Parathyroidectomy in end-stage kidney disease

INTRODUCTION — Parathyroid surgery in patients with end-stage kidney disease (ESKD) is an effective therapy for normalization or stabilization of calcium and parathyroid hormone (PTH) metabolism, and for improving renal osteodystrophy [1-5].

Although the initial and predominant management of hyperparathyroidism (HPT) in ESKD is with medical therapy, approximately 10 percent of patients ultimately require surgery for ESKD-related HPT (sometimes referred to as renal HPT) [6]. Parathyroid surgery is also an effective therapy for patients with persistent HPT after renal transplantation [7-15].

The surgical techniques of parathyroidectomy in ESKD patients are discussed here. The medical management of HPT in patients with ESKD is discussed elsewhere. (See "Management of secondary hyperparathyroidism in adult nondialysis patients with chronic kidney disease" and "Management of secondary hyperparathyroidism in adult patients on dialysis" and "Refractory hyperparathyroidism and indications for parathyroidectomy in adult patients on dialysis" and "Kidney transplantation in adults: Persistent hyperparathyroidism after kidney transplantation".)

INDICATIONS — Although medical therapies, including calcimimetics (eg, cinacalcet), have allowed some patients with end-stage kidney disease (ESKD) to be treated nonoperatively [7-15], symptomatic patients with markedly elevated parathyroid hormone (PTH) levels should be referred for parathyroid surgery if they become refractory to medical therapy. Preoperative hypocalcemia is a contraindication to surgery. The specific indications for parathyroidectomy in patients with ESKD are reviewed in detail separately. (See "Refractory hyperparathyroidism and indications for parathyroidectomy in adult patients on dialysis" and "Kidney transplantation in adults: Persistent hyperparathyroidism after kidney transplantation".)

SURGICAL ANATOMY — Knowledge of both normal and variant patterns of parathyroid anatomy is essential to successful parathyroid surgery. Normal parathyroid anatomy is reviewed elsewhere (see "Surgical anatomy of the parathyroid glands"). Variant patterns of parathyroid anatomy seen in end-stage kidney disease (ESKD) patients are briefly discussed below.

Number and location of parathyroid glands — Most ESKD patients with hyperparathyroidism (HPT) have four-gland enlargement. However, some glands may descend into deep retroesophageal or paratracheal spaces, which makes them difficult to discern [16]. Patients with ESKD may also have enlargement of ectopic parathyroid rests in the cervical thymus [17].

Parathyroid gland features — Compared with normal glands, parathyroid glands in ESKD patients have more nodularity with a preponderance of oxyphilic parathyroid cells, more fibrosis with a sclerosed architecture, and more dystrophic calcifications [18,19]. Such shape and texture changes obscure a clear vascular pedicle, which makes shaping a parathyroid remnant more difficult.

In ESKD patients, parathyroid glands can enlarge significantly (to 500 to 1000 mg per gland) but remain histologically hypercellular [18,19]. Single or double adenomas are rarely seen in ESKD patients [20] but have been reported in up to 24 percent of patients post-renal transplantation [21]. (See 'Four-gland exploration' below.)

CHOOSING A SURGICAL TECHNIQUE — Techniques of parathyroid surgery include:

●Targeted parathyroidectomy

●Sub- or near-total parathyroidectomy

●Total parathyroidectomy with autotransplantation

●Total parathyroidectomy without autotransplantation

The choice is dependent upon whether the surgery is primary or reoperative, whether the patient has an existing or planned renal transplant, and whether the patient has a compelling reason to avoid reoperative neck surgery.

For the initial parathyroid surgery — Most end-stage kidney disease (ESKD) patients have multigland hyperplasia, for which a subtotal, near-total, or total parathyroidectomy is typically performed as the initial surgery (figure 1) [22-24]. Targeted parathyroidectomy is an option for the rare post-renal-transplant patients who present with single or double adenomas [21].

Patients with existing or planned renal transplant — For patients with an existing or planned renal transplant, we suggest performing either a sub- or near-total parathyroidectomy, or a total parathyroidectomy with autotransplantation, rather than a total parathyroidectomy without autotransplantation. The choice further depends upon whether the patient has a compelling reason to avoid the possibility of a neck reoperation.

