Official reprint from UpToDate®

www-uptodate-com.bdigitaluss.remotexs.co © 2024 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Refractory hyperparathyroidism and indications for

parathyroidectomy in adult patients on dialysis
AUTHORS: L Darryl Quarles, MD, Jessica Kendrick, MD, MPH
SECTION EDITOR: Steve J Schwab, MD, FACP, FASN
DEPUTY EDITOR: Eric N Taylor, MD, MSc, FASN

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2024.

This topic last updated: Nov 29, 2023.

INTRODUCTION

This topic reviews refractory hyperparathyroidism and the indications for parathyroidectomy
among patients on chronic dialysis. The medical management of hyperparathyroidism 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".)

Surgical approaches to parathyroidectomy are discussed elsewhere. (See "Parathyroidectomy in

end-stage kidney disease".)

DEFINITIONS AND PATHOGENESIS

We define refractory hyperparathyroidism as severe, persistent, and progressive elevation of

serum parathyroid hormone (PTH) that cannot be treated adequately by medical therapy
(including both vitamin D analogs and calcimimetics) without causing significant
hyperphosphatemia or hypercalcemia.
There is no consensus on a PTH level that defines refractory hyperparathyroidism. Some
clinicians define refractory hyperparathyroidism as a PTH level persistently >800 pg/mL, which
is the level at which parathyroidectomy is often considered in symptomatic patients. Other
clinicians use the Kidney Disease: Improving Global Outcomes (KDIGO) PTH target threshold for
treatment, which is nine times above the upper limit of normal for the PTH assay (ie, 585 pg/mL
if upper range of normal is 65 pg/mL). However, a parathyroidectomy is generally not
performed at this level of PTH. (See "Management of secondary hyperparathyroidism in adult
patients on dialysis".)

Severe hyperparathyroidism that is refractory to medical therapy suggests tertiary

hyperparathyroidism, in which there is autonomous secretion of PTH that is not responsive to
the plasma calcium concentration [1]. Tertiary hyperparathyroidism is often associated with
hypercalcemia (in the absence of medications such as calcitriol, vitamin D, or calcium-containing
phosphate binders) and symptoms and signs of high bone turnover. (See 'Signs and symptoms'
below.)

Tertiary hyperparathyroidism develops after prolonged parathyroid stimulation from

hypocalcemia, calcitriol deficiency, and hyperphosphatemia. These stimuli increase PTH
synthesis and parathyroid cell proliferation [2-5]. Somatic mutations in the proliferating
parathyroid cells lead to monoclonal expansion or adenomatous transformation of the tissue
that can manifest as nodular hyperplasia and enlargement of the parathyroid glands [6]. Such
transformed parathyroid cells do not respond to the normal PTH-suppressive stimuli, such as
normalization of the serum calcium concentration or treatment with calcitriol. This lack of
response to PTH-suppressive stimuli may be caused by reduced expression of the extracellular
calcium-sensing receptor [2], lower-density of the vitamin D receptor [3], and decreased
expression of klotho and fibroblast growth factor receptor 1 [7].

EPIDEMIOLOGY

The prevalence of refractory hyperparathyroidism is difficult to estimate because of variability in

the definition and evolution in the medical therapies used to treat hyperparathyroidism.
Because it is a definitive treatment for refractory hyperparathyroidism, the rate of
parathyroidectomy is used to provide an estimate of prevalence.

Among patients on dialysis, the rate of parathyroidectomy for refractory hyperparathyroidism is

approximately 7 to 10 per 1000 patient-years [8,9]. This rate has remained largely constant over
the past several years despite advances in medical therapy, including the development of
calcimimetic agents, such as cinacalcet, which decrease the risk for hypercalcemia [10].
Cinacalcet reduces the risk of parathyroidectomy [11,12]. This was demonstrated in the
Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE)
randomized trial, in which patients were assigned to receive cinacalcet or placebo in addition to
conventional therapy including phosphate binders and/or active vitamin D or synthetic analogs
[11]. The rate of parathyroidectomy was lower in cinacalcet-treated patients compared with
placebo (relative hazard ratio [HR] 0.44, 95% CI 0.36-0.54) [10,11].

