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Sato T, Kikkawa Y, Yamamoto S, et al. Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism. Clin Kidney J. 2019;12(5):686-692doi: 10.1093/ckj/sfy136.
Sato, T., Kikkawa, Y., Yamamoto, S., Tanaka, Y., Kazama, J. J., Tominaga, Y., Ichimori, T., Okada, M., Hiramitsu, T., & Fukagawa, M. (2019). Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism. Clinical kidney journal, 12(5), 686-692. https://doi.org/10.1093/ckj/sfy136
Sato, Tetsuhiko, et al. "Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism." Clinical kidney journal vol. 12,5 (2019): 686-692. doi: https://doi.org/10.1093/ckj/sfy136
Sato T, Kikkawa Y, Yamamoto S, Tanaka Y, Kazama JJ, Tominaga Y, Ichimori T, Okada M, Hiramitsu T, Fukagawa M. Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism. Clin Kidney J. 2019 Jan 28;12(5):686-692. doi: 10.1093/ckj/sfy136. eCollection 2019 Oct. PMID: 31583093; PMCID: PMC6768296.
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Clin Kidney J. 2019 Jan 28;12(5):686-692. doi: 10.1093/ckj/sfy136. eCollection 2019 Oct.

Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism.

Clinical kidney journal

Tetsuhiko Sato, Yamato Kikkawa, Suguru Yamamoto, Yusuke Tanaka, Junichiro J Kazama, Yoshihiro Tominaga, Toshihiro Ichimori, Manabu Okada, Takahisa Hiramitsu, Masafumi Fukagawa

Affiliations

  1. Division of Diabetes and Endocrinology, Masuko Memorial Hospital/Nagoya Daini Red Cross Hospital, Nagoya, Japan.
  2. Laboratory of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
  3. Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Science, Niigata University, Niigata, Japan.
  4. Division of Nephrology and Hypertension, School of Medicine, Fukushima Medical University, Fukushima, Japan.
  5. Department of Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
  6. Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan.

PMID: 31583093 PMCID: PMC6768296 DOI: 10.1093/ckj/sfy136

Abstract

BACKGROUND: Parathyroidectomy (PTX) that alleviates clinical manifestations of advanced hyperparathyroidism, including hypercalcemia and hypophosphatemia, is considered the best protection from calcium overload in the kidney. However, little is known about the relationship between postsurgical robust parathyroid hormone (PTH) reduction and perisurgical renal tubular cell viability. Post-PTX kidney function is still a crucial issue for primary hyperparathyroidism (PHPT) and tertiary hyperparathyroidism after kidney transplantation (THPT).

METHODS: As a clinical study, we examined data from 52 consecutive patients (45 with PHPT, 7 with THPT) who underwent PTX in our center between 2015 and 2017 to identify post-PTX kidney injury. Their clinical data, including urinary liver-type fatty acid-binding protein (L-FABP), a tubular biomarker for acute kidney injury (AKI), were obtained from patient charts. An absolute change in serum creatinine level of 0.3 mg/dL (26.5 µmol/L) on Day 2 after PTX defines AKI. Post-PTX calcium supplement dose adjustment was performed to strictly maintain serum calcium at the lower half of the normal range. To mimic post-PTX-related kidney status, a unique parathyroidectomized rat model was produced as follows: 13-week-old rats underwent thyroparathyroidectomy (TPTX) and/or 5/6 subtotal nephrectomy (NX). Indicated TPTX rats were given continuous infusion of a physiological level of 1-34 PTH using a subcutaneously implanted osmotic minipump. Immunofluorescence analyses were performed by polyclonal antibodies against PTH receptor (PTHR) and a possible key modulator of kidney injury, Klotho.

RESULTS: Patients' estimated glomerular filtration rate (eGFR) did not have any clinically relevant change (62.5 ± 22.0 versus 59.4 ± 21.9 mL/min/1.73 m

CONCLUSIONS: Preexisting tubular damage is a potential risk factor for AKI after PTX although, overall patients with hyperparathyroidism are expected to keep favorable kidney function after PTX. Patients with elevated tubular cell biomarker levels may suffer post-PTX kidney impairment even though calcium supplement is meticulously adjusted after PTX. Our unique experimental rat model suggests that blunted tubular PTH/PTHR signaling may damage tubular cell viability and deteriorate kidney function through a Klotho-linked pathway.

© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.

Keywords: Klotho; PTH receptor; hyperparathyroidism; parathyroidectomy; tubular injury

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