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Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL gene variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by type I hyperlipoproteinemia due to LPL mutation. Renal biopsy was conducted to confirm the etiological factor of nephrotic syndrome in a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, and whole-exome sequencing were performed to confirm the dyslipidemia type and genetic factor. Analysis of the 3-dimensional protein structure and in vitro functional study were conducted to verify variant pathogenicity. Renal biopsy revealed numerous CD68 positive foam cells infiltrated in the glomeruli; immunoglobulin and complement staining were negative; and electron microscopy revealed numerous lipid droplets and cholesterol clefts in the cytoplasm of foam cells. Lipoprotein electrophoresis revealed that the patient fulfilled the diagnostic criteria of type I hyperlipoproteinemia. The apoE genotype of the patient was the ε3/ε3 genotype. Whole-exome sequencing revealed an LPL (c.292G > A, p.A98T) homozygous variant with α-helix instability and reduced post-heparin LPL activity but normal lipid uptake capability compared to the wild-type variant. LPL (c.292G > A, p.A98T) is a pathogenic variant that causes renal lipidosis associated with type I hyperlipoproteinemia. This study provides adequate evidence of the causal relationship between dyslipidemia and renal lesions. However, further research is needed to better understand the pathogenetic mechanism of LPL variant-related renal lesions. © 2023 International Society of Nephrology. Published by Elsevier Inc.

Citation

Hongyan Wu, Huan Xu, Song Lei, Zhi Yang, Shan Yang, Jingxue Du, Yi Zhou, Yunqiang Liu, Yuan Yang, Zhangxue Hu. Loss-of-Function Homozygous Variant in LPL Causes Type I Hyperlipoproteinemia and Renal Lipidosis. Kidney international reports. 2023 Nov;8(11):2428-2438


PMID: 38025240

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