Conflicting data and a number of options are generating confusion about treatment approaches.
Nephrologists have been well aware that renal osteodystrophy, also known as kidney bone disease, is a common complication of advanced CKD (stages 3 to 5). In the past few years, however, there has been intensified emphasis on kidney bone disease and its association with other complications, including disorders of mineral metabolism, vascular calcification, and poor survival, especially among CKD patients who undergo maintenance dialysis.
The emergence of a large number of observational studies and a few clinical trials has overwhelmed the field of kidney bone disease. At the same time, pharmaceutical companies use new findings to promote their products as “the medication of choice” for the fast growing CKD population with “bone and mineral disorders.”
Nephrologists and other health-care professionals such as renal dietitians and nurses have been bombarded by a large amount of commercially biased and sometimes contradictory information about the management of renal osteodystrophy.
As a result, both nephrology care providers and patients are somewhat confused as to the best management for kidney bone disease.
Renal osteodystrophy invariably has been recognized as a prominent feature of chronic uremic
syndrome. Hyperphosphatemia and hyperparathyroidism were originally considered the two fundamental causes of kidney bone disease, although the role of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D deficiency and its related hypocalcemia also was appreciated in this regard.
Consequently, the historical treatment regimens of the 1980s and early 1990s included controlling hyperphosphatemia by phosphorus binders and dietary phosphorus restrictions, and managing hyperparathyroidism by provision of supplementary calcium (such as dialysate bath calcium concentrations as high as 3.5 mEq/L) and active vitamin D in form of synthetic calcitriol. Emerging data on the association of aluminum-based binders and aluminum accumulation with demen- tia, refractory anemia, and worsening bone disease made the calcium-based binders the medication of choice by the mid 1990s.
Two major events in mid to late 1990s led to a drastic paradigm shift in the foregoing management regimen. First, the prevalence of the so-called low-turnover (adynamic) bone disease showed almost universal upward trend. This rising epidemic was attributed to hypercalcemia as a result of high calcium intake, high bath calcium concentration, and calcitriol administration.
Secondly, vascular calcification was found to be highly prevalent in CKD patients and associated with poor survival. As a result of this fast growing “calcium-phobia,” the default dialysate calcium concentration was decreased to 2.5 mEq/L by the early 2000s, and a strong trend towards using non-calcium-based binders was developed. During this new era, study after study was published on a monthly, and sometimes even weekly, basis implying the deleterious effects of high-serum calcium or high-calcium intake on many clinical measures including survival of CKD patients.
These events coincided with the emergence of new pharmaceutical products, including sevelamer HCl (Renagel), which was the first FDA-approved non-calcium, non-aluminum binder, and newer generations of active vitamin D that had fewer calcemic effects, including paricalcitol (Zemplar).
Hence, the pharmaceutical industry launched a relentless fight against calcium as the newest member of the “axis of evil”—hypercalcemia, hyperphosphatemia, and hyperparathyroidism. The anti-calcemic faction was further invigorated with the development of the first calcium-sensing receptor antagonist also known as calcimimetic, cinacalcet (Sensipar).