Total parathyroidectomy without autotransplantation should be avoided in this setting because it is associated with the highest risk of postoperative permanent hypocalcemia, which is more difficult to treat once the patient is no longer dialysis dependent after renal transplantation.

In a retrospective study of 105 kidney transplant recipients who underwent surgery for tertiary hyperparathyroidism, subtotal parathyroidectomy was associated with a lower incidence of hypoparathyroidism than total thyroidectomy with autotransplantation (23 versus 45 percent) [25]. The incidences of persistent or recurrent hyperparathyroidism were not statistically different between the two groups. Hypoparathyroidism can lead to graft kidney failure.

Patients without contraindications to reoperative neck surgery — For most patients who have no contraindications to reoperative neck surgery, we typically perform a sub- or near-total parathyroidectomy rather than a total parathyroidectomy with autotransplantation.

A sub- or near-total parathyroidectomy has a lower risk of postoperative permanent hypocalcemia because the remnant is attached to its original blood supply. Compared with an autograft supplied only by neovascularization, an anatomic parathyroid remnant is more resilient to ischemia and less likely to fail. (See 'Subtotal parathyroidectomy' below.)

However, the risk of neck recurrence is potentially greater in patients undergoing sub- or near-total rather than total parathyroidectomy (with autotransplantation), which may necessitate reoperations in the cervical area [26,27].

Patients with compelling reasons to avoid reoperative neck surgery — For patients who have a compelling reason to avoid the possibility of a neck reoperation, we prefer a total parathyroidectomy with autotransplantation, rather than a sub- or near-total parathyroidectomy. Examples of such reasons include thyroid conditions that potentially require additional surgical procedures, prior history of repeated neck surgery, known recurrent laryngeal nerve injury, significant medical comorbidities, or intolerance of general anesthesia.

Total parathyroidectomy with autotransplantation negates the risk of a major neck reoperation by relocating the surviving parathyroid remnant to a site where recurrent hyperparathyroidism (HPT) may be detected and treated more conveniently. However, there is an increased risk of temporary and permanent hypocalcemia. (See 'Total parathyroidectomy with heterotopic autotransplantation' below.)

Patients excluded from renal transplant — For patients excluded from renal transplant, we suggest performing a total parathyroidectomy without autotransplantation, rather than other procedures. In addition, patients who have calciphylaxis should also undergo total parathyroidectomy without autotransplantation [28,29]. Calciphylaxis is a serious disorder that most commonly occurs in ESKD patients. It is characterized by calcification of dermal arterioles and classically presents with skin ischemia and necrosis. (See "Calciphylaxis (calcific uremic arteriolopathy)".)

Patients excluded from renal transplantation require continued dialysis, which exposes them to a high risk of developing recurrent HPT. Total parathyroidectomy without autotransplantation is the most effective surgical treatment for severe refractory HPT in this group of patients [30]. (See 'Total parathyroidectomy without autotransplantation' below.)

Although patients undergoing total parathyroidectomy without autotransplantation have the highest risk of developing hypocalcemia, they can be supplemented with calcium during routine dialysis.

For reoperative parathyroid surgery — For patients who require reoperative parathyroid surgery, we prefer a targeted exploration of the recurrence sites, including the autograft site, guided by preoperative imaging and intraoperative parathyroid hormone (PTH) monitoring, rather than a blind bilateral neck exploration. (See 'Reoperative parathyroid surgery' below.)

SURGICAL TECHNIQUES — Commonly used surgical techniques for treating hyperparathyroidism in end-stage kidney disease (ESKD) patients include subtotal/near-total parathyroidectomy and total parathyroidectomy with or without autotransplantation (figure 1). The choice of techniques is dictated by whether the patient is a candidate for a renal transplant as detailed above (see 'Choosing a surgical technique' above). Whenever feasible, a thymectomy and parathyroid tissue cryopreservation should be performed with the primary procedure.

General principles — For ESKD patients with four enlarged glands, parathyroid surgery should be conducted in an orderly sequence as detailed below.

Four-gland exploration — First, all parathyroid glands should be exposed after a thorough bilateral neck exploration via a transverse cervical incision. Biopsy, capsular rupture, or fragmentation of the glands should be avoided to prevent parathyromatosis.

