title: The serum uric acid concentration is not causally linked to diabetic nephropathy in type 1 diabetes.
abstract: Previous studies have shown a relationship between uric acid concentration and progression of renal disease. Here we studied causality between the serum uric acid concentration and progression of diabetic nephropathy in 3895 individuals with type 1 diabetes in the FinnDiane Study. The renal status was assessed with the urinary albumin excretion rate and estimated glomerular filtration rate (eGFR) at baseline and at the end of the follow-up. Based on previous genomewide association studies on serum uric acid concentration, 23 single nucleotide polymorphisms (SNPs) with good imputation quality were selected for the SNP score. This score was used to assess the causality between serum uric acid and renal complications using a Mendelian randomization approach. At baseline, the serum uric acid concentration was higher with worsening renal status. In multivariable Cox regression analyses, baseline serum uric acid concentration was not independently associated with progression of diabetic nephropathy over a mean follow-up of 7 years. However, over the same period, baseline serum uric acid was independently associated with the decline in eGFR. In the cross-sectional logistic regression analyses, the SNP score was associated with the serum uric acid concentration. Nevertheless, the Mendelian randomization showed no causality between uric acid and diabetic nephropathy, eGFR categories, or eGFR as a continuous variable. Thus, our results suggest that the serum uric acid concentration is not causally related to diabetic nephropathy but is a downstream marker of kidney damage.
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Finland.
authors.forename: Aila J
authors.initials: AJ
authors.lastname: Ahola
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Finland.
authors.forename: Niina
authors.initials: N
authors.lastname: Sandholm
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Finland.
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Finland; Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Valma
authors.initials: V
authors.lastname: Harjutsalo
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Finland.
authors.forename: Emma
authors.initials: E
authors.lastname: Dahlström
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Research Program Unit, Diabetes and Obesity, University of Helsinki, Finland; Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. Electronic address: per-henrik.groop@helsinki.fi.
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid
keywords: Mendelian randomization; diabetic nephropathy; serum uric acid; type 1 diabetes