Meta-analysis: Sulforaphane reno-protective effects in animal models of kidney diseases

Research question: Does Sulforaphane present any reno-protective effects in pre-clinical animal models of kidney disease ?

Context and rationale: Chronic kidney disease (CKD) is characterized by the occurrence of kidney damage and progressive and irreversible
loss of kidney function. CKD constitutes an important public health problem worldwide since its prevalence is estimated
to be 10-16% in the World’s adult population. Many pharmacological strategies are being studied to improve the clinical
picture of these patients and prevent kidney failure. The Keap1-Nrf2 pathway is the major regulator of cytoprotective
responses to oxidative and cytotoxic stress. Keap1 (Kelch ECH associating protein 1), a repressor protein binds to Nrf2
and promotes its degradation by the ubiquitin proteasome pathway. The Keap1-Nrf2 pathway have received extensive
attention in the context of renal failure. In recent years, clinical studies were performed with bardoxolone methyl, a
potent inhibitor of Keap1, that proved to be efficient to prevent the decline of renal function in patients with diabetic
kidney disease, but unfortunately trials were stopped due to an increase in cardiovascular mortality. There is therefore a
growing interest to find other activator of Nrf2 system. Some natural compounds such as sulforaphane, present in many
vegetables such as cruciferous, are potent activator of Nrf2 pathway. Sulforaphane (SFN), a naturally-occurring
isothiocyanate enriched in cabbage and broccoli, has been tested in various animal models of kidney failure. This
systematic review intends to summarize the knowledges on this field and, if possible, meta-analyze the impact of
sulforaphane on renal outcomes especially biomarkers of renal function, in animal models of kidney disease. Evidencing
with the highest level of evidence the beneficial effects of sulforaphane on renal function in preclinical models could
stimulate the clinical interest for this compound and promote the implementation of clinical trials in patients with kidney
failure.

The present protocol was pre-registered on the open-access international prospective register of systematic reviews PROSPERO (https://www.crd.york.ac.uk/prospero/) under the registration number # CRD42022364229.