Create a parathyroid remnant — If a subtotal parathyroidectomy is planned, a parathyroid remnant should be created next, before any other gland is resected, so that the viability of the remnant can be monitored while the remaining glands are removed. Marking the remnant with a titanium clip facilitates its localization in the event of a reoperation. Alternatively, the remnant can be marked with a long permanent suture buried just below the strap muscles, to be traced back to the remnant during a reoperation.

Search for the missing gland(s) — In general, identification of fewer than four parathyroid glands in ESKD patients should prompt a search for the missing gland(s). The search should follow an organized and deliberate sequence, including searching the retroesophageal and deep paratracheal spaces, the carotid artery and jugular venous sheaths, potential intrathyroidal locations, and the thymus [16,22]. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Missing gland'.)

Intrathyroidal parathyroid glands in ESKD patients can be sizeable and mimic thyroid nodules. If a thyroid nodule is suspected to be of parathyroid origin, parathyroid hormone (PTH) measurement of fluid obtained from the nodule by needle aspiration may be confirmatory [31].

Cervical thymectomy — If an inferior parathyroid gland is missing, it is most likely located in one of the intrathymic locations [16]. Thymectomy is an important component of parathyroid surgery for ESKD patients who have missing inferior parathyroid glands because retained intrathymic glands can be the source of persistent or recurrent disease [17]. In one study, adding a cervical thymectomy increased the overall cure rate of HPT from 89 to 94 percent [32].

Cervical thymectomy must be performed with care. Many ESKD patients have friable cervical tissues and/or atrophic thymus. In addition, if a parathyroid remnant is inferiorly based, it is susceptible to devascularization by a cervical thymectomy performed in its vicinity.

Resect abnormal glands with intraoperative PTH monitoring — Despite a thorough search for the missing glands, some patients may only have two or three identifiable abnormal parathyroid glands. Intraoperative PTH monitoring may aid in the management of such patients.

Intraoperative PTH monitoring helps to guide the surgical decision-making process. In patients with primary hyperparathyroidism, established protocols (eg, the Miami protocol for primary HPT) provide assurance that all hyperfunctioning parathyroid tissue has been removed before surgery is concluded. (See "Intraoperative parathyroid hormone assays", section on 'Intraoperative PTH monitoring protocols'.)

However, an established intraoperative PTH monitoring protocol does not exist for ESKD-related HPT, and protocols validated in other patient populations do not apply to ESKD patients, because of delayed renal clearance of PTH [33-36]. In one study, the half-life of PTH was 6.6 minutes in ESKD patients, compared with 2.2 minutes in patients with normal renal function [37].

Nevertheless, intraoperative PTH monitoring is used in parathyroid surgery for ESKD patients. Typically, the PTH value measured after excision is completed is compared with the baseline value. In two studies, a decline of 80 percent predicted cure [37,38]. In another study of 105 patients with stage III chronic kidney disease, stricter criteria of a >50 percent decrease in PTH value and to the normal range (<65 pg/mL) were associated with greater operative success (100 versus 92 percent) compared with classic criteria (a >50 percent decrease in PTH value alone) [39]. Conversely, a postresection PTH level that is high or fails to decrease suggests the presence of additional abnormal glands and mandates further exploration [5,33,34]. Additionally, the laterality of a missing gland can also be determined by comparing the PTH levels of blood samples obtained from bilateral jugular veins [40-43].

Cryopreservation — Even with careful surgery, a small percentage of patients may develop postoperative hypoparathyroidism due to either ischemic necrosis of the parathyroid remnant or early failure of an autograft. Permanent hypoparathyroidism can potentially be prevented if there is cryopreservation of parathyroid tissue at the time of the original surgery [44]. (See "Parathyroid surgery for inherited syndromes", section on 'Cryopreservation'.)

Our technique of preparing parathyroid tissue for cryopreservation is illustrated (picture 1). However, fewer than 30 percent of surgeons have access to a facility that allows cryopreservation of parathyroid tissue [45]. In the absence of cryopreservation, the surgeon must carefully calibrate the size of the parathyroid remnant or autograft to avoid permanent hypoparathyroidism.

Subtotal parathyroidectomy — The basic concept of this operation is to remove nearly all abnormal parathyroid glands, leaving only a well-vascularized remnant of one gland in its anatomic location. Thus, in patients with four abnormal parathyroid glands, three are completely removed, and the fourth one is crafted into the parathyroid remnant. Near-total parathyroidectomy leaves a smaller remnant than subtotal parathyroidectomy. (See 'Create a parathyroid remnant' above.)

