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Recommendations Summary

CKD: Electrolytes: Phosphorus (2020)

Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.


  • Recommendation(s)

    CKD: Dietary Phosphorus Amount

    In adults with CKD 3-5D, we recommend adjusting dietary phosphorus intake to maintain serum phosphate levels in the normal range (1B).

    Rating: Strong
    Imperative

    CKD: Dietary Phosphorus Source

    In adults with CKD 1-5D or posttransplantation, it is reasonable when making decisions about phosphorus restriction treatment to consider the bioavailability of phosphorus sources (e.g. animal, vegetable, additives) (OPINION).

    Rating: Consensus
    Conditional

    CKD: Phosphorus Intake with Hypophosphatemia

    For posttransplantation adults with hypophosphatemia, it is reasonable to consider prescribing high-phosphorus intake (diet or supplements) in order to replete serum phosphate (OPINION).

    Rating: Consensus
    Conditional

    • Risks/Harms of Implementing This Recommendation

      The serum phosphate level at which supplementation should be considered in these patients or the dose of replacement to be given is, however, not well studied, and should be decided based on patient needs and clinical judgment.

      Recommendations to lower dietary phosphorus intake in patients with CKD have been met with concerns, often relating to the risk of limiting the intake of other nutrients, particularly protein, which is the main source of phosphate in the diet (Lynch et al 2011, Rufino et al 1998, Shinaberger et al 2008) These concerns are particularly relevant to patients treated with dialysis because of protein losses in dialysate and greater protein catabolism from hypermetabolic stress (Carrero et al 2013). Dietary counselling that includes information on not only the amount of phosphate but also on the source of protein from which the phosphate derives and suggestion on methods of cooking phosphate-rich foods can achieve phosphorus intake without compromising dietary quality or protein status (St. Jules et al 2016).

    • Conditions of Application

      Special Discussions
      Hypophosphatemia in kidney transplant patients: Hypophosphatemia is a relatively common complication after kidney transplantation, especially during the first months, and possibly leading to osteomalacia and osteodystrophy. Its pathogenesis has been attributed to increased renal phosphate excretion due to elevated levels of phosphaturic hormones, the effect of glucocorticoid, persistent elevated PTH levels, suboptimal recovery of vitamin D activation, and imbalance in fibroblast growth factor 23 (FGF23) (Tomida et al 2012, Trombetti et al 2011, Sakhaee 2010). It has been proposed that dietary intensification of phosphorus can solve this complication; one small randomized controlled trial (Rosman et al 1989) examined the effects of 12-week dietary phosphorus supplementation by means of a neutral phosphate salt (disodium phosphate) in patients with early post-transplantation hypophosphatemia. The authors observed that, compared to sodium chloride, supplementation of phosphorus improved hypophosphatemia as well as adenosine triphosphate in the muscles and the acid excretion capacity of the kidney. No adverse effects on serum calcium and PTH concentrations were noted during intervention.

      The serum phosphate level at which supplementation should be considered in these patients or the dose of replacement to be given is, however, not well studied, and should be decided based on patient needs and clinical judgment.

      Implementation Considerations
      Recommendations to lower dietary phosphorus intake in patients with CKD have been met with concerns, often relating to the risk of limiting the intake of other nutrients, particularly protein, which is the main source of phosphate in the diet (Lynch et al 2011, Rufino et al 1998, Shinaberger et al 2008) These concerns are particularly relevant to patients treated with dialysis because of protein losses in dialysate and greater protein catabolism from hypermetabolic stress (Carrero et al 2013). Dietary counselling that includes information on not only the amount of phosphate but also on the source of protein from which the phosphate derives and suggestion on methods of cooking phosphate-rich foods can achieve phosphorus intake without compromising dietary quality or protein status (St. Jules et al 2016).

