hypoparathyroidism, hyperphosphatemia & low/normal calcium

Dialysis Prescription

Lowering dialysis calcium from 1.25 to 1.0 mmol/L may allow increased doses of calcium based binders for phosphate control, and the resultant transient post-dialysis hypocalcemia may allow restoration of PTH secretion. Very prolonged dialysis times (e.g. daily or nocturnal dialysis) usually achieve better phosphate control, but increased intermittent times up to 5 hours may have little effect

Phosphate and Calcium Management

Explore dietary phosphate content, and adherence to prescribed dose of binder.

Phosphate Binders

Therapeutic avenues depend on medical insurance status and include;

Lower dose of calcium-based phosphate binder.

Switch to non-calcium based phosphate binder. If taking calcium based binder, the dose may be excessive, and is ineffective. Switch to non-calcium based phosphate binder, either aluminum in the short term , or sevelamer/lanthanum in the long term. Note that aluminum should not usually be used in the face of hypoparathyroidsm, since it it may cause suppression of PTH secretion. In this situation serum aluminum levels should be monitored carefully.

Current Guidelines include;

CSN

5. Give priority to phosphate and calcium targets over the management of PTH. (Grade D, opinion)

CSN does not specifically advise against the use of aluminum-based binders

KDIGO

4.1.6 In patients with CKD stages 3–5D, we recommend avoiding the long-term use of aluminum-containing phosphate binders and, in patients with CKD stage 5D, avoiding dialysate aluminum contamination to prevent aluminum intoxication (1C).

PTH Management

Vitamin D sterols

Active 1-hydroxylated vitamin D sterols (calcitriol, 1-alpha) cause direct suppression of  PTH, and “normalize” calcium absorption from diet and calcium supplements.

Therapeutic avenues include;

• Reduce the dose
• Switch from daily to alternate day, (night-time) oral dosing.
• Switch to intravenous dosing on dialysis 3- or 2- times weekly

Calcimimetics

Over suppression of parathyroid glands with a calcimimetic  is possible; reduce the dose to maintain serum intact PTH levels between 10-50 pmol/ L

Current Giudelines include;

CSN

7. Vitamin D sterols can be used in the treatment of secondary hyperparathyroidism, but should be discontinued when PTH levels decrease below target levels, or if calcium or phosphate levels increase above target levels.(Grade C)

KDIGO

4.2.4.f) We suggest that, if the intact PTH levels fall below two times the upper limit of normal for the assay, calcitriol, vitamin D analogs, and/or calcimimetics be reduced or stopped (Grade 2C).

Controversies in management

There is a clear epidemiologic association and biological plausibility between hyperphosphatemia, net calcium intake and important negative health consequences (including progressive vascular calcification and cardiovascular morbidity) for patients with CKD. However, randomized controlled trials and meta-analyses performed to date do not conclusively support the use of one type of phosphate binder in preference to another for important patient outcomes.

Specifically, controversy exists as to the efficacy of non-calcium based phosphate binders (i.e. sevelamer and lanthanum) on relevant clinical outcomes (cardiovascular events, mortality and hospitalization). The evidence to date was summarized in detail by the KDIGO working group. Given some significant methodological limitations and therefore concerns over study validity for the largest trials of non-calcium phosphate binders, the impact of non-calcium based binders on clinically relevant outcomes is uncertain.

Non-calcium based phosphate binders are more than twenty-fold more expensive than calcium carbonate. The recommendation by KDIGO to limit the use of calcium-based binders in the scenarios outlined (and presumably use noncalcium based binders) has generated significant controversy among Canadian nephrologists and there is no clear consensus. On the one hand the lack of conclusive evidence of benefit, the lack of randomized trials which have assessed morbidity and mortality among patients with vascular calcification, and the expense of sevelamer and lanthanum, use of these agents may not be justified until further evidence of clinical benefit can be established in valid randomized trials. On the other hand, others feel that the use of noncalcium-based binders in the situations recommended or suggested by KDIGO is justified on theoretical grounds, that the existing RCTs were underpowered to show statistically significant benefit, and that recent meta-analyses suggest clinical benefit. Moreover, calcium-based phosphate binders are likely to cause positive calcium balance in late stages of CKD, and have never been proven to be safe.

The use of aluminum-containing phosphate binders has been extensively evaluated in the KDOQI Bone and Mineral Metabolism Guidelines. The major toxicities are neurotoxicity and impairment of bone mineralization, both of which can be prevented by minimizing aluminum exposure. The KDIGO Work Group acknowledged that the literature, as detailed in the KDOQI guidelines, supports that the most severe cases of aluminum toxicity occurred in patients whose dialysate was contaminated with aluminum, and that aluminum-based binders only play a secondary role. The quantity of aluminum-based phosphate binders that is safe is unknown. Moreover, several conditions may favor intestinal aluminum absorption, such as diabetes mellitus, secondary HPT, vitamin D status, and a high citrate intake. The KDIGO Work Group was unanimous in recommending against the use of aluminum-based binders on the grounds that there is no ability to predict a safe aluminum dose, and numerous alternative phosphate binders have become available. However, Canadian nephrologists may still feel that short-term (several months) use of these agents is still justified when financial constraints make it impractical to use other non-calcium-based binders.