However, an analysis of data from a national database spanning 2002 to 2011 showed that,
although the rate of parathyroidectomies decreased between 2004 and 2005 (coinciding with
availability of cinacalcet in the United States), the rate rose again in 2006 and remained stable
thereafter, despite more widespread cinacalcet use [10]. A suggested reason for the
discrepancy is that doses used in EVOLVE were higher than those used in clinical practice [10].

It is unclear whether the introduction of newer calcimimetic agents may reduce rates of
parathyroidectomy among patients on dialysis. In patients on dialysis, the intravenous
calcimimetic etelcalcetide lowers PTH levels more than cinacalcet [13,14] and is effective in
many cases of severe hyperparathyroidism [15].

Refractory hyperparathyroidism requiring parathyroidectomy is far less common among

chronic kidney disease (CKD) patients who are not on dialysis. In an analysis of 32,971
admissions for parathyroidectomy for secondary hyperparathyroidism performed in the United
States between 2002 and 2011, 76 percent were performed in patient who had diagnostic or
procedure codes specific for dialysis, whereas the remainder had other codes for kidney failure
or transplantation [10].

SIGNS AND SYMPTOMS

The most common signs and symptoms of refractory hyperparathyroidism include [16,17]:

● Bone and joint pain

● Fractures
● Proximal muscle weakness
● Extraskeletal calcification (eg, in the vasculature)
● Calciphylaxis
● Pruritus
● Hypercalcemia
● Hyperphosphatemia
Bone and joint pain can be from osteitis fibrosa cystica, which is a high-turnover form of renal
osteodystrophy resulting from unremitting hyperparathyroidism [17]. Pain is primarily present
in weight-bearing joints, such as hips, knees, ankles, and lower back, and is generally relieved
by rest [16]. Periarticular calcium deposits may cause acute joint inflammation and manifest
with pain and stiffness [17]. Some patients present with nontraumatic or nonhealing fractures
[16]. Spontaneous tendon ruptures, primarily involving the quadriceps, Achilles, and patellar
tendons can occur, although these are uncommon [18-21].

Extraskeletal calcification may occur in vasculature and may be visible on imaging or present as
calciphylaxis. (See "Calciphylaxis (calcific uremic arteriolopathy)" and "Vascular calcification in
chronic kidney disease".)

Brown tumors, which are fibrotic, cystic, lytic bone lesions, can also occur in severe refractory
hyperparathyroidism. A rare disfiguring manifestation of severe hyperparathyroidism is
Leontiasis ossea or lion face syndrome [22].

Most clinical manifestations of hyperparathyroidism generally occur at a parathyroid hormone

(PTH) level of over 1000 pg/mL. In the studies reporting on tendon rupture, patients had PTH
levels of 1400 to 2000 pg/mL [20,21]. However, certain manifestations are often difficult to
ascribe solely to hyperparathyroidism due to their nonspecific nature and overlap with other
symptoms common among patients on dialysis. As examples: hyperphosphatemia is ubiquitous
and difficult to control among patients on dialysis regardless of refractory hyperparathyroidism;
hypercalcemia may occur from use of vitamin D analogs or calcium-containing phosphate
binders; and bone pain is common with other types of renal osteodystrophy, including those
not associated with hyperparathyroidism.

POTENTIAL INDICATIONS FOR PARATHYROIDECTOMY

Most experts agree that patients who have refractory hyperparathyroidism and significant
associated signs and symptoms should be referred for parathyroidectomy. A much more
controversial issue is whether patients with refractory hyperparathyroidism, but limited or no
associated signs or symptoms, should also undergo parathyroidectomy. Among such patients,
there is no consensus regarding indications for parathyroidectomy.

Symptomatic patients — We generally refer for a parathyroidectomy patients who have severe
hyperparathyroidism despite optimal medical management that is accompanied by
hyperparathyroid-related signs and symptoms. Parathyroidectomy is effective in treating the
signs and symptoms of severe hyperparathyroidism [23-27].
Optimal medical management is defined as treatment with phosphate binders, active vitamin D
analogs, and calcimimetics. (See "Management of secondary hyperparathyroidism in adult
patients on dialysis" and "Management of secondary hyperparathyroidism in adult patients on
dialysis", section on 'Treatment approach'.)

