Dialysis providers can disrupt the CKD-mineral bone disorder treatment paradigm
Chronic kidney disease-mineral bone disorder is a systemic disorder prevalent among individuals with advanced chronic kidney disease and end-stage kidney disease.
It is a constellation of lab abnormalities, skeletal abnormalities and vascular calcification, which increases the risk of bone fractures, cardiovascular events and mortality.
For several decades, the kidney care community has had a “vitamin D first” therapeutic approach to reducing parathyroid hormone (PTH), one of the key laboratory abnormalities related to chronic kidney disease-mineral bone disorder (CKD-MBD).
Active vitamin D
While typically effective at lowering PTH, activated vitamin D administration often results in undesirable increases in intestinal absorption and serum concentrations of calcium and phosphorus, which are established risk factors for cardiovascular events and mortality. In addition, substantial increases in the phosphate regulating hormone, FGF23, often result.
It is time we transform our approach to treatment of this important condition.
Fortunately, the science behind management of CKD-MBD – thoroughly reviewed in the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines – has evolved to provide an alternative to the standard vitamin D-first approach, one which might lead to meaningful improvement in patient outcomes.
When writing the guidelines for the management of CKD-MBD, KDIGO relied on a world-class evidence review team to identify randomized, controlled clinical trials which evaluated outcomes in critical, patient-focused areas such as fractures, pain, cardiovascular events and survival.
The EVOLVE trial is the largest randomized placebo-controlled trial conducted in patients receiving hemodialysis. In the trial, researchers evaluated the use of oral, daily cinacalcet vs. placebo in addition to standard of care therapy with activated vitamin D to reduce cardiovascular events in patients with moderate to severe elevations in PTH.
Data representing the cumulative evidence generated from EVOLVE have been published in numerous peer reviewed publications. An informed synthesis of the data leads to the conclusion that the use of cinacalcet demonstrated significant reduction in cardiovascular events, fractures and the need for surgical intervention for hyperparathyroidism as compared to standard of care with activated vitamin D alone.
The clinical evidence supports the recommendations contained in the 2017 KDIGO guidelines which indicate calcimimetics should be a first-line therapy for the reduction of PTH in the management of CKD-MBD. The demonstrated ability of cinacalcet to reduce serum calcium and phosphorus and to reduce the phosphate regulatory hormone, FGF23, is felt to underlie the improvement in cardiovascular risk.
Indeed, the improvement in cardiovascular outcomes observed with cinacalcet was independent of its ability to lower PTH but directly related to its ability to lower FGF23.
We believe it is important to acknowledge there have been no randomized controlled trials demonstrating an improvement in patient outcomes with the existing active vitamin-D first approach nor with the newer, intravenous calcimimetic, etelcalcetide. Thus, our approach centers around cinacalcet as first-line therapy.
To ensure and realize the demonstrated clinical benefits of calcimimetic therapy with cinacalcet for patients with CKD-MBD, U.S. Renal Care (USRC) will work with treating nephrologists to align treatment policy with the KDIGO guidelines. The foundation of this policy is focused on the treatment of the entire spectrum of mineral bone disorder, rather than focusing primarily on lowering PTH.
Specifically, the new clinical approach of USRC will include the following essential aspects of treating CKD-MBD:
- recommend the use of oral cinacalcet treatment as first-line therapy for CKD-MBD;
- strongly recommend the use of non-calcium containing phosphate binders as the preferred choice when phosphate binder therapy is indicated; and
- set an optimal clinical target to achieve normal phosphate levels, with a goal of 3.5 mg/dL to 4.5 mg/dL.
As practicing physicians, we are excited to implement evidence-based policies that challenge the status quo on our journey to continually achieve better patient outcomes. We firmly believe this new approach to care based on robust clinical trial evidence has the opportunity to improve quality of care, reduce mortality, reduce hospitalizations and significantly improve the quality of life for our patients.
- Moe SM, et al. JASN. 2014;doi:10.1681/asn.2014040414.
- Parfrey PS, et al. CJASN.2015;doi:10.2215/cjn.07730814.
- For more information
- Geoffrey A. Block, MD, is associate chief medical officer and senior vice president, clinical research and medical affairs at U.S. Renal Care. He can be reached at email@example.com.
- Mary Dittrich, MD, is executive vice president and chief medical officer of U.S. Renal Care. She can be reached at firstname.lastname@example.org.