Review

Current Concepts and Management Strategies in Chronic Kidney Disease-Mineral and Bone Disorder

Authors: Veeraish Chauhan, MD, Ellie Kelepouris, MD, Nishtha Chauhan, BDS, Megha Vaid, MPH

Abstract

The term renal osteodystrophy describes the pathological changes in bone structure in chronic kidney disease (CKD); however, this term fails to describe adequately the adverse changes in mineral and hormonal metabolism in CKD that have grave consequences for patient survival. CKD-mineral and bone disorder (CKD-MBD) is a broader, newly defined term that should be used instead of renal osteodystrophy to define the mineral, bone, hormonal, and calcific cardiovascular abnormalities that are seen in CKD. The new paradigm in the management of renal bone disease is to “think beyond the bones” and strive to improve cardiovascular outcomes and survival. This means treating other aspects of the disease process that go beyond merely controlling parathyroid hormone levels. Primary physicians need to take a proactive approach to the management of CKD-MBD because the disorder begins early in the course of CKD, well before a patient is referred to a nephrologist. This review outlines the evidence behind the understanding of CKD-MBD, its implications for overall mortality, and the latest recommendations for management of CKD-MBD in patients with predialysis CKD.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Hruska KA, Teitelbaum SL. Mechanisms of disease: renal osteodystrophy. N Engl J Med 1995; 333: 166–174.
 
2. Muntner P, Jones TM, Hyre AD, et al. Association of serum intact parathyroid hormone with lower estimated glomerular filtration rate. Clin J Am Soc Nephrol 2009; 4: 186–194.
 
3. London GM, Guérin AP, Marchais SJ, et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18: 1731–1740.
 
4. Sigrist MK, Taal MW, Bungay P, et al. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol 2007; 2: 1241–1248.
 
5. Moe S, Drueke T, Cunningham J, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 69: 1945–1953.
 
6. US Renal Data System. USRDS 2011 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2011.
 
7. Khan SS, Kazmi WH, Abichandani R, et al. Health care utilization among patients with chronic kidney disease. Kidney Int 2002; 62: 229–236.
 
8. Slatopolsky E, Robson AM, Elkan I, et al. Control of phosphate excretion in uremic man. J Clin Invest 1968; 47: 1865–1874.
 
9. Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 2007; 71: 31–38.
 
10. Llach F. Secondary hyperparathyroidism in renal failure: the trade-off hypothesis revisited. Am J Kidney Dis 1995; 25: 663–679.
 
11. Vanholder R, Patel S, Hsu CH. Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure. J Am Soc Nephrol 1993; 4: 1035–1038.
 
12. Gutierrez O, Isakova T, Rhee E, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005; 16: 2205–2215.
 
13. Parker BD, Schurgers LJ, Brandenburg VM, et al. The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med 2010; 152: 640–648.
 
14. Kendrick J, Cheung AK, Kaufman JS, et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol 2011; 22: 1913–1922.
 
15. Almaden Y, Hernandez A, Torregrosa V, et al. High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro. J Am Soc Nephrol 1998; 9: 1845–1852.
 
16. Silver J, Levi R. Cellular and molecular mechanisms of secondary hyperparathyroidism. Clin Nephrol 2005; 63: 119–126.
 
17. Canadillas S, Canalejo A, Santamaria R, et al. Calcium-sensing receptor expression and parathyroid hormone secretion in hyperplastic parathyroid glands from humans. J Am Soc Nephrol 2005; 16: 2190–2197.
 
18. Rodriguez M, Felsenfeld AJ, Llach F. Calcemic response to parathyroid hormone in renal failure: role of calcitriol and the effect of parathyroidectomy. Kidney Int 1991; 40: 1063–1068.
 
19. Indridason OS, Heath H III, Khosla S, et al. Non-suppressible parathyroid hormone secretion is related to gland size in uremic secondary hyperparathyroidism. Kidney Int 1996; 50: 1663–1671.
 
20. Neves KR, Graciolli FG, dos Reis LM, et al. Vascular calcification: contribution of parathyroid hormone in renal failure. Kidney Int 2007; 71: 1262–1270.
 
21. Krieger NS, Frick KK, Bushinsky DA. Mechanism of acid-induced bone resorption. Curr Opin Nephrol Hypertens 2004; 13: 423–436.
 
22. Llach F. Parathyroidectomy in chronic renal failure: indications, surgical approach, and the use of calcitriol. Kidney Int Suppl 1990; 29: S62–S68.
 
23. Ferreira A, Frazão JM, Monier-Faugere MC, et al. Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients. J Am Soc Nephrol 2008; 19: 405–412.
 
24. Spasovski GB, Bervoets ARJ, Behets GJS, et al. Spectrum of renal bone disease in end-stage renal failure patients not yet on dialysis. Nephrol Dial Transplant 2003; 18: 1159–1166.
 
25. Hercz G, Pei Y, Greenwood C, et al. Aplastic osteodystrophy without aluminum: the role of “suppressed” parathyroid function. Kidney Int 1993; 44: 860–866.
 
26. Mathew S, Lund RJ, Strebeck F, et al. Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. J Am Soc Nephrol2007; 18: 122–130.
 
27. Sherrard DJ, Hercz G, Pei Y, et al. The spectrum of bone disease in end-stage renal failure—an evolving disorder. Kidney Int 1993; 43: 436–442.
 
28. Coco M, Rush H. Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone. Am J Kidney Dis 2000; 36: 1115–1121.
 
29. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003; 42: S1–S201.
 
30. Kohlmeier M, Saupe J, Shearer MJ, et al. Bone health of adult hemodialysis patients is related to vitamin K status. Kidney Int 1997; 51: 1218–1221.
 
31. Gonzalez EA, Lund RJ, Martin KJ, et al. Treatment of a murine model of high-turnover renal osteodystrophy by exogenous BMP-7. Kidney Int 2002; 61: 1322–1331.
 
32. KDIGO CKD-MBD Work Group. KDIGO clinical practice guidelines for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD).Kidney Int 2009; 76: S1–S130.
 
33. Tentori F, Blayney MJ, Albert JM, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008; 52: 519–530.
 
34. Chertow GM, Pupim LB, Block GA, et al. Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview. Clin J Am Soc Nephrol 2007; 2: 898–905.
 
35. Chauhan V, Vaid M. Dyslipidemia in chronic kidney disease: managing a high-risk combination.Postgrad Med 2009; 121: 54–61.
 
36. Hashiba H, Aizawa S, Tamura K, et al. Inhibitory effects of etidronate on the progression of vascular calcification in hemodialysis patients. Ther Apher Dial 2004; 8: 241–247.
 
37. Fleckenstein-Grun G, Thimm F, Frey M, et al. Progression and regression by verapamil of vitamin D3-induced calcific medial degeneration in coronary arteries of rats. J Cardiovasc Pharmacol 1995; 26: 207–213.
 
38. Bleyer AJ, Burkart J, Piazza M, et al. Changes in cardiovascular calcification after parathyroidectomy in patients with ESRD. Am J Kidney Dis 2005; 46: 464–469.