      • Advise choosing natural foods that are lower in bioavailable phosphorus. Animal- and plant-based foods contain the organic form of phosphate. While animal-based phosphate is absorbed in the GI tract by 40-60%, the absorption of plant-based phosphorus is lower (20-50%).394 In line with this, a small crossover trial including CKD patients’ stage 4 found that a 7-day vegetarian diet led to lower serum phosphate levels and decreased FGF23 levels than a 7-day meat-based diet (Moe et al 2011). Furthermore, foods with only organic phosphorus typically are more nutrient dense and have a higher nutritional value compared with processed foods containing phosphate additives, which tend to have a lower nutritional value, and are often paired with sodium and potassium additives (Gutierrez et al 2013).
      • Advise choosing commercial food items prepared without phosphorus-containing food additives.  Phosphorus additives are increasingly being added to processed and fast foods to preserve moisture or color, to emulsify ingredients and enhance flavor, and to stabilize foods. Phosphorus additives contain, however, inorganic phosphorus with a close to 100% intestinal absorption (St-Jules et al 2016, Kalantar-Zadeh et al 2010). Meat and poultry products that report the use of additives have an average phosphate-protein ratio much higher than additive-free products (Sherman et al 2009, Parpia et al 2017). The most-commonly used phosphorus additives in food industry can be found, for instance, in bakery products, enhanced meats, and processed cheeses (Karalis et al 2006). 
      • Advise choosing natural foods that have low amount of organic phosphorus versus high amount of protein.  The content of organic phosphorus per gram of protein varies widely among foods. Nutrient composition tables reporting on phosphorus/protein ratio content can be used to recommend food substitutions that can considerably reduce the daily intake of organic phosphorus while ensuring adequate dietary protein intake (Cupisti et al 2003 and 2013, Barril-Cuadrado et al 2013, Kalantar-Zadeh et al 2010). 
      • Advise preparing foods at home, using wet cooking methods such as boiling (and discard the water). These methods are able to remove about 50% of phosphorus content from foods (Cupisti et al 2006, Ando et al 2015). Slicing the meat prior to boiling and the use of a pressure cooker has been shown more effective in terms of achieved protein to phosphorus content (Ando et al 2015). At the same time, these methods may remove other minerals (e.g. potassium) of concern for patients with CKD (Bethke et al 2008). Such practices, however, result in reduced palatability and texture of the food.

      The work group emphasizes to individualize recommendations after appropriate evaluation of the patient daily intake. It requires nutrition expertise (preferably consultation with a renal dietitian) and should take into consideration culturally appropriate food substitutions. Nutritional counselling sessions should evolve, from the simple concept of phosphate restriction to opportunities of educating the patient on differentiation between organic and inorganic sources of phosphate and avoidance of phosphate additives (Karavetian et al 2014). Simple educational programs on how to read food labels and look for phosphate additives proved to be successful in helping dialysis patients reduce their serum phosphate levels (Caldeira et al 2011, Sullivan et al 2009). A meta-analysis suggested that nutritional counselling based on a structured behavioral change are, in general,  successful in controlling hyperphosphatemia in these patients (Karavetian et al 2014). In this meta-analysis, however,  only about half of the studies were randomized controlled interventions with a short duration ranging from 1 to 6 months, which calls for a need of more dedicated long-term interventional studies on this topic.

    • Potential Costs Associated with Application

      There are no obvious costs in implementing this recommendation.

    • Recommendation Narrative

      Phosphorus intake is necessary for bone growth and mineralization, as well as for regulation of acid-base homeostasis. Phosphorus is an essential nutrient, occurring in most foods both as a natural component and as an approved ingredient added during food processing. Because of difficulties of persons with chronic kidney disease (CKD) to clear excess phosphorus, additional means of serum phosphate control is necessary to avoid hyperphosphatemia, which could lead to bone and mineral metabolism disorders of CKD.
       
      There are physiologic adaptations in the early stages of CKD that prevent excessive phosphorus retention, so the inability to promote phosphorus excretion to avoid phosphorus accumulation and hyperphosphataemia is generally seen when estimated glomerular filtration rate (eGFR) level decreases below 45 mL/min (Moranne et al 2009), being less common in earlier CKD stages. In the setting of anuria in patients on maintenance dialysis, hyperphosphatemia risks are particularly heightened (Block et al 1998), with a prevalence as high as 50% (Blayney et al 2009).

      How much should dietary phosphorus/phosphate be restricted in adult patients with CKD is not well established. Traditionally, CKD-specific recommendations suggest maintaining phosphorus intake between 800-1000 mg/day in patients with CKD Stages 3-5 and those in maintenance dialysis in order to maintain serum phosphate in the normal range (Ketteler et al 2017,   KDIGO 2017, Fouque et al 2007, KDOQI 2000 and 2003, Isakova et al 2017). The workgroup notes, however, that the efficacy of this recommendation has not been established. Further, such dietary phosphorus intake range is higher than current recommended dietary allowance for phosphorus in the adult general population (700 mg/d) (DRI 1997).

