KDOQI (Kidney Disease Outcomes Quality Initiative)


NKF KDOQI GUIDELINES

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KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Children With Chronic Kidney Disease


Guideline 15. Parathyroidectomy in Patients with CKD

15.1 Parathyroidectomy should be considered in patients with severe hyperparathyroidism (persistent serum levels of PTH >1,000 pg/mL [110 pmol/L]), and disabling bone deformities associated with hypercalcemia and/or hyperphosphatemia that are refractory to medical therapy. (OPINION)

15.2 Effective surgical therapy of severe hyperparathyroidism can be accomplished by subtotal parathyroidectomy or total parathyroidectomy with parathyroid tissue autotransplantation. (EVIDENCE)

15.2a Total parathyroidectomy probably is not the procedure of choice in patients who may subsequently receive a kidney transplant, since the subsequent control of serum calcium levels may be problematic.

15.3 In patients who undergo parathyroidectomy the following should be done:

15.3.a In the 72 hours prior to parathyroidectomy, consideration should be given to administration of calcitriol or other active vitamin D sterols, to lessen postoperative hypocalcemia.

15.3.b The blood level of ionized calcium should be measured every 4-6 hours for the first 24 hours after surgery, and then less frequently until less stable. (OPINION)

15.3.c If the level of ionized calcium falls below normal (<1 mM or <4 mg/dL, corresponding to corrected total calcium of 7.2 mg/dL [1.80 mmol/L]), a calcium gluconate infusion should be initiated at a rate of 1-2 mg elemental calcium per kilogram body weight per hour and adjusted to maintain an ionized calcium in the normal range (1.15-1.36 mM or 4.6-5.4 mg/dL). (OPINION) A 10-mL ampule of 10% calcium gluconate contains 90 mg of elemental calcium.

15.3.d The calcium infusion should be gradually reduced when the level of ionized calcium attains the normal range and remains stable. (OPINION)

15.3.e When oral intake is possible, the patient should receive elemental calcium 1-2 g, three times a day, as well as calcitriol 1-2 µg/day, and these therapies should be adjusted as necessary to maintain the level of ionized calcium in the normal range. (OPINION)

15.3.f If the patient was receiving phosphate binders prior to surgery, this therapy may need to be discontinued or reduced as dictated by the levels of serum phosphorus. (OPINION)

15.4 Imaging of parathyroid glands with 99Tc-Sestamibi scan, ultrasound, CT scan, or Magnetic Resonance Imaging (MRI) should be done prior to re-exploration parathyroid surgery. (OPINION)

Background

Hyperparathyroidism is a common complication of CKD that results in significant morbidity and warrants monitoring and therapy throughout the course of kidney disease. The cornerstones of the treatment of hyperparathyroidism include dietary phosphate restriction, the use of phosphate binders, correction of hypocalcemia, and the use of vitamin D sterols. While the majority of patients can be controlled in this way, medical therapy is not always successful in achieving adequate control of 2° HPT. Accordingly, some patients require surgical parathyroidectomy to correct the problem. Hyperparathyroidism is currently most often assessed using PTH measurements from 1st PTH-IMA. Newer assays which are more specific for the PTH 1-84 molecule have been developed, and are becoming available, but warrant further study of their clinical utility.

Rationale

While medical therapy is often effective for the control of hyperparathyroidism, surgical therapy can provide effective reductions in the serum levels of PTH. In general, it is felt that surgical parathyroidectomy is indicated in the presence of severe hyperparathyroidism associated with hypercalcemia, which precludes further approaches with medical therapy, and/or hyperphosphatemia which also may preclude medical therapy with vitamin D sterols. The presence and magnitude of the disabling bone deformities should be an additional consideration in the decision for parathyroidectomy. (See Table 1 in Introduction.) In these circumstances, surgical ablation of the parathyroid glands can provide effective therapy. The efficacy of surgical parathyroidectomy is well documented.519-525 An additional indication for surgical parathyroidectomy is the presence of calciphylaxis with PTH levels that are elevated (>500 pg/mL [55.0 pmol/L]), as there are several reports of clinical improvement in patients with calciphylaxis after such therapy. It is important to emphasize, however, that not all patients with calciphylaxis have high levels of PTH, and parathyroidectomy—in the absence of documented hyperparathyroidism—should not be undertaken.

