CKD: Electrolytes: Calcium (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.
CKD: Total Calcium Intake, CKD 3-4
In adults with CKD 3-4 not taking active Vitamin D analogs, we suggest that a total elemental calcium intake of 800-1, 000 mg/d (including dietary calcium, calcium supplementation and calcium-based phosphate binders) be prescribed to maintain a neutral calcium balance (2B).
CKD: Total Calcium Intake, CKD 5D
In adults with CKD 5D, it is reasonable to adjust calcium intake (dietary calcium, calcium supplements or calcium-based binders) with consideration of concurrent use of vitamin D analogs and calcimimetics in order to avoid hypercalcemia or calcium overload (OPINION).
Risks/Harms of Implementing This Recommendation
There are no obvious risks or harms associated with this recommendation.
Conditions of Application
In maintenance dialysis patients, calcium balance is more complex. In addition to dietary calcium load and use of vitamin D analogs, calcium concentration in the dialysate and mode of dialysis also determine the mass balance of calcium. Studies using a mathematical modeling have shown a positive calcium balance mass in patients on MHD (Bushinsky et al 2010, Gotch et al 2010). According to estimates and assumptions made, extracellular fluid calcium increased with an elemental daily calcium intake >1.5 g and was numerically more positive when patients are given active vitamin D analogs (Bushinsky et al 2010). The excess of extracellular calcium is deposited in either osseous or extraosseous sites. The extensive soft tissue calcification highly prevalent in MHD patients suggests that extraosseous sites seem to be the repository for this calcium (London et al 2003).
Although calcium balance studies are demanding, they are essential to provide data to make conclusive recommendation for calcium intake from diet or supplements for patients on maintenance dialysis. In KDIGO (CKD-MBD) 2009 and 2017 there is no recommendation regarding calcium intake for patients on maintenance dialysis or with kidney transplantation.
Hypercalcemia is relatively common in patients on maintenance dialysis. Evidence has been accumulated linking higher serum calcium concentrations to increased nonfatal cardiovascular events (Gallieni et al 2012) and mortality (Coen et al 2010, Floege et al 2011, Fukagawa et al 2014, Markaki et al 2012). In the event of hypercalcemia the following adjustments are recommended (K/DoQI et al 2003):
- In patients taking calcium-based phosphate binders the dose should be reduced or therapy switched to a non-calcium phosphate binding.
- In patients taking active vitamin D analogs the dose should be reduced or therapy discontinued until serum concentration of calcium return to normal.
- If hypercalcemia persists, consider using low dialysate calcium (1.5 to 2.0 mEq/L). This should be done with caution because observational studies have linked this approach with increased risk for arrhythmia and heart failure (Pun et al 2013, Brunelli et al 2015).
Potential Costs Associated with Application
There are no obvious costs associated with modifying dietary calcium intake. The cost of nutrition supplements should be considered before recommending to a patient.
Calcium is a multivalent cation important for many biologic and cellular functions. Approximately 99% of total body calcium is found in the skeleton and the remainder is present in the extracellular and intracellular spaces. In addition to its role in maintenance of bone health, calcium serves a vital role in nerve impulse transmission, muscular contraction, blood coagulation, hormone secretion, and intercellular adhesion.
Calcium balance is tightly regulated by the concerted action of calcium absorption in the intestine, reabsorption in the kidney, and exchange from bone, which are all under the control of calciotropic hormones triggered by demand for calcium.
Serum calcium concentrations are maintained in the normal range until very late in CKD (CKD) when it decreases slightly (Levin et al 2007). However, calcium balance in CKD is poorly understood. Calcium deficiency due to decreased intestinal calcium absorption is a stimulus for the development of secondary hyperparathyroidism and resultant bone disorders. On the other hand, calcium excess may promote extra-osseous calcification contributing to increasing the risk of cardiovascular disease and mortality of these patients (Sigrist et al 2007). In kidney transplant, calcium balance is complex and depends on several factors such as the post-transplant renal function, the persistence of hyperparathyroidism, the previous bone disease and the immunosuppressive therapy (Hirukawa et al 2015).
Serum calcium levels do not reflect the overall body calcium balance and may not be very informative except at extremes. The maintenance of serum calcium in the normal range in CKD depends on several factors such as bone turnover, mineral regulating hormones, degree of kidney function, use of vitamin D analogues, dialysate calcium concentration and calcium intake especially from supplements. A careful medical and nutritional history may provide some insight into the adequacy of calcium intake. However, due to the multifactorial causes of altered calcium metabolism in CKD, the establishment of adequate amount of dietary calcium is challenging and depends on the investigation of calcium balance.
The evidence review included three small short-term clinical trials in pre-dialysis CKD patients that investigated the effect of calcium intake in food or supplements on mineral bone biomarkers and on calcium balance (Martinez et al 1997, Spiegel et al 2012, Hill et al 2013). No other outcomes were investigated in these studies.
Calcium Balance and other Lab Measures
In an NRCT, 51 patients in the early stage of CKD (creatinine clearance: 66 to 82 mL/min) were placed in a low protein (40g/d) and low phosphorus (600 mg/d) diet supplemented with or without 0.5 g/d of elemental calcium for 10 days (Martinez et al 1997). A decrease in intact parathyroid hormone (iPTH) was observed only in the group receiving calcium supplementation and no changes in serum calcium, phosphorus and calcitriol were found in the other groups.