      While dietary intake influences serum phosphate in CKD patients, factors other than intestinal phosphorus/phosphate absorption (namely exchange with bone and excretion by the kidneys in patients with residual renal function) may be major determinants of serum phosphate levels.  Thus, the workgroup prefers not suggesting specific dietary phosphate ranges, and instead emphasize on the need to individualize treatments based on patient needs and clinical judgment, taking into consideration natural sources of organic phosphorus (animal vs. vegetal protein-based dietary phosphorus), or the use phosphorus additives in processed foods (Sherman et al 2009, Parpia et al 2011, Benini et al 2011).

      With the goal to better understand the effect of dietary phosphate control, the workgroup decided in this evidence analysis to focus on reports that addressed dietary phosphorus intake/output/balance. This resulted in the exclusion of studies reporting solely on serum phosphorus levels.

      Phosphorus Control
      Limiting dietary phosphorus intake (per se or in combination with dietary protein restriction-the major source of dietary phosphorus) may be recommended to prevent / treat complications related to high phosphate load patients with CKD Stages 3-5 and maintenance dialysis. This can be achieved by intensified patient educational strategies or individualized dietary plans (Caldeira et al 2011). This evidence review included 5 short-term clinical trials that evaluated the effect of reduced dietary phosphorus on phosphorus intake, phosphate levels and urinary phosphorus excretion:
      • Phosphate restriction regimes in non-dialysis CKD: Two randomized controlled trials (Williams et al 1991,  Martinez, et al 1997) examined the effects of reduced dietary phosphorus in patients with CKD not undergoing dialysis. These studies evaluated the effect of a low phosphorus diet alone or in combination with a low protein diet, and observed significant reductions in serum phosphate, and urinary phosphorus excretion post-intervention.
      • Reducing phosphorus by limiting protein intake in non-dialysis CKD: Five randomized controlled trials in CKD patients not undergoing dialysis stages 4-5 (Feiten et al 2005, Garneata et al 2016,  Malvy et al 1999,  Mircescu et al 2007, Rosman et al 1989) evaluated the effect of a low protein diet (LPD) or a very low protein diet (VLPD) supplemented with keto-analogs on serum phosphate levels. All five studies reported statistically significant (Garneata et al 2016,  Malvy et al 1999, Mircescu et al 2007,  Rosman et al 1989) or borderline-significant (Feiten et al 2005) reductions in serum phosphate levels at the end of intervention. The interested reader can find more information on this topic in the evidence analysis of dietary protein restriction in these guidelines.
      • Phosphate restriction regimes in maintenance dialysis: Two randomized controlled trials (Lou et al 2012,  Sullivan et al 2009) examined the effects of limiting dietary phosphorus in patients with CKD undergoing hemodialysis. Lou, et al. 2012 tested the effect of 3-month intensified dietary counseling in order to achieve 800 – 900 mg/d of dietary phosphorus, and observed a greater decrease in serum phosphorus concentration compared to standard care. Sullivan et al., tested the effect of patient education on identifying foods with phosphorus additives and observed, compared to standard care, a significant reduction in serum phosphorus levels after 3 months. No studies were identified that included peritoneal dialysis patients.

      Although dietary phosphorus restriction may be a valid stand-alone strategy in patients with CKD-stage 3-4, the working group notes that, collectively, the serum phosphate reductions achieved solely by limiting dietary intake are modest (especially for dialysis patients) and recommend this strategy as one in the armamentarium of interventions to maintain serum phosphate levels in the normal range.  For other non-dietary phosphate management strategies, the interested reader can consult recent guidelines on the management of mineral and bone disorders of CKD (Ketteler et al 2017, KDIGO 2017, Fouque et al 2007, KDOQI 2000 and 2003; Isakova et al 2017). Aligning with those guidelines, we recommend decisions to restrict dietary phosphorus be based on the presence of progressively or persistently elevated serum phosphate (that is, trends rather than a single laboratory value), and after consideration of concomitant calcium and PTH levels.

      Clinical Consequences of Dietary Phosphorus Control
      Whereas many studies have explored the outcome associations with serum phosphate levels throughout the spectrum of CKD, the clinical consequences of restricting dietary phosphorus are not well studied.