There are many variations on the procedure performed to accomplish surgical parathyroidectomy, which include subtotal or total parathyroidectomy, with or without implantation of parathyroid tissue (usually in the forearm). All of these methods can result in satisfactory outcomes, and no one technique appears to provide superior outcomes.519-525 Accordingly, the choice of procedure may be at the discretion of the surgeons involved. It is important to emphasize that, if reimplantation of parathyroid tissue is considered, a portion of the smallest parathyroid gland (i.e., one less likely to have severe nodular hyperplasia) should be reimplanted. It would be helpful if noninvasive assessments of parathyroid function or of parathyroid mass were available that could predict whether medical therapy would be helpful. There is insufficient evidence at the present time to support this approach, although there are some preliminary suggestions that this might be helpful.526 Parathyroid imaging is not usually required, preoperatively, although it may be helpful in cases where re-exploration is required, such as persistent hypercalcemia or recurrent hyperparathyroidism.527-529 Of the methods used, 99Tc-sestamibi with or without subtraction techniques appears to have the highest sensitivity, although MRI, CT, and ultrasound have also been regarded to be useful.526-528,530-538

Strength of Evidence

The indications for surgical parathyroidectomy are not well defined and there are no studies to define absolute biochemical criteria which would predict whether medical therapy will not be effective and surgery is required to control the hyperparathyroidism. There has been some suggestion that those patients with large parathyroid mass might fail attempts at medical therapy and, therefore, assessments of parathyroid mass with ultrasonographic or radionuclide techniques could conceivably be useful as a predictor of efficacy of medical therapy. Unfortunately, there is insufficient evidence to support this at the present time.

The type of surgery performed has been variable and, while subtotal parathyroidectomy or total parathyroidectomy with or without autotransplantation have all been shown to be successful, there are no comparative studies. Efficacy and recurrence rates are all comparable. There is some concern that total parathyroidectomy may not be suitable for patients who will receive a kidney transplant since the control of serum calcium levels may be difficult following kidney transplantation.

While some advocate parathyroid imaging for re-exploration surgery and have shown it to be useful in some cases, others do not feel that it is necessary. There are no studies comparing the results with and without preoperative imaging.

An alternative to surgical removal of parathyroid glands has recently been introduced in which parathyroid tissue is ablated by direct injection of alcohol into the parathyroid gland under ultrasound guidance. Additional long-term studies with this technique are needed to evaluate its role in long-term therapy.539

Limitations

In the absence of firm criteria for surgery, the use of different operations, the use of parathyroidectomy in limited, selected groups of patients, limited follow-up, and heterogeneity of the patients studied, it is difficult to provide conclusive guidelines to address this complication of CKD.

Clinical Applications

Clearly, hyperparathyroidism is a frequent complication of CKD which requires monitoring and therapy. Many cases can be managed with phosphate control, calcium supplementation, and the use of vitamin D sterols. Some, however, fail these measures and therefore, surgical ablation becomes an option which can effectively control the overactivity of the parathyroid, although recurrence rates are high. There are no data about the use of calcimimetics in children with CKD Stage 5.

Recommendations for Research

The monitoring and control of hyperparathyroidism remains a difficult problem and further information is needed in several areas. Correlations of PTH values with bone histology are necessary in the current era. New PTH assays need to be evaluated for their clinical utility. The appropriate target values for PTH that are achieved by medical therapy need to be defined and related to bone histology. The appropriate target values for PTH during the course of CKD at various stages of kidney dysfunction need to be defined. Comparative studies of medical and surgical therapy would be of interest. Novel approaches to the control of hyperparathyroidism will be forthcoming with calcimimetic agents.