Abstract
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.
Similar content being viewed by others
References
Six I, Maizel J, Barreto FC, Rangrez AY, Dupont S, Slama M (2012) Effects of phosphate on vascular function under normal conditions and influence of the uraemic state. Cardiovasc Res 96:130–139
Ganesh SK, Stack AG, Levin NW, Hulbert-Shearon T, Port FK (2001) Association of elevated serum PO4, Ca * PO4 product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 12:2131–2139
Block GA, Hulbert-Shearon TE, Levin NW, Port FK (1998) Association of serum phosphorus and calcium × phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 31:607–624
Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA (2008) The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol 19:1092–1105
Levin A, Li YC (2005) Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease. Kidney Int 68:1973–1981
Tonelli M, Pannu N, Manns B (2010) Oral phosphate binders in patients with kidney failure. N Engl J Med 362:1312–1324
Hutchison AJ, Smith CP, Brenchley PE (2011) Pharmacology, efficacy and safety of oral phosphate binders. Nat Rev Nephrol 7:578–589
Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM (2012) Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 23:1407–1415
Manns B, Stevens L, Miskulin D, Owen WF Jr, Winkelmayer WC, Tonelli M (2004) A systematic review of sevelamer in ESRD and ananalysis of its potential economic impact in Canada and the United States. Kidney Int 66:1239–1247
Lenglet A, Liabeuf S, Guffroy P, Fournier A, Brazier M, Massy Z (2013) Use of nicotinamide to treat hyperphosphatemia in dialysis patients. Drugs R&D 13:165–173
O’Brien T, Silverberg J, Nguyen T (1992) Nicotinic acid induced toxicity associated with cytopenia and decrease level of thyroxin-binding globulin. Mayo Clin Proc 67:465–468
Katai K, Tanaka H, Tatsumi S (1999) Nicotinamide inhibits sodium-dependent phosphate cotransport activity in rat small intestine. Nephrol Dial Transplant 14:1195–1201
Kempson SA, Colon-Otero G, Ou SY, Turner ST, Dousa TP (1981) Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat. J Clin Invest 67:1347–1360
Maccubbin D, Tipping D, Kuznetsova O, Hanlon WA, Bostom AG (2010) Hypophosphatemic effect of niacin in patients without renal failure: a randomized trial. Clin J Am Soc Nephrol 5:582–589
Eto N, Miyata Y, Ohno H, Yamashita T (2005) Nicotinamide prevents the development of hyperphosphatemia by suppressing intestinal sodium-dependent phosphate transporter in rats with a renin-induced renal failure. Nephrol Dial Transplant 20:1378–1384
Takahashi Y, Tanaka A, Nakamura T, Fukuwatari T, Shibata K, Shimada N (2004) Nicotinamide suppress hyperphosphatemia in hemodialysis patients. Kidney Int 65:1099–1104
Sabbagh Y, O’Brien SP, Song W, Boulanger JH, Stockmann A, Arbeeny C (2009) Intestinal npt2b plays a major role in phosphate absorption and homeostasis. J Am Soc Nephrol 20:2348–2358
Schiavi SC, Tang W, Bracken C, O’Brien SP, Song W, Boulanger J (2012) Npt2b deletion attenuates hyperphosphatemia associated with CKD. J Am Soc Nephrol 23:1691–1700
Cheng SC, Young DO, Huang Y, Delmez JA, Coyne DW (2008) A randomized, double-blind, placebo-controlled trail of niacinamide for reduction of phosphorus in hemodialysis patients. Clin J Am Soc Nephrol 3:1131–1138
Young DO, Cheng SC, Delmez JA, Coyne DW (2009) The effect of oral niacinamide on plasma phosphorus levels in peritoneal dialysis patients. Perit Dial Int 29:562–567
Sampathkumar K, Selvam M, Sooraj YS, Gowthaman S, Ajeshkumar RN (2006) Extended release nicotinic acid: a novel oral agent for phosphate control. Int Urol Nephrol 38:171–174
Vasantha J, Soundararajan P, Vanitharani N, Kannan G, Thennarasu P, Neenu G (2011) Safety and efficacy of nicotinamide in the management of hyperphosphatemia in patients on hemodialysis. Indian J Nephrol 21:245–249
Shahbazian H, Mohtashami A, Ghorbani A, Abbaspour MR, Belladi Musavi SS, Hayati F (2011) Oral nicotinamide reduces serum level of phosphorus, increase HDL, and induces thrombocytopenia in hemodialysis patients: a double-blind, randomized clinical trial. Nefrologia 31:58–65
Muller D, Mehling H, Otto B, Otto B, Bergmann-Lips R, Luft F, Jordan J (2007) Niacin lowers serum phosphorus and increases HDL cholesterol in dialysis patients. Clin J Am Soc Nephrol 2:1249–1254
Knip M, Douek IF, Moore WP, Gillmor HA, McLean AEM, Bingley PJ (2000) Safety of high doses nicotinamide: a review. Diabetologia 43:1337–1345
Rottembourg J, Launay-Vacher V, Massard J (2005) Thrombocytopenia induced by nicotinamide in hemodialysis patients. Kidney Int 68:2911–2912
Gale E, Bingley P, Emmett C, Collier T (2004) European Nicotinamide Diabetes Intervention Trial (ENDIT) Group: a randomized controlled trial of intervention before the onset of type 1 diabetes. Lancet 363:925–931
Delanaye P, Weekers L, Krzesinski J (2006) Diarrhea induced by high doses of nicotinamide in dialysis patients. Kidney Int 69:1914
Disclosure of funding
No pharmaceutical and/or industrial support, and no funding was received from National Institute of Health (NIH), Welcome Trust, Howard Hughes Medical Institute (HHMI) or others.
Compliance with ethical standards
The study protocol was revised and approved by the ethics committee of the Faculty of Pharmacy, Ain Shams University. The study was performed in accordance with the Declaration of Helsinki. Prior to participation all caregivers of eligible children were informed about the study protocol and signed a written informed consent.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
El Borolossy, R., El Wakeel, L.M., El Hakim, I. et al. Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis. Pediatr Nephrol 31, 289–296 (2016). https://doi.org/10.1007/s00467-015-3208-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-015-3208-1