Bone and mineral disorders in pre-dialysis CKD

Csaba P. Kövesdy1,2, Kamyar Kalantar-Zadeh3,4,5
1Division of Nephrology, Salem VA Medical Center, Salem, USA
2University of Virginia, Charlottesville, USA
3David Geffen School of Medicine at UCLA, Torrance, USA
4Harold Simmons Center for Kidney Disease Research and Epidemiology, Torrance, USA
5Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, USA

Tóm tắt

Từ khóa


Tài liệu tham khảo

Levin A, Bakris GL, Molitch M et al (2007) 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 71:31–38

Block GA, Klassen PS, Lazarus JM et al (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218

Kalantar-Zadeh K, Kuwae N, Regidor DL et al (2006) Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 70:771–780

Moe S, Drueke T, Cunningham J et al (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69:1945–1953

Yu AS (2004) Renal transport of calcium, magnesium and phosphate. In: Brenner BM (ed) Brenner & Rector’s the kidney, 7th edn. Saunders, Philadelphia

Yangawa N, Nakhoul F, Kurokawa K, Lee DB (1994) Physiology of phosphorus metabolism. In: Narins RG (ed) Maxwell and Kleeman’s clinical disorders of fluid and electrolyte metabolism, 5th edn. McGraw-Hill, pp 307–371

Portale AA, Booth BE, Tsai HC, Morris RC Jr (1982) Reduced plasma concentration of 1,25-dihydroxyvitamin D in children with moderate renal insufficiency. Kidney Int 21:627–632

Eknoyan G, Levin A, Levin N (2003) Bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:1–201

Gupta A, Winer K, Econs MJ et al (2004) FGF-23 is elevated by chronic hyperphosphatemia. J Clin Endocrinol Metab 89:4489–4492

Bricker NS (1972) On the pathogenesis of the uremic state. An exposition of the “trade-off hypothesis”. N Engl J Med 286:1093–1099

Fukagawa M, Kazama JJ (2006) FGF23: its role in renal bone disease. Pediatr Nephrol 21:1802–1806

Gutierrez O, Isakova T, Rhee E et al (2005) Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 16:2205–2215

Mucsi I, Hercz G (1998) Control of serum phosphate in patients with renal failure—new approaches. Nephrol Dial Transplant 13:2457–2460

K/DOQI (2002) Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39:S1–S266

Jono S, McKee MD, Murry CE et al (2000) Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87:E10–E17

Kestenbaum B, Sampson JN, Rudser KD et al (2005) Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16:520–528

Menon V, Greene T, Pereira AA et al (2005) Relationship of phosphorus and calcium—phosphorus product with mortality in CKD. Am J Kidney Dis 46:455–463

Voormolen N, Noordzij M, Grootendorst DC et al (2007) High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 22:2909–2916

Tonelli M, Sacks F, Pfeffer M et al (2005) Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112:2627–2633

Chen NX, O’Neill KD, Duan D, Moe SM (2002) Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells. Kidney Int 62:1724–1731

Schwarz S, Trivedi BK, Kalantar-Zadeh K, Kovesdy CP (2006) Association of disorders in mineral metabolism with progression of chronic kidney disease. Clin J Am Soc Nephrol 1:825–831

Norris KC, Greene T, Kopple J et al (2006) Baseline predictors of renal disease progression in the African American study of hypertension and kidney disease. J Am Soc Nephrol 17:2928–2936

Barsotti G, Morelli E, Giannoni A et al (1983) Restricted phosphorus and nitrogen intake to slow the progression of chronic renal failure: a controlled trial. Kidney Int Suppl 16:S278–S284

Maschio G, Oldrizzi L, Tessitore N et al (1982) Effects of dietary protein and phosphorus restriction on the progression of early renal failure. Kidney Int 22:371–376

Ibels LS, Alfrey AC, Haut L, Huffer WE (1978) Preservation of function in experimental renal disease by dietary restriction of phosphate. N Engl J Med 298:122–126

Karlinsky ML, Haut L, Buddington B et al (1980) Preservation of renal function in experimental glomerulonephritis. Kidney Int 17:293–302

