Mineral Handling in Hemodialysis Patients

There is an association between chronic kidney disease (CKD) and an increased risk of cardiovascular morbidity and mortality. In patients with CKD, increased circulating concentrations of phosphate and fibroblast growth factor-23 (FGF23) are highly predictive of cardiovascular disease.

In order to maintain long-term calcium and phosphate balance, in healthy individuals an ingested mineral load is acutely buffered by a rapidly exchangeable calcium phosphate pool in the bone and excess minerals are disposed of via renal excretion. In patients with CKD with glomerular filtration rate >30 mL/min/1.73 m2, phosphate balance is maintained by increased secretion of parathyroid hormone (PTH) and FGF23.

In patients with severe CKD, GFR <30 mL/min/1.73 m2, there are no compensatory mechanisms sufficient to maintain phosphate balance, and patients are characterized by increased plasma phosphate despite often very high concentrations of PTH and FGF23. In addition, plasma calcium may be low due to high plasma phosphate and low 1,25-dihydroxyvitamin D (1,25(OH)D).

Following meal intake in patients with end-stage renal disease (ESRD), the ingested calcium and phosphate cannot be effectively eliminated by the renal route, making it necessary to neutralize the excess calcium and phosphate via other mechanisms. However, there are few available data regarding the way patients on hemodialysis adapt to a mineral load following meal intake.

Mark Richard, MD, PhD, and colleagues recently conducted a controlled intervention study designed to examine the acute handling of a mineral load in hemodialysis patients compared with a cohort of individually matched health controls. The researchers reported results in the Journal of Renal Nutrition [2018;28(3):175-182].

The study matched 12 nondiabetic hemodialysis patients with 12 healthy controls, based on sex, age, height, and weight. The study was conducted between January and June 2012. Eligible patients were >18 years of age, on stable hemodialysis for at least 3 months, and had well-functioning arteriovenous fistulas with a recirculation <5%. Exclusion criteria were diabetes mellitus, body mass index <18.5 or >35.0 kg/m2, malnutrition (defined as Subjective Global Assessment score C), active malignant disease, immunosuppressive treatment (including glucocorticoid treatment), evidence of an ongoing inflammatory disease, or pregnancy. Eligible diagnoses were chronic glomerulonephritis (n=4), chronic renal failure of unknown origin (n=4), autosomal dominant polycystic kidney disease (n=2), sclerodermia progressiva diffusa (n=1), and granulomatosis with polyangiitis (n=1).

The intervention consisted of blood samples taken for the 9 hours after a weight-adjusted standardized meal; the samples were tested for ionized calcium, phosphate, PTH, and FGF23. The fractional excretion of calcium and phosphate was also measured in the control group. Participants in the patient group were not allowed to take phosphate binders 24 hours prior to the experiment; the intervention was performed on a non-hemodialysis day.

At baseline, compared with controls, participants in the patient group had significantly higher fasting concentrations of circulating phosphate, PTH, and FGF23. Serum FGF23 concentrations were 217-fold times higher in the hemodialysis patients than in the control group (P<.001).

There were no significant differences in postprandial changes in plasma ionized calcium between the hemodialysis patient and the control group; further, there were no significant deviations in concentrations from baseline at any point in the hemodialysis patients or controls.

There were statistically significant differences in plasma phosphate between controls and the hemodialysis patients (P=.03). In the hemodialysis patients, there was a decrease shortly below baseline at 60 to 120 minutes after the meal by maximum 10% (P<.001); among the controls, there were no significant deviations from baseline. In subgroup analysis among the hemodialysis patients, changes in plasma phosphate did not differ based on treatment status with calcium-containing phosphate binders, sevelamer, lanthanum, cinacalcet, or vitamin D analogs.

There were no significant differences between the two groups in post-meal changes in PTH. PHT increased above baseline at 240 minutes in the hemodialysis group and remained above baseline to the end of the study, with a peak at 300 minutes of 11% above baseline. In the control group, PTH decreased shortly below baseline at 60 minutes by 15%, and then increased above baseline at 300 to 360 minutes by a maximum 11%.

There were significant differences in postprandial FGF23 between the hemodialysis group and controls (P<.001). There were no significant deviations in FGF23 from baseline in the hemodialysis patients (P=.09); in the control group, FGF23 concentrations decreased below baseline at 120 minutes and continued to decline with nadir values at the end of the study at 16% below baseline (P<.001).

Among the healthy controls, there was significant increase in the fractional excretion of calcium, with an excretion rate above baseline from 60 minutes and to the end of the study, with peak excretion at 120 minutes of 153% above baseline values (P<.001). The controls also demonstrated an increase in the fractional excretion of phosphate immediately after the meal, remaining above baseline to the end of the study. The increase was more modest compared with calcium, showing a late peak at 360 minutes of 58% above baseline.

There were some limitations to the study cited by the authors, including estimating rather than directly measuring the mineral contents in the meals.

“In conclusion, the postprandial mineral handling is severely impaired in hemodialysis patients who lack the ability to excrete excess minerals in the urine. Since hemodialysis patients cannot excrete calcium and phosphate in the urine, the formation of ionic calcium–phosphate complexes may be extensive and enhance soft tissue and vascular calcification. In the healthy subjects, PTH seemed to play a role in the acute adaption to a phosphate load, whereas FGF23 did not. In hemodialysis patients, the apparent normal circadian rhythm of FGF23 seemed to be disrupted, and it is unknown if FGF23 is still modifiable by dietary interventions,” the researchers said.

Takeaway Points

  1. In patients on maintenance hemodialysis, excess calcium and phosphate must be neutralized by mechanisms other than excretion in the urine.
  2. Researchers conducted a controlled intervention study to assess the acute handling of a mineral load in hemodialysis patients compared with healthy controls.
  3. In the hemodialysis patients, the mineral load induced a decrease in plasma phosphate; ionized calcium remained unchanged, and PTH increased.