ArticlePLoS medicine2019
No causal effects of serum urate levels on the risk of chronic kidney disease: A Mendelian randomization study.
Article in PLoS medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 3 of them syntheses that pooled it.
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Who cites it
82 citing papers in PubMed, 3 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Hyperuricemia and the gut microbiota: current research hotspots and future trends.Frontiers in microbiology · 2025Pooled it
- Correlation does not equal causation: the imperative of causal inference in machine learning models for immunotherapy.Frontiers in immunology · 2025Pooled it
- Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease.Diabetologia · 2022Pooled it
- Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes.The New England journal of medicine · 2020Trial
- Urate-lowering therapy modifies associations between urinary urate and kidney outcome.Renal failure · 2026Article
- Risk factor analysis and predictive model construction and evaluation of fractional uric acid excretion in Chinese inpatients with type 2 diabetes.Scientific reports · 2026Article
- Review
- Moving Mendelian Randomization From Traditional Risk Factors to Molecular Targets for Drug Development and Clinical Trials in Nephrology.Kidney international reports · 2026Review
- Disentangling Uric Acid and Renal Pathways in SGLT2 Inhibitor Effects After Acute Myocardial Infarction: A Retrospective Mediation Analysis.Biomedicines · 2026Article
- Dynamic Uric Acid Changes and Outcomes in CKD in the African American Study of Kidney Disease and Hypertension.Kidney international reports · 2025Article
- Adipokines and Vascular Modulators in CKM: Emerging Biomarkers as Diagnostic and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Uric Acid Trajectories and CKD Progression in the African American Study of Kidney Disease and Hypertension.Kidney international reports · 2025Article
- Genetically predicted serum urate and cancer risk: a Mendelian randomization study.Scandinavian journal of rheumatology · 2025Article
- Genomic insertion of ancestral uricase into human liver cells to determine metabolic consequences of pseudogenization.Scientific reports · 2025Article
- Effectiveness of Allopurinol on Uric Acid and Pediatric Chronic Kidney Disease Severity in the Chronic Kidney Disease in Children Study.Kidney medicine · 2025Article
- Mendelian Randomization Studies: A Metric for Quality Evaluation.Gout, urate, and crystal deposition disease · 2025Article
- Machine learning-based prediction models for renal impairment in Chinese adults with hyperuricaemia: risk factor analysis.Scientific reports · 2025Article
- Serum amino acid alterations in hyperuricemia: potential targets for renal disease prevention.Amino acids · 2025Article
- Asymptomatic Hyperuricemia and the Kidney: Lessons from the URRAH Study.Metabolites · 2025Review
- Analysis of risk factors for abnormal renal function in patients with gout in Southwest China: a cross-sectional study.Rheumatology advances in practice · 2025Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundStudies have shown strong positive associations between serum urate (SU) levels and chronic kidney disease (CKD) risk; however, whether the relation is causal remains uncertain. We evaluate whether genetic data are consistent with a causal impact of SU level on the risk of CKD and estimated glomerular filtration rate (eGFR). METHODS AND
findingsWe used Mendelian randomization (MR) methods to evaluate the presence of a causal effect. We used aggregated genome-wide association data (N = 110,347 for SU, N = 69,374 for gout, N = 133,413 for eGFR, N = 117,165 for CKD), electronic-medical-record-linked UK Biobank data (N = 335,212), and population-based cohorts (N = 13,425), all in individuals of European ancestry, for SU levels and CKD. Our MR analysis showed that SU has a causal effect on neither eGFR level nor CKD risk across all MR analyses (all P > 0.05). These null associations contrasted with our epidemiological association findings from the 4 population-based cohorts (change in eGFR level per 1-mg/dl [59.48 μmol/l] increase in SU: -1.99 ml/min/1.73 m2; 95% CI -2.86 to -1.11; P = 8.08 × 10(-6); odds ratio [OR] for CKD: 1.48; 95% CI 1.32 to 1.65; P = 1.52 × 10(-11)). In contrast, the same MR approaches showed that SU has a causal effect on the risk of gout (OR estimates ranging from 3.41 to 6.04 per 1-mg/dl increase in SU, all P < 10-3), which served as a positive control of our approach. Overall, our MR analysis had >99% power to detect a causal effect of SU level on the risk of CKD of the same magnitude as the observed epidemiological association between SU and CKD. Limitations of this study include the lifelong effect of a genetic perturbation not being the same as an acute perturbation, the inability to study non-European populations, and some sample overlap between the datasets used in the study.
conclusionsEvidence from our series of causal inference approaches using genetics does not support a causal effect of SU level on eGFR level or CKD risk. Reducing SU levels is unlikely to reduce the risk of CKD development.
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