Selamerex: regional real-world practice and perspective of therapy optimisation

Перенести в английский вариант

   BACKGROUND. Hyperphosphatemia in CKD is spread widely, represents as independent factor of mortality at all stages of CKD, after transplantation, reduces the effectiveness of nephroprotection, leads to vascular calcification, stimulates hyperparathyroidism. Achieving the phosphatemia target is a difficult task and is based on a combination of a hypophosphate diet, effective dialysis, the antihyperparathyroidic measures and the phosphate-binders (PBs).

   THE AIM. The aim is to evaluate the effectiveness of sevelamer
therapy in real clinical practice as part of a hypophosphatemic strategy with clarification of the conditions and measures under which it is optimal.

   PATIENTS AND METHODS. In an eight-month study in a region where there are no restrictions on access to calcium-free PBs, 127 patients were included in the study after the "washing period ": the of sevelamer doses were titrated until phosphatemia reaches below 1.58 mmol/l in parallel with individual measures of four-component hypophosphatemic strategy.

   RESULTS. From the starting dose of 3-6 tablets/day, 38 patients experienced either dose increase (+ 1016 ± 760 mg) or in 28 patients
– decrease (- 1427 ± 1059 mg). By the third month of therapy, the proportion of patients with phosphatemia < 1.58 mmol/l reached 70 %, < 1.78 mmol/l – 90 %. The decrease magnitude depended on the initial phosphatemia, the level of PTH (maximum in the range of 150-600 pg/ml), occurs more slowly in men. During therapy, there was a decrease in the need for antihyperparathyroid therapy in the absence of dynamics in the parathyroid hormone level. In multiple regression analysis models, the independent factors associated with phosphatemia during treatment were sevelamer dose, dialysis dose, baseline phosphate and parathyroid hormone levels; the magnitude of phosphatemia reduction was independently associated with sevelamer dose, dialysis dose, baseline parathyroid hormone level, and assessment of treatment compliance.

   CONCLUSION. Sevelamer in a moderate well–tolerated doses as part of an individualized hyperphosphatemia correction strategy is able to achieve target phosphatemia (< 1.58 mmol/L) in 70 % of cases, and relatively safe level (< 1.78 mmol/L) – in 90 %.

1. Zemchenkov A. Yu., Konakova I. N. The chronic kidney disease progression rates according to St.-Petersburg CKD register. Nephrology and Dialysis 2015; 17 (1): 34–51 (in Russ.)

2. Chartsrisak K., Vipattawat K., Assanatham K. et al. Mineral metabolism and outcomes in chronic kidney disease stage 2-4 patients. BMC Nephrol 2013; 14: 14. doi: 10.1186/1471-2369-14-14

3. Rivara M. B., Ravel V., Kalantar-Zadeh K. et al. Uncorrected and albumin-corrected calcium, phosphorus, and mortality in patients undergoing maintenance dialysis. J Am Soc Nephrol 2015; 26 (7): 1671–1681. doi: 10.1681/ASN.2014050472

4. Connolly G. M., Cunningham R., McNamee P. T. et al. Elevated serum phosphate predicts mortality in renal transplant recipients. Transplantation 2009; 87 (7): 1040–1044. doi: 10.1097/TP.0b013e31819cd122

5. Zoccali C., Ruggenenti P., Pernaet A. et al. Phosphate may promote CKD progression and attenuate renoprotective effect of ACE inhibition. J Am Soc Nephrol 2011; 22 (10): 1923–1930. doi: 10.1681/ASN.2011020175

6. Shimamoto S., Yamada S., Hiyamuta H. et al. Association of serum phosphate concentration with the incidence of intervention for peripheral artery disease in patients undergoing hemodialysis: 10-year outcomes of the Q-Cohort Study. Atherosclerosis 2020; 304: 22–29. doi: 10.1016/j.atherosclerosis.2020.04.022

7. Moon J. Y., Lee Н. M., Lee S. H. et al. Hyperphosphatemia is associated with patency loss of arteriovenous fistula after 1 year of hemodialysis. Kidney Res. Clin Pract 2015; 34 (1): 41–46. doi: 10.1016/j.krcp.2015.02.001

