Introduction:
Vascular endothelial factor inhibitors (VEGFi) are widely used in the treatment of certain types of cancer. Side effects of VEGFi are mainly presented by blood hypertension (BH) and proteinuria (Pr), less often by nephrotic syndrome (NS) and thrombotic microangiopathy (TMA). We demonstrate the spectrum of kidney disease associated with VEGFi in children.
Methods:
The clinical and laboratory data of 3 pts were summarized. The GFR was calculated based on cystatin and creatinine blood level (CKiDU25).
Results:
Case 1. The 8-yrs old girl with “Left nephroblastoma stage 4, chemotherapy AVD SIOP-RTSG 2016, left tumor nephrectomy, radiotherapy; Early bilateral lung metastatic relapse” was treated with VITb combination (vincristine, irinotecan, temozolomide, bevacizumab (15 mg/kg/3 weeks)). Uncontroled BH occurred on day 2+ of fourth bevacizumab infusion (Hb 100 g/l, WBC 4.89x103/μl, PLT 100x103/μl; eGFR 92 ml/min/1.73m2, no proteinuria) followed by pretibial edema, TMA (Hb 89 g/l, PLT 26x103/μl, LDH 571U, haptoglobin 0.01g/l) with AKI (eGFR 50 ml/min/1.73m2) and high proteinuria (1440 mg/m2) on day 11+. Blood activity ADAMTS-13 (67%), CH50 (54 U/ml) were within normal range; Coombs test, antiDNA and antinuclear antibodies were negative. Despite Bevacizumab withdrawal and steroid treatment (solumedrol 500 mg/m2 №3 followed by prednisone 1 mg/kg/day) NS with decreased eGFR (43 ml/min/1.73 m2) and TMA progression was seen. Eculizumab infusion (600 mg/week №3) resulted in significant clinical and laboratory improvement with partial kidney function recovery (eGFR 83 ml/min/1.73m2).
Case2. The 9-yrs old boy with “Medulloblastoma RxMx stage, chemotherapy HIT-MED 2014: SKK, radiotherapy, anti-relapse therapy (Carbo/VP), proton radiation therapy, metronome therapy (TEMIRI); Disease progression” was treated with MEMMAT protocol (oral thalidomide, daily oral fenofibrate, celecoxib, and alternating 21-day cycles of low-dose etoposide and cyclophosphamide supplemented by IV bevacizumab 10 mg/kg/2 weeks and intraventricular alternating etoposide and liposomal cytarabine). After 4th month of treatment he developed resistant BH, followed by NS and AKI (eGFR decreased from 80 to 31 ml/min/1.73m2). Prednisone 1 mg/kg/day for 3 weeks with slow reduction led to NS remission and GFR-improvement (eGFR 70 ml/min/1.73m2).
Case 3. The 11-yrs old boy with “Left nephroblastoma stage 4, therapy AVD SIOP-RTSG 2016, left tumor nephrectomy, radiotherapy; Metastatic relapse” was treated with VITb combination including bevacizumab (15 mg/kg/3 weeks). Severe BH occurred after 4th mo of therapy followed by proteinuria (600 mg/m2/day) and eGFR decline (89 to 62 ml/min/1.73m2). VEGFi withdrawal and antihypertensive therapy including ACEi (0,2 mg/kg/day by ramipril) led to proteinuria reduction (200 mg/m2/day) and GFR improvement (eGFR 81 ml/min/1.73m2).
Conclusions:
In all cases VEGFi-induced kidney diseases manifested after 4 months of therapy primarily with uncontrolled BH followed by Pr. Thus, blood pressure levels and proteinuria should be strictly monitored in pts. The spectrum of kidney diseases ranged from Pr with/without NS to TMA. Unlike adults, children rarely undergo biopsy to clarify the diagnosis.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.