Background: Diabetic kidney disease (DKD) is one of the main complications of diabetes, the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. The etiopathogenesis of DKD is complex and multifactorial; recently, genetic susceptibility has gained relevance since certain ethnicities, such as Native Americans and Mexican Americans, have a higher risk of developing this disease. Numerous studies have described that single nucleotide polymorphisms (SNPs), including those for ELMO1 and AGTR1 genes, could be associated with DKD. Objective: To carry out a systematic review of the scientific literature on the association of SNPs of the ELMO1 and AGTR1 gene with DKD in adult patients with type 2 diabetes mellitus (T2D). Methods: Systematic review in PubMed, Google Scholar, Worldwide Science, and Science Direct databases. The selection of publications was carried out following the guidelines proposed by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses). Original articles that reported results in the adult population with T2D were included. Information about the allelic and genotypic frequencies of the SNPs and their association with DKD was obtained. Results: The polymorphisms most frequently associated with a DKD higher risk were rs741301, rs1345365, and rs10951509 for the ELMO1 gene, whereas the rs5186 and rs388915 for the AGTR1 gene. Conclusion: The risk of developing DKD depends on several factors, including the genetic susceptibility conferred by the ELMO1 and AGTR1 gene polymorphisms, without ignoring the patient's lifestyle and environmental factors. The studies about these polymorphisms' association with DKD will allow a better understanding of non-modifiable risk factors for developing this disease and recognize the differences between different studied ethnicities, which would allow faster detection of patients with T2D susceptible to developing DKD, become early markers of kidney damage, as well as implementing preventive strategies on the most susceptible ethnicities. Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Nefrolog & imath;a. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).