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We examined the association of the G allele in the single-nucleotide polymorphism (SNP) rs738409 in the third exon of patatin-like phospholipase domain-containing 3 gene (PNPLA3) gene, with chronic kidney disease in diabetes endotypes. Participants with recent-onset diabetes (n = 707) from the prospective German Diabetes Study (GDS) underwent cluster assignment, detailed phenotyping, genotyping and magnetic resonance spectroscopy to quantify hepatocellular lipid content (HCL). Severe insulin-resistant diabetes (SIRD) had the lowest glomerular filtration rates (eGFR) and highest HCL compared to severe insulin-deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes endotypes (all p < 0.05). HCL was negatively associated with eGFR (r = −0.287, p < 0.01) across all groups. Stratification by G-allele carrier status did not reveal any association between HCL and eGFR among the endotypes. However, the proportion of G-allele carriers increased from 44 % for eGFR >60 ml/min to 52 % for eGFR <60 ml/min (p < 0.05). The PNPLA3 polymorphism may contribute to declining kidney function independently of liver lipids. • Diabetes subtypes differ in risk for chronic kidney disease. • Genetic traits hallmark severe insulin resistant diabetes. • Genetic variation may contribute to declining kidney function in diabetes. [ABSTRACT FROM AUTHOR]