Plant-derived nanovesicles in kidney disease: emerging preclinical evidence and translational challenges.

Plant-derived nanovesicles (PDNVs) are lipid-bilayer nanoparticles isolated from plant extracellular fluids, juices, or tissues. Preparations obtained from disrupted tissues may contain both extracellular vesicles and membrane particles formed during processing, making product identity central to interpretation. Seven direct renal studies have examined native or engineered PDNVs in cisplatin- and sepsis-associated acute kidney injury, diabetic kidney disease, hyperuricemia-associated renal injury, and calcium oxalate nephrolithiasis. Current evidence supports three overlapping modes of use: renal cellular protection, oral modulation of intestinal and metabolic pathways, and engineered cargo delivery. Reported effects involve mitochondrial function, endoplasmic reticulum stress, ferroptosis, inflammation, microbiota, and host metabolism, but mechanistic support is uneven. SLC7A11 perturbation provides functional evidence for ferroptosis in one model, whereas most microbiota-metabolite-kidney relationships remain associative. Fluorescent tissue signals also do not establish intact-vesicle delivery or cell-specific kidney targeting. This review distinguishes direct renal PDNV evidence from adjacent plant-bioactive nanomedicines and phytochemical-modified mammalian extracellular vesicles, and critically examines product identity, preparation, dose, biodistribution, mechanism, safety, and clinical translation. No registered renal PDNV trial was identified; existing human studies concern nonrenal mucosal or intestinal applications and plant-vesicle-assisted cargo delivery. Progress toward renal translation will depend on reproducible manufacturing, mechanism-linked potency, quantitative biodistribution, causal validation, and repeated-dose safety.