Nivolumab plus ipilimumab induced endocrinopathy and acute interstitial nephritis in metastatic sarcomatoid renal-cell carcinoma: A case report and review of literature

Hino, Christopher; Nishino, Kevin; Pham, Bryan; Jeon, Won Jin; Nguyen, Michael; Cao, Huynh

doi:10.3389/fimmu.2022.993622

Cited by 7 publications

(7 citation statements)

References 45 publications

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“…Further heterogeneity was difficult to assess in our study because some of the associated factors were not reported in the original articles. With an increasing appearance of new studies [ 51 , 52 , 53 ], our understanding of ICI-kidney IRAEs will be deepened gradually. Further studies are needed to explore the related mechanism and help better manage the disease.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review

Zhao

et al. 2023

JCM

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(1) Background: Despite increasing recognition of immune checkpoint inhibitors (ICIs) and kidney immune-related adverse events (IRAEs), no large-sample studies have assessed the pathological characteristics and outcomes of biopsy-proven kidney IRAEs. (2) Methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane for case reports, case series, and cohort studies for patients with biopsy-proven kidney IRAEs. All data were used to describe pathological characteristics and outcomes, and individual-level data from case reports and case series were pooled to analyze risk factors associated with different pathologies and prognoses. (3) Results: In total, 384 patients from 127 studies were enrolled. Most patients were treated with PD-1/PD-L1 inhibitors (76%), and 95% presented with acute kidney disease (AKD). Acute tubulointerstitial nephritis/acute interstitial nephritis (ATIN/AIN) was the most common pathologic type (72%). Most patients (89%) received steroid therapy, and 14% (42/292) required RRT. Among AKD patients, 17% (48/287) had no kidney recovery. Analyses of pooled individual-level data from 221 patients revealed that male sex, older age, and proton pump inhibitor (PPI) exposure were associated with ICI-associated ATIN/AIN. Patients with glomerular injury had an increased risk of tumor progression (OR 2.975; 95% CI, 1.176, 7.527; p = 0.021), and ATIN/AIN posed a decreased risk of death (OR 0.164; 95% CI, 0.057, 0.473; p = 0.001). (4) Conclusions: We provide the first systematic review of biopsy-proven ICI-kidney IRAEs of interest to clinicians. Oncologists and nephrologists should consider obtaining a kidney biopsy when clinically indicated.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review

Zhao

et al. 2023

JCM

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“…Three irAEs, such as thyroid disease, diabetes mellitus, and hypophysitis, developed in this case. In 7 previous reports of triple endocrine irAEs due to ICI therapy (Table 4), [21–27] thyroid disease and/or T1D mellitus developed before onset of hypophysitis. In 3 cases, ICI therapies were continued or reinitiated after resolution of irAEs.…”

Section: Discussionmentioning

confidence: 99%

“…Table 5 shows cases reporting hypophysitis and T1D. [3,[21][22][23][24][25][26][27][28][29][30][31][32] ICIs are anti-PD-1 monotherapy, anti-PD-L1 monotherapy, and combination therapy of anti-PD-1/anti-PD-L1 and anti-CTLA-4. No cases with hypophysitis and T1D due to ipilimumab monotherapy were reported.…”

Section: Endocrinologymentioning

confidence: 99%

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Fulminant ACTH decrease following diabetic ketoacidosis induced by immune checkpoint inhibitor combination therapy with nivolumab and ipilimumab: A case report

Iesaka,

Kameda,

Miya

et al. 2023

Medicine

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Rationale: The increasing use of immune checkpoint inhibitors (ICIs) for treating malignant tumors result in the concomitant rise of immune-related adverse events (irAEs). This case report may provide useful insight to understanding the etiology of ICI-induced hypophysitis, a severe irAE leading to potentially fatal secondary adrenal insufficiency. Patient concerns: An 81-year-old Japanese man was hospitalized for diabetic ketoacidosis following 4 courses of ICI combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma. Diagnosis: Insulin secretion was depleted, leading to diagnosis of fulminant type 1 diabetes. Adrenocorticotropic hormone (ACTH) and cortisol levels were very high (60.8 pmol/L and 1575 nmol/L, respectively) upon admission. ACTH and cortisol returned to normal ranges on the 2nd day. On the 8th day, an ACTH loading test showed intact cortisol response (peak value 519 nmol/L). However, on the 14th day, there was a sharp decrease in ACTH and cortisol levels (10.5 pmol/L and 47 nmol/L, respectively) accompanied by fatigue and a drop in blood pressure to 97/63 mm Hg. As secondary adrenal insufficiency was suspected, hydrocortisone replacement was initiated. An ACTH loading test on the 17th day revealed low cortisol peak (peak value 232 nmol/L), indicating sudden disruption of adrenal function. Magnetic resonance imaging showed no abnormal findings and there was no other pituitary hormone deficiency. These findings, along with the patient clinical course, suggest that secondary adrenal insufficiency was caused by acute ACTH producing cell destruction as an irAE associated with ICI therapy. Interventions: The patient hyperglycemia and ketoacidosis were treated using extracellular fluid and insulin therapy. After development of adrenal insufficiency, hydrocortisone 20 mg was started, and the patient symptoms improved. Outcomes: He was continued on insulin therapy, hydrocortisone, and reinitiated nivolumab. Lessons: This case provides a detailed course of the fulminant onset of ACTH deficiency during ICI administration, emphasizing the importance of close monitoring.

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“…ICIs besides their direct effect on adrenals, have been also associated with hypophysitis with an incidence of up to 17% of the cases [23–29,30 ▪▪ ]. Its prevalence generally depends on the dosage and specific drug class (anti-CTLA-4, anti-PD-1 or anti-PD-L1) [30 ▪▪ ,31].…”

Section: Causes Of Adrenal Insufficiencymentioning

confidence: 99%

Diagnostic strategies in adrenal insufficiency

Siampanopoulou

Tasouli

Angelousi

2023

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

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Purpose of reviewAdrenal insufficiency (AI) is the clinical manifestation of deficient production of glucocorticoids with occasionally deficiency also in mineralocorticoids and adrenal androgens and constitutes a fatal disorder if left untreated. The aim of this review is to summarize the new trends in diagnostic methods used for determining the presence of AI. Recent findingsNovel aetiologies of AI have emerged; severe acute respiratory syndrome coronavirus 2 infection was linked to increased frequency of primary AI (PAI). A new class of drugs, the immune checkpoint inhibitors (ICIs) widely used for the treatment of several malignancies, has been implicated mostly with secondary AI, but also with PAI. Salivary cortisol is considered a noninvasive and patient-friendly tool and has shown promising results in diagnosing AI, although the normal cut-off values remain an issue of debate depending on the technique used. Liquid chromatography--mass spectrometry (LC--MS/MS) is the most reliable technique although not widely available. SummaryOur research has shown that little progress has been made regarding our knowledge on AI. Coronavirus disease 2019 and ICIs use constitute new evidence on the pathogenesis of AI. The short synacthen test (SST) remains the 'gold-standard' method for confirmation of AI diagnosis, although salivary cortisol is a promising tool.

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Nivolumab plus ipilimumab induced endocrinopathy and acute interstitial nephritis in metastatic sarcomatoid renal-cell carcinoma: A case report and review of literature

Cited by 7 publications

References 45 publications

Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review

Clinicopathological Features of Kidney Injury Related to Immune Checkpoint Inhibitors: A Systematic Review

Fulminant ACTH decrease following diabetic ketoacidosis induced by immune checkpoint inhibitor combination therapy with nivolumab and ipilimumab: A case report

Diagnostic strategies in adrenal insufficiency

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