Subtotal parathyroidectomy is associated with a low rate of postoperative permanent hypocalcemia but a risk of potentially having to reoperate in the neck when recurrent HPT develops, reportedly in 5 to 30 percent of patients [26,27]. The risk of reoperative neck surgery can be reduced but not eliminated by performing a near-total parathyroidectomy [5]. (See 'Patients without contraindications to reoperative neck surgery' above.)

Creating a parathyroid remnant — The volume of the only remaining gland is reduced to create the parathyroid remnant. Experienced surgeons can estimate the weight of a parathyroid gland in situ prior to resection [26]. The weight in milligrams is approximately the same as the volume in cubic millimeters calculated as an ellipsoid (eg, a 8 x 4 x 4 mm fragment is 64 mg) (figure 2) [5,18,19].

In general, the aim is to leave approximately 50 to 100 mg of residual parathyroid tissue, equivalent to the size of two normal parathyroid glands. Remnants as small as 50 mg can be created if more extensive (eg, near-total) parathyroid excision is desired. A larger remnant (eg, >100 mg) may be used to avoid postoperative hypocalcemia in patients who are noncompliant with medications or are expected to have severe postoperative bone hunger but is associated with a greater risk of disease recurrence.

Most abnormal parathyroid glands in ESKD patients weigh between 500 and 1000 mg, larger than those in patients with any other types of HPT. Thus, the traditional subtotal, or "3+1/2 gland" parathyroidectomy, which leaves 50 percent of an abnormal parathyroid gland as the remnant, may not be appropriate for ESKD patients.

A 75 percent resection of the remnant gland (near-total parathyroidectomy) has been used for ESKD patients. A more aggressive resection can be attempted when parathyroid cryopreservation is available; when cryopreservation is not available, accurate assessment of remnant size is crucial to avoid postoperative permanent hypocalcemia.

The parathyroid remnant should be created from a gland that is most readily accessible (eg, inferior glands) should a reoperation be needed. In addition, glands with well-defined vascular pedicles are preferred as remnants over those with globular or calcified features.

Total parathyroidectomy with heterotopic autotransplantation — This procedure removes all cervical parathyroid glands that can be identified and simultaneously autotransplants a small portion of a gland to a new, nonanatomic site.

Although some have suggested a lower rate of recurrence after total, rather than subtotal, parathyroidectomy, the observed incidence of recurrence is still quite high (17 percent at 10 years after surgery), especially in cases of prolonged patient survival with long-term dialysis [46]. However, autograft recurrences are easier to treat than neck recurrences. (See "Parathyroid surgery for inherited syndromes", section on 'Management of recurrent disease'.)

The disadvantage of a total parathyroidectomy with autotransplantation is the potential for profound hypoparathyroidism and hypocalcemia if the autograft fails. Permanent hypoparathyroidism can be countered by autotransplantation of cryopreserved parathyroid tissue (where available) at a later date, although the ideal shelf life of cryopreserved tissue is limited to under two years [47,48]. (See 'Patients with compelling reasons to avoid reoperative neck surgery' above.)

Creating an autograft — The autotransplantation procedure entails mincing a portion of the excised glands into 1 to 2 mm pieces (a total of 10 to 15 pieces) (picture 1), which are then inserted into several muscular or subcutaneous pockets (picture 2). Variations of this technique have been described, including inserting each piece into an individual pocket, inserting several pieces into a pocket, or injecting a suspension of fragments into a muscle with a syringe [49].

Autograft sites — A number of different sites have been utilized to host autotransplanted parathyroid tissue, including neck, chest, and forearm. The nondominant forearm is our preferred site of parathyroid autotransplantation. At each site, autografts can be placed either intramuscularly or subcutaneously.

In general, subcutaneous implantation and explantation of parathyroid autografts are simpler to perform than intramuscular procedures [50,51]. Subcutaneous implantation also permits a more radical excision than intramuscular implantation in case of a recurrent hyperparathyroidism. In one study, intramuscular autografts were more likely to require removal than subcutaneous autografts (23 versus 2 percent), but subcutaneous autografts were removed sooner after than intramuscular autografts (3.3 versus 6.6 years after implantation) [52].

