Description of the condition
Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic dysfunction of mineral and bone metabolism in people with chronic kidney disease (CKD). CKD-MBD results from abnormalities in calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism levels; bone turnover, mineralisation, volume, linear growth or strength, vascular or other soft tissue calcification (KDIGO 2009). In its early stages, CKD-MBD is characterised by bone fractures, bone pain, skeletal deformities in growing children, reduced velocity in bone growth, abnormal height, vascular and other soft tissue calcification (Mejía 2011). Developments in dialysis technology have meant that fewer patients with CKD die from uremia and have longer rates of survival. However, CKD-MBD is a significant contributor to decreased quality of life and increased mortality and morbidity risks, and progression of CKD (Moe 2006; Moe 2007).
Phosphate retention plays an important role in the development of CKD-MBD. As kidney function declines, excretion of phosphate becomes more difficult. Phosphate retention stimulates PTH and FGF-23 function before hyperphosphataemia is detected during the early stages of CKD. In general, FGF-23 and PTH can suppress renal reabsorption of phosphorus. However, as CKD develops kidney response to these hormones decreases (Razzaque 2011). In contrasting, residual kidney function is challenged in converting 25(OH)D to 1,25(OH)₂D, which may reduce intestinal calcium absorption and increase PTH and FGF-23 levels (Komaba 2008). Recent research has also indicated that the Klotho gene, which encodes a transmembrane co-receptor specific for FGF-23, declines in people with CKD. The Klotho gene also causes FGF-23 resistance and stimulates PTH (Kuro-O 2011). Both FGF-23 and PTH increase as CKD progresses, eventually leading to renal osteodystrophy, cardiovascular and soft issue calcification. CKD-MBD has been associated with both renal bone disease and higher mortality (Moe 2007; Tentori 2008).
Description of the intervention
Phosphate retention usually begins early in the course of developing CKD. Dietary phosphate restriction and use of phosphate binders are two principal measures for the management of elevated phosphate levels. It has been shown that if serum phosphate can be decreased in relation to the glomerular filtration rate (GFR), plasma PTH elevation could be prevented (Slatopolsky 1973). Small sample research has also demonstrated that prolonged limiting of dietary phosphate intake is effective in suppressing secondary hyperparathyroidism, and was recommended for implementation at all stages of kidney disease (McCrory 1987; Takeda 2007). However, challenges persist in the treatment of hyperphosphataemia. At present, calcium-containing and non-calcium containing phosphate binders, such as sevelamer and lanthanum, are the major drugs used to lower phosphate levels. Calcium-containing phosphate binders may increase the risk of positive calcium balance, and lead to cardiovascular and soft tissue calcification, particularly when associated with vitamin D therapy. Sevelamer for reducing serum phosphate has been demonstrated to decrease progression of coronary artery calcification compared with calcium salts. However, high treatment cost of sevelamer limits its use, and the same is true for lanthanum. Pelletier 2010 compared older haemodialysis patients with younger dialysis patients and reported better control of serum phosphorus with less phosphate binder and cinacalcet. This study indicated that phosphate binders may not be the determinant in maintaining serum phosphorus. Moreover, the increasing number of patients with CKD requires a large number of conventional drugs which imposes a significant burden for both patients and society (Navaneethan 2009). Thus, searching for interventions that are both efficient and affordable is a pivotal target for preventing and treating CKD-MBD.
Compared with drug therapies, dietary interventions seem to be simple, inexpensive and feasible. Therefore, dietary phosphate restriction is recommended in many guidelines. The KDOQI 2003 guidelines suggest that dietary phosphorus should be restricted to 800 to 1000 mg/day when plasma levels of intact PTH are elevated above the target range of the CKD stage. The KDIGO 2009 guidelines recommend that patients with CKD stages 3 to 5D limit their dietary phosphate intake for the treatment of hyperphosphataemia, alone or in combination with other treatments; however, there is currently little evidence to support this recommendation.
Because phosphate intake usually parallels protein intake, dietary phosphate restriction is often achieved by restricting protein intake. Cianciaruso 2008 and Klahr 1994 conducted studies to investigate the effects of different protein diets on metabolic control and CKD progression. Sullivan 2009 focused on the effects of food additives on hyperphosphataemia in people with end-stage kidney disease and reported benefits when phosphorus-containing food additives were avoided. Soroka 1998 investigated feasibility low phosphate diets and showed that a low-phosphorus vegan diet in which only an appropriate cereal-legume mixture was consumed could achieve the same goal as a conventional low-protein diet. Patients not only avoided protein malnutrition, but also reduced phosphate intake, which is an abundant mineral in animal-based foods.
How the intervention might work
Phosphate retention plays a significant role in the development of CKD-MBD. Lowering dietary phosphate by restricting food additives, processed foods and protein, and sometimes in combination with phosphate binders, should therefore be the first step to protect people with CKD from developing mineral and bone disorder.
Why it is important to do this review
Although dietary interventions are well recognised as important ways to help prevent and treat CKD-MBD, there has been no systematic review of these interventions. The safety and efficacy of dietary interventions for people with CKD-MBD remain unknown.