Renal Function Decline With Small Interfering RNA Silencing Aminolevulinic Acid Synthase 1 (ALAS1)
Hélène Lazareth1, Antoine Poli2,3, Yohan Bignon4
1Service de Néphrologie, Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, France.
Kidney International Reports
|July 26, 2021
Summary
Givosiran treatment for acute intermittent porphyria (AIP) caused a temporary decline in kidney function in most patients. Long-term effects on renal function require further investigation.
Area of Science:
- Nephrology
- Pharmacology
- Genetics
Background:
- Givosiran is an RNA interference therapy targeting aminolevulinic acid (ALA) synthase 1 (ALAS1) in acute intermittent porphyria (AIP).
- Potential adverse renal effects of givosiran warrant investigation.
Purpose of the Study:
- To assess the impact of givosiran on renal function in AIP patients.
- To evaluate short-term and long-term changes in kidney function parameters.
Main Methods:
- A descriptive case series analyzed renal function in 20 French patients treated with givosiran (March 2018-July 2020).
- Patients included those from the ENVISION trial and a rare disease network.
Main Results:
- Ninety percent of patients experienced a transient decrease in renal function within 3 months of starting givosiran.
- No patients developed acute kidney injury; long-term follow-up showed variable estimated glomerular filtration rate (eGFR) changes.
- Kidney biopsy in one patient revealed no active disease or abnormal ALAS1 expression.
Conclusions:
- Givosiran is linked to a transient, moderate serum creatinine increase without evidence of kidney injury.
- Long-term renal impact of ALAS1 inhibition remains uncertain due to AIP's association with chronic kidney disease.
Keywords:
acute intermittent porphyriaacute kidney injurychronic kidney diseasegivosiranrenal functionMore Related Videos
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