Renoprotective effects of SGLT2 inhibitors in patients with Fabry disease

IF 1.9 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports Pub Date : 2025-10-17 DOI:10.1016/j.ymgmr.2025.101271

Hayaki Okamoto, Shunsuke Goto, Mika Fujita, Hideki Fujii

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引用次数: 0

Abstract

Background

Fabry disease (FD) is a rare X-linked lysosomal storage disorder characterized by globotriaosylceramide (Gb3) accumulation, resulting in kidney and cardiac dysfunction. Although enzyme replacement therapy (ERT) and chaperone therapy are the standard therapies, progression of renal decline persists. Sodium–glucose co-transporter 2 (SGLT2) inhibitors exert renoprotective effects in chronic kidney disease (CKD), but their efficacy in FD remains unknown.

Methods

We retrospectively analyzed data of 10 patients with FD treated with SGLT2 inhibitors and compared their renal outcomes to 18 patients with CKD without FD. The estimated glomerular filtration rate (eGFR) slope, urinary albumin-to-creatinine ratio (UACR), and plasma brain natriuretic peptide (BNP) levels were assessed 1 year before and after initiating SGLT2 inhibitor therapy. Linear mixed-effects models were employed for statistical analysis.

Results

In patients with FD, the annual eGFR decline significantly improved from −4.38 mL/min/1.73 m²/year (IQR: −10.57 to 0.59) before treatment to 1.25 (IQR: −4.16 to 9.74) after treatment (p < 0.05). This improvement remained significant after adjusting for confounding factors. In contrast, the annual eGFR decline in patients with CKD without FD also tended to improve, albeit without significance. Notably, the initial eGFR decline usually seen with SGLT2 inhibitors in CKD was not observed in the FD cohort. UACR and plasma BNP levels remained unchanged after SGLT2 inhibitor therapy.

Conclusions

SGLT2 inhibitors substantially attenuated the decline in eGFR in patients with FD. These findings support their potential as a renoprotective adjunct in the management of FD.

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SGLT2抑制剂对Fabry病患者的肾保护作用

法布里病（FD）是一种罕见的x连锁溶酶体贮积疾病，其特征是globotriaosylceramide （Gb3）积聚，导致肾脏和心脏功能障碍。虽然酶替代疗法（ERT）和伴侣疗法是标准的治疗方法，肾脏衰退的进展仍然存在。钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂在慢性肾脏疾病（CKD）中发挥肾脏保护作用，但其在FD中的功效尚不清楚。方法回顾性分析10例接受SGLT2抑制剂治疗的FD患者的数据，并将其与18例无FD的CKD患者的肾脏预后进行比较。在开始SGLT2抑制剂治疗前后1年评估肾小球滤过率（eGFR）斜率、尿白蛋白与肌酐比值（UACR）和血浆脑钠肽（BNP）水平。采用线性混合效应模型进行统计分析。结果FD患者eGFR年下降率由治疗前的- 4.38 mL/min/1.73 m2/年（IQR: - 10.57 ~ 0.59）显著改善至治疗后的1.25 (IQR: - 4.16 ~ 9.74) （p < 0.05）。在调整混杂因素后，这种改善仍然显著。相比之下，没有FD的CKD患者的eGFR年下降也有改善的趋势，尽管没有显著性。值得注意的是，在FD队列中没有观察到CKD患者通常使用SGLT2抑制剂时出现的初始eGFR下降。SGLT2抑制剂治疗后UACR和血浆BNP水平保持不变。结论ssglt2抑制剂可显著减轻FD患者eGFR的下降。这些发现支持了它们在FD治疗中作为肾保护辅助药物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics and Metabolism Reports Biochemistry, Genetics and Molecular Biology-Endocrinology

CiteScore

4.00

自引率

5.30%

发文量

105

审稿时长

33 days

期刊介绍： Molecular Genetics and Metabolism Reports is an open access journal that publishes molecular and metabolic reports describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, sequence reports, brief communication reports and letters to the editor are considered.