In a crossover study, six patients with CKD stages 3 and 4 consumed controlled high (2, 000 mg/d) and low calcium diets (800 mg/d) for 9 days (Spiegel et al 2012). Calcium balance was slightly negative to neutral in both patients and healthy controls on the low calcium diet (- 91±113 and -144±174 mg/d respectively, p>0.05) and more positive in patients than in controls on the high calcium diet (759±120 and 464±225 mg/d respectively, p<0.05). Serum calcium and phosphate concentrations were unchanged and iPTH and 1, 25-dihydroxivitamin D decreased in the high calcium diet.
In a 3-week randomized cross-over balance study, eight patients with CKD stages 3 and 4 were randomized to a controlled calcium intake of 2457 mg/day (1, 500 mg of elemental calcium from calcium carbonate used as phosphate binder + 957 mg/day of dietary calcium) versus placebo (957 mg/day of dietary calcium) (Hill et al 2013). The calcium balance was neutral in the placebo and positive in the calcium carbonate groups (508 vs. 61 mg/d, respectively, p=0.002). Serum calcium, phosphate and iPTH concentrations were unchanged in both groups.
Despite the small number of patients investigated, these well performed balance studies showed that a dietary calcium intake of approximately 800 to 1, 000 mg/d may be adequate to maintain calcium balance in patients CKD stages 3 and 4 who are not receiving active vitamin D analogs, at least at short term (DRI et al 2011). These values are close to the current estimated average requirement (EAR-800-1000 mg/d) and the recommended dietary allowance (RDA- 1000-1200 mg/d) for healthy individuals proposed by the Institute of Medicine.
Recommendation Strength Rationale
The evidence supporting the recommendation on calcium is based on Grade II/Grade B evidence.
- Risks/Harms of Implementing This Recommendation
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
What is the effect of calcium intake on electrolyte levels in adults with CKD 1-5D and post-transplant?
Hill K, Martin B, Wastney M, McCabe G, Moe S, Weaver C, Peacock M. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney International 2013; 83:959-66
Martinez I, Saracho R, Montenegro J, Llach F. The importance of dietary calcium and phosphorous in the secondary hyperparathyroidism of patients with early renal failure. American Journal of Kidney Diseases : the official journal of the National Kidney Foundation 1997; 29:496-502
Spiegel D, Brady K. Calcium balance in normal individuals and in patients with chronic kidney disease on low- and high-calcium diets. Kidney International 2012; 81:1116-22
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
Brunelli SM, Sibbel S, Do TP, Cooper K, Bradbury BD. Facility Dialysate Calcium Practices and Clinical Outcomes Among Patients Receiving Hemodialysis: A Retrospective Observational Study. Amer J Kidney Dis. 2015;66(4):655-65. PMID: 26015274
Bushinsky DA. Contribution of intestine, bone, kidney, and dialysis to extracellular fluid calcium content. Clin J Am Soc Nephrol 2010;5 Suppl 1:S12-22. PMID: 20089498
Coen G, Pierantozzi A, Spizzichino D, et al. Risk factors of one year increment of coronary calcifications and survival in hemodialysis patients. BMC Nephrology. 2010;11:10. PMID: 20565936
Dietary Reference Intake. Calcium and Vitamin D. In: Institute of Medicine; 2011.
Floege J, Kim J, Ireland E, et al. Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population. Nephrol Dial Transplant. 2011;26(6):1948-55. PMID: 20466670
Fukagawa M, Kido R, Komaba H, et al. Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding. Am J Kidney Dis. 2014;63(6):979-87. PMID: 24119541
Gallieni M, Caputo F, Filippini A, et al. Prevalence and progression of cardiovascular calcifications in peritoneal dialysis patients: A prospective study. Bone. 2012;51(3):332-7. PMID: 22699014
Gotch F, Levin NW, Kotanko P. Calcium balance in dialysis is best managed by adjusting dialysate calcium guided by kinetic modeling of the interrelationship between calcium intake, dose of vitamin D analogues and the dialysate calcium concentration. Blood Purif. 2010;29(2):163-76. PMID: 20093823
Hirukawa T, Kakuta T, Nakamura M, Fukagawa M. Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities. Clin Exp Nephrol. 2015;19(4):543-55. PMID: 25931403
K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Amer J Kidney Dis. 2003;42(4 Suppl 3):S1-201.
Levin A, Bakris GL, Molitch M, et al. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int. 2007;71(1):31-8. PMID: 17091124
London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18(9):1731-40. PMID: 12937218.
Markaki A, Kyriazis J, Stylianou K, et al. The role of serum magnesium and calcium on the association between adiponectin levels and all-cause mortality in end-stage renal disease patients. PLoS One. 2012;7(12):e52350. PMID: 23285003
Pun PH, Horton JR, Middleton JP. Dialysate calcium concentration and the risk of sudden cardiac arrest in hemodialysis patients. Clin J Amer Soc Nephrol. 2013;8(5):797-803. PMID: 23371957
Sigrist MK, Taal MW, Bungay P, McIntyre CW. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Amer Soc Nephrol 2007;2(6):1241-8. PMID: 17928470