PMID- 32234009 OWN - NLM STAT- MEDLINE DCOM- 20210907 LR - 20210907 IS - 1471-2369 (Electronic) IS - 1471-2369 (Linking) VI - 21 IP - 1 DP - 2020 Mar 31 TI - Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report. PG - 113 LID - 10.1186/s12882-020-01775-z [doi] LID - 113 AB - BACKGROUND: The advent of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with advanced malignancies. On the other hand, these drugs might cause immune-related adverse events (irAEs) including endocrinopathies and nephropathies. Thyroid dysfunction is one of the most common irAEs. For ICIs-induced nephropathies, most cases are due to tubulointerstitial nephritis, which might require steroid treatment. Here, we report a patient with non-small cell lung cancer treated with ICI who developed increased serum creatinine (s-Cr) levels due to ICIs-induced hypothyroidism. CASE PRESENTATION: A 57-year-old Asian man with refractory non-small cell lung cancer under ICIs therapy (pembrolizumab, an anti-programmed cell death-1 monoclonal antibody) developed increased s-Cr levels 5 months after the pembrolizumab initiation. His laboratory data, renal biopsy, and Gallium-67 scintigraphy findings denied pembrolizumab-induced tubulointerstitial nephritis. His renal function was correlated with thyroid function. Despite the increase of s-Cr levels, serum cystatin C levels were normal, which could be explained by the hypothyroidism. Levothyroxine treatment improved renal function as well as thyroid function. Then pembrolizumab was resumed, and both his thyroid and renal function remained normal level. Ultimately, we concluded that the increased s-Cr levels were caused by pembrolizumab-induced hypothyroidism. CONCLUSION: All clinicians involved in ICI treatment need to recognize the possible increase in s-Cr levels caused by ICIs-induced hypothyroidism, and we propose monitoring serum cystatin C levels to differentiate ICIs-induced hypothyroidism from tubulointerstitial nephritis before invasive renal biopsies or steroid treatment, which are recommended by the prescribing information for pembrolizumab, are performed. FAU - Matsuoka, Natsumi AU - Matsuoka N AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. FAU - Tsuji, Kenji AU - Tsuji K AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. gmd422036@s.okayama-u.ac.jp. FAU - Ichihara, Eiki AU - Ichihara E AD - Department of Hematology, Oncology, Allergy and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. FAU - Hara, Takayuki AU - Hara T AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. FAU - Fukushima, Kazuhiko AU - Fukushima K AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. FAU - Toma, Kishio AU - Toma K AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. FAU - Kitamura, Shinji AU - Kitamura S AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. FAU - Inagaki, Kenichi AU - Inagaki K AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. FAU - Sugiyama, Hitoshi AU - Sugiyama H AD - Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. FAU - Wada, Jun AU - Wada J AD - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. LA - eng GR - 18K15978/the Japanese Society for the Promotion of Science/International PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200331 PL - England TA - BMC Nephrol JT - BMC nephrology JID - 100967793 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Cystatin C) RN - 0 (Immune Checkpoint Inhibitors) RN - AYI8EX34EU (Creatinine) RN - DPT0O3T46P (pembrolizumab) RN - Q51BO43MG4 (Thyroxine) SB - IM MH - *Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects MH - Antineoplastic Agents, Immunological/administration & dosage/adverse effects MH - Biopsy/methods MH - Carcinoma, Non-Small-Cell Lung/*drug therapy MH - Creatinine/*blood MH - Cystatin C/blood MH - Hormone Replacement Therapy/methods MH - Humans MH - *Hypothyroidism/blood/chemically induced/therapy MH - Immune Checkpoint Inhibitors/administration & dosage/adverse effects MH - Kidney/pathology MH - Lung Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Thyroid Function Tests/methods MH - Thyroxine/*administration & dosage MH - Treatment Outcome PMC - PMC7110789 OTO - NOTNLM OT - Creatinine OT - Cystatin C OT - Hypothyroidism OT - Pembrolizumab COIS- The authors declare that they have no competing interests. EDAT- 2020/04/03 06:00 MHDA- 2021/09/08 06:00 PMCR- 2020/03/31 CRDT- 2020/04/03 06:00 PHST- 2019/07/01 00:00 [received] PHST- 2020/03/20 00:00 [accepted] PHST- 2020/04/03 06:00 [entrez] PHST- 2020/04/03 06:00 [pubmed] PHST- 2021/09/08 06:00 [medline] PHST- 2020/03/31 00:00 [pmc-release] AID - 10.1186/s12882-020-01775-z [pii] AID - 1775 [pii] AID - 10.1186/s12882-020-01775-z [doi] PST - epublish SO - BMC Nephrol. 2020 Mar 31;21(1):113. doi: 10.1186/s12882-020-01775-z.