Gold nanomaterials in the diagnosis and treatment of kidney diseases: from fundamental transport mechanisms to clinical translation prospects

With the continuously increasing global incidence of kidney diseases, traditional diagnostic and therapeutic approaches face significant limitations, including low sensitivity, poor specificity, and substantial drug-related side effects. Gold nanomaterials, owing to their unique physicochemical properties, tunable size and surface chemistry, and favorable biocompatibility, have opened new avenues for the precision diagnosis and treatment of kidney diseases. This review systematically examines the kinetic principles governing the transport of gold nanomaterials across renal physiological barriers, delving into the decisive influence of size, shape, surface charge, and protein corona effects on their in vivo fate. Building on this foundation, we elaborate on cutting-edge research progress involving gold nanomaterials as optical/CT/multimodal imaging contrast agents, drug/gene delivery vectors, photothermal/photodynamic therapeutic agents, and direct therapeutic nanomedicines across various disease models, including acute kidney injury, chronic kidney disease, renal fibrosis, and renal cell carcinoma. Concurrently, this review provides an in-depth analysis of the biosafety profile of gold nanomaterials, summarizing the impact of factors such as dosage, size, and surface modification on their toxicity spectrum and the underlying molecular mechanisms. Critically, we highlight the often overlooked liver kidney axis as a pivotal determinant of AuNP biotransformation and clearance, and we discuss the unresolved “targeting versus clearance” conundrum that complicates clinical translation. Finally, we discuss the primary challenges facing clinical translation in this field—including the absence of standardized toxicity assessment protocols and the reproducibility hurdles in large scale manufacturing—and offer perspectives on future research directions, such as the development of “smart” nanoplatforms responsive to the disease microenvironment and the application of multi-omics technologies to guide personalized diagnosis and treatment in the context of the burgeoning epidemic of metabolism associated kidney disease.