Acute Kidney Injury Induced by Immune Checkpoint Inhibitors

Abstract

<b><i>Background:</i></b> Recent advances in immune therapy have focused on several agents that target tumor suppression; specifically, use of immune checkpoint inhibitors (ICIs), such as ipilimumab, pembrolizumab, and nivolumab, has become an important strategy in cancer therapy as they improve outcomes in malignant disease. However, the incidence of renal complications arising from the widespread use of ICIs may be underestimated. <b><i>Summary:</i></b> The most frequently reported renal condition caused by ICI use is acute interstitial nephritis, and for clinicians, the crucial question is how to effectively manage patients who develop renal side effects due to cancer treatment. Currently, treatment of kidney injury associated with ICIs adheres to clinical guidelines described in Kidney Disease Improving Global Outcomes, which entails drug withdrawal and glucocorticoids or combined immunosuppressant use based on disease stage; however, there is no consensus on renal biopsy. <b><i>Key Messages:</i></b> Despite significant progress in prevention and treatment, the incidence and mortality of ICI-induced acute kidney injury (AKI) remain very high. This article will discuss the general clinical manifestations, mechanisms of toxicity, renal complications of ICI therapy, and related biomarkers of renal damage. It is envisaged that this information would help clinicians effectively manage AKI due to ICI therapy.

Immune Checkpoint Inhibitors and the Kidney: A Focus on Diagnosis and Management for Personalised Medicine

“…Some symptoms—such as fatigue, dysgeusia, and nausea—are not specific to AKI and can be linked to malignancy [ 41 ]; increased sCr and sterile pyuria are the only clinical signs in most cases [ 22 , 42 ]. ICI-AKI can be suspected when haematuria, pyuria, and moderate proteinuria are present with increased sCr levels [ 43 ]. Simultaneously, extrarenal irAEs (e.g., colitis, thyroiditis, hypophysitis, dermatitis, or rash) are observed in 43% of patients who develop ICI-AKI [ 44 ].…”

Nivolumab‐induced acute tubular injury: A case report

“…The clinical manifestation of AIN is similar to ATI, but AIN has a more hidden onset while ATI arises from direct tubular epithelial injury with rapid deterioration of renal function. 8,19 The median time from ICI start to AKI is variable. In the patient of our case, the time relapsed from the initial exposure to nivolumab plus longer half-life acemetacin until the onset of AKI was 30 days.…”

“…Medications such as PPIs, NSAIDs, and antibiotics are an important cause of AIN on their own and have been very commonly reported as concomitant drugs in patients who develop ICI‐related AIN resulting in shorter progression‐free survival and overall survival 17 . Among patients diagnosed with ICI‐related kidney injury, 69% were provided combination therapy, including antibiotics (9%), NSAIDs (22%), or PPIs (54%) 18,19 . Therefore, we believe that the patient's ICI‐induced AKI is highly related to the combinational use of other medications and that the presentation of AKI may not be AIN but other possible manifestations.…”

Nivolumab-induced acute tubular injury: a case report

“…However, our case proved to be ATI. The clinical manifestation of AIN is similar to ATI, but AIN has a more hidden onset while ATI arises from direct tubular epithelial injury with rapid deterioration of renal function 8,19 .…”

“…Medications such as PPIs, NSAIDs, and antibiotics are an important cause of AIN on their own and have been very commonly reported as concomitant drugs in patients who develop ICI-related AIN resulting in shorter progression-free survival and overall survival 17 . Among patients diagnosed with ICI-related kidney injury, 69% were provided combination therapy, including antibiotics (9%), NSAIDs (22%), or PPIs (54%) [18][19] . Therefore, we believe that the patient's ICI-induced AKI is highly related to the combinational use of other medications and that the presentation of AKI may not be AIN but other possible manifestations.…”