Abstract: SA-PO020

Reversible AKI from Erlotinib Due to Glomerular Endotheliosis

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Latcha, Sheron, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Gutgarts, Victoria, Weill Cornell, New York, New York, United States
  • Seshan, Surya V., Weill Cornell Medical Center, New York, New York, United States
Background

Erlotinib is an oral epidermal growth factor receptor associated tyrosine kinase inhibitor approved for the treatment of metastatic non small cell lung (NSCLC) with exon 19 deletions or L858R substitution mutations. Renal toxicity is rare with one report of crescenteric glomerulonephritis.

Methods

A 67 year old female with metastatic lung adenocarcinoma (+EGFR L858R) was sent for renal evaluation for AKI. At start of erlotinib, creatinine (SCr) was 0.9mg/dl and UA showed no proteinuria.Thereafter, the SCr increased. At evaluation, blood pressure (BP) was 146/72 (no change from baseline), no edema was present, UA showed 100+ protein and spot urine total protein creatinine ratio was 0.64. Renal biopsy showed diffuse glomerular endothelial injury, global glomerulosclerosis (16/44 glomeruli), mild to moderate acute tubular injury, moderate widespread tubular atrophy, severe arterio and arteriolosclerosis and extensive arteriolar intimal hyalinosis. No proliferative or immune complex glomerular lesions were seen. The foot processes were partially effaced. Her disease had been well controlled on erlotinib so it was continued at a reduced dose. Subsequently it stopped for increases in SCr. After stopping erlotinib, the SCr decreased to 1.3mg/dl. Because of previously good response to an EGFR TKI, gefitinib was started. Subsequently, an increased SCr, proteinuria and BP were noted. At last followup on gefitinib, the BP was 167/83, no edema was present, SCr was 1.8mg/dl, a 24H urine collection showed 4.8gms of protein and there was no progression of disease on CAT scan.

Conclusion

Erlotinib treatment was associated with mild proteinuria and reversible AKI. The renal biopsy was consistent with glomerular endothelial injury which may be consistent with a mild form of thrombotic microangiopathy. The presence of significant arteriolar intimal hyalinosis may represent healed endothelial injury. The recurrence of AKI and worsening proteinuria with gefitinib may indicate that this is a “class effect” of EGFR TKIs.