Lumlertgul D, Burke TJ, Gillum DM et al (1986) Phosphate depletion arrests progression of chronic renal failure independent of protein intake. Kidney Int 29:658–666

Kraus ES, Cheng L, Sikorski I, Spector DA (1993) Effect of phosphorus restriction on renal response to oral and intravenous protein loads in rats. Am J Physiol 264:F752–F759

Ritz E, Gross ML, Dikow R (2005) Role of calcium–phosphorous disorders in the progression of renal failure. Kidney Int Suppl 99:S66–S70

Klahr S, Levey AS, Beck GJ et al (1994) The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of diet in renal disease study group. N Engl J Med 330:877–884

Sampathkumar K, Selvam M, Sooraj YS et al (2006) Extended release nicotinic acid—a novel oral agent for phosphate control. Int Urol Nephrol 38:171–174

Llach F, Massry SG (1985) On the mechanism of secondary hyperparathyroidism in moderate renal insufficiency. J Clin Endocrinol Metab 61:601–606

Salusky IB, Foley J, Nelson P, Goodman WG (1991) Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease. N Engl J Med 324:527–531

Thurston H, Swales JD (1971) Aluminium and chronic renal failure. Br Med J 4:490

Slatopolsky E, Weerts C, Lopez-Hilker S et al (1986) Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis. N Engl J Med 315:157–161

Braun J, Oldendorf M, Moshage W et al (1996) Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 27:394–401

Goodman WG, Goldin J, Kuizon BD et al (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483

Guerin AP, London GM, Marchais SJ, Metivier F (2000) Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 15:1014–1021

London GM, Guerin AP, Marchais SJ et al (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731–1740

Kovesdy CP, Mehrotra R, Kalantar-Zadeh K (2008) Battleground: chronic kidney disorders mineral and bone disease—calcium obsession, vitamin D, and binder confusion. Clin J Am Soc Nephrol 3:168–173

Mehrotra R, Budoff M, Christenson P et al (2004) Determinants of coronary artery calcification in diabetics with and without nephropathy. Kidney Int 66:2022–2031

Mehrotra R, Budoff M, Hokanson JE et al (2005) Progression of coronary artery calcification in diabetics with and without chronic kidney disease. Kidney Int 68:1258–1266

Qunibi WY, Abouzahr F, Mizani MR et al (2005) Cardiovascular calcification in Hispanic Americans (HA) with chronic kidney disease (CKD) due to type 2 diabetes. Kidney Int 68:271–277

Russo D, Palmiero G, De Blasio AP et al (2004) Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis 44:1024–1030

Tomiyama C, Higa A, Dalboni MA et al (2006) The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients. Nephrol Dial Transplant 21:2464–2471

Russo D, Miranda I, Ruocco C et al (2007) The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int 72(10):1255–1261

Shantouf R, Budoff MJ, Ahmadi N et al (2007) Effects of sevelamer and calcium-based phosphate binders on lipid and inflammatory markers in hemodialysis patients. Am J Nephrol 28:275–279

De Boer IH, Gorodetskaya I, Young B et al (2002) The severity of secondary hyperparathyroidism in chronic renal insufficiency is GFR-dependent, race-dependent, and associated with cardiovascular disease. J Am Soc Nephrol 13:2762–2769

Fajtova VT, Sayegh MH, Hickey N et al (1995) Intact parathyroid hormone levels in renal insufficiency. Calcif Tissue Int 57:329–335

Martinez I, Saracho R, Montenegro J, Llach F (1997) The importance of dietary calcium and phosphorous in the secondary hyperparathyroidism of patients with early renal failure. Am J Kidney Dis 29:496–502

Pitts TO, Piraino BH, Mitro R et al (1988) Hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency in mild, moderate, and severe renal failure. J Clin Endocrinol Metab 67:876–881

Reiss E, Canterbury JM, Kanter A (1969) Circulating parathyroid hormone concentration in chronic renal insufficiency. Arch Intern Med 124:417–422

