Our results suggest a working model where obesity induces renal HA accumulation and CD44 and RHAMM expression, which activates the TGF-β1/Smad2/3, P38/JNK MAPK, and ROCK2/ERK/Akt pathways, promoting transcription of profibrotic and proinflammatory genes and contributing to the development of ORKP. This evidence concerns the gene TGFB1 and obesity due to melanocortin 4 receptor deficiency.