Law, Steven;
Arnold, Julia;
Rauf, Muhammad U;
Heptinstall, Lauren;
Gilbertson, Janet;
Rowczenio, Dorota;
Baharani, Jyoti;
... Gillmore, Julian D; + view all
(2022)
Focal Segmental Glomerulosclerosis Complicating Therapy With Inotersen, an Antisense Oligonucleotide Inhibitor: A Case Report.
American Journal of Kidney Diseases
10.1053/j.ajkd.2022.08.018.
(In press).
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Abstract
Inotersen is an antisense oligonucleotide inhibitor licensed for the treatment of polyneuropathy complicating hereditary transthyretin amyloidosis (ATTRv). Nephrotoxicity has been reported with inotersen, including progression to end stage renal disease. We describe the first reported case of inotersen-associated nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS) and review the literature concerning inotersen-induced nephrotoxicity. We report a woman in her early 30s with ATTRv associated with the (p.V50M) transthyretin (TTR) variant, who presented with nephrotic syndrome 7 months after commencement of inotersen. Renal histology demonstrated focal segmental glomerulosclerosis and scanty glomerular amyloid deposition. Discontinuation of inotersen alone resulted in complete clinical and biochemical resolution of nephrotic syndrome. Inotersen is associated with significant nephrotoxicity. In the phase III NEURO-TTR clinical trial, 3% of patients in the treatment arm developed a crescentic glomerulonephritis. All affected patients carried the (p.V50M) TTR variant which is known to be associated with renal amyloid deposition. This case adds to spectrum of renal disease associated with inotersen and indicates that discontinuation of the drug alone may result in resolution of renal complications without additional immunosuppression. Monitoring of renal function is essential in patients with ATTRv receiving inotersen, particularly if there is evidence of existing renal amyloid.
| Type: | Article |
|---|---|
| Title: | Focal Segmental Glomerulosclerosis Complicating Therapy With Inotersen, an Antisense Oligonucleotide Inhibitor: A Case Report |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1053/j.ajkd.2022.08.018 |
| Publisher version: | https://doi.org/10.1053/j.ajkd.2022.08.018 |
| Language: | English |
| Additional information: | © 2022 Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | Amyloidosis, antisense oligonucleotide inhibitor, glomerulonephritis, inotersen, transthyretin |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10157513 |
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