As noted above, the threshold parathyroid hormone (PTH) value that provides an indication for
parathyroidectomy among patients with signs or symptoms is not known. We believe that, for
most patients, parathyroidectomy should not be performed unless PTH levels are consistently
>800 pg/mL [28]. This is because many of the symptoms that may be attributed to
hyperparathyroidism (such as pain, weakness, and pruritus) are nonspecific and are present in
patients on dialysis who do not have significant hyperparathyroidism. PTH levels lower than 800
pg/mL are less likely to be the cause of such symptoms.

Symptoms should be critically evaluated to make sure that other obvious causes are not
present. The medical management should be reviewed to make sure treatment is optimized.
(See "Management of secondary hyperparathyroidism in adult patients on dialysis", section on
'Treat high parathyroid hormone'.)

The following signs and symptoms potentially warrant parathyroidectomy in the setting of
elevated PTH values. Data supporting parathyroidectomy are provided.

● Hypercalcemia and refractory hyperphosphatemia – Hypercalcemia and refractory

hyperphosphatemia are the most common reasons for parathyroidectomy to treat
refractory hyperparathyroidism [23]. Other causes of hypercalcemia should be excluded,
and the treatment of hyperphosphatemia should be reviewed before the
parathyroidectomy to be certain that medical options have been tried. (See "Diagnostic
approach to hypercalcemia" and "Management of hyperphosphatemia in adults with
chronic kidney disease", section on 'Patients on dialysis'.)

Parathyroidectomy effectively treats hyperparathyroidism-related hypercalcemia and

hyperphosphatemia [24-26]. In a study of 1402 patients, the median calcium concentration
fell from 9.6 to 7.9 mg/dL, and the serum phosphorus fell from 6.8 to 3.8 mg/dL following
parathyroidectomy [29].

● Bone pain, pruritus, and myopathy – Bone pain and/or fractures; severe, unexplained
muscle weakness; or pruritus are potential indications for parathyroidectomy. These
symptoms are nonspecific, however, and, as noted above, commonly observed in patients
on dialysis who do not have refractory hyperparathyroidism. Symptoms should not be
attributed to hyperparathyroidism (particularly if the PTH is <800 pg/mL) unless other
 causes have been excluded. (See "Chronic kidney disease-associated pruritus", section on
'Diagnosis' and "Myopathies of systemic disease".)

Bone pain, in particular, may be due to other forms of renal osteodystrophy, such as
adynamic bone disease, which may be worsened by parathyroidectomy. While adynamic
bone disease is virtually excluded by PTH >800 pg/mL, lower PTH values (particularly closer
to 450 pg/mL) do not conclusively exclude this form of bone disease [27]. Thus, if
parathyroidectomy is considered in a patient who has bone pain and PTH <800 pg/mL, a
bone biopsy should be performed first. (See "Evaluation of renal osteodystrophy".)

Parathyroidectomy effectively treats hyperparathyroidism-related bone pain, pruritus, and

myopathy [24-26]. In one study that included 91 end-stage kidney disease (ESKD) patients
(80 on dialysis and 11 transplant patients), symptoms of bone pain and weakness were
alleviated in 95 percent [24].

● Calciphylaxis – Calciphylaxis (calcific uremic arteriolopathy) is associated with severe

hyperparathyroidism and is a potential indication for parathyroidectomy. However,
parathyroidectomy has not been conclusively shown to provide a beneficial effect. (See
"Calciphylaxis (calcific uremic arteriolopathy)", section on 'Summary and
recommendations'.)

There have been no systematic or prospective evaluations of the effectiveness of

parathyroidectomy due to the sporadic nature of calciphylaxis. Observational reports have
suggested improved survival among patients with calciphylaxis who underwent
parathyroidectomy. As an example, in a retrospective review of the literature, 38 of 58
patients (66 percent) who underwent parathyroidectomy survived compared with 13 of 37
patients (35 percent) who did not undergo parathyroidectomy [30].

In addition to alleviating the signs and symptoms of hyperparathyroidism, parathyroidectomy

may also improve survival and other outcomes, although only observational studies are
available. (See 'Asymptomatic patients' below.)

