We demonstrated that: (a) obese children with NAFLD had a small but significant deterioration of kidney function when compared to those without NAFLD; (b) the PNPLA3 rs738409 variant, but not those in TM6SF2, GCKR, and MBOAT7 genes, was associated with mildly decreased eGFR levels and higher albuminuria; (c) the PNPLA3 G allele had an impact on kidney function only in children with NAFLD; and (d) NAFLD, but not the PNPLA3 G allele, emerged as the major independent predictor of abnormal renal function in obese children. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.