8. Ix J. H., De Boer I. H., Peralta C. A. et al. Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in MESA. Clin J Am Soc Nephrol 2009; 4 (3): 609–615. doi: 10.2215/CJN.04100808

9. Adeney K. L., Siscovick D. S., Ix J. H. et al. Association of serum phosphate with vascular and valvular calcification in moderate CKD. J Am Soc Nephrol 2009; 20 (2): 381–387. doi: 10.1681/ASN.2008040349

10. Tsai W. C., Wu H. Y., Chiu Y. L. et al. Acute effects of dietary phosphorus intake on markers of mineral metabolism in hemodialysis patients: post hoc analysis of a randomized crossover trial. Ren Fail 2021; 43 (1): 141–148. doi: 10.1080/0886022X.2020.1870138

11. Isaka Y., Hamano T., Fujii H. et al. Optimal phosphate control related to coronary artery calcification in dialysis patients. J Am Soc Nephrol 2021; 32 (3): 723–735. doi: 10.1681/ASN.2020050598

12. Drueke T. В., Massy Z. A. Lowering expectations with niacin treatment for CKD-MBD. Clin J Am Soc Nephrol 2018; 13 (1): 6–8. doi: 10.2215/CJN.12021017

13. Saglimbene V. M., Su G., Wong G. et al. Dietary intake in adults on hemodialysis compared with guideline recommendations. J Nephrol 2021; 34 (6): 1999–2007. doi: 10.1007/s40620-020-00962-3

14. Kalantar-Zadeh K., Gutekunst L., Mehrotra R. et al. Understanding sources of dietary phosphorus in the treatment of patients with chronic kidney disease. Clin J Am Soc Nephrol 2010; 5 (3): 519–530. doi: 10.2215/CJN.06080809

15. Leypoldt J. K., Storr M., Agar B. U. et al. Intradialytic kinetics of middle molecules during hemodialysis and hemodiafiltration. Nephrol Dial Transplant 2019; 34 (5): 870–877. doi: URL: https://pubmed.ncbi.nlm.nih.gov/30307514/

16. Rumyantsev A., Zemchenkov G. A., Sabodash A. B. To the question about the prospective for the updates of clinical guidelines for hemodialysis. Nephrology (Saint-Petersburg) 2019; 23 (2): 49–76 (In Russ.) doi: 10.24884/1561-6274-2019-23-2-49-76

17. Jamal S. A., Vandermeer B., Raggi P. et al. Effect of calciumbased versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet 2013; 382 (9900): 1268–1277. doi: 10.1016/S0140-6736(13)60897-1

18. Patel L., Bernard L. M., Elder G. J. Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials. Clin J Am Soc Nephrol 2016; 11 (2): 232–244. doi: 10.2215/CJN.06800615

19. Ruospo M., Palmer S. C., 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

20. Phannajit J., Wonghakaeo N., Takkavatakarn K. et al. The impact of phosphate lowering agents on clinical and laboratory outcomes in chronic kidney disease patients: a systematic review and meta-analysis of randomized controlled trials. J Nephrol 2022; 35 (2): 473–491. doi: 10.1007/s40620-021-01065-3

21. Cannata-Andía J. B., Fernández-Martín J. L., 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

22. Zemchenkov A. Yu., Gerassimchuk R. P., Omelchenko A. M., Bakulin I. G. Sevelamer efficiency in real practice: the Saint-Petersburg experience. Nephrology and Dialуsis 2021; 23 (1): 73–82. (in Russ.) doi: 10.28996/2618-9801-2021-1-73-82

23. Covic A. C., Sprague S. M., Rastogi A. et al. Characteristics of Patients Who Achieve Serum Phosphorus Control on Sucroferric Oxyhydroxide or Sevelamer Carbonate: A post hoc Analysis of a Phase 3 Study. Nephron 2020; 144 (9): 428–439. doi: 10.1159/000507258

24. Ketteler M., Sprague S. M., Covic A. C. et al. Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease-mineral bone disorder parameters in dialysis patients. Nephrol Dial Transplant 2019; 34 (7): 1163–1170. doi: 10.1093/ndt/gfy127

25. Zulkarnaev A. B. Pitfalls of statistical analysis and clinical interpretation of the estimates in patients with chronic kidney disease Part I: Risk assessment. Nephrology and Dialysis 2019; 21 (4): 419–429. (In Rus.)