Asymptomatic patients — We refer for parathyroidectomy select patients on dialysis who have
PTH levels persistently >1000 pg/mL despite optimal medical management, even in the absence
of associated clinical symptoms [31]. Among such patients, parathyroidectomy may reduce
mortality, cardiovascular risk, and the risk of fracture, although benefits have only been shown
in observational studies.

Optimal medical management is defined as treatment with phosphate binders, active vitamin D
analogs, and calcimimetics. (See "Management of secondary hyperparathyroidism in adult
patients on dialysis" and "Management of secondary hyperparathyroidism in adult patients on
dialysis", section on 'Treatment approach'.)

However, this is a controversial issue, and there is little consensus among experts regarding the
indication for parathyroidectomy [32].

In particular, there is concern that increased PTH alone is insufficient evidence of high-turnover
bone disease. However, in our experience, very high PTH concentrations (such as that which
provides indication for parathyroidectomy) correlate better with bone turnover than do those in
target range of two to nine times the upper limit of normal.

Some clinicians use bone-specific alkaline phosphatase in addition to PTH as an indication for
parathyroidectomy; concordantly, elevated levels of PTH and alkaline phosphatase have been
proposed as a useful indicator of severity. However, in a large bone biopsy study, both PTH and
bone-specific alkaline phosphatase were able to predict high-turnover bone disease, and the
combination of the two tests added minimal additional predictive value [33].

The selection of patients for parathyroidectomy must be individualized, depending on age and
comorbidities. We generally reserve parathyroidectomy for younger patients (ie, <65 years) who
have few comorbidities. Such patients are most likely to tolerate surgery and reap the potential
long-term benefits of parathyroidectomy.

The absence of clinical symptoms may warrant a closer examination for underlying bone
disease since symptoms are often subtle and many patients who actually do have bone disease
may not describe pain. However, even in patients who do have subtle symptoms that may be
attributed to hyperparathyroidism, these symptoms would not provide an indication for
parathyroidectomy with PTH <1000 pg/mL.

Possible benefits of parathyroidectomy include decreased mortality, increased bone density and
reduced fracture risk, decreased resistance to erythropoietin, and improved nutrition [34-46].
These are discussed below.

● Survival – Outcomes data following parathyroidectomy are entirely from observational

studies. A number of studies have suggested that parathyroidectomy is associated with
increased survival [34,35,47]. In one study, 150 patients on dialysis who underwent
parathyroidectomy at one institution were compared with 1044 matched control patients
who did not undergo parathyroidectomy, identified from the United States Renal Data
System (USRDS) registry [35]. The mean PTH value among the parathyroidectomy cohort
was 1776 pg/mL. At a mean follow-up of 3.6 years, compared with controls,
 parathyroidectomy was associated with decreased mortality (hazard ratio [HR] 0.68, 95%
CI 0.52-0.89).

Improved survival may be related to decreased cardiovascular mortality. In a study of 4428

patients who underwent parathyroidectomy and were compared with matched controls
who did not undergo parathyroidectomy despite severe hyperparathyroidism,
parathyroidectomy was associated with 34 and 41 percent lower risks for all-cause and
cardiovascular mortality at one year [47]. This survival benefit was not evident in patients
who had persistent secondary hyperparathyroidism postoperatively. In fact, the hazard
ratio for mortality was lowest in those with the lowest postoperative PTH levels.

However, there is a relatively high mortality immediately following the procedure, and
morbidity increases during the first year following parathyroidectomy. Using data
obtained from the medical evidence report (which provides diagnostic information on all
new ESKD patients in the United States), the United Network for Organ Sharing (UNOS)
database, and Medicare claims, one analysis compared adverse events that occurred
before and after parathyroidectomy in 4435 selected ESKD patients [48].

Mortality was 2 percent during the immediate hospitalization and in the 30 days following
discharge. Twenty-five percent of patients required an intensive care unit (ICU) admission
during the immediate hospitalization.

Twenty-four percent of patients were rehospitalized in the 30 days following discharge,

and 29 percent of these required an ICU admission. One-year morbidity and mortality
rates have been reported from analyses of data from the USRDS [34,48].

