Table 1.

Fundamental questions to be answered in CKD-MBDa

1. What is the benefit of treating the abnormalities of CKD-MBD?No RCT was ever done to show that interventions to lower PTH or phosphorus improve mortality, even though there is biological plausibility and observational studies show a strong association. Beneficial impact on various morbid conditions is established.
2. What are the ideal calcium and phosphorus levels in patients with various levels of CKD?Observational studies in dialysis patients are not unanimous on the ideal serum levels of calcium and phosphorus. No RCT has ever addressed this issue. Data on ideal levels in non–dialysis-dependent patients with CKD is scarce.
3. Should diet modification be advocated as a treatment for hyperphosphatemia?It remains unclear whether strict restriction of dietary phosphorus can be achieved without compromising dietary protein intake; protein restriction may worsen malnutrition and increase mortality.
4. What is the best phosphate binder?Head-to-head comparisons using relevant end points such as mortality or coronary calcification are available only for sevelamer hydrochloride and calcium-based binders.
Cost considerations, comorbidity profiles, and adverse effects are often limiting factors and make the availability of multiple binders helpful in individualizing therapy.
5. Should calcium intake be minimized?This involves dietary, medication, and dialysate-associated calcium intake. Observational studies suggest an association between higher calcium intake and coronary calcification in patients on dialysis. Available RCT were not designed to study outcomes as a function of the amount of ingested calcium (but rather to compare the impact of competing phosphate binders). No contemporary studies have examined calcium mass balance in patients on dialysis; such studies are needed before we can fully determine what “too much calcium intake” means.
6. What is the role of vitamin D in the treatment of patients with CKD?The various activated vitamin D products are used as a means to treat SHPT and are often limited by adverse effects such as hypercalcemia and hyperphosphatemia. Observational studies show a survival benefit from treatment with activated vitamin D in dialysis patients that is independent of PTH, calcium, or phosphorus level, suggesting that all patients with CKD could benefit from some form of vitamin D replacement therapy. No RCT are available to prove this hypothesis.
7. What is the best vitamin D product for patients with CKD?The main advantage of more modern (and expensive) activated vitamin D analogues is their lesser hypercalcemic and hyperphosphatemic effect. If the benefit of vitamin D replacement is indeed universal and independent of PTH, calcium, and phosphorus levels, then this may not be as important after all. Head-to-head comparisons of various products (including generic ones, not just “competitors”) using relevant “hard” end points are needed to clarify this.
8. What is the role of calcium-sensing receptor agonists in the treatment of CKD-MBD?There are no data on the impact of calcium-sensing receptor management on patient survival.
9. What is the most cost-effective way to manage CKD-MBD?The high price of several medications represents a serious limitation in everyday practice. Many of these products have cheaper generic alternatives, but both the economic and the biologic advantages of one versus the other need to be better studied.
  • a CKD-MBD, mineral and bone disorders in chronic kidney disease; PTH, parathyroid hormone; RCT, randomized, controlled trial; SHPT, secondary hyperparathyroidism.