EFFECT OF ULTRASOUND-GUIDED DIRECT VITAMIN D INJECTIONS INTO PARATHYROID GLANDS ON LABORATORY MARKERS AND SURVIVAL OF PATIENTS WITH REFRACTORY SECONDARY HYPERPARATHYROIDISM

Aim. To evaluate the effect of local vitamin D injections into parathyroid glands on laboratory markers and survival in refractory hyperparathyroidism.

 Materials and methods. A comparison of the dynamics of secondary hyperparathyroidism laboratory markers and survival was performed in 37 patients with local vitamin D injections into the parathyroid glands under ultrasound guidance and in 62 patients with PTH higher than 600 pg/ml without reduction in PTH levels by more than 10% during 6 months, who continued to receive available conservative therapy. The mean duration of follow-up for groups was 40.5 and 33.2 months, respectively.

Results. In the local injection group (LIG) PTH level reduced by 347 ± 360 pg/ml (38%) during the first month after injection course, and by 214 ± 255 pg/ml (28%) between annual average levels before and after injection course, while in control group (CG) it rose by 84 ± 277 pg/ml (11%). In LIG phosphate level significantly reduced by 0.18 ± 0.24 mmol/l (9%) after injection course and annual average level did not change. In CG annual average phosphate level significantly rose by 0.15 ± 0.37 mmol/l (7%). Cumulative survival by Kaplan–Maier was significantly higher in LIG (p = 0.025). Differences in survival in univariate and multivariate Cox regression models were significantly associated only with the fact of local injections course (p =0.04 inboth models).

Conclusion. In current clinical practice the application of ultrasound-guided local vitamin D injections into parathyroid glands in patients with refractory hyperparathyroidism leads to a better control over laboratory markers and to significantly improved survival.

1. Tentori F, Wang M, Bieber BA et al. Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study. Clin J Am Soc Nephrol. 2015; 10 (1): 98–109. doi: 10.2215/ CJN.12941213. Epub 2014 Dec 16. PMID: 25516917.

2. Dan Li, Leping Shao, Haiyan Zhou, Wei Jiang, Wei Zhang, Yan Xu. The efficacy of cinacalcet combined with conventional therapy on bone and mineral metabolism in dialysis patients with secondary hyperparathyroidism: a meta-analysis. Endocrine. February 2013; 43; 1: 68– 77. doi: 10.1007/s12020-012-9711-2. Epub 2012 Jun 6. PMID: 22669774.

3. Raggi P, Chertow GM, Torres PU, Csiky B, Naso A, Nossuli K et al. ADVANCE Study Group. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011 Apr; 26 (4): 1327–1339. doi: 10.1093/ndt/gfq725. Epub 2010 Dec 8. PMID: 21148030.

4. Lau WL, Leaf EM, Hu MC, Takeno MM, Kuro-o M, Moe OW, Giachelli CM. Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet. Kidney Int. 2012; 82: 1261–1270. doi: 10.1038/ki.2012.322. Epub 2012 Aug 29. PMID: 22932118.

5. Mathew S, Lund RJ, Chaudhary LR, Geurs T, Hruska KA. Vitamin D receptor activators can protect against vascular calcification. J Am Soc Nephrol. 2008; 19: 1509–1519. doi: 10.1681/ASN.2007080902. Epub 2008 Apr 30. PMID: 18448587.

6. Behets GJ, Spasovski G, Sterling LR, Goodman WG, Spiegel DM, De Broe ME, D‘Haese PC. Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism. Kidney Int. 2015 Apr; 87 (4): 846–856. doi: 10.1038/ki.2014.349. Epub 2014 Oct 22. PMID: 25337774.

7. Shiizaki K1, Negi S, Hatamura I, Sakaguchi T, Saji F, Kunimoto K et al. Biochemical and cellular effects of direct maxacalcitol injection into parathyroid gland in uremic rats. J Am Soc Nephrol. 2005 Jan; 16 (1): 97–108. PMID: 15574509.

8. Tanaka R1, Kakuta T1, Koiwa F2, Fukagawa M3, Saito A. Long-term prognosis of parathyroid function in chronic dialysis patients after PEIT-a single-centre trial. NDT Plus. 2008 Aug; 1(Suppl 3): iii29–iii34. doi: 10.1093/ndtplus/sfn084. PMID: 25983970.

9. Matsushita H. Different responses between the upper and the lower parathyroid gland in a state of secondary hyperfunction. A study on chronic renal failure by morphometry and nuclear DNA analysis. Virchows Arch A Pathol Anat Histopathol. 1989; 414 (4): 331–337. PMID: 2496521.