It is not clear whether these results may be generalized to a broader ESKD population,
since all included patients were Medicare participants who were undergoing in-center
hemodialysis.

● Bone density and fracture risk – Parathyroidectomy may increase bone density and
reduce the risk of fracture. Multiple single-center case series have reported increased
bone mineral density after parathyroidectomy [36-38]. One retrospective, case-control
study found that parathyroidectomy was associated with reduced risk for hip fracture
(0.68, 95% CI 0.54-0.86) and all fractures (0.69, 95% CI 0.57-0.83) [39].

● Other – Some studies have suggested improvements in erythropoietin-resistant anemia

[40-42], nutritional status, and humoral and cellular immunity [43,44].
PATIENTS AWAITING TRANSPLANTATION

For patients who are actively awaiting transplantation and have refractory hyperparathyroidism,
we consult with the transplant center regarding the timing of parathyroidectomy. There is
variability among transplant centers in the recommended approach for potential transplant
recipients who have refractory hyperparathyroidism.

Most transplant experts suggest parathyroidectomy for patients with severe refractory
hyperparathyroidism and moderate to severe symptoms, particularly if transplantation is not
imminent. For patients with refractory hyperparathyroidism who have mild or no symptoms,
transplant nephrologists have differing recommendations, although the threshold PTH for
parathyroidectomy is typically lower compared with patients who are not awaiting
transplantation. (See "Kidney transplantation in adults: Persistent hyperparathyroidism after
kidney transplantation", section on 'Prevention'.)

A rationale for performing parathyroidectomy prior to transplant is that refractory

hyperparathyroidism fails to resolve in many patients after transplantation (see "Kidney
transplantation in adults: Persistent hyperparathyroidism after kidney transplantation", section
on 'Pathophysiology') [49-51]. Persistent hyperparathyroidism following transplantation may
lead to hypercalcemia, hypophosphatemia, and decreased graft function [52-54]. In addition,
parathyroidectomy may be safer if performed prior to transplantation. Parathyroidectomy
performed after transplantation has been associated with abrupt deterioration of kidney
allograft function [55].

For potential recipients of deceased-donor kidneys, but not living-donor kidneys, the decision
regarding parathyroidectomy may also depend on the anticipated time on the waiting list,
which will vary based upon the geographic region. The indications for parathyroidectomy for
patients who are expected to have a prolonged wait on the deceased-donor waiting list are
likely the same as for patients who are not awaiting transplantation. (See 'Symptomatic
patients' above and 'Asymptomatic patients' above.)

KIDNEY TRANSPLANT RECIPIENTS

The indications for parathyroidectomy in transplant recipients are discussed separately. (See
"Kidney transplantation in adults: Persistent hyperparathyroidism after kidney transplantation".)

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: Chronic kidney disease-
mineral and bone disorder".)

SUMMARY AND RECOMMENDATIONS

● Definition of refractory hyperparathyroidism – We define refractory

hyperparathyroidism as persistent and progressive elevations of serum parathyroid
hormone (PTH) that cannot be lowered to acceptable levels by medical therapy (including
both vitamin D analogs and calcimimetics) without causing significant hyperphosphatemia
or hypercalcemia. (See 'Definitions and pathogenesis' above.)

● Symptomatic patients – We refer for parathyroidectomy most patients on dialysis who

have persistent hyperparathyroidism (PTH levels >800 pg/mL), which is refractory to
medical therapies and is accompanied by clearly related signs and symptoms.
Parathyroidectomy is effective in mitigating most hyperparathyroidism-associated signs
and symptoms. It is important to exclude other potential causes of the signs and
symptoms prior to parathyroidectomy. (See 'Symptomatic patients' above.)

● Asymptomatic patients – We perform parathyroidectomy for selected patients on dialysis

who have very severe, sustained hyperparathyroidism (PTH levels >1000 pg/mL) that is
refractory to medical therapies, even if not accompanied by associated signs and
symptoms. The selection of patients must be individualized, depending on age and
comorbidities. We generally reserve parathyroidectomy for younger patients (ie, <65
years) and with few comorbidities. Potential but unproven benefits may include improved
survival, fracture risk, nutrition, and anemia. (See 'Asymptomatic patients' above.)

