Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis

Abstract

Aims: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1 cytoprotective pathway. In this review, a meta-analysis and systematic review of the renoprotective effects of SFN were performed in various preclinical models of kidney diseases.

Main methods: The primary outcome was the impact of SFN on renal function biomarkers (uremia, creatininemia, proteinuria or creatinine clearance) and secondary outcomes were kidney lesion histological indices/kidney injury molecular biomarkers. The effects of SFN were evaluated according to the standardized mean differences (SMDs). A random-effects model was applied to estimate the overall summary effect.

Key findings: Twenty-five articles (out of 209 studies) were selected from the literature. SFN administration significantly increased creatinine clearance (SMD +1.88 95 % CI: [1.09; 2.68], P < 0.0001, I² = 0 %) and decreased the plasma creatinine (SMD -1.24, [-1.59; -0.88], P < 0.0001, I² = 36.0 %) and urea (SMD -3.22 [-4.42, -2.01], P < 0.0001, I² = 72.4 %) levels. SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD -2.20 [-2.68; -1.73], P < 0.0001, I² = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I² = 73.7 %) and glomerulosclerosis (SMD -2.24 [-2.96; -1.53], P < 0.0001, I² = 9.7 %) and decreased kidney injury molecular biomarkers (SMD -1.51 [-2.00; -1.02], P < 0.0001, I² = 0 %).

Significance: These findings provide new insights concerning preclinical strategies for treating kidney disease or kidney failure with SFN supplements and should stimulate interest in clinical evaluations of SFN in patients with kidney disease.

Keywords: Acute kidney injury; Animal model; Chronic kidney disease; Cisplatin; Creatinine; D,L sulforaphane; Gentamicin; Nephroprotection; Preclinical study; Renal failure; Sulforaphane; Urea.