St John A, Thomas MB, Davies CP et al (1992) Determinants of intact parathyroid hormone and free 1,25-dihydroxyvitamin D levels in mild and moderate renal failure. Nephron 61:422–427

Korkor AB (1987) Reduced binding of [3H]1,25-dihydroxyvitamin D3 in the parathyroid glands of patients with renal failure. N Engl J Med 316:1573–1577

Gogusev J, Duchambon P, Hory B et al (1997) Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 51:328–336

Kates DM, Sherrard DJ, Andress DL (1997) Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure. Am J Kidney Dis 30:809–813

Yamamoto M, Igarashi T, Muramatsu M et al (1989) Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat. J Clin Invest 83:1053–1056

Llach F, Massry SG, Singer FR et al (1975) Skeletal resistance to endogenous parathyroid hormone in patients with early renal failure. A possible cause for secondary hyperparathyroidism. J Clin Endocrinol Metab 41:339–345

Fuleihan GE, Gundberg CM, Gleason R et al (1994) Racial differences in parathyroid hormone dynamics. J Clin Endocrinol Metab 79:1642–1647

Gupta A, Kallenbach LR, Zasuwa G, Divine GW (2000) Race is a major determinant of secondary hyperparathyroidism in uremic patients. J Am Soc Nephrol 11:330–334

Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K (2007) Obesity is associated with secondary hyperparathyroidism in men with moderate and severe chronic kidney disease. Clin J Am Soc Nephrol 2:1024–1029

Vincenti F, Arnaud SB, Recker R et al (1984) Parathyroid and bone response of the diabetic patient to uremia. Kidney Int 25:677–682

Hutchison AJ, Whitehouse RW, Boulton HF et al (1993) Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. Kidney Int 44:1071–1077

Malluche HH, Ritz E, Lange HP et al (1976) Bone histology in incipient and advanced renal failure. Kidney Int 9:355–362

Rix M, Andreassen H, Eskildsen P et al (1999) Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int 56:1084–1093

Sherrard DJ, Hercz G, Pei Y et al (1993) The spectrum of bone disease in end-stage renal failure—an evolving disorder. Kidney Int 43:436–442

Massry SG, Popovtzer MM, Coburn JW et al (1968) Intractable pruritus as a manifestation of secondary hyperparathyroidism in uremia. Disappearance of itching after subtotal parathyroidectomy. N Engl J Med 279:697–700

Rao DS, Shih MS, Mohini R (1993) Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia. N Engl J Med 328:171–175

Bogicevic M, Stefanovic V (1988) Relationship between parathyroid hormone and pituitary-testicular axis in patients on maintenance hemodialysis. Exp Clin Endocrinol 92:357–362

Tonner DR, Schlechte JA (1993) Neurologic complications of thyroid and parathyroid disease. Med Clin North Am 77:251–263

Fellner SK, Lang RM, Neumann A et al (1991) Parathyroid hormone and myocardial performance in dialysis patients. Am J Kidney Dis 18:320–325

London GM (2002) Left ventricular alterations and end-stage renal disease. Nephrol Dial Transplant 1 [17 Suppl]:29–36

Tseke P, Grapsa E, Stamatelopoulos K et al (2006) Atherosclerotic risk factors and carotid stiffness in elderly asymptomatic HD patients. Int Urol Nephrol 38:801–809

Kovesdy CP, Ahmadzadeh A, Anderson JE, Kalantar-Zadeh K (2008) Outcomes associated with secondary hyperparathyroidism in men with moderate to severe chronic kidney disease. Kidney Int (in press)

Avram MM, Mittman N, Myint MM, Fein P (2001) Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation. Am J Kidney Dis 38:1351–1357

Fouque D, Guebre-Egziabher F (2007) An update on nutrition in chronic kidney disease. Int Urol Nephrol 39:239–246

Mafra D, Farage NE, Azevedo DL et al (2007) Impact of serum albumin and body-mass index on survival in hemodialysis patients. Int Urol Nephrol 39:619–624