10. Kilpatrick RD, Danese MD, Belozeroff V, Smirnakis K, Goodman WG, Rothman KJ. The association of vitamin D use with hypercalcemia and hyperphosphat,emia in hemodialysis patients: a case-crossover study. Pharmacoepidemiol Drug Saf. 2011 Sep; 20 (9): 914–921. doi: 10.1002/pds.2183. Epub 2011 Jul 7. PMID: 21735509.

11. EVOLVE Trial Investigators, Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Goodman WG et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012 Dec 27; 367 (26): 2482–2494. doi: 10.1056/NEJMoa1205624. Epub 2012 Nov 3. PMID: 23121374.

12. Fukagawa M, Fukuma S, Onishi Y, Yamaguchi T, Hasegawa T, Akizawa T et al. Prescription patterns and mineral metabolism abnormalities in the cinacalcet era: results from the MBD-5D study. Clin J Am Soc Nephrol. 2012 Sep; 7 (9): 1473–1480. PMID: 22822017.

13. Шутов ЕВ, Лашутин СВ, Люосев ВС, Рябинская ГВ, Горелова ЕА, Леванковская ЕИ. Новые возможности в лечении вторичного гиперпаратиреоза у больных на программном гемодиализе при комбинированной терапии цинакальцетом и малыми дозами активного метаболита витамина D. Клиническая нефрология. 2011; 5: 41–46. Shutov EV, Lashutin SV, Lyuosev VS, Rya binskaya GV, Gorelova EA, Levankovskaya EI. Novye vozmozhnosti v lechenii vtorichnogo giperparatireoza u bol’nyh na programmnom gemodialize pri kombinirovannoj terapii cinakal’cetom i malymi dozami aktivnogo metabolita vitamina D. Klinicheskaya nefrologiya. 2011; 5: 41–46.

14. Koiwa F1, Kakuta T, Tanaka R, Yumita S. Efficacy of percutaneous ethanol injection therapy (PEIT) is related to the number of parathyroid glands in haemodialysis patients with secondary hyperparathyroidism. Nephrol Dial Transplant. 2007 Feb; 22 (2): 522–528. PMID: 17127701.

15. Shiizaki K, Negi Sh, Hatamura I, Tatsuta K, Shibata M, Shimada S et al. Direct vitamin D injection induces apoptosis of parathyroid cells. Kidney Int. 2006; 70: S12– S15. PMID: 16810304.

16. Герасимчук Р, Земченков А, Кондаков С, Медведева Е. Малоинвазивный метод коррекции вторичного гиперпаратиреоза при хронической болезни почек. Врач. 2009; 11: 15–22. Gerasimchuk R, Zemchenkov A, Kondakov S, Medvedeva E. Miniinvasive technique in the correction of secondary hyperparathyroidism in cronic renal disease. Vrach. 2009; 11: 15–22 [English abstract].

17. Полухина ЕВ, Езерский ДВ. Использование чрескожного введения этанола под контролем ультразвука в лечении вторичного гиперпаратиреоза. Диагностическая интервенционная радиология. 2015; 9 (1): 11–19. Poluhina EV, Ezerskii` DV. Ispol`zovanie chreskozhnogo vvedeniia e`tanola pod kontrolem ul`trazvuka v lechenii vtorichnogo giperparatireoza. Diagnosticheskaia interventcionnaia radiologiia. 2015; 9 (1): 11–19.

18. Герасимчук РП, Кондаков СБ, Земченков АЮ. Коррекция умеренного вторичного гиперпаратиреоза местными инъекциями препаратов витамина D в паращитовидные железы. Нефрология и диализ. 2015; 17 (1): 58–66. Gerasimchuk RP, Kondakov SB, Zemchenkov AYu. The correction of secondary hyperthyroidism by local vitamin D injection in parathyroid glands. Nephrology and Dialysis. 2015; 17 (1): 58–66 [English abstract].

19. Iwamoto N, Sato N, Nishida M et al. Total parathyroidectomy improves survival of hemodialysis patients with secondary hyperparathyroidism. J. Nephrol. 2012; 25 (5): 755–763. doi: 10.5301/jn.5000056. PMID: 22135031.

20. Ma TL, Hung PH, Jong IC, Hiao CY, Hsu YH, Chiang PC et al. Parathyroidectomy Is Associated with Reduced Mortality in Hemodialysis Patients with Secondary Hyperparathyroidism. Biomed Res. Int. 2015:639587. doi: 10.1155/2015/639587. PMID: 26064934.

21. Sharma J, Raggi P, Kutner N, Bailey J, Zhang R, Huang Y et al. Improved long-term survival of dialysis patients after near-total parathyroidectomy. J Am Coll Surg. 2012; 214 (4): 400–407. doi: 10.1016/j.jamcollsurg.2011.12.046. PMID: 22463880.