A rare case of combined kidney damage in a patient with neurofibromatosis type 2

Background: neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by the formation of multiple tumors in the central and peripheral nervous system. Kidney involvement in NF2, including the formation of renal sclerosing peritubular nodules (RSPN), is uncommon and typically subclinical. Most of previous descriptions of this renal changes are based on the results of autopsy studies of patients who died from NF2.

Case presentation: we report a 21-year-old patient with a confirmed diagnosis of NF2 treated with bevacizumab who developed combined kidney injury. Renal involvement was detected during a routine follow-up 14 months after initiating bevacizumab therapy and manifested as persistent proteinuria (1.0-3.6 g/day) and significant hematuria. Kidney biopsy revealed a combined lesion consisting of RSPN and IgA nephropathy with focal proliferative and sclerosing features. Morphological interpretation required evaluating the contribution of each lesion to disease progression and determining whether the glomerulonephritis was primary or secondary to the underlying disorder or therapy. Despite the potential association of renal pathology with ongoing bevacizumab therapy, treatment could not be discontinued due to the worsening clinical manifestations of NF2.

Over time, renal function gradually declines (serum creatinine 128-303 mmol/L). Second kidney biopsy demonstrated increased glomerulosclerosis and interstitial fibrosis.

Conclusion: this case illustrates previously unreported combined kidney damage – renal sclerosing peritubular nodules and IgA nephropathy – in a patient with NF2 undergoing bevacizumab therapy.

1. Plotkin SR, Messiaen L, Legius E et al. Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation. Genet Med. 2022;24(9):1967-1977. DOI: 10.1016/j.gim.2022.05.007

2. Colvin R B, Chang A, Cornell L.D. Diagnostic Pathology Diseases 4e Copyright © 2023 by Elsevier ISBN: 978-0-443-10717-7

3. Han M, Criado E. Renal artery stenosis and aneurysms associated with neurofibromatosis. J Vasc Surg. 2005;41(3):539-543. DOI: 10.1016/j.jvs.2004.12.021.

4. Rhee H, Kim S, Lee W et al. Immunoglobulin A nephropathy in a patient with neurofibromatosis type 1: A case report and literature review. Medicine (Baltimore). 2021;100(42):e27572. DOI: 10.1097/MD.0000000000027572.

5. Mandybur TI, Weiss MA. Sclerosing peritubular nodules: a hereditary renal abnormality in von Recklinghausen’s disease. Hum Pathol 1981; 12: 704-712

6. Gökden N, El Jamal S, Gökden M, Lamps LW. Renal sclerosing peritubular nodules in a patient with neurofibromatosis type 2: a case report with immunohistochemical and electron microscopic studies. Hum Pathol. 2009;40(11):1650-1654. DOI: 10.1016/j.humpath.2009.04.014.

7. Thomas S, Pahoff C, McClymont K, Parnham A. Renal sclerosing peritubular nodule-how rare is it? Clin Kidney J. 2013;6(4):426-428. DOI: 10.1093/ckj/sft056.

8. Salman LA, Kallis C, Palmer M et al. New-Onset Proteinuria in a Patient With Schwannoma. American Journal of Kidney Diseases, 2021;78(3):A12-A15, ISSN 0272-6386, DOI: 10.1053/j.ajkd.2021.03.031.

9. Wu S, Kim C, Baer L, Zhu X. Bevacizumab increases risk for severe proteinuria in cancer patients. J Am Soc Nephrol. 2010;21(8):1381-1389. DOI: 10.1681/ASN.2010020167.

10. Yahata M, Nakaya I, Sakuma T et al. Immunoglobulin A nephropathy with massive paramesangial deposits caused by antivascular endothelial growth factor therapy for metastatic rectal cancer: a case report and review of the literature. BMC Res Notes 2013; 6: 450. DOI: 10.1186/1756-0500-6-450

11. Endo Y, Negishi K, Hirayama K et al. Bevacizumab-induced immunoglobulin A vasculitis with nephritis: A case report. Medicine 2019;98(45):p e17870. DOI: 10.1097/MD.0000000000017870

12. Izzedine H, Escudier B, Lhomme C et al. Кidney diseases associated with anti-vascular endothelial growth factor (VEGF): an 8-year observational study at a single center. Medicine (Baltimore). 2014;93(24):333-339. DOI: 10.1097/MD.0000000000000207.