Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report

Abstract

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.

Hypothyroidism-induced kidney dysfunction: an under-recognized phenomenon in patients on immune checkpoint inhibitors

“…Although kidney biopsy was not performed in these cases to confirm the cause of creatinine rise due to the presence of relative contraindications, their creatinine trends closely paralleled the course of their thyroid dysfunction, supporting the diagnosis of hypothyroidism-related kidney dysfunction. To our knowledge, our findings are corroborated by only one other report [ 3 ]. However, this phenomenon is likely under-recognized and under-reported.…”

“…The magnitude of creatinine rise seen is highly variable, although reported creatinine levels have been in the range of 1.5–2.5 mg/dL [ 4 ]. Cystatin-C levels are either normal or decreased in hypothyroid patients [ 3 , 4 ]. Cystatin-C was unavailable and not performed in either case.…”

Pembrolizumab-Induced Rhabdomyolysis in a Clear Cell Renal Cell Carcinoma Patient: A Case Report

“…Our patient was found to have hypothyroidism which can be due to pembrolizumab treatment, and it requires a life-time replacement treatment [25, 26]. It is noteworthy that hypothyroidism can itself cause an increase in creatinine level [27], and in our patient, it was difficult to accurately identify whether the high creatinine is due to rhabdomyolysis alone, or hypothyroidism alone, or both.…”

First line Immunotherapy for Non-Small Cell Lung Cancer

“…Most common adverse reactions in patients treated with Pembrolizumab as a single agent are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, and abdominal pain [30][31][32][33]. Immune-mediated side effects were reported and includes pneumonitis [34], colitis [35,36], hepatitis [37,38], adrenal insufficiency [39,40], hypophysitis [39], hyperthyroidism [41] and hypothyroidism [42,43], type 1 diabetes mellitus [44,45], and nephritis [46,47].…”