● Patients awaiting transplantation – For patients with refractory hyperparathyroidism

who are actively awaiting transplantation, decisions regarding parathyroidectomy should
be jointly made with the transplant center. (See 'Patients awaiting transplantation' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Robert E Cronin, MD, and Michael Berkoben, MD,
who contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Terms of Use.

REFERENCES

1. Indridason OS, Heath H 3rd, Khosla S, et al. Non-suppressible parathyroid hormone

secretion is related to gland size in uremic secondary hyperparathyroidism. Kidney Int
1996; 50:1663.
2. Gogusev J, Duchambon P, Hory B, et al. Depressed expression of calcium receptor in
parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 1997; 51:328.
3. Fukuda N, Tanaka H, Tominaga Y, et al. Decreased 1,25-dihydroxyvitamin D3 receptor
density is associated with a more severe form of parathyroid hyperplasia in chronic uremic
patients. J Clin Invest 1993; 92:1436.
4. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis,
disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011; 6:913.
5. Krause MW, Hedinger CE. Pathologic study of parathyroid glands in tertiary
hyperparathyroidism. Hum Pathol 1985; 16:772.
6. van der Plas WY, Noltes ME, van Ginhoven TM, Kruijff S. Secondary and Tertiary
Hyperparathyroidism: A Narrative Review. Scand J Surg 2020; 109:271.

7. Komaba H, Goto S, Fujii H, et al. Depressed expression of Klotho and FGF receptor 1 in
hyperplastic parathyroid glands from uremic patients. Kidney Int 2010; 77:232.
8. Foley RN, Li S, Liu J, et al. The fall and rise of parathyroidectomy in U.S. hemodialysis
patients, 1992 to 2002. J Am Soc Nephrol 2005; 16:210.
9. Li S, Chen YW, Peng Y, et al. Trends in parathyroidectomy rates in US hemodialysis patients
from 1992 to 2007. Am J Kidney Dis 2011; 57:602.
10. Kim SM, Long J, Montez-Rath ME, et al. Rates and Outcomes of Parathyroidectomy for
Secondary Hyperparathyroidism in the United States. Clin J Am Soc Nephrol 2016; 11:1260.

11. EVOLVE Trial Investigators, Chertow GM, Block GA, et al. Effect of cinacalcet on
cardiovascular disease in patients undergoing dialysis. N Engl J Med 2012; 367:2482.

12. Parfrey PS, Chertow GM, Block GA, et al. The clinical course of treated hyperparathyroidism
among patients receiving hemodialysis and the effect of cinacalcet: the EVOLVE trial. J Clin
Endocrinol Metab 2013; 98:4834.
13. Block GA, Bushinsky DA, Cheng S, et al. Effect of Etelcalcetide vs Cinacalcet on Serum
Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary
Hyperparathyroidism: A Randomized Clinical Trial. JAMA 2017; 317:156.
14. Stephens JM, Fox KM, Desai P, et al. Calcimimetic use in US hemodialysis facilities in first 2
years after the launch of etelcalcetide: A descriptive analysis of real-world clinical practice
and outcomes. Hemodial Int 2022; 26:243.
15. Cunningham J, Block GA, Chertow GM, et al. Etelcalcetide Is Effective at All Levels of Severity
of Secondary Hyperparathyroidism in Hemodialysis Patients. Kidney Int Rep 2019; 4:987.
16. Moe, Sharon M, Sprague SM. Mineral Bone Disorders in Chronic Kidney Disease. In: The Kid
ney, 8th, Barry M. Brenner (Ed), Saunders Elsevier, Philadelphia 2008. Vol 2, p.1785.

