Parathyroidectomy in Chronic Kidney Disease - An Outline

Introduction

Parathyroid hormone (PTH) is a protein released by the parathyroid gland. PTH plays a pertinent role in bone mineralization by enhancing calcium reabsorption in the kidneys, phosphate excretion from the kidneys, and various other mechanisms. PTH also regulates serum calcium homeostasis (balance). Chronic kidney disease (CKD) leads to hypocalcemia (decreased calcium levels), resulting in a compensatory increase in PTH production and causing hyperparathyroidism (secondary hyperparathyroidism; SHP). As a result, PTH removes calcium from the bone. Hence, patients with CKD can present with a mineral and bone disorder (CKD-MBD) leading to bone and muscle pain, bone fractures and deformities, and soft tissue and blood vessel calcifications. CKD-related SHP treatment comprises clinical and surgical management (parathyroidectomy; surgical removal of the parathyroid glands).

Why Is Parathyroidectomy Required in Chronic Kidney Disease?

CKD- related SHP is associated with increased mortality (death) rates due to the following consequences.

1. CKD Osteodystrophy and Fracture Risk: Studies show that a continuous infusion of PTH in rats leads to bone disease and an osteoporotic (a condition in which the bones become brittle) effect. Studies also reveal that the risk of hip, vertebral, or wrist fractures is 31 percent lower after parathyroidectomy than in controls.

2. Vascular and Tissue Calcifications: Various studies show that a continuous PTH infusion develops hypercalcemia (increased blood calcium) and severe aortic (aorta is a blood vessel) calcification. It can also cause skin necrosis and nonhealing ulcers with a poor prognosis. Parathyroidectomy has been associated with lower mortality among patients with tissue calcifications.

3. Anemia (Low Red Blood Cell Count): Potential mechanisms by which elevated PTH may affect red blood cell (RBC) production include direct toxicity on bone marrow (parent RBCs are in bone marrow) and increased hemolysis (RBC destruction). Bone biopsy (surgical removal of the bone sample) data suggests improvement in anemia after parathyroidectomy.

What Are the Indications for Parathyroidectomy?

1. Parathyroidectomy is required in 15 to 40 percent of CKD patients after dialysis.

2. Parathyroidectomy is indicated for patients with SHP refractory to medications (elevated PTH for more than six months).

However, preoperative (before the surgery) hypocalcemia is a contraindication to parathyroidectomy.

Over the last twenty years, improvements in medical management with vitamin D analogs, phosphate binders, and calcimimetic drugs (a drug that mimics the action of calcium on tissues), such as Cinacalcet have expanded treatment options for patients with SHP. However, parathyroidectomy is an important option for many patients. Parathyroidectomy is also more practical and reasonable than Cinacalcet in patients fit for kidney surgery or transplant.

What Are the Parathyroidectomy Procedures for Chronic Kidney Disease Patients?

Parathyroidectomy is the surgical treatment of choice for patients with CKD-SHP. Further, the patient's surgery requirement increases with a longer CKD duration. Before surgery, parathyroid ultrasonography (an imaging technique that uses ultrasound waves) and scintigraphy (a bone scan using a radioactive tracer) are done. Surgery's success is linked to the careful identification of all parathyroid glands. Supernumerary (more than normal) glands, ectopic (at an abnormal place) parathyroids, or misinterpretation of other structures as parathyroid glands (that is, lymph nodes) are major reasons for surgical failure. Two parathyroidectomy techniques done in SHP patients are:

1. Subtotal Parathyroidectomy: In subtotal (partial) parathyroidectomy, the surgeon chooses the gland with the best macroscopic (gross) appearance, leaving it whole or performing its partial resection. The advantages of subtotal parathyroidectomy include a lower rate of severe hypoparathyroidism after surgery. In addition, there is less need for postoperative calcium replacement. However, studies reveal a higher recurrence rate of SHP after subtotal parathyroidectomy.

2. Total Parathyroidectomy (With Parathyroid Tissue Autograft): In this technique, all parathyroid glands are removed. Further, a part of the gland with the best macroscopic appearance is grafted onto a muscle bed (autograft is graft transfer from one location to another in the same body). The most common sites are the forearm, neck, and presternal region (in front of the sternum, the breastbone).

Total parathyroidectomy with autograft shows the advantages of removal of all glands and a lower recurrence rate. The disadvantages of this technique are the high rate of postoperative (after-surgery) hypoparathyroidism and the time liability regarding graft functioning. Further, a patient requires the replacement of large amounts of calcium in the postoperative period.

Studies show that both techniques are effective in controlling SHP. The decision regarding the techniques should consider clinical and surgical aspects, such as the degree of alteration of the parathyroid glands and kidney transplant options. Parathyroidectomy is a safe surgical procedure with a low complication rate. Moreover, it is associated with clinical improvement and decreased deaths in SHP patients. Despite a reduction in the number of surgical procedures worldwide (due to the introduction of advanced medications), surgery still plays a very important role in CKD- related SHP. It is especially true in developing countries, where patients depend on surgery as their main treatment because they have limited access to the healthcare system.

What Are the Considerations After Parathyroidectomy in Chronic Kidney Disease Patients?

After hospital discharge, frequent monitoring of biochemical parameters (related to bone metabolism) is essential for dose adjustments for oral calcium. The monitoring aims to prevent recurrence and act early in cases of persistent SHP. It is a therapeutic success when PTH values reach the target range in dialysis patients, and calcium level normalization occurs in transplant patients with a reduction of PTH of more than 50 percent. In addition to surgery complications, others include:

1. Hungry Bone Syndrome (HBS): HBS can occur after a parathyroidectomy. It is a state of prolonged hypocalcemia. The hypo calcemic state can be challenging to manage and requires different doses of calcium supplementation to avoid untoward consequences. HBS occurs in five to eight percent of patients with SHP after parathyroidectomy.

2. Recurrent Hyperparathyroidism: A subsequent parathyroid surgery is done in patients with recurrent hyperparathyroidism. It is further warranted in patients with initially successful surgery who develop recurrent disease after more than six months postoperatively.

Hypophosphatemia (decreased phosphate), hypocalcemia (decreased calcium levels), and the occurrence and progression of hungry bone syndrome are the most severe and common complications following parathyroidectomy (due to sudden serum PTH reduction).

Conclusion

SHP is a frequent complication in CKD patients that requires monitoring, energetic treatment, and prevention measures. In cases of medication failure, a parathyroidectomy is a safe option with low complication rates. Further, symptoms of MBD, such as itching, bone pain, and fractures, and mortality rates are improved in many patients after parathyroidectomy.