biomarkers of endothelial dysfunction and inflammation in hypertensive children with end-stage kidney disease on maintenance hemodialysis. METHODS: In a randomized, double-blind, placebo-controlled trial, 135 (72 males/63 females) children and adolescents (age 7-15 years) were randomly assigned to treatment with either 2.5 mg once daily ramipril (n=68) or placebo (n=67) for 16 weeks. Primary outcome were the serum concentrations of asymmetrical dimethylarginine, a marker of endothelial dysfunction and hs-CRP (high-sensitivity C-reactive protein), a marker of inflammation. Changes in IL-6 (interleukin-6), TNF-α (tumor necrosis factor-alpha), systolic (S), and diastolic (D) blood pressure were secondary outcomes. Change in potassium levels and incidence of hyperkalemia were among the safety parameters. RESULTS: Ramipril, but not placebo, significantly reduced serum levels of asymmetrical dimethylarginine (-79.6%; P<0.001), hs-CRP (-46.5%; P<0.001), IL-6 (-27.1%; P<0.001), and TNF-α (-51.7%; P<0.001). Systolic blood pressure and diastolic blood pressure were significantly lowered in both groups with a greater reduction in children receiving ramipril (median between-group differences -12.0 [95% CI -18.0 to -9.5] and -9.0 [95% CI -12.0 to -4.5]; P<0.001, respectively). Changes in asymmetrical dimethylarginine, hs-CRP, IL-6, or TNF-α in the ramipril group did not significantly correlate with blood pressure reductions. No severe cases of hyperkalemia or other serious treatment-associated adverse events were observed. CONCLUSIONS: Ramipril improves biomarkers of endothelial dysfunction and inflammation in hypertensive children on maintenance hemodialysis in addition to its efficacious and safe potential to lower blood pressure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04582097.

Marital status and paternity in patients with Transfusion- Dependent Thalassemia (TDT) and Non Transfusion-Dependent Thalassemia (NTDT): an ICET - A survey in different countries.

BACKGROUND: More than five decades ago, thalassemia major (TDT) was fatal in the first decade of life. Survival and quality of life have improved progressively thanks to the implementation of a significant advance in diagnostic and therapeutic methods, consisting mainly of a frequent transfusion program combined with intensive chelation therapy. Improvement also includes imaging methods used to measure liver and cardiac iron overload. Improved survival has led to a growing number of adults requiring specialised care and counselling for specific life events, such as sexual maturity and acquisition of a family. AIMS OF THE STUDY: The main aim is to present the results of a survey on the marital and paternity status in a large population of adult males with TDT and NTDT living in countries with a high prevalence of thalassemia and a review of current literature using a systematic search for published studies. RESULTS: Ten out of 16 Thalassemia Centres (62.5%) of the ICET-A Network, treating a total of 966 male patients, aged above 18 years with ß- thalassemias (738 TDT and 228 NTDT), participated in the study. Of the 966 patients, 240 (24.8%) were married or lived with partners, and 726 (75.2%) unmarried. The mean age at marriage was 29.7 ± 0.3 years. Of 240 patients, 184 (76.6%) had children within the first two years of marriage (2.1 ± 0.1 years, median 2 years, range 1.8 - 2.3 years). The average number of children was 1.32 ± 0.06 (1.27 ± 0.07 in TDT patients and 1.47 ± 0.15 in NTDT patients; p: >0.05). Whatever the modality of conception, 184 patients (76.6%) had one or two children and 1 NTDT patient had 6 children. Nine (4.8%) births were twins. Of 184 patients, 150 (81.5%) had natural conception, 23 (12.5%) required induction of spermatogenesis with gonadotropins (hCG and hMG), 8 (4.3%) needed intracytoplasmic sperm injection (ICSI) and 3 adopted a child. 39 patients with TDT and NTDT asked for medical help as they were unable to father naturally: 7 TDT patients (17.9%) were azoospermic, 17 (37.7%) [13 with TDT and 4 with NTDT] had dysspermia and 15 (33.3%) [13 with TDT and 2 with NTDT] had other "general medical and non-medical conditions". CONCLUSIONS: Our study provides detailed information in a novel area where there are few contemporary data. Understanding the aspects of male reproductive health is important for physicians involved in the care of men with thalassemias to convey the message that prospects for fatherhood are potentially good due to progressive improvements in treatment regimens and supportive care.

