Anaplastic lymphoma kinase inhibitors and their effect on the kidney

Bonilla, Marco; Jhaveri, Kenar D.; Izzedine, Hassan

doi:10.1093/ckj/sfac062

Cited by 10 publications

(8 citation statements)

References 73 publications

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“…ALK inhibitors have been associated with the occurrence of acute kidney injury and chronic kidney disease in clinical practice. Acute elevation of serum creatinine when initiating first-generation crizotinib may not be a reflection of true kidney injury, but rather a pseudo-kidney injury due to creatinine transporter inhibition, thereby interfering with creatinine secretion in the proximal tubule ( 58 ).…”

Section: Alk Inhibitorsmentioning

confidence: 99%

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Nephrotoxicity of targeted therapy used to treat lung cancer

Li,

Lin,

Hao

et al. 2024

Front. Immunol.

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Lung cancer is the leading cause of cancer-related death worldwide, especially non-small cell lung cancer. Early diagnosis and better treatment choices have already provided a more promising prognosis for cancer patients. In targeted therapy, antagonists target specific genes supporting cancer growth, proliferation and metastasis. With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents must be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. Drug-related nephrotoxicity has attracted attention when initiating cancer therapy. Our review aims to summarize the adverse renal effects caused by targeted therapy during lung cancer treatment, mainly focusing on EGFR and ALK tyrosine kinase inhibitors. Also, we discuss the possible mechanism of the side effect and provide managements to help improve the renal function in clinical practice.

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Section: Alk Inhibitorsmentioning

confidence: 99%

“…It is thought that MET is mainly expressed in the proximal convoluted tubule, proximal loop of Henle loop and distal convoluted tubule. Crizotinib competitively inhibits creatinine and water secretion by inhibiting the c-Met pathway, which may be the mechanism that predisposes to acute kidney injury ( 58 , 70 ).…”

Section: Alk Inhibitorsmentioning

confidence: 99%

Nephrotoxicity of targeted therapy used to treat lung cancer

Li,

Lin,

Hao

et al. 2024

Front. Immunol.

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“…Anaplastic lymphoma kinase (ALK) inhibitors are used in the treatment of NSCLC harbouring the oncogenic EML4-ALK fusion or other ALK rearrangements, which occur in 3%–7% of patients with NSCLC [ 3 ]. Increased SCr levels are frequent in patients treated with ALK inhibitors and have been reported to occur in 23% with crizotinib, 26% with alectinib, 33%–58% with ceritinib, 2% with brigatinib, 19% with ensartinib and 13%–15% with entrectinib; no data are available for lorlatinib [ 3 , 9 ]. Until this day, only for crizotinib has pseudo-AKI been formally described.…”

Section: Alk Inhibitors (Eg Crizotinib Ceritinib Lorlatinib)mentioning

confidence: 99%

“…In addition to pseudo-AKI, ALK inhibitors have been implicated in the development of true kidney injury, both tubular and glomerular diseases [ 3 ]. Gastaud et al .…”

Section: Alk Inhibitors (Eg Crizotinib Ceritinib Lorlatinib)mentioning

confidence: 99%

Pseudo-AKI associated with targeted anti-cancer agents—the truth is in the eye of the filtration marker

Vanhoutte

Sprangers

2023

Clinical Kidney Journal

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Besides true AKI, the occurrence of pseudo-AKI has been associated with several targeted agents. To improve the management of cancer patients treated with targeted agents, we need to be aware of this and use diagnostic approaches to differentiate between pseudo-AKI and AKI. In an article by Wijtvliet et al. in this issue of CKJ, tepotinib is added to the list of targeted agents associated with pseudo-AKI. In this editorial we discuss the current literature regarding pseudo-AKI and true AKI associated with targeted agents, and subsequently propose a management strategy to monitor kidney function in patients treated with targeted agents.