26. Bover J., Cozzolino M. Small steps towards the potential of 'preventive' treatment of early phosphate loading in chronic kidney disease patients. Clin Kidney J 2019; 12 (5): 673–677. doi: 10.1093/ckj/sfz082

27. Díaz-De la Cruz E. N., Cerrillos-Gutiérrez J. I., García-Sánchez A. et al. The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up. Front Med (Lausanne) 2021; 8: 714205. doi: 10.3389/fmed.2021.714205

28. Smith E. R., Pan F. F. M., Hewitson T. D. 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 (9): 1432–1447. doi: 10.1016/j.ekir.2020.06.014

29. Brønden A., Hansen M., Sonne D. P., Rohde U., Vilsbøll T., Knop F. K. Sevelamer in a diabetologist's perspective: a phosphatebinding resin with glucose-lowering potential. Diabetes Obes Metab 2015; 17 (2): 116–120. doi: 10.1111/dom.12355

30. Mason D. L., Godugu K., Nnani D., Mousa S. A. Effects of sevelamer carbonate versus calcium acetate on vascular calcification, inflammation, and endothelial dysfunction in chronic kidney disease. Clin Transl Sci 2022; 15 (2): 353–360. doi: 10.1111/cts.13151

31. Biruete A., Hill Gallant K. M., Lindemann S. R. et al. Phosphate Binders and Nonphosphate Effects in the Gastrointestinal Tract. J Ren Nutr 2020; 30 (1): 4–10. doi: 10.1053/j.jrn.2019.01.004

32. Milazi M., Douglas C., Bonner A. A bundled phosphate control intervention (4Ds) for adults with end-stage kidney disease receiving haemodialysis: A cluster randomized controlled trial. J Adv Nurs 2021; 77 (3): 1345–1356. doi: 10.1111/jan.14700

33. Coyne D. W., Sprague S. M., Vervloet M. et al. Sucroferric oxyhydroxide for hyperphosphatemia: a review of real-world evidence. J Nephrol 2022; 35 (3): 875–888. doi: 10.1007/s40620-021-01241-5

34. Floege J., Covic A. C., Ketteler M. et al; PA21 Study Group. A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients. Kidney Int 2014; 86 (3): 638–647. doi: 10.1038/ki.2014.58

35. Wald R., Thorpe K. E., Walsh M. W. Leveraging pragmatic clinical trial design to advance phosphate management in end-stage renal disease. Curr Opin Nephrol Hypertens 2019; 28 (1): 34–39. doi: 10.1097/MNH.0000000000000460

36. Edmonston D. L., Isakova T., Dember L. M. et al. Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphate Management for Patients Receiving Maintenance Hemodialysis. Am J Kidney Dis 2021; 77 (6): 920–930.e1. doi: 10.1053/j.ajkd.2020.10.008

37. Rodríguez-Osorio L., Zambrano D. P., Gracia-Iguacel C. et al. Use of sevelamer in chronic kidney disease: beyond phosphorus control. Nefrologia 2015; 35 (2): 207–217. doi: 10.1016/j.nefro.2015.05.022

38. Nagano N., Fukushima T., Shikata R., Ando T., Tsutsui T., Ogawa T., Ito K. Impact of phosphate binders on medication dosing frequency, timing, and number of prescribed pills in hemodialysis patients. Ther Apher Dial 2022 Feb 9. doi: 10.1111/1744-9987.13813. Epub ahead of print.

39. Fishbane S., Delmez J., Suki W. N. et al. A randomized, parallel, open-label study to compare once-daily sevelamer carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing in CKD patients on hemodialysis. Am J Kidney Dis 2010; 55 (2): 307–315. doi: 10.1053/j.ajkd.2009.10.051

40. Fan S., Ross C., Mitra S. et al. A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis. Nephrol Dial Transplant 2009; 24 (12): 3794–3799. doi: 10.1093/ndt/gfp372