Author(s): Rana Bahaa Mohammed, Mohammed Mahmood Mohammed

Email(s): ,

DOI: 10.52711/0974-360X.2022.00358   

Address: Rana Bahaa Mohammed1, Mohammed Mahmood Mohammed2
1Dialysis Center, Al-karama Teaching Hospital, Baghdad, Iraq.
2Clinical Pharmacy Department (Head), College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.
*Corresponding Author

Published In:   Volume - 15,      Issue - 5,     Year - 2022

Hyperphosphatemia is a serious biochemical abnormality that affected almost patients undergoing maintenance hemodialysis and has independent association with high risk of mortality due to cardiovascular diseases. The mechanism linking hyperphosphatemia to cardiovascular mortality is vascular calcification that it is promoted by elevated serum phosphorus level. The control of hyperphosphatemia remains a major challenge. All currently phosphate binders have requirement for dosing with each meals that contributed to high pill burden and reduce patient compliance. Calcium-based binders preferred to be avoided due to their high risk of vascular classification, while the expensiveness of non-calcium based binder represent their major drawbacks. Niacin; a naturally occurring water-soluble vitamin and the first used antidyslipidemic drug, has been demonstrated to show therapeutic potential for hyperphosphatemia treatment in hemodialysis patients. It decreases phosphorus absorption in the GIT, thereby lowering serum phosphorus level. This study is designed to evaluate the efficacy of niacin as adjuvant therapy to sevelamer carbonate (as a phosphate binder) in hemodialysis patients. This prospective, randomized clinical trial was conducted among patients with hyperphosphatemia. Seventy nine patients were enrolled in this study; only 39 patients completed the study. Thirty nine patients were assigned randomly into two groups; group (1) 19 patients treated with sevelamer alone (2400mg/day), group (2) 20 patients treated with a combination of sevelamer (2400mg/day) and niacin (1000 mg/day) for 2 months . Clinical outcomes (Pi, Ca, Ca x P product) serum levels were evaluated at time of enrolment, after 1 month and after 2 month of treatment. Results of this study showed that the patients who administered orally niacin as adjuvant to sevelamer had the superiority over using sevelamer alone in the reduction of both serum phosphorus level and (Ca x P) product level (-30% and -37%) respectively after 2 months of treatment in respect to baseline levels. Meanwhile, there was no statistically significant difference observed in serum calcium level. Administration of niacin for hemodialysis patients is an effective strategy for reducing the serum levels of inorganic phosphorus and calcium-phosphorus product which subsequently reduce risks of cardiovascular diseases associated with hyperphosphatemia.

Cite this article:
Rana Bahaa Mohammed, Mohammed Mahmood Mohammed. Potential role of Niacin as Adjuvant to Sevelamer on Serum levels of Inorganic phosphorus, Calcium and Calcium-phosphorus product in Hemodialysis patients with Hyperphosphatemia. Research Journal of Pharmacy and Technology. 2022; 15(5):2158-2. doi: 10.52711/0974-360X.2022.00358

Rana Bahaa Mohammed, Mohammed Mahmood Mohammed. Potential role of Niacin as Adjuvant to Sevelamer on Serum levels of Inorganic phosphorus, Calcium and Calcium-phosphorus product in Hemodialysis patients with Hyperphosphatemia. Research Journal of Pharmacy and Technology. 2022; 15(5):2158-2. doi: 10.52711/0974-360X.2022.00358   Available on:

1.    Shaman AM, Kowalski SR. Hyperphosphatemia management in patients with chronic kidney disease. Saudi Pharm J. 2016; 24:494-505
2.    Wojcicki, J.M. Hyperphosphatemia is associated with anemia in adults without chronic kidney disease: results from the National Health and Nutrition Examination Survey (NHANES): 2005–2010.  BMC Nephrol.2013; 14:178.
3.    Wagner CA. Novel insights into the regulation of systemic phosphate homeostasis and renal phosphate excretion. J Nephrol. 2007;20:130–134.  
4.    Adrian C., Anjay R.Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence. BMC Nephrology 2013, 14:153.
5.    Wilkieson TJ, Rahman MO, Gangji AS, Voss M, Ingram AJ, Ranganath N, et al. Coronary artery calcification, cardiovascular events, and death: a prospective cohort study of incident patients on hemodialysis. Can J Kidney Health Dis. 2015 Aug 12; 2:29.
6.    Slinin Y, Foley RN, Collins AJ. Calcium, phosphorus, parathyroid hormone, and cardiovascular disease in hemodialysis patients: the USRDS waves 1, 3, and 4 study. J Am Soc Nephrol 2005; 16: 1788–1793.
7.    Senthilkumar S, Dhivya K. Prognostic Potential of Serum Biomarkers as Predictors for Cardiovascular Complications and Disease Progression in Chronic Kidney Disease Patients. Research J. Pharm. and Tech. 2016; 9(3): 227-234.
8.    Taniguchi M, Fukagawa M, Fujii N, Hamano T, Shoji T, Yokoyama K, et al. Serum phosphate and calcium should be primarily and consistently controlled in prevalent hemodialysis patients. Ther Apher Dial. 2013; 17:221–228.
9.    Martinez-Moreno JM, Herencia C, de Oca AM, Díaz-Tocados JM, Vergara N, Gómez-Luna MJ, et al. High phosphate induces a pro-inflammatory response by vascular smooth muscle cells and modulation by vitamin D derivatives. Clin Sci (Lond). 2017;131:1449–1463.
10.    Yamada S, Tokumoto M, Tatsumoto N, Taniguchi M, Noguchi H, Nakano T, et al. Phosphate overload directly induces systemic inflammation and malnutrition as well as vascular calcification in uremia. Am J Physiol Renal Physiol. 2014;306: 1418–1428.
11.    Villa-Bellosta R. Vascular calcification revisited: a new perspective for phosphate transport. Curr Cardiol Rev. 2015
12.    London GM, Pannier B, Marchais SJ, Guerin AP. Calcification of the aortic valve in the dialyzed patient. J Am Soc Nephrol. 2000;11(4):778-783
13.    Priya C. Mouli, Sneha S, Shivangi A. Balekundri, Shlini P. Efficacy of Sevelamer Hydrochloride and Sevelamer Carbonate in Hyperphosphatemia Condition- A Review. Asian J. Research Chem. 2018; 11(4):768-77213- Floege J. Phosphate binders in chronic kidney disease: a systematic review of recent data. J Nephrol. 2016 ;29(3):329-340.
14.    Wang AY. Calcium balance and negative impact of calcium load in peritoneal dialysis patients. Perit Dial Int. 2014 ;34(4):345-352.
15.    Kirkland JB. Niacin status, NAD distribution and ADP-ribose metabolism. Curr Pharm Des. 2009; 15:3-11.
16.    Akula G, Venkatesh B, Sanjayraj K, Phanindra SS, Jaswanth A. Validated RP-HPLC Method for the Simultaneous Estimation of Simvastatin and Niacin. Asian J. Research Chem. 2016;  9(2): 62-66.
17.    Altschul R, Hoffer A, Stephen JD. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys. 1955;54(2): 558–559.
18.    Yasmeen G, Dawani ML, Mahboob T. Hypophosphatemic effect of niacin extended release in ischemic kidney disease. EXCLI J. 2015;14:1095-1103
19.    Shin S, Lee S.Niacin as a drug repositioning candidate for hyperphosphatemia management in dialysis patients. Ther Clin Risk Manag. 2014;10:875-883.
20.    Carfagna F, Del Vecchio L, Pontoriero G, Locatelli F. Current and potential treatment options for hyperphosphatemia. Expert Opin Drug Saf. 2018; 17(6):597–607.
21.    Ahmadi F, Shamekhi F, Lessan-Pezeshki M, Khatami MR.Coparison of efficacy of the phosphate binders nicotinicacid and sevelamerhydrochloride in hemodialysis patients. Saudi J Kidney Dis Transpl. 2012;23(5):934-938.
22.    Restrepo Valencia CA, Cruz J. Safety and effectiveness of nicotinic acid in the management of patients with chronic renal disease and hyperlipidemia associated to hyperphosphatemia. Nefrologia. 2008;28(1):61-66.
23.    Thakkar RB, Kashyap ML, Lewin AJ, Krause SL, Jiang P, Padley RJ. Acetylsalicylic acid reduces niacin extended-release-induced flushing in patients with dyslipidemia. Am J Cardiovasc Drugs. 2009;9(2):69-79.
