〔Abstract〕 Objective To investigate the mechanism of long non-coding ribonucleic acid (LncRNA) human myodynamin phosphatase homologous pseudogene 1 (TPTEP1)/microrna-137 (miR-137)/Kruppel-like factor 15 (KLF15) axis in obesity-related nephropathy (ORKD). Methods A total of 20 patients with ORKD hospitalized from the First Affiliated Hospital of Gannan Medical University from February 2022 to January 2024 were selected as the ORKD group, and 20 patients with non-ORKD hospitalized during the same period were selected as the control group. Blood samples were collected for biochemical examination, and pathological changes of renal biopsy specimens were examined by immunohistochemistry and electron microscopy. The bioinformatics tools were used to compare and analyze the expression levels of KLF15 messenger ribonucleic acid (mRNA) in ORKD tissues and normal renal tissues, and enzyme-linked immunosorbent assay was used to analyze serum adiponectin and leptin levels. Results The levels of serum creatinine (Scr), uric acid (UA) and 24h urinary protein (24H-UTP) in ORKD group were higher than those in the control group, with statistical significances (P < 0.05). Compared with the control group, the expressions of KLF15 in renal tissue and serum adiponectin level in the ORKD group were significantly reduced compared to the control group, while the level of leptin was significantly increased, and the differences were statistically significant (P < 0.05). After LncRNA screening by high-throughput sequencing, it was found that the expression of ENSG00000100181.15 in ORKD group was significantly different, and miR-137 may be the target gene of LncRNA TPTEP1, which was expressed in various tissues of the body, including kidney and adipose tissue. Conclusion The abnormal function of KLF15 in ORKD renal tissue and adiponectin may be related to the development of the disease, and the LncRNA TPTEP1/ miR-137 /KLF15 axis plays an important role in the development of ORKD.