Efficacy and Safety of Nicotinamide in Management of Hyperphosphatemia in Pediatric Patients on Regular Hemodialysis- a Pilot study

Abstract

Hyperphosphatemia is a common complication in the ESRD patients where the diminished phosphorous filtration and excretion with the progression of CKD is the main underlying cause. Elevated serum phosphorus contributes to the development of secondary hyperparathyroidism and renal osteodystrophy. In dialysis patients, hyperphosphatemia can lead to metastatic calcifications and is associated with increased cardiovascular mortality. The majority of dialysis patients require dietary phosphorus restrictions and phosphate binders to control serum phosphorus. Despite these measures, most patients fail to achieve predialysis serum phosphorus levels <5.5 mg/dl. Nicotinamide (NAM) (also known as niacinamide) and niacin are the principle forms of vitamin B3. Despite structural similarities and equivalent nutritional properties, NAM and niacin have differing actions and adverse effect profiles. Although NAM can cause gastrointestinal discomfort and reportedly lowers platelet counts, it does not cause flushing, which is commonly seen with niacin. In vitro studies have shown that NAM decreases phosphate uptake by inhibiting sodium/phosphorus co-transporters in the renal proximal tubule (Na/Pi2a) and intestine (Na/Pi2b). Keeping in view the need of inexpensive phosphate control, NAM was studied to find out the efficacy and safety in reducing serum phosphorus in Hemodialysis patients. Our study aimed to evaluate the efficacy and safety of NAM in management of hyperphosphatemia in addition to calcium based phosphate binder in pediatric patients undergoing hemodialysis. - Sixty eligible patients at the Pediatric nephrology and dialysis unit, Ain Shams University Children's Hospital were simply randomized to be assigned to either Group I or Group II. • Group I (Control group): received the calcium based phosphate binder (calcium acetate or calcium carbonate) 500mg 2-3 times daily for 6 months. • Group II (Nicotinamide group): received the calcium based phosphate binder (calcium acetate or calcium carbonate) 500mg 2-3 times daily in addition to NAM tablet for 6 months. - The following data were collected from all patients at baseline: patient demographics, history of medications administered, history of presence of peptic ulcer, sever liver disease, diabetes mellitus and blood pressure measurement pre dialysis session. - The following laboratory parameters were collected from all patients at baseline and at end of the study: KFT, CBC, PTH, and ALP. - At baseline and at end of study blood samples were collected from all patients to assess the LFT, Lipid profile and BGL. - Calcium, Phosphorus and Ca*P product were evaluated every month till the end of the study. Results of our study showed the following: • At baseline, there was no significant difference (p≥0.05) between both the control and NAM groups in the mean patients’ age, the mean patients’ weight, the proportion of male to female patients, clinical characteristics. • There was no significant difference (p>0.05) in neither the baseline mean systolic blood pressure nor diastolic blood pressure nor baseline laboratory data between both control, NAM groups. After 6 months of NAM administration to test group, the following were observed: • The control group showed no significant change (p>0.05) in the mean serum calcium over the baseline, 3rd month and 6th month measurements. Moreover NAM group showed no significant change (p>0.05) in the mean serum calcium over the baseline, 3rd month and 6th month measurements. • The control group showed significant increase (p = 0.0013) in mean serum phosphorus over baseline, 3rd month and 6th month measurements. Moreover NAM group showedsignificant decrease (p= 0.0001) in the mean serum phosphorus over the baseline, 3rd month and 6th month measurements. • The control group showed significant increase (p = 0.0011) in mean serum Ca* P product over baseline, 3rd month and 6th month measurements. Moreover NAM group showed significant decrease (p= 0.0001) in the mean serum Ca* P product over the baseline, 3rd month and 6th month measurements. • The NAM group showed a significant decrease (p=0.02) in the median serum PTH levels while the control group showed no significant change (p>0.05) in their median serum PTH level as compared to their baseline values. • The NAM group showed no significant change (p>0.05) in the median serum ALP levels, also the control group showed no significant change (p>0.05) in their median serum ALP level as compared to their baseline values. • The NAM group showed no significant change (p> 0.05) in the mean serum LDL level, also the control group showed no significant change (p> 0.05) in the mean serum LDL level as compared to their baseline values. • The NAM group showed a highly significant decrease (p< 0.01) in the mean serum HDL level, while the control group showed no significant change (p> 0.05) in the mean serum HDL level as compared to their baseline values. • The NAM group showed no significant change (p>0.05) in the median serum TC levels, also the control group showed no significant change (p>0.05) in their median serum TC level as compared to their baseline values. • The NAM group showed a highly significant decrease (p<0.01) in the median serum TG levels, while the control group showed no significant change (p>0.05) in their median serum TG level as compared to their baseline values. • 20 patients of the NAM group experienced the following adverse effects: 24% reported diarrhea, 24% reported flushing, 9% reported diarrhea and flushing, 5% reported flushing and nausea, 19% reported nausea, 9% reported nausea and diarrhea, 5% reported nausea and vomiting and 5% reported nausea, vomiting and diarrhea. • There were no significant differences (p>0.05) between NAM and control group in neither the liver function (AST, ALT) nor the kidney function (creatinine, blood urea nitrogen, uric acid). • There were no significant differences (p>0.05) between the NAM and control group in neither the mean hemoglobin nor the mean white blood cells. • Concerning the platelets, the NAM group showed significant (p=0.014) decrease in the mean platelets count as compared to their baseline values but remain in the normal range and no patients developed bleeding during the study.