Regardless of implantation sites, parathyroid fragments are sturdy and can survive in any tissue environment. Furthermore, they are small and can migrate or disperse in unpredictable directions such that resection of all foci can be challenging regardless of where the autograft is originally placed. As an example, local problems, such as parathyromatosis, have been found to complicate intramuscular implantation and subsequent resection [53].

Forearm — The nondominant forearm is our preferred site of parathyroid autotransplantation (picture 2). The advantage of implanting parathyroid tissue into the nondominant forearm is that re-exploration, if needed for recurrent HPT, can be easily carried out under local anesthesia. Forearm autotransplantation also provides the ability to determine if an autograft is functional by comparing PTH levels of blood samples drawn from the antecubital vein of the implanted arm versus the contralateral arm.

In ESKD patients who may require parathyroid autotransplantation to the forearm, it is important to identify the nondominant arm preoperatively and to protect any present or potential future sites of dialysis access (ie, arteriovenous fistula or graft) in that forearm. (See "Approach to the adult patient needing vascular access for chronic hemodialysis".)

Neck — The sternocleidomastoid muscle is in the operative field of parathyroid surgery and, therefore, a convenient location for placing a parathyroid autograft. However, compared with forearm autografts, neck autografts are more difficult to retrieve at reoperations and can potentially confound imaging studies performed in search of supernumerary glands in the neck.

Chest — Some surgeons place parathyroid autografts subcutaneously in the middle to lower third of the presternal area, where they can be easily located and excised under local anesthesia in the event of a recurrence [54]. Autografts are rarely placed intramuscularly in the chest due to retrieval difficulties.

Total parathyroidectomy without autotransplantation — Total parathyroidectomy without autotransplantation is the most effective surgical treatment for patients with severe refractory HPT [30,55]. It results in a faster reduction in serum calcium and PTH than subtotal parathyroidectomy [56]. It is widely practiced in countries such as Japan.

In a randomized trial of 100 patients who developed (secondary) HPT when on long-term (59±37 months) dialysis, total parathyroidectomy with or without autotransplantation resulted in comparable perioperative outcomes [57]. At three years, patients who underwent total parathyroidectomy without autotransplant had lower PTH levels (31.7±43.6 versus 98.2±156.8) and lower rates of persistent (1.9 versus 4.1 percent) or recurrent (0 versus 8.3 percent) HPT. Although parathyroid tissue was cryopreserved, no patients in either group required delayed autotransplantation for permanent hypoparathyroidism. Approximately 50 and 85 percent of patients required oral calcium and vitamin D supplementation, respectively. Approximately one-quarter of patients in each group received a renal transplant within the study follow-up period. This trial suggested that total parathyroidectomy without autotransplantation may be as safe and effective for patients with ESKD as total parathyroidectomy with autotransplantation.

In the United States, the preferred surgical treatment of HPT in patients with ESKD depends heavily on whether they are excluded from renal transplant and varies by local practices. Because total parathyroidectomy without autotransplantation has the highest risk of causing permanent hypocalcemia, it should be reserved for patients who suffer from severe complications of HPT due to lifelong dialysis (eg, bone osteodystrophy) and should be performed with parathyroid cryopreservation whenever possible [47,48,58]. (See 'Patients excluded from renal transplant' above.)

Reoperative parathyroid surgery — Patients with ESKD are at a higher risk of developing multisite recurrences compared with primary HPT patients. Therefore, prior to a reoperative procedure, the surgeon should examine all available medical records, especially operative and pathology reports, to determine the most likely site(s) of recurrences. Preoperative imaging studies can help localize the recurrences as well. For patients who have previously undergone autotransplantation of parathyroid tissue, all known sites of autografts (eg, forearm) should be included in the field of view of the imaging studies. Vocal cord examination by laryngoscopy or ultrasound is also recommended prior to reoperation to exclude an occult recurrent laryngeal nerve injury from prior surgery. (See 'Imaging for parathyroid localization' below.)

At reoperation, a targeted exploration of the recurrence site(s) guided by preoperative imaging is preferred to blind bilateral neck exploration. For patients with a forearm autograft, it is not unusual to require several reoperations to completely remove autografts from the forearm because of regrowth [46]. Thus, if appropriate, a surgeon may choose to excise all visible autograft tissue without leaving a new, smaller autograft behind.