17. Coyne DW, Larson DS, Delmez JA. Bone Disease. In: Handbook of Dialysis, 5th, Daugirdas JT,
Blake PG, Ing TS (Eds), Wolters Kluwer, Philadelphia 2015. p.665.
18. Grecomoro G, Camarda L, Martorana U. Simultaneous chronic rupture of quadriceps
tendon and contra-lateral patellar tendon in a patient affected by tertiary
hyperparatiroidism. J Orthop Traumatol 2008; 9:159.
19. Anderson WE 3rd, Habermann ET. Spontaneous bilateral quadriceps tendon rupture in a
patient on hemodialysis. Orthop Rev 1988; 17:411.
20. Kalantar-Zadeh K, Singh K, Kleiner M, et al. Nontraumatic bilateral rupture of patellar
tendons in a diabetic dialysis patient with secondary hyperparathyroidism. Nephrol Dial
Transplant 1997; 12:1988.
21. Jones N, Kjellstrand CM. Spontaneous tendon ruptures in patients on chronic dialysis. Am J
Kidney Dis 1996; 28:861.
22. Gameiro J, Duarte I, Outerelo C, Lopes JA. Uremic lion face syndrome. J Bras Nefrol 2019;
41:304.

23. Tang JA, Friedman J, Hwang MS, et al. Parathyroidectomy for tertiary hyperparathyroidism:
A systematic review. Am J Otolaryngol 2017; 38:630.

24. Punch JD, Thompson NW, Merion RM. Subtotal parathyroidectomy in dialysis-dependent
and post-renal transplant patients. A 25-year single-center experience. Arch Surg 1995;
130:538.
25. Tominaga Y, Uchida K, Haba T, et al. More than 1,000 cases of total parathyroidectomy with
forearm autograft for renal hyperparathyroidism. Am J Kidney Dis 2001; 38:S168.
26. Sato T, Tominaga Y, Ueki T, et al. Total parathyroidectomy reduces elevated circulating
fibroblast growth factor 23 in advanced secondary hyperparathyroidism. Am J Kidney Dis
2004; 44:481.
27. Hercz G, Pei Y, Greenwood C, et al. Aplastic osteodystrophy without aluminum: the role of
"suppressed" parathyroid function. Kidney Int 1993; 44:860.
28. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and
disease in chronic kidney disease. Am J Kidney Dis 2003; 42:S1.

29. Wetmore JB, Liu J, Do TP, et al. Changes in secondary hyperparathyroidism-related

biochemical parameters and medication use following parathyroidectomy. Nephrol Dial
 Transplant 2016; 31:103.
30. Hafner J, Keusch G, Wahl C, et al. Uremic small-artery disease with medial calcification and
intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and
benefit from parathyroidectomy. J Am Acad Dermatol 1995; 33:954.
31. Moorthi RN, Moe SM. CKD-mineral and bone disorder: core curriculum 2011. Am J Kidney
Dis 2011; 58:1022.
32. Wetmore JB, Liu J, Dluzniewski PJ, et al. Geographic variation of parathyroidectomy in
patients receiving hemodialysis: a retrospective cohort analysis. BMC Surg 2016; 16:77.
33. Sprague SM, Bellorin-Font E, Jorgetti V, et al. Diagnostic Accuracy of Bone Turnover Markers
and Bone Histology in Patients With CKD Treated by Dialysis. Am J Kidney Dis 2016; 67:559.
34. Kestenbaum B, Andress DL, Schwartz SM, et al. Survival following parathyroidectomy
among United States dialysis patients. Kidney Int 2004; 66:2010.
35. Sharma J, Raggi P, Kutner N, et al. Improved long-term survival of dialysis patients after
near-total parathyroidectomy. J Am Coll Surg 2012; 214:400.
36. Abdelhadi M, Nordenström J. Bone mineral recovery after parathyroidectomy in patients
with primary and renal hyperparathyroidism. J Clin Endocrinol Metab 1998; 83:3845.
37. Chou FF, Chen JB, Lee CH, et al. Parathyroidectomy can improve bone mineral density in
patients with symptomatic secondary hyperparathyroidism. Arch Surg 2001; 136:1064.
38. Yano S, Sugimoto T, Tsukamoto T, et al. Effect of parathyroidectomy on bone mineral
density in hemodialysis patients with secondary hyperparathyroidism: possible usefulness
of preoperative determination of parathyroid hormone level for prediction of bone regain.
Horm Metab Res 2003; 35:259.
39. Rudser KD, de Boer IH, Dooley A, et al. Fracture risk after parathyroidectomy among
chronic hemodialysis patients. J Am Soc Nephrol 2007; 18:2401.
40. Rault R, Magnone M. The effect of parathyroidectomy on hematocrit and erythropoietin
dose in patients on hemodialysis. ASAIO J 1996; 42:M901.
41. Jemcov TK, Petakov M, Bogdanovic A, et al. Parathyroidectomy and improving anemia. Arch
Surg 2008; 143:97.
42. Chow TL, Chan TT, Ho YW, Lam SH. Improvement of anemia after parathyroidectomy in
Chinese patients with renal failure undergoing long-term dialysis. Arch Surg 2007; 142:644.
43. Yasunaga C, Nakamoto M, Matsuo K, et al. Effects of a parathyroidectomy on the immune
system and nutritional condition in chronic dialysis patients with secondary
hyperparathyroidism. Am J Surg 1999; 178:332.
 44. Tzanno-Martins C, Futata E, Jorgetti V, Duarte AJ. Restoration of impaired T-cell proliferation
after parathyroidectomy in hemodialysis patients. Nephron 2000; 84:224.
45. Pizzarelli F, Fabrizi F, Postorino M, et al. Parathyroidectomy and blood pressure in
hemodialysis patients. Nephron 1993; 63:384.
46. Ifudu O, Matthew JJ, Macey LJ, et al. Parathyroidectomy does not correct hypertension in
patients on maintenance hemodialysis. Am J Nephrol 1998; 18:28.

