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NDT Plus 2008 1(Supplement 3):iii26-iii28; doi:10.1093/ndtplus/sfn083
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

This article appears in the following NDT Plus issue: Parathyroid Intervention - Current themes and future perspectives [View the issue table of contents]

New clinical guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients

Noritaka Onoda, Masafumi Fukagawa, Yoshihiro Tominaga, Masafumi Kitaoka, Tadao Akizawa, Fumihiko Koiwa, Takatoshi Kakuta, Kiyoshi Kurokawa and for the Japanese Society for Parathyroid Intervention

Correspondence: Noritaka Onoda, Division of Endocrinology and Metabolism, Sekishin-kai Sayama Hospital, 1-33 Unoki, Sayana-shi, Saitaka-ken 350-1323, Japan. E-mail: noritaka-onoda{at}sayamahp.org


   Abstract
Top
 Abstract
Introduction
 Indications
 Techniques
 References
 
In 2000, the Japanese Society for Parathyroid Intervention issued the ‘Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients’. Since then, the concept of ‘selective PEIT’ has been well accepted and the number of patients treated by this method in Japan has increased. Recently, it has been reported that the effect of PEIT differs depending on the degree of nodular hyperplasia. Several new drugs have become available since 2000, and active vitamin D and its analogue have also been used for direct injection into the parathyroids. We present the new ‘Guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients’, a revised version of the 2000 Guidelines. We believe that these new guidelines are useful for selecting direct injection therapy in patients with advanced secondary hyperparathyroidism.

Key Words: percutaneous ethanol injection therapy (PEIT) • percutaneous vitamin D injection therapy (PDIT) • secondary hyperparathyroidism • ultrasonography • nodular hyperplasia

Received for publication March 2, 2008. Accepted for publication March 17, 2008.


   Introduction
Top
 Abstract
 Introduction
Indications
 Techniques
 References
 
Previously, surgical parathyroidectomy (PTx) was the only therapeutic approach for patients with severe secondary hyperparathyroidism. Then, in the 1980s, an epoch-making new technique, percutaneous ethanol injection therapy (PEIT), was introduced in Europe [1,2]. Though some Japanese pioneers started using this method in the early 1990s [3], details of the indications, techniques and post-PEIT management were not widely known. The PEIT procedure at that time was mostly carried out in an ‘experience-based fashion’, with no official standard.

The accumulated clinical and basic data now clearly suggest that in dialysis patients with severe secondary hyperparathyroidism, at least one parathyroid gland develops nodular hyperplasia [4], in which the receptors for vitamin D and calcium are decreased in number [5,6]. Parathyroid glands with nodular hyperplasia are resistant to medical therapy [5,7,8], and the method of ‘selective PEIT’ has been adopted throughout Japan [9–12].

The concept of ‘selective PEIT’ is to destroy the glands with nodular hyperplasia and then to manage the remaining glands with diffuse hyperplasia [13]. This post-PEIT management is the key to maintaining optimal parathyroid function [14]. After carefully assessing all aspects of PEIT, we established the first practical Japanese guidelines for PEIT in 2000 [15] by modifying tentative guidelines that were published in 1999 [16]. These guidelines published in 2000 have been widely used to guide bedside practice. By 2004, more than 2000 patients had been treated by PEIT in Japan. The cost of the technique is now covered by the Japanese health insurance system approved by the Japanese Ministry of Health, Labour and Welfare.

Since the 2000 guidelines, several aspects of the management of secondary hyperparathyroidism have changed. In the early 2000s, more importance was attached to the control of the parathyroid hormone (PTH) level, and there was a close focus on the optimizing bone turnover. The Japanese Society for Dialysis Therapy recently issued their ‘Guidelines for the management of secondary hyperparathyroidism in chronic dialysis patients’ [17]. These guidelines strongly emphasize survival as the basis for determining target levels for clinical parameters. Injectable active vitamin D, calcitriol, the vitamin D analogue maxacalcitol and sevelamer hydrochloride became available after 2000 in Japan, and these agents have also been directly injected into enlarged parathyroid glands [18,19].

Considering all of these developments, we present ‘A new version of the clinical guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients’ (Table 1), which is a revised version of the guidelines published in 2000 [15]. We believe that these guidelines are useful not only for selecting those cases that are resistant to medical treatment, but also for choosing between PEIT and PTx as the suitable intervention. In fact, the earlier use of active vitamin D is highly recommended to prevent the parathyroid gland overgrowth [20].


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  		Table 1 A new version of the clinical guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients

 

   Indications
Top
 Abstract
 Introduction
 Indications
Techniques
 References
 
An intact PTH level >400 pg/ml should be considered as onlya rough guide. Since continued vitamin D therapy for patients with hyperphosphataemia and/or hypercalcaemia leads to progressive ectopic calcification, PEIT can be considered for such patients who have an intact PTH level of <400 pg/ml.

More than 80% of glands with an estimated volume >0.5 cm3 proceed to nodular hyperplasia [4]. Therefore, parathyroid gland volumetry is important for predicting the effectiveness of vitamin D therapy [20]. Koiwa et al. [21] noted that superior results are obtained in patients with one nodular hyperplastic gland. This is one of the major revisions in the new guidelines. Thus, ‘three or more glands’, one of the criteria for refractory response in the former guideline, is now changed to ‘two or more glands’. In addition to the principal indications mentioned in the new guidelines, high-risk PTx patients may also be candidates for PEIT [22].


   Techniques
Top
 Abstract
 Introduction
 Indications
 Techniques
References
 
As there are various technical differences in equipment and needles used and the number of persons involved in PEIT procedures among facilities, there are no major revisions in the chapter on techniques in the new guidelines.

Post-PEIT management
The use of active vitamin D is mandatory to prevent the recurrence of hyperparathyroidism, since glands with diffuse hyperplasia, which are not injected, are usually responsive to vitamin D therapy.

Understanding the limits of PEIT is important. If the target parathyroid is surrounded with leaked ethanol, subsequent surgical detachment will be difficult due to tissue adhesion. The average number of treatment sessions is 2.9 in the good-responder group, with an average duration of 3.4 ± 2.5 months [21]. Similarly, if the PTH concentration does not decrease even after five sessions of PEIT, then such cases are considered PEIT refractory and PTx is indicated [22]. One should always be aware of the possible existence of ectopic or supernumerary parathyroid glands.

Percutaneous vitamin D injection therapy (PDIT)
A statement on injectable agents other than ethanol appears in the new guidelines for the first time. This technique originated in Japan [18,19], and clinical data are accumulating. The mechanism of PTH suppression is thought to differ from that of PEIT [23,24]. Further discussion will be needed.


   Acknowledgements
 
The council for these guidelines expresses its appreciation for discussion with members and participants of the Japanese Society for Parathyroid Intervention.

Conflict of interest statement. None declared.


   References
Top
 Abstract
 Introduction
 Indications
 Techniques
 References
 

  1. Solbiati L, Giangrande A, Pra LD, et al. Percutaneous ethanol injection of parathyroid tumors under US guidance: treatment for secondary hyperparathyroidism. Radiology (1985) 155:607–610.[Abstract/Free Full Text]
  2. Karstrup S, Holm HH, Torp-Pedersen S, et al. Ultrasonically guided percutaneous inactivation of parathyroid tumours. Br J Radiol (1987) 60:667–670.[Abstract/Free Full Text]
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  12. Tanaka M, Itoh K, Matsushita K, et al. Efficacy of percutaneous ethanol injection therapy for secondary hyperparathyroidism in patients on hemodialysis as evaluated by parathyroid hormone levels according to K/DOQI guidelines. Ther Apher Dial (2005) 9:48–52.[CrossRef][Web of Science][Medline]
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  14. Tanaka M, Itoh K, Matsushita K, et al. Combination therapy of intravenous Maxacalcitol and percutaneous ethanol injection therapy lowers serum parathyroid hormone level and calcium x phosphorus product in secondary hyperparathyroidism. Nephron Clin Pract (2006) 102:c1–c7.[CrossRef][Web of Science][Medline]
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  16. Tominaga Y, Kitaoka M, Fukagawa M, et al. Guideline of selective parathyroid percutaneous ethanol injection therapy for patients with advanced renal hyperparathyroidism. J Jpn Soc Dial Ther (1999) 32:1099–1103. in Japanese.
  17. The Japanese Society for Dialysis Therapy. Guidelines for the management of secondary hyperparathyroidism in chronic dialysis patients. J Jpn Soc Dial Ther (2006) 39:1435–1455. in Japanese.
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  23. Shiizaki K, Hatamura I, Negi S, et al. Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia. Kidney Int (2003) 64:992–1003.[CrossRef][Web of Science][Medline]
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This Article
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