24.    COBAS C311 Phosphorus (Inorganic) method sheet (Catalog Number. 03183793122,[product insert on the internet].Germany:Roche/HitachiInc. [cited at JAN/2018] Available from ts /GetDocument?documentId=6a46a66e-4802-e911-edbb-00215a9b3428.
25.    COBAS C311 calcium method sheet (Catalog Number. 20763128322, [product insert on the internet]. Germany:Roche/Hitachi Inc. [cited at MAY/2018] Available From: https://pim- eservices. eLD_SF/us/en/Documets/ GetDocument?documentId=1c5021b2-51f2-e311-98a1-00215a9b0ba8.
26.    National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. AmJ  Kidney  Dis2003;42:  S77–S84.
27.    Rabbani S, Sathvik BS, Rao P, Kurian M, EL essawy B H. Hyperphosphatemia End stage renal disease:prevelance and patients characterstics of multiethnic population of united arab emirates.. Int J Pharm Pharm Sci.2017;9(12): 283-287.
28.     Abdu A,  Abdu A,  Arogundade FA. Prevalence and pattern of chronic kidney disease-mineral bone disorders among hemodialysis patients in kano, northwest Nigeria. Ann Afr Med.2019;18(4): 191-195.
29.    Salhab  N.; Alrukhaimi  M.; Kooman  J.; Fiaccadori  E.; Aljubori  H.; Rizk R.; Karavetian  M. Effect of Intradialytic Exercise on Hyperphosphatemia and Malnutrition. Nutrients 2019, 11, 2464.
30.    Mohamed Koya SM. Management of phosphate abnormalities in hemodialysis patients: Findings from Malaysia. Saudi J Kidney Dis Transpl 2019;30:670-677  
31.    Nafar M, Sabaghian T, Khoshdel A, Alipour B, Samavat S. Serum Calcium and Phosphorus Levels in Hemodialysis Patients: A Large Population-Based Multicenter Study, Iran Red Crescent Med J. 2019 ; 21(1):1-9
32.    Gray K, Ficociello LH, Hunt AE, Mullon C, Brunelli SM.Phosphate binder pill burden, adherence, and serum phosphorus control among hemodialysis patients converting to sucroferric oxyhydroxide. Int J Nephrol Renovasc Dis. 2019;12:1-8
33.    Amann K, Gross ML, London GM, Ritz E. Hyperphosphataemia-a silent killer of patients with renal failure? Nephrol Dial Transplant. 1999;14(9):2085-2087.
34.    Palmer SC, Hayen A, Macaskill P, Pellegrini F, Craig JC, Elder GJ, et al. Serum levels of phosphorus,  parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. JAMA 2011;305:1119–27.
35.    Alattiya TN, Mohammed MM, Jaleel NA, Jamil NS, Al-Sabbag MS. Effect of Oral L-carnitine Supplementation on the Mortality Markers in Hemodialysis Patients. Int. J. Pharm. Sci. Rev. Res., 41(1), November - December 2016; Article No. 14, Pages: 64-69.
36.    Zahed NS, Zamanifar N, Nikbakht H. Effect of low dose nicotinic acid on hyperphosphatemia in patients with end stage renal disease. Indian J Nephrol. 2016;26(4):239-243
37.    Khalid SA, Inayat F, Tahir MK, Younus A, Ahmad HI, Bokhari SRA, Yaqoob U. Nicotinic acid as a Phosphate-lowering Agent in Patients with End-stage Renal Disease on Maintenance Hemodialysis: A Single-center Prospective Study. Cureus. 2019 30;11(4):e4566
38.    Sampathkumar K. Niacin and analogs for phosphate control in dialysis–perspective from a developing country. Int Urol Nephrol. 2009;41:913–918.
39.    Sabbagh Y, O’Brien SP, Song W, Boulanger JH, Stockmann A, Arbeeny C, et al. Intestinal npt2b plays a major role in phosphate absorption and homeostasis. J Am Soc Nephrol. 2009;20(11):2348–58.
40.    El Borolossy R, El Wakeel LM, El Hakim I, Sabri N. Efficacy and safety of nicotinamide in the management of hyperphosphatemia in pediatric patients on regular hemodialysis. Pediatr Nephrol. 2016;31(2):289–96.
41.    Ikuta K, Segawa H, Sasaki S, Hanazaki A, Fujii T, Kushi A, et al. Effect of Npt2b deletion on intestinal and renal  inorganic   phosphate (Pi) handling. Clin Exp Nephrol. 2018 ;22(3):517-528.
42.    Nomura K, Tatsumi S, Miyagawa A, Shiozaki Y, Sasaki S, Kaneko I, et al . Hepatectomy-related hypophosphatemia: a novel phosphaturic factor in the liver-kidney axis. J Am Soc Nephrol.  2014;25(4):761–72.
43.    Wu KI, Bacon RA, Al-Mahrouq HA, Kempson SA. Nicotinamide as a rapid-acting inhibitor of renal brush-border phosphate transport. Am J Physiol. 1988; 255(1): 15–21.
44.    Block GA, Wheeler DC, Persky MS, Kestenbaum B, Ketteler M, Spiegel DM, et al. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol. 2012;23(8):1407-1415.
45.    Ketteler M, Liangos O, Biggar PH. Treating hyperphosphatemia-current and advancing drugs. Expert Opin Pharmacother. 2016 ;17(14):1873-1879

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