ArticleJournal of the American Society of Nephrology : JASN2020
Only Hyperuricemia with Crystalluria, but not Asymptomatic Hyperuricemia, Drives Progression of Chronic Kidney Disease.
Article in Journal of the American Society of Nephrology : JASN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Macrophages in Renal Injury, Repair, Fibrosis Following Acute Kidney Injury and Targeted Therapy.Frontiers in immunology · 2022Pooled it
- Impact of adding urine alkalization therapy to xanthine oxidase inhibitor in gout management: a prospective cohort study.Rheumatology (Oxford, England) · 2025Trial
- A treat-to-target urate management strategy does not improve kidney outcome in patients with chronic kidney disease and asymptomatic hyperuricemia: a target trial emulation.Annals of medicine · 2026Article
- Tubulointerstitial inflammation in glomerular diseases: mechanistic pathways, prognostic value, and translational therapeutic targets.Renal failure · 2026Review
- Association between serum uric acid level and cataract Arisk: A cross-sectional study based on two databases (CHARLS and NHANES).The Journal of international medical research · 2026Article
- Soluble uric acid suppresses neutrophil-mediated host defense in sepsis.Nature communications · 2026Article
- Review
- Metabolic and inflammatory mechanisms in uric acid-induced tubular dysfunction: Emerging perspectives.Clinics (Sao Paulo, Brazil) · 2026Article
- Efficacy and Safety of Dotinurad in Patients with Advanced Chronic Kidney Disease.Internal medicine (Tokyo, Japan) · 2026Observational
- Back to the Physiology: Renal Tubular Handling of Uric Acid and Emerging Strategies for Managing Hyperuricemia.Internal medicine (Tokyo, Japan) · 2026Review
- Uric acid-based nutritional and inflammatory biomarkers for predicting cardiovascular-kidney-metabolic syndrome and mortality: a population-based study with external validation.Frontiers in endocrinology · 2026Article
- Increased serum uric acid-to-urinary urate excretion ratio with the kidney function decline in male CKD patients without diabetes: a retrospective cohort study.BMC nephrology · 2025Article
- Inflammation in cardiovascular-kidney-metabolic syndrome: key roles and underlying mechanisms-a comprehensive review.Molecular and cellular biochemistry · 2025Review
- Mild Hyperuricemia Attenuates Salt-Sensitive Hypertension and Kidney Damage.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Hyperuricemia in Chronic Kidney Disease: Emerging Pathophysiology and a Novel Therapeutic Strategy.International journal of molecular sciences · 2025Review
- Dynamic changes in metabolic syndrome components and chronic kidney disease risk: a population-based prospective cohort study.BMC endocrine disorders · 2025Article
- Machine learning-based prediction models for renal impairment in Chinese adults with hyperuricaemia: risk factor analysis.Scientific reports · 2025Article
- Comparative assessment of the effects of dotinurad and febuxostat on the renal function in chronic kidney disease patients with hyperuricemia.Scientific reports · 2025Article
- Serum amino acid alterations in hyperuricemia: potential targets for renal disease prevention.Amino acids · 2025Article
- Gut microbiota-derived SCFAs and MetS-related nephropathy.Frontiers in nutrition · 2025Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe roles of asymptomatic hyperuricemia or uric acid (UA) crystals in CKD progression are unknown. Hypotheses to explain links between UA deposition and progression of CKD include that (
methodsMALDI-FTICR mass spectrometry, immunohistochemistry, 3D confocal microscopy, and flow cytometry were used to characterize a novel mouse model of hyperuricemia and chronic UA crystal nephropathy with granulomatous nephritis. Interventional studies probed the role of crystal-induced inflammation and macrophages in the pathology of progressive CKD.
resultsAsymptomatic hyperuricemia alone did not cause CKD or drive the progression of aristolochic acid I-induced CKD. Only hyperuricemia with UA crystalluria due to urinary acidification caused tubular obstruction, inflammation, and interstitial fibrosis. UA crystal granulomas surrounded by proinflammatory M1-like macrophages developed late in this process of chronic UA crystal nephropathy and contributed to the progression of pre-existing CKD. Suppressing M1-like macrophages with adenosine attenuated granulomatous nephritis and the progressive decline in GFR. In contrast, inhibiting the JAK/STAT inflammatory pathway with tofacitinib was not renoprotective.
conclusionsAsymptomatic hyperuricemia does not affect CKD progression unless UA crystallizes in the kidney. UA crystal granulomas develop late in chronic UA crystal nephropathy and contribute to CKD progression because UA crystals trigger M1-like macrophage-related interstitial inflammation and fibrosis. Targeting proinflammatory macrophages, but not JAK/STAT signaling, can attenuate granulomatous interstitial nephritis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.