      CKD Progression
      Three observational studies evaluated the effects of dietary phosphate restriction on CKD progression. Results were mixed and evidence was limited. Williams et al 1991 studied impact of a dietary phosphorus restriction (alone or in combination with protein restriction) on creatinine clearance among 90 CKD patients of unreported aetiology or CKD stage over a median intervention time of 19 months.  Compared to routine care, dietary protein and phosphate restriction or phosphate restriction only did not show any significant difference in the mean rate of fall of creatinine clearance. In an observational analysis from the Modification of Diet in Renal Disease (MDRD) study (Selamet et al 2016), greater 24-hr urinary phosphate excretion (taken in this study as an estimate of dietary phosphorus intake) was not associated with the future risk of ESRD. We note that in this study baseline phosphate levels were well controlled and normal on average, which may not be the case of real-world settings. A small retrospective observational analysis from Japan (Kawasaki et al 2015) including CKD patients stages 2-5 observed that higher phosphorus excretion per creatinine clearance was associated with a higher 3-year risk of CKD progression (defined as the composite of ESKD or 50 % reduction of eGFR).

      It has been proposed that hyperphosphatemia in non-dialysis patients stages 2-5 may reduce the antiproteinuric effect of ACE inhibition (Zoccali et al 2011) or of very low protein diets (Di Iorio et al 2013). In a post hoc observational analysis from the Ramipril Efficacy In Nephropathy (REIN) trial, Zoccali et al 2011 evaluated the relationships between serum phosphate concentration at baseline, disease progression, and response to ACE inhibition among 331 patients with proteinuric nephropathies. Independent of treatment, patients with higher phosphate progressed significantly faster either to ESRD or to a composite endpoint of doubling of serum creatinine or ESRD compared with patients with phosphate levels below the median, and the renoprotective effect of ramipril decreased as serum phosphate increased (P ≤ 0.008 for interaction). In another post hoc study from a non-randomized, study in which 99 proteinuric CKD patients who sequentially underwent low-protein diet (LPD; 0.6 g/kg/day) and VLPD (0.3 g/kg/day) supplemented with keto-analogues, each for periods longer than 1 year, Di Lorio et al 2013 observed that 24-h proteinuria was reduced modestly in patients who maintained relatively higher serum phosphate levels or relatively higher phosphaturia to be maximal in those who achieved the lowest level of serum and urine phosphate.

      Mortality
      In observational studies involving CKD patients, the associations of dietary phosphorus intake on mortality are mixed, impacted by residual confounding and probably pointing to a null association. Three studies evaluated the cross-sectional association between measures of dietary phosphorus and mortality in individuals with non-dialysis CKD (Salamet, et al. 2016; Murtaugh, et al. 2012; Palomino, et al. 2013). Murtaugh et al. 2012 evaluated the association between 24-h dietary recall estimation of phosphorus intake in participants with eGFR<60 ml/min/1.73m2 from the community-based U.S survey National Health and Nutrition Examination Survey III, and observed no association between dietary phosphorus and mortality. Palomino et al. 2013 examined myocardial infarction patients from the Heart and Soul Study, the majority of which with normal kidney function, and observed no association between higher urinary phosphorus excretion and mortality, but noted an association with CVD-related mortality (P-trend across tertiles = 0.02). Selamet et al. 2016 involved nephrology referred patients with CKD from the MDRD study and failed to observe an association between 24-hr urinary phosphorus excretion and mortality.

      One study in MHD patients that examined the association between dietary phosphate (as estimated from 3-day food recalls) and mortality (Noori, et al. 2010). Patients with higher dietary phosphorus intake were associated with greater 5-year mortality risk (p-trend across tertiles= 0.04). Lynch et al. 2011 explored the between prescribed dietary phosphorus restriction and mortality in a post hoc analysis of the Hemodialysis (HEMO) study, which included 1751 MHD patients. The study exposure was ascertained by the serum phosphate targets that the dietitians from the clinical dialysis centers settled annually to prescribe their dietary recommendations. A more restrictive prescribed dietary phosphate was associated with poorer indices of nutritional status on baseline analyses and a persistently greater need for nutritional supplementation but not longitudinal changes in caloric or protein intake. There was a stepwise trend toward greater survival with more liberal phosphate prescription, which reached statistical significance among subjects prescribed 1001 to 2000 mg/d and those with no specified phosphate restriction: hazard ratios (95% CIs) 0.73 (0.54 to 0.97) and 0.71 (0.55 to 0.92), respectively.

    • Recommendation Strength Rationale

      The evidence supporting the recommendation phosphorus amount is based on Grade II /Grade B evidence. The remaining recommendations are based on consensus/expert opinion. 

    • Minority Opinions

      Consensus reached.