Endocrinology Express Report

ENDO 2006 - The Endocrine Society’s 88th Annual Meeting on June 25, 2006, in Boston, Massachusetts

Publication date: 2006-09-01

Early Detection and Effective Management of Diabetic Patients with CKD and Secondary Hyperparathyroidism

This report was reviewed for medical and scientific accuracy by Mark A. Gendreau, MD, Consulting Physician, Lahey Clinic, Burlington, Massachusetts.

Expert Commentary

Provided by Mark E. Molitch, MD, Professor, Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine; Northwestern Memorial Hospital; Chicago, Illin

Diabetes is the most common cause of chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) often develops as CKD progresses.^1-5 Decreasing renal function results in diminishing production of 1,25-dihydroxyvitamin D (calcitriol), the active form of vitamin D, and phosphorus retention. SHPT develops in response to vitamin D deficiency and abnormalities in mineral metabolism, including hyperphosphatemia and hypocalcemia. Histological features of SHPT can occur even with only a moderate increase in parathyroid hormone levels. Therefore, it is incumbent upon clinicians to screen early for CKD, assessed through estimated glomerular filtration rate (eGFR) rather than serum creatinine, ⁶ and SHPT assessed through measurement of parathyroid hormone, and to intervene promptly. Patients in stage 3 CKD with elevated parathyroid hormone levels should be treated with active vitamin D therapy as first-line therapy and a phosphorus-binder should only be considered if phosphate levels increase.

The development of treatment options that can safely and effectively suppress elevated parathyroid hormone levels in patients with SHPT continues to evolve. Oral calcitriol has been used in patients with mild to moderate CKD to suppress parathyroid hormone levels. ^7,8 However, calcitriol use is limited to a narrow therapeutic index due to adverse effects, such as hypercalcemia, hypercalciuria, hyperphosphatemia, and an elevated calcium-phosphorus product. ^9-12 Elevations in serum calcium, phosphorus, or both can result in an elevated serum calcium-phosphorus product, which has been associated with increased risk of cardiovascular complications and mortality in patients with CKD. ^13,14 Doxercalciferol, a prohormone that requires hydroxylation in the liver to become active, ^15,16 has also been used to suppress parathyroid hormone levels in CKD. ¹⁷ As with calcitriol, the use of doxercalciferol has been associated with increases in urinary calcium levels, ¹⁷ as well as increases in phosphorus levels necessitating doubling of phosphate-binder usage. ¹⁷ Recent data on the use of oral paricalcitol in patients with stages 3 and 4 CKD with SHPT indicate oral paricalcitol is well tolerated and effectively decreases parathyroid hormone levels, with minimal or no impact on calcium levels, phosphorus balance, and kidney function. ¹⁸ Intravenously, paricalcitol has been shown to effectively and significantly suppress parathyroid hormone levels, with minimal impact on serum calcium and phosphorous levels in patients with CKD. ^3,19-21 Moreover, retrospective analyses of hemodialysis patients have shown that intravenous paricalcitol appears to have a significant survival advantage compared to calcitriol. ²²

Early intervention with active vitamin D therapy, in combination with appropriate glycemic, lipid, and hypertensive control, greatly help reduce the morbidity in patients with CKD and diabetes, according to presentations in a satellite symposium held during ENDO 2006 - The Endocrine Society's 88^th Annual Meeting on June 25, 2006, in Boston, Massachusetts.

This Endocrinology Express Report^TM highlights the important concepts on the management of patients with CKD and diabetes and treatment options for secondary hyperparathyroidism that were discussed in those presentations.

Chronic Kidney Disease- A Growing Epidemic

“Chronic kidney disease is a growing epidemic,” advised Mark E. Molitch, MD, Professor, Division of Endocrinology, Metabolism, and Mole