Hyperparathyroidism, hyperphosphatemia & hypercalcemia

Dialysis Prescription

Significant prolongation of dialysis times (nocturnal dialysis) may bring about reduction in phosphate and help control calcium levels. Daily intermittent dialysis up to 5 hours may have little effect. Reducing dialysis calcium from 1.25 – 1.0 mmol/L may temporarily help the hypercalcemia but would not be expected to help the hyperphosphatemia and may worsen the hyperparathyroidism.

Phosphate and Calcium Management

Therapeutic avenues include:

1.    Reduction or discontinuation of calcium containing phosphate binders
2.    Switch to non-calcium containing binders (including rescue aluminum)
3.    Dietary phosphate intake and adherence to dose and timing of binder ingestion should be reviewed.

PTH Management

If vitamin D sterol therapy is being used in this patient, the dose should be decreased to reduce the hypercalcemia, and, to a lesser extent, the hyperphosphatemia. This may result in a further increase in PTH levels. It would not be wise to initiate vitamin D sterol therapy while the phosphate and calcium were both high.

This patient has hyperparathyroidism despite hypercalcemia. This suggests that the parathyroid glands are poorly responsive or unresponsive to calcium levels. The hyperparathyroidism may prove difficult to control medically. The use of a calcimimetic agent such may result in a fall in PTH, calcium and phosphate in this patient, but the hyperparathyroidism may be such that it is autonomous and poorly responsive to calcimimetics. Consideration should be given to parathyroidectomy in this case.

Other Controversies in Management

Aluminum use:

The K/DOQI guidelines allow for the use of “rescue aluminum”:

GUIDELINE 5. USE OF PHOSPHATE BINDERS IN CKD
Chapter 5.8 In patients with serum phosphorus levels >7.0 mg/dL (2.26 mmol/L), aluminum-based phosphate binders may be used as a short-term therapy (4 weeks), and for one course only, to be replaced thereafter by other phosphate binders. (OPINION)

This opinion based guideline is not accepted by all, and many authors recommend complete avoidance of aluminum. The following position was adopted by the KDIGO group:

Chapter 4.1: Treatment of CKD–MBD targeted at lowering high serum phosphorus and maintaining serum calcium
4.1.6 In patients with CKD stages 3–5D, we recommend avoiding the long-term use of aluminum-containing phosphate binders.

Duration of Dialysis

Excellent control of phosphate has been achieved during long (8 hour) sessions of hemodialysis. Short daily dialysis has not achieved the same degree of phosphate control.
(Semin Dial. 2007 Jul-Aug;20(4):342-5. Phosphorus balance with daily dialysis. Kooienga L)

Parathyroidectomy

While registry data (USRDS) have suggested a survival benefit to parathyroidectomy in CKD5D patients, the timing and indications for parathyroidectomy are not clear.
The K/DOQI guidelines suggest the following:

GUIDELINE 14. PARATHYROIDECTOMY IN PATIENTS WITH CKD Parathyroidectomy should be recommended in patients with severe hyperparathyroidism (persistent serum levels of intact PTH >800 pg/mL [88.0 pmol/L]), associated with hypercalcemia and/or hyperphosphatemia that are refractory to medical therapy. (OPINION)

The following position was adopted by the KDIGO group:

Chapter 4.2: Treatment of abnormal PTH levels in CKD–MBD
4.2.5 In patients with CKD stages 3–5D with severe hyperparathyroidism (HPT) who fail to respond to medical/pharmacological therapy, we suggest parathyroidectomy.

References

1. Phosphorus balance with daily dialysis. Division of Nephrology, University of Colorado Health Sciences Center, Denver, Colorado 80230, USA. [email protected]
   Hyperphosphatemia is an almost universal finding in patients with end-stage renal disease and is associated with increased all-cause mortality, cardiovascular mortality, and vascular calcification. These associations have raised the question of whether reducing phosphorus levels could result in improved survival. In light of the recent findings that increased per-session dialysis dose, as assessed by urea kinetics, did not result in improved survival, the definition of adequacy of dialysis should be re-evaluated and consideration given to alternative markers. Two alternatives to conventional thrice weekly dialysis (CHD) are nocturnal hemodialysis (NHD) and short daily hemodialysis (SDHD). The elimination kinetics of phosphorus as they relate to these alternative daily dialysis schedules and the clinical implications of overall phosphorus balance are discussed here. The total weekly phosphorus removal with NHD is more than twice that removed by CHD (4985 mg/week +/- 1827 mg vs. 2347 mg/week +/- 697 mg) and this is associated with a significantly lower average serum phosphorous (4.0 mg/dl vs. 6.5 mg/dl). In spite of the observed increase in protein and phosphorus intake seen in patients on SDHD, phosphate binder requirements and serum phosphorus levels are generally stable to decrease although this effect is strongly dependent on the frequency and overall treatment time.
   PubMed Abstract Link
2. Parathyroidectomy in the calcimimetic era.Centre for Transplant and Renal Research, Westmead Millennium Institute, Department of Renal Medicine, Westmead Hospital, Westmead, NSW 2145, Australia. [email protected]
   With the introduction of the calcimimetic cinacalcet HCl, some patients who would previously have undergone parathyroidectomy are likely to remain on medical therapy. Data is available on complication rates and some important outcome measures of parathyroidectomy, but the efficacy of calcimimetics to influence patient-based endpoints such as cardiovascular mortality and renal osteodystrophy has not been established. Nevertheless, cinacalcet HCl has been demonstrated to improve levels of calcium, phosphate, the calcium phosphate product and parathyroid hormone (PTH). Based on available data, parathyroidectomy is proposed as the preferred treatment option when averaged levels of intact PTH (iPTH) exceed 85-95 pmol/L despite optimal therapy. When iPTH levels exceed 50 pmol/L, parathyroidectomy should be considered if levels of serum calcium, phosphate or the calcium phosphate product are above established target ranges or when patients with established osteoporosis have progressive loss of bone mineral density. Because the currently-recommended biochemical targets are difficult to achieve and maintain for many patients on dialysis, parathyroidectomy rates are likely to increase if these management proposals are followed. This highlights the need for prospective studies with 'hard' endpoints, to establish evidence-based roles for parathyroidectomy and calcimimetic therapy.
   PubMed Abstract Link