Mineral and Bone Disorder in CKD Stage 3 and 4

New York, NY
January 4, 2007

Disturbances in mineral and bone metabolism is an insidious disorder that begins early in the course of kidney disease and is an important cause of morbidity and decreased quality of life in our patients. By the start of Stage 5 CKD (GFR<15 mL/min/1.73 m2 ) essentially all patients have some manifestation of this systemic disorder. CKD-Mineral and Bone Disorder (MBD) is the term used to describe the constellation of inter-related abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; abnormalities of bone turnover, mineralization, volume, linear growth, or strength; and v ascular or other soft tissue calcification – related to CKD.1 The initial onset of Mineral and Bone Disorder is in the early stages of CKD. The first clinical indication of this disorder is a progressive decline in serum 1,25-dihydroxyvitamin D (calcitriol) levels. By late Stage 2 CKD (GFR 60-89 mL/min/1.73 m2 ) many patients will have below normal calcitriol levels. 2;3 This is accompanied by a progressive increase in the number of patients with PTH levels above normal. By late Stage 3 CKD (GFR 30-59 mL/min) a majority of patients will exhibit secondary hyperparathyroidism and nearly all patients will have elevated PTH levels by the time they reach Stage 5 CKD. Serum calcium and phosphorus levels often remain within the normal range in Stage 3 and early Stage 4 CKD; however, hypocalcemia and hyperphosphatemia become increasingly prevalent in Stage 4 CKD (GFR 15-29 mL/min). 3;4 It is also in these later stages that alterations in bone metabolism and general bone loss are frequently found. Vascular calcification, which may be related to the alteration in mineral and bone metabolism, also becomes increasingly prevalent in CKD Stage 4.

Based on these findings, the K/DOQI Clinical Practice Guidelines 5 recommend that all adult patients with GFR <60 mL/min/1.73 m 2 (Stages 3 and 4 CKD) should be evaluated for MBD. Serum calcium, phosphorus, PTH, total alkaline phosphatases, 25(OH)D, bicarbonate, and albumin are all critical biomarkers of mineral and bone metabolism and should be part of the initial screening for and ongoing evaluation of mineral and bone abnormalities in CKD. The minimum frequency of evaluation of calcium, phosphorus, and PTH should be every 12 months in CKD Stage 3 and every 3 months in Stage 4. Evaluation should occur more frequently if abnormal values have previously been noted or if the patient is receiving therapy for abnormalities in calcium, phosphorus or PTH. Table 1 provides the recommended target ranges for PTH, calcium and phosphorus by CKD Stage.

The pathologic processes that cause Mineral and Bone Disorder have their onset in the early stages of CKD and worsen throughout the progressive decline in kidney function. Apart from the musculoskeletal abnormalities, the long-term effects of these derangements include altered cardiovascular function related to extraskeletal calcification. Evaluation and treatment of Mineral and Bone Disorder early in the course of CKD may pre-empt the progression and severity of the associated morbidity and mortality.

References:

  1. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G: Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69:1945-1953, 2006
  2. Andress DL: Vitamin D in chronic kidney disease: a systemic role for selective vitamin D receptor activation. Kidney Int 69:33-43, 2006
  3. Bakris GL, Levin A, Molitch M, Griff S, Smulders M, Tian J, Williams LA, and Andress DL. Disturbances of 1,25-dihydroxyvitamin D in patients with chronic kidney disease. J Am Soc Nephrol 16(495A). 2005.
  4. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL: 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, 2007
  5. National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:1-201, 2003

Based on K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in CKD, Am J Kidney Dis 42:1-201, 2003.
Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate; PTH, parathyroid hormone.
*Adjustments in the target PTH range might be required based on the laboratory assay method used to measure PTH.