The principles of reoperative parathyroidectomy for ESKD patients are the same as those for primary HPT patients and are discussed elsewhere. (See "Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism", section on 'Reoperation for recurrent or persistent hyperparathyroidism'.)

PERIOPERATIVE CONSIDERATIONS

Preoperative risk assessment — A thorough preoperative risk assessment of end-stage kidney disease (ESKD) patients is important for the selection of appropriate surgical candidates, as patients who have ESKD may have comorbidities that preclude safe surgery.

ESKD patients often have chronic medical conditions such as coronary artery disease, heart failure, myocardial infarction, hypertension, stroke, anemia, uremic coagulopathy, pulmonary disease, and general debility [59-61]. In addition, patients with calciphylaxis have unique complications such as peripheral vascular disease and wound sepsis [28,29,62] (see "Calciphylaxis (calcific uremic arteriolopathy)"). Although patients are generally healthier after a renal transplant, their immune system is medically suppressed, which increases their risk of developing postoperative complications.

The preoperative medical evaluation of patients with ESKD is discussed elsewhere. (See "Medical management of the dialysis patient undergoing surgery", section on 'Preoperative evaluation' and "Evaluation of cardiac risk prior to noncardiac surgery".)

Patient counseling — Prior to parathyroid surgery, patients need to be counseled about the potential outcomes in order for them to formulate realistic expectations. Specifically, patients should be advised that they may face a lengthy recovery, during which time they could develop hungry bone syndrome, and that they are at risk of developing recurrent hyperparathyroidism (HPT) as long as they remain on dialysis.

Hungry bone syndrome — Hungry bone syndrome is a condition of hyperdynamic calcium reabsorption into bones following parathyroidectomy, leading to protracted and symptomatic hypocalcemia. In one study, severe postoperative hypocalcemia requiring intravenous calcium repletion occurred in 97 percent of ESKD patients with HPT but only 2 percent of those with primary HPT [63]. Prevention and treatment of hungry bone syndrome are discussed separately. (See "Hungry bone syndrome following parathyroidectomy in patients with end-stage kidney disease".)

Recurrent hyperparathyroidism — The risk of developing recurrent HPT in patients who remain on dialysis after a successful parathyroidectomy can be as high as 80 percent [22,64-66]. Thus, some ESKD patients need repeated parathyroid surgeries for HPT. Patients need to be counseled about the natural history of their disease prior to surgery in order for them to set realistic expectations about the outcomes. (See "Overview of chronic kidney disease-mineral and bone disorder (CKD-MBD)", section on 'Abnormalities of parathyroid hormone, calcium, phosphorus, fibroblast growth factor 23, and vitamin D metabolism'.)

Expected length of recovery — Following parathyroid surgery in ESKD patients, it may take several months to achieve an optimal calcium, parathyroid hormone (PTH), and vitamin D balance, an even longer time to get symptomatic relief from HPT-related sequelae, and several years to restore a normal bone density [1,5]. During that time, patients should be assessed at regular intervals to document progress, which can alleviate their anxiety.

Imaging for parathyroid localization — For patients undergoing parathyroid surgery for HPT, including those with ESKD, cervical ultrasound can be performed to assist with operative planning [67,68]. Preoperative ultrasound examination improves the efficiency of parathyroid surgery by facilitating surgical exposure, guiding the sequence of exploration, and optimizing the choice of a parathyroid remnant. Cervical ultrasound can also identify abnormalities in the thyroid gland that may require further evaluation and/or concomitant surgical management during the parathyroidectomy [69-80]. (See 'Patients with thyroid cancer' below.)

Other modalities of parathyroid imaging have limited accuracies in ESKD patients and are not routinely required [81-83]. Patients undergoing targeted parathyroidectomy for either tertiary HPT (post-renal-transplant HPT) or recurrent HPT, however, may require further studies to localize the abnormal glands. (See "Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism", section on 'Role of preoperative localization'.)

Coordination of care with nephrologists and dialysis centers — For patients who are on scheduled dialysis, parathyroid surgery needs to be planned according to their dialysis schedule to avoid unnecessary delay caused by conditions such as hyperkalemia. After surgery, the patient's nephrologist can assist in the administration of calcium and vitamin D. The involvement of a nephrologist has been shown to reduce the length of hospital stay after parathyroid surgery [84].

