A patient diagnosed with hereditary transthyretin amyloidosis (hATTR) developed nephrotic syndrome due to treatment with inotersen (Tegsedi®), as published in the American Journal of Kidney Diseases.

“This case indicates that agents such as patisiran, or the recently approved vutrisiran, which are not associated with nephrotoxicity, may be preferred in patients with renal hATTR,” the authors wrote.

The patient was diagnosed in her early 30s with hATTR with dominant neuropathic involvement. At the time, she had a 2-year history of progressive peripheral and autonomic neuropathy. She also had family history of p.V50M variant-associated hATTR, including 2 first-degree relatives who underwent liver transplantation. Neither she nor her relatives had a history of renal disease.

She had amyloid in her kidneys but no evidence of cardiac amyloidosis. She had no history of renal disease. Her treatment included amitriptyline for neuropathic pain, inotersen, and vitamin A supplementation.

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Eight months after her diagnosis, she was admitted to the hospital with a 2-week history of shortness of breath, facial swelling, and leg edema. Further examination and analyses suggested nephrotic syndrome. Native renal biopsy revealed alterations in several glomeruli. Molecular analysis of amyloid deposition areas confirmed the ATTR origin.

“Subsequent renal histology identified only small amounts of mesangial amyloid deposition and withdrawal of inotersen alone (without immunosuppressive therapy) led to resolution of nephrotic syndrome and a fall in proteinuria back to baseline levels within a few months, suggesting a causal relationship between inotersen and our patient’s presentation,” the authors explained.

Two months after she discontinued inotersen and began furosemide as supportive treatment, her condition improved. However, after a break in therapy, she experienced a gradual progression of neuropathy, and patisiran (Onpattro®) was initiated as treatment.


Law S, Arnold J, Rauf MU, et al. Focal segmental glomerulosclerosis complicating therapy with inotersen, an antisense oligonucleotide inhibitor: a case report. Am J Kidney Dis. Published online October 10, 2022. doi:10.1053/j.ajkd.2022.08.018