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Kidney Week

Abstract: SA-PO196

Isosorbide Mononitrate (IMN) for Anti-vascular Endothelial Growth Factor (VEGF)-Induced Kidney Injury

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Kala, Jaya, The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
  • Finkel, Kevin W., The University of Texas Health Science Center at Houston John P and Katherine G McGovern Medical School, Houston, Texas, United States
Background

Antiangiogenic drugs that target VEGF and its receptors are standard treatment for several cancers. Their action on VEGF expression has been associated with acute kidney injury(AKI), proteinuria and hypertension(HTN) which result in delay, interruption or reduction of effective dose in cancer patients. These effects have been attributed to the downregulation of nitric oxide(NO). Current recommendations for treatment of anti-VEGF induced HTN include use of ACE inhibitors and non-dihydropyridine calcium channel blockers but strategies to prevent proteinuria or AKI are lacking. NOdonors normalize blood pressure in anti-VEGF induced HTN. Studies have shown pre-treatment with long lasting NOdonors protect against development of anti-VEGF induced HTN. Paucity of large clinical studies using NOdonors for proteinuria, AKI and HTN prompted us to investigate this modality of treatment

Methods

Study-Population:Adult patients with AKI(≥ 25%decrease in eGFR)), HTN (systolicBP≥140mmHg and/or diastolicBP≥90 mmHg) and/or proteinuria(UPC of>500mg/g) while on anti-VEGF therapy. Treatment:Patients were randomized to treatment(IMN 60mg/d with dose escalation to 120mg/d in 4weeks if no response) or placebo arm. Criteria for Response(≥1) included improved eGFR≥25%;reduction in UPC by >500 mg/day;reduction in SBP≥10mm Hg and/or DBP≥5mmHg. Follow-up:UPC and eGFR were monitored monthly and blood pressure weekly. PrimaryEndPoint:Reduction in UPC by>500mg/day. SecondaryEndPoints:Improved eGFR≥25%;reduction in SBPof≥10mmHg and/or DBP≥5mmHg

Results

42 patients were screened and 9 were enrolled. Seven were randomized to treatment and two to placebo. In treatment arm, two patients showed proteinuria response but none showed eGFR response. Four showed responses in their SBP. The two patients who showed improvement in proteinuria had preceding improvement in HTN. Neither patient in placebo arm showed response in UPC or eGFR, but unexpectedly showed improved systolicBP. Unfortunately,COVID-19 pandemic precluded further recruitment and study was terminated

Conclusion

Treatment with NOdonors could be considered when ACEinhibition and non-dihydropyridine calcium channel blockers fail to control proteinuria in anti-VEGF treated patients. Larger population-based studies are needed to evaluate the use of NOdonors to improve renal prognosis in patients while allowing them to continue anti-VEGF treatment

Funding

  • Government Support – Non-U.S.