Effect of Omega-3 Fatty Acids on Serum Lipid Profile and Oxidative Stress in Pediatric Patients on Regular Hemodialysis: A Randomized Placebo-Controlled Study.

OBJECTIVE: We sought to evaluate the effects of omega-3 fatty acids supplementation on serum lipid profile and oxidative stress markers in pediatric patients with end-stage renal disease on regular hemodialysis (HD). DESIGN: This study was a double-blinded, randomized, placebo-controlled trial conducted on 49 pediatric patients on regular HD for at least 6 months. INTERVENTION: Patients were randomly divided into either omega-3 group (n = 25) who received 1-g oral omega-3 capsule once daily for 16 weeks or placebo group (n = 24) who received 1-g matching oral placebo capsule once daily for 16 weeks. MAIN OUTCOME MEASURE: Lipid profile markers including: total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and oxidative stress markers including the following: malondialdehyde, glutathione peroxidase, and superoxide dismutase were measured at baseline and after 16 weeks of supplementation. RESULTS: By the end of the study, children in omega-3 group showed a highly significant reduction in total cholesterol and a highly significant increase in glutathione peroxidase and superoxide dismutase levels. CONCLUSION: The administration of omega-3 has a beneficial effect on serum lipid profile and oxidative stress in children undergoing HD.

Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis.

BACKGROUND: Hyperphosphatemia is a common problem in patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (HD) and contributes to the development of secondary hyperparathyroidism and cardiovascular complications. Nicotinamide (NAM) has been shown in some studies to inhibit intestinal and renal sodium/phosphorus co-transporters and reduce serum phosphorus levels. We have therefore evaluated the efficacy and safety of NAM as adjunctive therapy to calcium-based phosphate binders to control hyperphosphatemia in hemodialysis patients. METHODS: Sixty pediatric HD outpatients were randomly divided into two equally sized groups (30 children each). One group received calcium-based phosphate binder (control group), and the other received both the calcium-based phosphate binder + NAM at a dose of 100 mg twice or three times daily (nicotinamide group). Both groups were followed for a 6-month period. RESULTS: Over the 6-month treatment period, children in the NAM group showed a significant decline in the levels of serum phosphorus (p = 0.0001), serum calcium-phosphorus (Ca × P; p = 0.0001) product and parathyroid hormone (p = 0.02) versus baseline values and those of the control group. After 6 months of NAM treatment, the mean serum high-density lipoprotein cholesterol levels had increased significantly (p = 0.01), and the median serum triglyceride levels had decreased (p = 0.009). There was no significant change in any of these parameters among the children of the control group. The major adverse events associated with the NAM therapy were diarrhea, flushing and nausea. CONCLUSION: The addition of NAM to therapy with phosphate binders is effective in lowering phosphorus levels and has a beneficial effect on the lipid profile with only mild side effects.

Implementation of clinical pharmacy services in a pediatric dialysis unit.

BACKGROUND: End-stage renal disease patients on hemodialysis are on complex drug regimens consisting of multiple medications, many of which are administered in several doses per day. Consequently, such patients are at high risk for developing drug therapy-related problems (DTRPs). The aim of this study was to detect DTRPs in children undergoing hemodialysis and to assess and evaluate the impact of interventions by the clinical pharmacist on the clinical outcome of children undergoing hemodialysis. METHODS: Fifty hemodialysis outpatients were randomly divided into two groups (25 each): the control group and the test group. During the 9-month study period, patients in the control group received the usual medical care, and those in the test group received pharmaceutical care 3 times weekly in addition to the usual medical care. RESULTS: After 9 months of pharmaceutical care implementation, the test group showed a significant decline in systolic and diastolic blood pressure (p = 0.0001), serum phosphorus level (p = 0.006) and parathyroid hormone level (p = 0.001) versus their baseline values and versus the control. The serum Ca*P product level of the test group decreased (p = 0.001) after intervention versus baseline. Serum calcium level significantly increased in test group (p = 0.02) and decreased in the control group (p = 0.001) versus the respective baseline values. Satisfaction with the renal treatment significantly improved in the test group (p = 0.0001) versus the control group after 9 months of pharmaceutical care implementation based on Renal Treatment Satisfaction Questionnaire scores. CONCLUSIONS: Pharmacist-initiated pharmaceutical care improved the satisfaction and biochemical findings of patients on hemodialysis.