Method of safely and effectively treating and preventing secondary hyperparathyroidism in chronic kidney disease

Abstract

A method of treating and preventing secondary hyperparathyroidism in CKD by increasing or maintaining blood concentrations of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in a patient by administering 25-hydroxyvitamin D3 with or without 25-hydroxyvitamin D2 and, as necessary, 1,25-dihydroxyvitamin D2 as a Vitamin D hormone replacement therapy.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This is a continuation of U.S. patent application Ser. No. 12 / 597,234 filed Dec. 4, 2009, which is the National Phase of International Application No. PCT / US2008 / 61594 filed Apr. 25, 2008, which claims the benefit of priority under 35 U.S.C. §119(e) of U.S. Provisional Patent Application Ser. No. 60 / 913,850 filed Apr. 25, 2007. The disclosure of each priority application is incorporated herein by reference.BACKGROUND[0002]Secondary hyperparathyroidism is a disorder which develops primarily because of Vitamin D deficiency. It is characterized by abnormally elevated blood levels of parathyroid hormone (PTH) and, in the absence of early detection and treatment, it becomes associated with parathyroid gland hyperplasia and a constellation of metabolic bone diseases. It is a common complication of chronic kidney disease (CKD), with rising incidence as CKD progresses. Secondary hyperparathyroidism can also develop in individuals with healthy kidn...

AI Technical Summary

Problems solved by technology

Secondary hyperparathyroidism can also develop in individuals with healthy kidneys, due to environmental, cultural or dietary factors which prevent adequate Vitamin D supply.

However, there is little evidence of feedback regulation of extrahepatic prohormone production.

Vitamin D prohormones can be metabolized into hormones outside of the kidneys in keratinocytes, lung epithelial cells, enterocytes, cells of the immune system (e.g., macrophages) and certain other cells containing CYP27B1 or similar enzymes, but such extrarenal hormone production is incapable of sustaining normal blood levels of 1,25-dihydroxyvitamin D in advanced CKD.

Oversuppression of PTH secretion can cause or exacerbate disturbances in calcium homeostasis and has been linked to vascular calcification.

Without early detection and treatment, followed by consistent maintenance or preventative therapy, secondary hyperparathyroidism progressively increases in severity, causing debilitating metabolic bone diseases, including osteoporosis and renal osteodystrophy.

Chronically low blood levels of 1,25-dihydroxyvitamin also develop because of a deficiency of Vitamin D prohormones, since renal hormone production cannot proceed without the required precursors.

Unfortunately, early detection and treatment of secondary hyperparathyroidism in CKD is rare, let alone prevention.

However, they cannot be administered in high enough doses to control elevated iPTH in all patients and they sporadically cause side effects, including hypercalcemia, hyperphosphatemia, hyercalciuria and oversuppression of iPTH, in a significant minority of the patients.

Health care professionals are cautious in raising the dose of these hormone replacement therapies for purposes of improving the control of secondary hyperparathyroidism in patients with excessive iPTH levels due to the increasing risk of causing such side effects.

As explained above, all CKD patients eventually develop decreased levels of renal CYP27B1 as kidney insufficiency becomes more severe, making it even more difficult, and eventually impossible, to treat secondary hyperparathyroidism with Vitamin D repletion therapies alone.