Abstract: PO1866
Kidney Pathology Findings in Patients with AKI Associated with Tyrosine Kinase Inhibitors
Session Information
- Cancer and Kidney Diseases: Nephrotoxins, RCC, and More
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Mukku, Venkata Kishore R., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Mamlouk, Omar, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
- Glass, William F., The University of Texas Health Science Center at Houston, Houston, Texas, United States
- Tchakarov, Amanda, The University of Texas Health Science Center at Houston, Houston, Texas, United States
- Mandayam, Sreedhar A., The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Background
Tyrosine kinase inhibitors (TKIs) are widely used targeted cancer therapy as they play a critical role in the modulation of growth factor signaling. Nephrotoxicity associated with TKIs can lead to interruption of therapy. However, the literature on the kidney pathology associated with TKIs nephrotoxicity is limited. Here, we present our center observation of tubular and glomerular lesions attributed to possible TKIs.
Methods
We retrospectively reviewed all cancer patients from 2018 to 2020 who we were treated with TKIs and underwent a kidney biopsy at the University of Texas MDACC.
Results
We identified 13 cancer patients treated with Sunitinib, Cabozantinib, Lenvatinib, Regorafenib, Erlotinib, Osimertinib and Ibrutinib between 2018-2020 and developed acute kidney injury (AKI) attributed to possible TKI nephrotoxicity. The median age was 70 (range, 43 to 80) and the median time to develop AKI was 4 months (range, 1 to 58 months) of starting TKI. AKI was severe (stage ≥3) in 6 patients, among which 4 required hemodialysis. Most of the patients had bland urine (7 out of 13) and proteinuria was observed only in 6 patients. Thrombotic microangiopathy (TMA) was the most common pathological finding followed by acute tubular injury (ATI) as they were observed in 5 and 4 patients, respectively. One patient had proliferative glomerulonephritis, one patient had chronic lymphocytic leukemia infiltration, and one patient had no active lesion. TKIs were discontinued in nine patients, and nine patients had partial kidney recovery. Five patients had disease progression and died within 4 months of AKI.
Conclusion
Our case series has demonstrated that kidney limited TMA and ATI were common pathology findings in patients with suspected TKI nephrotoxicity. Nonetheless, half of patients with TMA were on concurrent checkpoint inhibitor therapy with TKI and half of the patients with ATI had associated sepsis diagnosis. The mechanism is likely multifactorial and possibly related to mTOR and VGEF inhibition leading to endothelial injury, and inhibition of the downstream signaling pathway of MAPK/ERK1/2 leading to ATI. Urine analysis was not predictive of the kidney pathology. Treating nephrotoxicity by discontinuation of the offending TKI was associated with partial kidney recovery, however patients had poor overall prognosis.