47. Komaba H, Taniguchi M, Wada A, et al. Parathyroidectomy and survival among Japanese
hemodialysis patients with secondary hyperparathyroidism. Kidney Int 2015; 88:350.
48. Ishani A, Liu J, Wetmore JB, et al. Clinical outcomes after parathyroidectomy in a nationwide
cohort of patients on hemodialysis. Clin J Am Soc Nephrol 2015; 10:90.
49. Schmid T, Müller P, Spelsberg F. Parathyroidectomy after renal transplantation: a
retrospective analysis of long-term outcome. Nephrol Dial Transplant 1997; 12:2393.
50. Ferreira GF, Montenegro FL, Machado DJ, et al. Parathyroidectomy after kidney
transplantation: short-and long-term impact on renal function. Clinics (Sao Paulo) 2011;
66:431.
51. Evenepoel P, Claes K, Kuypers D, et al. Natural history of parathyroid function and calcium
metabolism after kidney transplantation: a single-centre study. Nephrol Dial Transplant
2004; 19:1281.
52. Messa P, Cafforio C, Alfieri C. Clinical impact of hypercalcemia in kidney transplant. Int J
Nephrol 2011; 2011:906832.

53. Gwinner W, Suppa S, Mengel M, et al. Early calcification of renal allografts detected by
protocol biopsies: causes and clinical implications. Am J Transplant 2005; 5:1934.
54. Egbuna OI, Taylor JG, Bushinsky DA, Zand MS. Elevated calcium phosphate product after
renal transplantation is a risk factor for graft failure. Clin Transplant 2007; 21:558.
55. Rostaing L, Moreau-Gaudry X, Baron E, et al. Changes in blood pressure and renal function
following subtotal parathyroidectomy in renal transplant patients presenting with
persistent hypercalcemic hyperparathyroidism. Clin Nephrol 1997; 47:248.
Topic 1838 Version 38.0

Contributor Disclosures
L Darryl Quarles, MD Equity Ownership/Stock Options: Amgen [Bone and mineral metabolism]. All of the
relevant financial relationships listed have been mitigated. Jessica Kendrick, MD,
MPH Grant/Research/Clinical Trial Support: Bayer [Finerenone]; Pathalys [Calcimimetic].
Consultant/Advisory Boards: AstraZeneca [Metabolic acidosis]; Pathalys [Secondary hyperparathyroidism
and mineral metabolism]; ProKidney [CKD progression]. All of the relevant financial relationships listed
have been mitigated. Steve J Schwab, MD, FACP, FASN No relevant financial relationship(s) with ineligible
companies to disclose. Eric N Taylor, MD, MSc, FASN No relevant financial relationship(s) with ineligible
companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy