Advertisement

Clinical and Experimental Nephrology

, Volume 21, Issue 4, pp 563–572 | Cite as

Feasibility of photodynamic therapy for secondary hyperparathyroidism in chronic renal failure rats

  • Takayo Miyakogawa
  • Genta Kanai
  • Ryoko Tatsumi
  • Hiroo Takahashi
  • Kaichiro Sawada
  • Takatoshi Kakuta
  • Masafumi Fukagawa
Original article

Abstract

Background

Feasibility of photodynamic therapy (PDT) for secondary hyperparathyroidism (SHPT) was examined in a rat model of SHPT.

Methods

A photosensitizer, 5-aminolevulinic acid (5-ALA), was injected intraperitoneally, and the parathyroid glands were irradiated either after surgical exposure with 385-nm light or transdermally with 630-nm light from a light-emitting diode (LED) lamp.

Results

PDT with high 5-ALA and irradiation doses caused severe hypoparathyroidism in SHPT rats within two days. Low-dose invasive PDT reduced intact parathyroid hormone (iPTH) levels in all rats from 748.9 ± 462.6 pg/mL at baseline to 138.7 ± 117.5 pg/mL at week 6, followed by a further decrease to 80.5 ± 54.0 pg/mL at week 9 in 60 % of rats or an increase to 970.0 ± 215.6 pg/mL at week 9 in 40 % of rats. Low-dose noninvasive PDT reduced iPTH levels from 1612.5 ± 607.8 pg/mL at baseline to 591.9 ± 480.1 pg/mL at week 4 in all rats. Thereafter, iPTH levels remained low in 43 % of rats and were 233.7 ± 51.6 pg/mL at week 9, whereas 57 % showed an increase, reaching 3305.9 ± 107.3 pg/mL at week 9. Control SHPT rats had iPTH levels of 2487.8 ± 350.9 and 2974.6 ± 372.1 pg/mL at week 4 and 9, respectively. The parathyroid glands of the rats with low iPTH levels were atrophied and had few parathyroid cells surrounded by fibrotic materials and no recognizable blood vessels. Those of the rats with high iPTH levels showed well-preserved gland structure, clusters of parathyroid cells, and blood vessels.

Conclusion

These results demonstrate that 5-ALA-mediated PDT for SHPT is feasible.

Keywords

5-Aminolevulinic acid Hyperparathyroidism Parathyroid gland Parathyroid hormone Photodynamic therapy 

Notes

Acknowledgments

This study was supported by grants from Torii Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd and Kidney Foundation Japan (grant No. 15J013). We thank Yukiko Seki, Hitomi Moriya and the Support Center for Medical Research and Education, Tokai University School of Medicine for their valuable technical assistance.

Compliance with ethical standards

Disclosure of potential conflict of interest

Kyowa Hakko Kirin Co. Ltd. Consultancy: Masafumi Fukagawa, Honoraria: Takatoshi Kakuta, Masafumi Fukagawa, Grants: Takatoshi Kakuta, Masafumi Fukagawa; Torii Pharmaceutical Co., Ltd. Grants: Takatoshi Kakuta; Kidney Foundation Japan. Grants: Takayo Miyakogawa. The other authors declare that they have no Conflict of interests. The funding organizations, Torii Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd. and Kidney Foundation Japan played no roles in data collection and analysis or decision to publish.

Ethical approval

All procedures performed in studies involving animal were in accordance with the ethical standards of the institution or practice at which the studies were conducted (IRB approval number 161016).

Research involving human participants and animals

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

For this type of article, informed consent is not required.

References

  1. 1.
    Wilson BC, Patterson MS. The physics, biophysics and technology of photodynamic therapy. Phys Med Biol. 2008;53:R61–109.CrossRefPubMedGoogle Scholar
  2. 2.
    Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer: an update. CA Cancer J Clin. 2011;61:250–81.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Huang Z, Xu H, Meyer AD, Musani AI, Wang L, Tagg R, Barqawi AB, Chen YK. Photodynamic therapy for solid tumors—potential and technical challenges. Technol Cancer Res Treat. 2008;7:309–20.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Wachowska M, Muchowicz A, Firczuk M, Gabrysiak M, Winiarska M, Wanczyk M, Bojarczuk K, Golab J. Aminolevulinic acid (ALA) as a prodrug in photodynamic therapy of cancer. Molecules. 2011;16:4140–64.CrossRefGoogle Scholar
  5. 5.
    Komaba H, Kakuta T, Fukagawa M. Diseases of the parathyroid gland in chronic kidney disease. Clin Exp Nephrol. 2011;15:797–809.CrossRefPubMedGoogle Scholar
  6. 6.
    Goodman WG, Hladik GA, Turner SA, Blaisdell PW, Goodkin DA, Liu W, Barri YM, Cohen RM, Coburn JW. The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol. 2002;13:1017–24.PubMedGoogle Scholar
  7. 7.
    Fukagawa M, Yumita S, Akizawa T, Uchida E, Tsukamoto Y, Iwasaki M, Koshikawa S. KRN1493 study group, Cinacalcet (KRN1493) effectively decreases the serum intact PTH levels with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients. Nephrol Dial Transplant. 2008;23:328–35.CrossRefPubMedGoogle Scholar
  8. 8.
    Komaba H, Taniguchi M, Wada A, Iseki K, Tsubakihara Y, Fukagawa M. Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int. 2015;88:350–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Prosst RL, Schroeter L, Gahlen J. Kinetics of intraoperative fluorescence diagnosis of parathyroid glands. Eur J Endocrinol. 2004;150:743–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Asher SA, Peters GE, Pehler SF, Zinn K, Newman JR, Rosenthal EL. Fluorescent detection of rat parathyroid glands via 5-aminolevulinic acid. Laryngoscope. 2008;118:1014–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Liu WW, Li CQ, Guo ZM, Li H, Zhang Q, Yang AK. Fluorescence identification of parathyroid glands by aminolevulinic acid hydrochloride in rats. Photomed Laser Surg. 2011;29:635–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Prosst RL, Willeke F, Schroeter L, Post S, Gahlen J. Fluorescence-guided minimally invasive parathyroidectomy: a novel detection technique for parathyroid glands. Surg Endosc. 2006;20:1488–92.CrossRefPubMedGoogle Scholar
  13. 13.
    Prosst RL, Gahlen J, Schnuelle P, Post S, Willeke F. Fluorescence-guided minimally invasive parathyroidectomy: a novel surgical therapy for secondary hyperparathyroidism. Am J Kidney Dis. 2006;48:327–31.CrossRefPubMedGoogle Scholar
  14. 14.
    Prosst RL, Schroeter L, Gahlen J. Enhanced ALA-mediated fluorescence in hyperparathyroidism. J Photochem Photobiol, B. 2005;79:79–82.CrossRefGoogle Scholar
  15. 15.
    Gahlen J, Winkler S, Flechtenmacher C, Prosst RL, Herfarth C. Intraoperative fluorescence visualization of the parathyroid gland in rats. Endocrinology. 2011;142:5031–4.CrossRefGoogle Scholar
  16. 16.
    Prosst RL, Weiss J, Hupp L, Willeke F, Post C. Fluorescence-guided minimally invasive parathyroidectomy: clinical experience with a novel intraoperative detection technique for parathyroid glands. World J Surg. 2010;34:2217–22.CrossRefPubMedGoogle Scholar
  17. 17.
    Kakuta T, Tanaka R, Satoh Y, Izuhara Y, Inagi R, Nangaku M, Saito A, Miyata T. Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats. Kidney Int. 2005;68:1326–36.CrossRefPubMedGoogle Scholar
  18. 18.
    Fingar VH, Vieman TJ, Wiehle SA, Cerrito PB. The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion. Cancer Res. 1992;52:4914–21.PubMedGoogle Scholar
  19. 19.
    Fingar VH, Kik PK, Haydon PS, Cerrito PB, Tseng M, Abang E, Wieman TJ. Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD). Br J Cancer. 1999;79:1702–8.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gomer CJ, Rucker N, Murphree AL. Differential photosensitivity following porphyrin photodynamic therapy. Cancer Res. 1988;48:4539–42.PubMedGoogle Scholar
  21. 21.
    Gomer CJ, Luna M, Ferrario A, Wong S, Fisher AM, Rucker N. Cellular targets and molecular responses associated with photodynamic therapy. J Clin Laser Med Surg. 1996;14:315–21.PubMedGoogle Scholar
  22. 22.
    Henderson BW, Fingar VH. Relationship of tumor hypoxia and response to photodynamic treatment in an experimental mouse tumor. Cancer Res. 1987;47:3110–4.PubMedGoogle Scholar
  23. 23.
    Fingar VH. Vascular effects of photodynamic therapy. J Clin Laser Med Surg. 1996;14:323–8.PubMedGoogle Scholar
  24. 24.
    Abels C. Targeting of the vascular system of solid tumors by photodynamic therapy (PDT). Photochem Photobiol Sci. 2004;3:765–71.CrossRefPubMedGoogle Scholar
  25. 25.
    Collaud S, Juzeniene A, Moran J, Lange N. On the sensitivity of 5-aminolevulinic acid-induced protoporphyrin IX formation. Curr Med Chem Anticancer Agents. 2004;4:301–16.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2016

Authors and Affiliations

  • Takayo Miyakogawa
    • 1
  • Genta Kanai
    • 1
  • Ryoko Tatsumi
    • 1
  • Hiroo Takahashi
    • 1
  • Kaichiro Sawada
    • 1
  • Takatoshi Kakuta
    • 1
    • 2
  • Masafumi Fukagawa
    • 1
  1. 1.Division of Nephrology, Endocrinology and Metabolism, Department of MedicineTokai University School of MedicineIseharaJapan
  2. 2.Division of Nephrology, Endocrinology and Metabolism, Department of MedicineTokai University Hachioji HospitalHachiojiJapan

Personalised recommendations