Anesthesia — General anesthesia is required for most patients undergoing parathyroidectomy with bilateral neck exploration [45]. Other options, including local anesthesia, have been described but are rarely used [45,85]. Patient monitoring follows established routine practices. (See "Anesthesia for dialysis patients".)

Equipment — Instruments required to perform parathyroid surgery vary depending upon the surgeon and technique [86-88]. A basic setup is shown in the picture (picture 3).

Patient positioning — Patients undergoing parathyroid surgery are placed in the supine position with the neck gently hyperextended. Potential sites of autotransplantation should be exposed and prepared [1,5,49,89,90]. (See 'Autograft sites' above and "Parathyroid exploration for primary hyperparathyroidism", section on 'Positioning'.)

Patients with thyroid cancer — ESKD patients who have newly diagnosed thyroid cancer by preoperative neck ultrasound or intraoperatively during parathyroid surgery may require concomitant thyroid surgery [91]. Patients with clinically significant thyroid cancer are excluded from renal transplantation for at least two years after their treatment. Thus, these patients should be comanaged by a multidisciplinary team consisting of nephrologists, surgeons, and endocrinologists to address unique issues such as the dosing of radioactive iodine in patients with renal failure. (See "Differentiated thyroid cancer: Radioiodine treatment", section on 'Radioiodine dose (activity)'.)

Post-renal-transplant patients with thyroid cancer have similar prognosis compared with the general population. (See "Differentiated thyroid cancer: Overview of management", section on 'Prognosis'.)

POSTOPERATIVE CARE — General postparathyroidectomy care is the same for end-stage kidney disease (ESKD) patients as for those with primary hyperparathyroidism (HPT) and is detailed elsewhere. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Postoperative care'.)

Compared with patients with primary HPT, ESKD patients are more likely to develop transient hypocalcemia after parathyroid surgery due to hungry bone syndrome. A retrospective study of 2756 parathyroidectomies performed in patients with chronic kidney disease showed an unplanned readmission rate of 17 percent, which is nearly five times that of the general population; almost one-half of the admissions were for hypocalcemia/hungry bone syndrome [92]. Furthermore, parathyroid surgery performed for secondary hyperparathyroidism was more than two times as likely to require readmissions as surgery performed for primary hyperparathyroidism.

Thus, many institutions have protocols in place to administer preoperative calcitriol as well as postoperative intravenous calcium gluconate, along with oral calcium, magnesium, and vitamin D (calcitriol) when necessary. Once patients are weaned off intravenous calcium, they are discharged home on an aggressive regimen of oral calcium and vitamin D replacement, with which they must be compliant for best results. Additional intravenous calcium replacement may be required during dialysis or readmission for patients who develop severe symptoms of hypocalcemia. The treatment of symptomatic hypocalcemia is also discussed in another topic. (See "Treatment of hypocalcemia".)

Wound care for both the cervical and autograft site incisions is standard and basic. Patients typically do not require pain medications stronger than acetaminophen. Patients may resume dialysis after surgery, although some surgeons prefer to omit heparin during the first few sessions of dialysis after surgery to minimize the risk of neck hematoma.

FOLLOW-UP CARE — Laboratory values obtained over time indicate the adequacy of vitamin D repletion and the degree of long-term cure. At two weeks after surgery, the following are typically obtained as a baseline laboratory profile:

●Serum and ionized calcium

●Magnesium

●Intact parathyroid hormone (PTH)

Then, at three and six months, the levels of 25-hydroxyvitamin D and 1,25-hydroxyvitamin D are also measured. Dialysis and transplant services may obtain laboratory studies more frequently.

The time it takes for end-stage kidney disease (ESKD) patients to achieve new homeostasis of calcium, vitamin D, and PTH can vary significantly. Thus, ESKD patients require long-term follow-up after surgery for possible endocrinopathies such as hyper-/hypocalcemia and hyper-/hypoparathyroidism. Although laboratory values at six months after surgery have traditionally been used to predict durable cure in patients with primary hyperparathyroidism, no similar consensus exists for ESKD patients. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Postoperative care'.)

