Woman in 30s With FAP Develops Kidney Disease Due to Tegsedi: Case
Patient's kidney disease resolved after stopping weekly Tegsedi injections
A woman with familial amyloid polyneuropathy (FAP) developed a type of kidney disease called focal segmental glomerulosclerosis — characterized by scarring in the kidneys — several months after starting treatment with Tegsedi (inotersen), according to a recent case report.
Once the patient stopped taking Tegsedi, the kidney disease resolved, indicating that the medication was the cause of the problem. Based on this and other cases, researchers speculated the risk of Tegsedi-induced kidney disease may be highest in FAP patients who have underlying kidney involvement.
“Monitoring of [kidney] function is essential in patients with [FAP] receiving [Tegsedi], particularly if there is evidence of existing” kidney problems, the researchers wrote.
The report, “Focal Segmental Glomerulosclerosis Complicating Therapy With Inotersen, an Antisense Oligonucleotide Inhibitor: A Case Report,” was published in the American Journal of Kidney Diseases.
Tegsedi is an approved treatment for FAP that works by lowering the production of the abnormal TTR protein that causes the disease. In clinical trials, an inflammatory kidney disease called crescentic glomerulonephritis was reported as an uncommon side effect of the medication.
First case report
Now, a team of scientists in the U.K. described the case of a woman in her early 30s who had been diagnosed with FAP and started treatment with Tegsedi soon after. Notably, when she was diagnosed, tests indicated she had a buildup of TTR deposits in her kidneys, though she did not have noteworthy signs of kidney dysfunction.
Seven months after starting treatment with Tegsedi, the woman sought medical attention after developing shortness of breath and swelling in her face and legs.
Laboratory tests showed high levels of protein, blood, and white blood cells in the patient’s urine, suggesting kidney impairment. This prompted a kidney biopsy, which led to a diagnosis of focal segmental glomerulosclerosis — a kidney disease whose hallmark signs are scarring in the blood-filtering compartments of the kidneys, which are called glomeruli.
“To our knowledge, this is the first case report of focal segmental glomerulosclerosis complicating treatment of [FAP] with [Tegsedi],” the researchers wrote.
After kidney disease was identified, the patient stopped taking Tegsedi, and was started on additional supportive treatments to manage the swelling she was experiencing. After discontinuing the medication, her kidney function returned to normal within a few months, suggesting Tegsedi was the direct cause of her kidney problems.
The woman was later started on Onpattro (patisiran), another approved FAP treatment.
Researchers noted that, like this patient, participants in NEURO-TTR (NCT01737398) study — a previous Phase 3 clinical trial of Tegsedi — who developed kidney disease had pre-existing TTR kidney involvement. All of these individuals also carried the same disease-causing mutation, called p.V50M, which has been associated with kidney disease.
This underlying disease may be a risk factor for the development of kidney disease in patients treated with Tegsedi, the team speculated.
“Risk of [Tegsedi]-induced nephrotoxicity [kidney toxicity] should be borne in mind when considering TTR-lowering therapy for [FAP],” they concluded.
Tegsedi was developed by Ionis Pharmaceuticals, which was not involved in this study, though one of the study co-authors disclosed having received funding from Ionis and other companies in the past.