Good News for CKD-MBD Patients - Latest Invention of Phosphate Binders
CKD & CKD-MBD in MALAYSIA: Phosphorus is an electrolyte found primary in the bones (80-85%) and in the intracellular fluid. The normal serum phosphorus level is between 2.7 to 4.5mg/dL. Patient with chronic kidney disease (CKD) and on renal replacement therapy (RRT) frequently have secondary
hyperparathyroidism (SHPT) and hyper-phosphataemia requiring treatment to slow the progression of this disease. Both SHPT and hyper-phosphataemia are important common complications of advanced CKD. Although bone disease is the most recognized manifestation of SHPT, vascular calcification and cardiovascular morbidity and mortality are the major concerns.
The management of hyperphosphatemia included both dietary phosphate restriction and the use of phosphate binders (both calcium and non-calcium containing binders) in patients with CKD and End-Stage Renal Failure. In line with recommendations from The Kidney Disease: Improving Global Outcomes KDIGO CPG guidelines on CKD-MBD in 2009 and Malaysian CKD-MBD and Parathyroidetomy Guidelines and SOP, 2018, the treatment target for serum phosphate level are as summarized in Table 1.
The prevalence of CKD has increased from 9.1% in the 2011 National Health and Morbidity survey to 15.5% in 2018. The incidence and prevalence of treated ESKD have also risen markedly over the last 25 years.
The 2018 Malaysian Dialysis and Transplant Registry reported number of new dialysis patients continues to increase over the last 10 years - from 4,606 in 2008 to 8,431 in 2018, with a cumulative total of 44,136 patients on dialysis in 2018, affecting 1,295 person per million population as per United States Renal Data System 2017 data. It was found that many nephrologists in Malaysia, as well as from other countries were unable to implement and achieve targets recommended in KDIGO when managing CKD patients with CKD-MBD for various reasons. The 2016 Malaysian Dialysis and Transplant Registry reported about 41% of patients achieved phosphate level of 1.3-1.8mmol/L, with less than 25% of dialysis patients achieved target phosphate level recommended by KDIGO (0.8 to 1.3mmol/L) - (HD vs PD, 15% vs 25%).
Phosphate binders and It’s Use in Malaysia:
Phosphate binders broadly classified into calcium-containing (e.g , calcium carbonate, calcium acetate) and calcium sparing agents (e.g. sevelamer and lanthanum). Calcium containing phosphate binders are less expensive than non-calcium-containing binders and may be clinically better tolerated by patients with CKD. As of 2016, Calcium carbonate remained as the main phosphate binder for both HD patients (93%) and PD patients (84%) in 2016. Alternative used of Aluminium-based binder been largely avoided since its removal from MOH formulary for some years now.
As per reported in 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update Implementation: Asia Summit Conference Report - Calcium-based phosphate binders are most commonly used and reimbursed in Malaysia, while
Sevelamer carbonate and Lanthanum-based binder, although available, requires specific criteria for reimbursement and subject to quota in number of patients supported by the respective department budget.
The binding capacity of the available phosphate binders are as below:
Rationale of Instant Palatable Calcium Carbonate 1300mg (potassium free) Sachet Powder
The daily pill burden in CKD patients is one of the highest reported to date in any chronic disease state. The higher pill burden is also associated with lower HR-QoL. The median daily pill burden in CKD patients was 19-25 pills per day. Phosphate binders accounted for about half of the daily pill burden, hence resulted in nonadherent. Apart from that, factors such as palatable taste, tablet size are also among the factors which may affect the compliance of CKD patients. Chewable formulation been shown to improve patient adherence, with Chewable Calcium Carbonate showing comparable phosphate binding capacity as per normal tablet formulation.
In addition, a recent publication in Jordan showed that chewable tablet of combined calcium carbonate and magnesium carbonate had a significant appetizing effect in HD patients than normal calcium carbonate tablet, rendering the author postulating that chewable form may have a positive
impact on both quality of life and mortality of HD patients.
With that basis, an alternative form of Calcium Carbonate in sachet powder with palatable taste is produced to address the compliance issue amongst CKD/ ESRD. The rationales for an instant palatable sachet powder Calcium Carbonate 1300mg (potassium free):
- Calcium-based phosphate binder is the most inexpensive and cost-effective treatment comparing to non-calcium-based formulation
Factors attributes to compliance of phosphate binder
- Pill burden (10-12 phosphate binder tablets per day)
- less-palatable formulation
This new formulation of instant palatable sachet powder Calcium carbonate contains elemental Calcium of 520mg and Yeast extract 1300mg (enhance the flavor). This instant palatable sachet powder formulation is the 1st ready mixed formulation that can go with the patients’ meal.