COMPLICATIONS — Despite a higher preoperative risk due to tissue fragility and uremic coagulopathy, parathyroid surgery for end-stage kidney disease (ESKD) patients is safe and has a similar complication rate when compared with surgery for primary HPT patients [5,23]. The main technical complications include:

●Bleeding (including hematoma)

●Infection

●Voice hoarseness or change (due to recurrent laryngeal nerve injury)

●Hypoparathyroidism

●Persistent/recurrent hyperparathyroidism

Specific complications of parathyroid surgery and their treatment are reviewed in detail elsewhere. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Complications'.)

OUTCOMES — The immediate goal of parathyroid surgery is to reduce the parathyroid hormone (PTH) level; the ultimate goal is to achieve long-lasting symptom relief and end organ improvement. It is not clear, however, what percentage of PTH needs to be reduced before the ultimate goal can be achieved. Patient outcomes also depend heavily upon the progression of their underlying renal disease.

Several studies have shown that parathyroid surgery halted progression or reversed bone loss from end-stage kidney disease (ESKD) or from steroid use (in renal transplant recipients) [5,22]. Other patient-specific outcomes (eg, hypercalcemia, hyperphosphatemia, bone pain, pruritus, and myopathy) are discussed separately. (See "Refractory hyperparathyroidism and indications for parathyroidectomy in adult patients on dialysis", section on 'Potential indications for parathyroidectomy'.)

However, in hemodialysis patients with secondary hyperparathyroidism, surgery significantly improves quality of life, regardless of whether a subtotal parathyroidectomy or a total parathyroidectomy with autotransplantation is performed [93].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Parathyroid surgery".)

SUMMARY AND RECOMMENDATIONS

●Parathyroid surgery in patients with end-stage kidney disease (ESKD) is an effective therapy for normalization or stabilization of calcium and parathyroid hormone (PTH) metabolism and for improving renal osteodystrophy. ESKD patients who have markedly elevated, medical-therapy-refractory PTH levels and related signs and symptoms should be referred for parathyroidectomy. (See 'Introduction' above and 'Indications' above and "Refractory hyperparathyroidism and indications for parathyroidectomy in adult patients on dialysis".)

●Most patients with ESKD have multigland hyperplasia and, for initial parathyroid surgery, therefore, require subtotal or total parathyroidectomy after identifying all four glands, rather than targeted parathyroidectomy. (See 'For the initial parathyroid surgery' above.)

•For ESKD patients with an existing or planned renal transplant, we perform either a subtotal parathyroidectomy or a total parathyroidectomy with autotransplantation. Total parathyroidectomy without autotransplantation should be avoided in this setting because it is associated with the highest risk of postoperative permanent hypocalcemia, which is difficult to treat once the patient is no longer dialysis dependent after renal transplantation. (See 'Patients with existing or planned renal transplant' above.)

During a subtotal parathyroidectomy, a parathyroid remnant equivalent to the size of two normal parathyroid glands (approximately 50 to 100 mg) should be created from a gland that is most accessible and has the best possible blood supply before the other glands are resected. (See 'Subtotal parathyroidectomy' above.)

During a total parathyroidectomy with autotransplantation, the autograft can be placed subcutaneously or intramuscularly in the neck (sternocleidomastoid muscle), chest, or nondominant forearm by surgeon preference. (See 'Total parathyroidectomy with heterotopic autotransplantation' above.)

•For patients excluded from renal transplant, we suggest performing a total parathyroidectomy without autotransplantation rather than the other surgical options (Grade 2C). Total parathyroidectomy without autotransplantation is the most effective surgical treatment for severe refractory hyperparathyroidism, which commonly occurs in this group of patients. (See 'Patients excluded from renal transplant' above and 'Total parathyroidectomy without autotransplantation' above.)

●For ESKD patients with recurrent hyperparathyroidism, we perform a targeted exploration of recurrent sites (including autograft sites), guided by preoperative imaging studies and intraoperative PTH assays, rather than blind bilateral neck exploration. (See 'Reoperative parathyroid surgery' above.)

●Compared with patients with primary hyperparathyroidism, ESKD patients are more likely to develop transient hypocalcemia after parathyroid surgery due to hungry bone syndrome. Thus, many institutions have protocols in place to administer intravenous calcium gluconate along with oral calcium, magnesium, and vitamin D (calcitriol) when necessary. Patients are discharged home on an aggressive regimen of oral calcium and vitamin D replacement.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Dr. Benjamin O Lawson, who contributed significantly to this topic review.