Massry SG, Smogorzewski M (1994) Mechanisms through which parathyroid hormone mediates its deleterious effects on organ function in uremia. Semin Nephrol 14:219–231

Mazzaferro S, Coen G, Bandini S et al (1993) Role of ageing, chronic renal failure and dialysis in the calcification of mitral annulus. Nephrol Dial Transplant 8:335–340

Chiu KC, Chuang LM, Lee NP et al (2000) Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone level. Metabolism 49:1501–1505

Wareham NJ, Byrne CD, Carr C et al (1997) Glucose intolerance is associated with altered calcium homeostasis: a possible link between increased serum calcium concentration and cardiovascular disease mortality. Metabolism 46:1171–1177

Gadallah MF, el-Shahawy M, Andrews G et al (2001) Factors modulating cytosolic calcium. Role in lipid metabolism and cardiovascular morbidity and mortality in peritoneal dialysis patients. Adv Perit Dial 17:29–36

Meytes D, Bogin E, Ma A et al (1981) Effect of parathyroid hormone on erythropoiesis. J Clin Invest 67:1263–1269

Neves PL, Trivino J, Casaubon F et al (2002) Elderly patients on chronic hemodialysis: effect of the secondary hyperparathyroidism on the hemoglobin level. Int Urol Nephrol 34:147–149

Neves PL, Trivino J, Casaubon F et al (2006) Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol. Int Urol Nephrol 38:175–177

Massry SG, Alexiewicz JM, Gaciong Z, Klinger M (1991) Secondary hyperparathyroidism and the immune system in chronic renal failure. Semin Nephrol 11:186–201

Baczynski R, Massry SG, Kohan R et al (1985) Effect of parathyroid hormone on myocardial energy metabolism in the rat. Kidney Int 27:718–725

Amann K, Ritz E (1997) Cardiac disease in chronic uremia: pathophysiology. Adv Ren Replace Ther 4:212–224

Kosch M, Hausberg M, Vormbrock K et al (2000) Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy. Cardiovasc Res 47:813–818

Amann K, Tornig J, Flechtenmacher C et al (1995) Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH. Nephrol Dial Transplant 10:2043–2048

Kamycheva E, Sundsfjord J, Jorde R (2004) Serum parathyroid hormone levels predict coronary heart disease: the Tromsø study. Eur J Cardiovasc Prev Rehabil 11:69–74

Ichikawa I, Humes HD, Dousa TP, Brenner BM (1978) Influence of parathyroid hormone on glomerular ultrafiltration in the rat. Am J Physiol 234:F393–F401

Marchand GR (1985) Effect of parathyroid hormone on the determinants of glomerular filtration in dogs. Am J Physiol 248:F482–F486

Lee K, Brown D, Urena P et al (1996) Localization of parathyroid hormone/parathyroid hormone-related peptide receptor mRNA in kidney. Am J Physiol 270:F186–F191

Endlich N, Nobiling R, Kriz W, Endlich K (2001) Expression and signaling of parathyroid hormone-related protein in cultured podocytes. Exp Nephrol 9:436–443

Shigematsu T, Caverzasio J, Bonjour JP (1993) Parathyroid removal prevents the progression of chronic renal failure induced by high protein diet. Kidney Int 44:173–181

Baker LR, Abrams L, Roe CJ et al (1989) 1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. Kidney Int 35:661–669

Bianchi ML, Colantonio G, Campanini F et al (1994) Calcitriol and calcium carbonate therapy in early chronic renal failure. Nephrol Dial Transplant 9:1595–1599

Goodman WG, Coburn JW (1992) The use of 1,25-dihydroxyvitamin D3 in early renal failure. Annu Rev Med 43:227–237

Martin KJ, Gonzalez EA, Gellens M et al (1998) 19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol 9:1427–1432

Kazama JJ, Maruyama H, Narita I, Gejyo F (2005) Maxacalcitol is a possible less phosphatemic vitamin D analog. Ther Apher Dial 9:352–354

Goodman WG, Hladik GA, Turner SA et al (2002) The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 13:1017–1024

