Sevelamer efficiency in real practice: the Saint-Petersburg experience

Aid: hyperphosphatemia in hemodialysis patients remains one of the difficult challenges in correcting uremic syndromes associated with overall and cardiovascular mortality, adverse cardiovascular remodeling and calcification, although lowering of phosphatemia was never been shown to be associated with better outcomes. The stringent clinical trial conditions do not always correspond to real practice, where many factors can have opposite influence; their results should be applied with considering the specific circumstances, an analysis of real clinical practice is necessary. Methods: the treatment group included 240 patients who started sevelamer therapy. The control group was matched for baseline phosphatemia, age, duration of RRT. Results: for 17±3 months, 29 patients died in the treatment group (12%) compared to 46 patients (19%) in the control group, the hazard ratio was 0.616 (95%CI 0.389÷0.981). The decrease in phosphate levels was 0.19±0.09 vs. its increase by 0.03±0.07 mmol/l in the control group; effect size -2.73 (95%CI -2.74÷-2.73SD). The decrease in calcemia was 0.03±0.06 vs. growth 0.04±0.08 mmol/L in control (effect size -0.99 (95%CI -1.18÷-0.80SD). A decrease in PTH level by 46±84 vs. its increase by 188±114 pg/ml; effect size -2.33 (95%CI -2.56÷-2.10). In the multiple regression model for the whole group, the significance of entering the treatment group slightly changed compared to unadjusted (-43% risk). Each 0.1 mmol/L of higher calcemia added 20% risk, phosphatemia - 17%. Compared with the similar risks for ranges of 300-600 and >600 pg/ml (median 782) for ranges 150-300 and <150 pg/ml, the risks of death were 2 and 6.5 times higher. In separate analysis, the initially higher level of phosphate (for every 0.1 mmol/L) was associated with a higher (by 28%) the risk of death (similar in the treatment and control). To an even greater degree, the decrease in phosphate during therapy was associated with the risk: a decrease in phosphate by every 0.1 mmol/L in multiple regression was correlated with a 56% lower risk. For every 100 pg/ml above baseline PTH, therapy resulted in lesser decrease in phosphate levels by 0.01 mmol/L (p<0.001); for each decrease in PTH level by 100 pg/ml during therapy, a greater decrease in phosphate level by 0.08 mmol/L was obtained (p<0.001); for every 0.1 mmol/L higher baseline phosphate level, therapy produced a 0.02 mmol/L larger decrease. Conclusion: Sevelamer use was associated with reduction of mortality risk. The greater the severity of hyperparathyroidism and its resistance prevented effective reduction of phosphatemia during therapy with sevelamer, the better effect was observed at higher baseline phosphate levels.

гемодиализ, гиперфосфатемия, севеламер, hemodialysis, hyperphosphatemia, sevelamer

1. Lynch KE, Lynch R, Curhan GC, Brunelli SM. Prescribed dietary phosphate restriction and survival among hemodialysis patients. Clin J Am Soc Nephrol. 2011;6(3):620-629. doi:10.2215/CJN.04620510

2. Carrigan A, Klinger A, Choquette SS, et al. Contribution of food additives to sodium and phosphorus content of diets rich in processed foods. J Ren Nutr. 2014;24(1):13-19e1. doi:10.1053/j.jrn.2013.09.003

3. Maduell F, Moreso F, Pons M, et al. High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol. 2013;24(3):487-497. doi:10.1681/ASN.2012080875

4. Maduell F, Arias M, Durán CE et al. Nocturnal, every-other-day, online haemodiafiltration: an effective therapeutic alternative. Nephrol Dial Transplant. 2012;27(4):1619-31. doi: 10.1093/ndt/gfr491.

5. Sekercioglu N, Thabane L, Díaz Martínez JP et al. Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis. PLoS One. 2016;11(6):e0156891. doi:10.1371/journal.pone.0156891

6. Palmer SC, Gardner S, Tonelli M, et al. Phosphate-Binding Agents in Adults With CKD: A Network Meta-analysis of Randomized Trials [published correction appears in Am J Kidney Dis. 2017 Sep;70(3):452]. Am J Kidney Dis. 2016;68(5):691-702. doi:10.1053/j.ajkd.2016.05.015

7. Ruospo M, Palmer SC, Natale P, et al. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2018;8(8):CD006023. doi:10.1002/14651858.CD006023.pub3

8. Wald R, Rabbat CG, Girard L, et al. Two phosphAte taRGets in End-stage renal disease Trial (TARGET): A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2017;12(6):965-973. doi:10.2215/CJN.10941016

9. Bhargava R, Kalra PA, Hann M et al. A randomized controlled trial of different serum phosphate ranges in subjects on hemodialysis. BMC Nephrol. 2019;20(1):37. doi:10.1186/s12882-019-1216-2

10. Chen L, He JX, Chen YY, Ling YS, Lin CH, Guan TJ. Intensified treatment of hyperphosphatemia associated with reduction in parathyroid hormone in patients on maintenance hemodialysis. Ren Fail. 2018;40(1):15-21. doi:10.1080/0886022X.2017.1419966

11. Новокшонов К.Ю., Карелина Ю.В., Земченков А.Ю. и соавт. Результаты скрининга на маркеры минеральных и костных нарушений при хронической болезни почек среди диализных пациентов Северо-Западного Федерального Округа. Нефрология 2016; 20(1):36-50.

12. Земченков А.Ю. Вишневский К.А. Сабодаш А.Б. и соавт. Сроки начала и другие факторы на старте диализа, влияющие на выживаемость: Санкт-Петербургский регистр пациентов на заместительной почечной терапии. Нефрология и диализ, 2017; 19(2): 255-270.

13. Goldenstein PT, Elias RM, Pires de Freitas do Carmo L, et al. Parathyroidectomy improves survival in patients with severe hyperparathyroidism: a comparative study. PLoS One. 2013;8(8):e68870. doi:10.1371/journal.pone.0068870

14. Bärnighausen T, Røttingen JA, Rockers P et al. Quasi-experimental study designs series-paper 1: introduction: two historical lineages. J Clin Epidemiol. 2017;89:4-11. doi:10.1016/j.jclinepi.2017.02.020

15. Komaba H, Wang M, Taniguchi M, et al. Initiation of Sevelamer and Mortality among Hemodialysis Patients Treated with Calcium-Based Phosphate Binders. Clin J Am Soc Nephrol. 2017;12(9):1489-1497. doi:10.2215/CJN.13091216

16. Cannata-Andía JB, Fernández-Martín JL, Locatelli F, et al. Use of phosphate-binding agents is associated with a lower risk of mortality. Kidney Int. 2013;84(5):998-1008. doi:10.1038/ki.2013.185

17. Fernández-Martín JL, Martínez-Camblor P, Dionisi MP, et al. Improvement of mineral and bone metabolism markers is associated with better survival in haemodialysis patients: the COSMOS study. Nephrol Dial Transplant. 2015;30(9):1542-1551. doi:10.1093/ndt/gfv099

18. Smith ER, Pan FFM, Hewitson TD et al. Effect of Sevelamer on Calciprotein Particles in Hemodialysis Patients: The Sevelamer Versus Calcium to Reduce Fetuin-A-Containing Calciprotein Particles in Dialysis (SCaRF) Randomized Controlled Trial. Kidney Int Rep (2020) 5, 1432-1447; https://doi.org/10.1016/j.ekir.2020.06.014