ArticleThe Journal of clinical investigation2021
Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 111 citations in OpenAlex.
- Renoprotective effects of gut NHE3 inhibitor tenapanor in a rat model of unilateral renal ischemia-reperfusion injury with contralateral nephrectomy.Biochemistry and biophysics reports · 2026Article
- Calcium Crystal Deposits in Kidney Allografts: The Interplay of PTH Levels and Phosphaturia.Kidney medicine · 2026Article
- Transforming growth factor-β in kidney disease in dogs and cats: a review of the evidence of its role in renal fibrosis.Journal of veterinary internal medicine · 2026Review
- From cross-section to prognosis: risk factors for renal function deterioration in primary hyperparathyroidism.Endocrine journal · 2026Article
- Article
- Phosphaturia Exacerbates Tubular Injury and Cyst Formation in Polycystic Kidney Disease.Kidney360 · 2026Article
- Acute severe hyperphosphatemia and secondary hypocalcemia after phosphate enema administration in a constipated post-trauma patient recovering from pelvic surgery: a case report.Journal of surgical case reports · 2026Article
- Renal tubular calcium phosphate microcrystallopathy and age-related kidney function decline: The Aging Kidney Study.Clinical kidney journal · 2026Article
- Dietary phosphate exposure-strategies to protect vulnerable population groups.Archives of toxicology · 2026Review
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- Calciprotein particles in cats with naturally occurring chronic kidney disease.Journal of veterinary internal medicine · 2026Article
- The renal response to FGF23 shifts from phosphaturia toward inflammation in kidney disease.Journal of cell communication and signaling · 2026Article
- Elevated FGF23 Despite Biochemical Control Reveals Hidden Mineral Dysregulation in Chronic Hypoparathyroidism.Journal of the Endocrine Society · 2026Article
- Cell Calcification Models and Their Implications for Medicine and Biomaterial Research.Advanced healthcare materials · 2026Review
- Fibroblast Growth Factor 23, Urinary Phosphate, and Risk of Progression of CKD.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Bone mineral loss damages renal tubules in mice.Communications biology · 2026Article
- Circulating fibroblast growth factor 23 and physical performance in middle-aged and older adults with normal kidney function.Scientific reports · 2025Article
- The Aging Kidney and Exercise Training Study: protocol for a randomized controlled trial within cohorts (TwiCs) study.BMC nephrology · 2025Article
- Exploring the relationship between serum magnesium levels, genetic variants and chronic kidney disease: a prospective study.Clinical kidney journal · 2025Article
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 7 institutions in 2 countries.
Funding
Abstract
The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.
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Registered trials
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.