Taskapan H, Wei M, Oreopoulos DG (2006) 25(OH) vitamin D3 in patients with chronic kidney disease and those on dialysis: rediscovering its importance. Int Urol Nephrol 38:323–329

Saab G, Young DO, Gincherman Y et al (2007) Prevalence of vitamin D deficiency and the safety and effectiveness of monthly ergocalciferol in hemodialysis patients. Nephron Clin Pract 105:c132–c138

Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ (2006) 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int 70:654–659

Teng M, Wolf M, Ofsthun MN et al (2005) Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 16:1115–1125

Tentori F, Hunt WC, Stidley CA et al (2006) Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int 70:1858–1865

Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K (2008) Association of treatment with activated vitamin D and mortality in chronic kidney disease. Arch Intern Med 168:397–403

Shoben AB, Rudser KD, de Boer IH et al (2007) Oral calcitriol use and mortality in non-dialyzed patients with chronic kidney disease [abstract]. J Am Soc Nephrol 18:98A

Bellows CG, Reimers SM, Heersche JN (1999) Expression of mRNAs for type-I collagen, bone sialoprotein, osteocalcin, and osteopontin at different stages of osteoblastic differentiation and their regulation by 1,25 dihydroxyvitamin D3. Cell Tissue Res 297:249–259

Drissi H, Pouliot A, Koolloos C et al (2002) 1,25-(OH)2-vitamin D3 suppresses the bone-related Runx2/Cbfa1 gene promoter. Exp Cell Res 274:323–333

Virdi AS, Cook LJ, Oreffo RO, Triffitt JT (1998) Modulation of bone morphogenetic protein-2 and bone morphogenetic protein-4 gene expression in osteoblastic cell lines. Cell Mol Biol (Noisy-le-grand) 44:1237–1246

Fraser JD, Otawara Y, Price PA (1988) 1,25-Dihydroxyvitamin D3 stimulates the synthesis of matrix gamma-carboxyglutamic acid protein by osteosarcoma cells. Mutually exclusive expression of vitamin K-dependent bone proteins by clonal osteoblastic cell lines. J Biol Chem 263:911–916

Panichi V, De Pietro S, Andreini B et al (1998) Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium. Kidney Int 54:1463–1469

Staeva-Vieira TP, Freedman LP (2002) 1,25-dihydroxyvitamin D3 inhibits IFN-gamma and IL-4 levels during in vitro polarization of primary murine CD4 + T cells. J Immunol 168:1181–1189

Barrat FJ, Cua DJ, Boonstra A et al (2002) In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 195:603–616

Boonstra A, Barrat FJ, Crain C et al (2001) 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167:4974–4980

Aihara K, Azuma H, Akaike M et al (2004) Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem 279:35798–35802

Wolf M, Shah A, Gutierrez O et al (2007) Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 72:1004–1013

Watson KE, Abrolat ML, Malone LL et al (1997) Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 96:1755–1760

Bertoli M, Luisetto G, Ruffatti A et al (1990) Renal function during calcitriol therapy in chronic renal failure. Clin Nephrol 33:98–102

Coen G, Mazzaferro S, Manni M et al (1994) No acceleration and possibly slower progression of renal failure during calcitriol treatment in predialysis chronic renal failure. Nephrol Dial Transplant 9:1520

Agarwal R, Acharya M, Tian J et al (2005) Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 68:2823–2828

Nagakura K, Abe E, Suda T et al (1986) Inhibitory effect of 1 alpha,25-dihydroxyvitamin D3 on the growth of the renal carcinoma cell line. Kidney Int 29:834–840

Penna G, Adorini L (2000) 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164:2405–2411

Gysemans C, Van EE, Overbergh L et al (2002) Treatment of autoimmune diabetes recurrence in non-obese diabetic mice by mouse interferon-beta in combination with an analogue of 1alpha,25-dihydroxyvitamin-D3. Clin Exp Immunol 128:213–220

Li YC, Kong J, Wei M et al (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110:229–238

Charytan C, Coburn JW, Chonchol M et al (2005) Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. Am J Kidney Dis 46:58–67