Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia.
BACKGROUND
A high level of parathyroid hormone (PTH) is considered to be an indicator of poor prognosis and a poor quality of life of dialysis patients; therefore, an effective and safe therapy for secondary hyperparathyroidism (SHPT) has been developed.


METHODS
In 20 patients with SHPT resistant to maxacalcitol (OCT) intravenously administered, all detectably enlarged parathyroid glands were treated by percutaneous maxacalcitol injection therapy (PMIT) under ultrasonographic guidance consecutively 6 times, which was followed by OCT that was intravenously administered. The clinical effects of PMIT were evaluated based on the changes in the serum intact-PTH, adjusted Ca, phosphorus, and bone marker levels, and the parathyroid gland volume determined by ultrasonography. Morphologic examination, apoptosis analysis, and PTH mRNA expression level determination by reverse transcription-polymerase chain reaction (RT-PCR) using parathyroid tissues obtained by a biopsy technique were performed.


RESULTS
PMIT and subsequent intravenous OCT administrations significantly decreased the serum intact-PTH level and parathyroid gland volume for at least 12 weeks after PMIT without major complications. Parathyroid tissues obtained after PMIT exhibited some partial defects of parathyroid cells, a marked increase in the number of the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells, the ladder formation determined by DNA electrophoresis, and the decrease in the PTH mRNA expression level.


CONCLUSIONS
PMIT is effective and safe for the treatment of refractory SHPT, and a locally high level of OCT suppresses PTH secretion and regresses parathyroid hyperplasia, which is involved in the induction of apoptosis of parathyroid cells.
Shiizaki
Kazuhiro
K
Center of Blood Purification Therapy, Wakayama Medical University, Wakayama, Japan. shiizaki@wakayama-med.ac.jp
Hatamura
Ikuji
I
Negi
Shigeo
S
Narukawa
Nobuhiko
N
Mizobuchi
Masahide
M
Sakaguchi
Toshifumi
T
Ooshima
Akira
A
Akizawa
Tadao
T
D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D002117:Calcitriol / Q000008:administration & dosage* / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000473:pathology*; D006965:Hyperplasia; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000187:drug effects / Q000473:pathology*; D010281:Parathyroid Hormone / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014511:Uremia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D002117:Calcitriol; C051883:maxacalcitol