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“…Anaplastic lymphoma kinase inhibitors, such as crizotinib, ceritinib, and alectinib, are primarily used in the treatment of advanced non–small cell lung cancer (NSCLC) in which around 3% to 7% of patients are positive for the ALK gene rearrangement or the fusion with echinoderm microtubule–associated protein-like 4. 15 A recent study done by Arakawa et al evaluated the in vitro inhibitory effects of crizotinib on OCT2 by directly measuring the creatinine uptake by OCT2 and demonstrated that crizotinib inhibited creatine uptake by OCT2 in a competitive and substrate-dependent manner. 16 Therefore, at clinically relevant concentrations, crizotinib can cause a rise in serum creatinine levels without representing true kidney injury through its direct actions on renal transporters.…”

Section: Targeted Cancer Therapies and Inhibition Of Tubular Creatini...mentioning

confidence: 99%

Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature

Mach

Bouganim

et al. 2022

Can J Kidney Health Dis

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Rationale: Targeted cancer therapies have revolutionized the field of oncology by selecting for specific molecular pathways, thus improving overall clinical prognosis. However, many of these targeted treatments have been reported to have adverse kidney effects, including acute kidney injury, interstitial nephritis, and glomerular disease. Furthermore, some of these targeted therapies have also been found to cause an asymptomatic rise in serum creatinine levels through inhibition of active tubular secretion. Presenting concerns: A 79-year-old woman was being followed for stage 4 A2 chronic kidney disease secondary to type 2 diabetes and longstanding hypertension. She was diagnosed with invasive mammary carcinoma and was initiated on letrozole, an aromatase inhibitor, and palbociclib, a selective cyclin-dependent kinase inhibitor, was subsequently added. Prior to the initiation of her treatments, her baseline estimated glomerular filtration rate (eGFR) fluctuated between 25 and 28 mL/min/1.73 m2 over the previous year. After initiating palbociclib, her serum creatinine progressively increased, despite having well-controlled blood pressure and diabetes. In addition, there was no history of pre-renal events nor any sonographic evidence of obstruction. Within 7 months, her eGFR based on serum creatinine had decreased down to 12 mL/min/1.73 m2. Interventions: Given that there were no clinical or other biochemical changes suggestive of worsening renal function, a serum cystatin C was measured using an immunoturbidimetric assay, which was 1.71 mg/L and correlated with an eGFR of 33 mL/min/1.73 m2 based on the chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C equation (2012). This value was consistent with her previous baseline. Based on these findings, the significant decrease in eGFR measured by serum creatinine was attributed to the inhibitory effects of palbociclib on tubular creatinine secretion, rather than representing true kidney damage. Thus, a kidney biopsy was not performed in this context. Outcomes: Seven months later, a repeat serum cystatin C was repeated to assess for any worsening of the patient’s kidney function and revealed an eGFR of 35 mL/min/1.73 m2 based on the CKD-EPI cystatin C equation (2012), thus revealing stable kidney function and reinforcing the inhibitory effects of palbociclib on tubular creatinine secretion through its direct effects on kidney transporters. Teaching points: This case report and literature review acknowledges the importance of using alternative methods of assessing kidney function when patients are undergoing targeted cancer therapies known to affect tubular creatinine secretion, which include cyclin-dependent kinase 4/6 inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, tyrosine kinase inhibitors, and mesenchymal-epithelial transition inhibitors. The use of non–creatinine-based markers of glomerular filtration rate (GFR), such as cystatin C and nuclear renal scans, will allow for more accurate estimation of kidney function in the appropriate setting, thus avoiding invasive diagnostic tests and unnecessary adjustments of treatment plans. However, certain targeted cancer therapies have also been proven to cause true kidney injury; therefore, physicians must still maintain a high degree of suspicion and consider invasive investigations and/or cessation or reduction of treatments when alternative measurements of kidney function do not suggest an underestimation of GFR via serum creatinine.

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Anaplastic lymphoma kinase inhibitors and their effect on the kidney

Cited by 10 publications

References 73 publications

Nephrotoxicity of targeted therapy used to treat lung cancer

Nephrotoxicity of targeted therapy used to treat lung cancer

Pseudo-AKI associated with targeted anti-cancer agents—the truth is in the eye of the filtration marker

Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature

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