Calcium phosphate crystals and kidney damage in animals and people
What it found
Tiny calcium phosphate crystals formed inside kidney tubes when phosphate levels were high, damaging the kidneys in mice.
In 5039 people followed for 5 years, higher blood levels of a hormone linked to phosphate handling predicted more kidney problems.
What they found
Studies in people
Hormone threshold in people
In 148 people with varying kidney function, blood levels of the hormone FGF23 started rising once the estimated phosphate concentration in the kidney tubes passed 2.32 mg/dL. The authors say people with FGF23 above 53 pg/mL have likely already developed kidney tube damage.
FGF23 predicted kidney problems
Among 5039 people followed for 5 years, those starting with FGF23 above 53 pg/mL had more kidney events than those below it. Kidney events happened in 3.2% of the higher group (86 of 2703 patients) and 0.6% of the lower group (14 of 2336 patients).
Animal and lab studies
Crystals damaged kidney cells
In lab tests using human kidney cells, raising phosphate levels created tiny calcium phosphate crystals. These crystals killed the cells, but removing the crystals from the liquid stopped the damage.
High-phosphate diet harmed mice
Mice fed a diet with 2.0% phosphate for 8 to 9 days developed many calcium phosphate crystals inside their kidney tubes. Mice on a regular 0.35% phosphate diet did not have these crystals.
Blocking crystals protected kidneys
Giving mice a drug called alendronate stopped the crystals from forming in the kidney tubes. Making the urine more acidic with ammonium chloride also reduced the crystals and lessened kidney scarring in the animals.
What the authors conclude
- They suggest that calcium phosphate particles in the kidney tubes are a useful target for slowing down kidney damage during aging and disease.
- The authors propose that limiting phosphate intake could help older adults and early-stage kidney patients whose FGF23 levels are above 53 pg/mL.
- They call for controlled clinical trials to test whether lowering phosphate intake actually prevents further kidney damage.
How it was done
Western diets contain a lot of phosphate, but scientists do not yet know much about how too much phosphate might harm the kidneys. The authors wanted to find out exactly how dietary phosphate damages kidney tissue and whether this could be stopped.
They grew human kidney cells in dishes with different amounts of phosphate and fed mice diets containing 0.35%, 1.0%, 1.5%, or 2.0% phosphate for up to 12 weeks. They also measured a hormone called FGF23 in 148 kidney patients and followed 5039 people for 5 years to track kidney problems.
What it can’t tell you
- This study followed people over time, so it can show a link between higher FGF23 levels and kidney problems but cannot prove one causes the other.
- Most of the detailed work on how calcium phosphate crystals form and cause damage was done in mice and lab dishes, which may not match exactly what happens in human bodies.
Who paid
- Funding
- Funded by NIA NIH HHS; NIDDK NIH HHS (from the PubMed record).
- Conflicts
- Conflict of interest: The authors have declared that no conflict of interest exists.
- Authors work at
- Jichi Medical University, Japan; University of Tokyo, Japan; Department of Clinical Laboratory Medicine, and
The paper
- Title
- Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression
- Type
- Study
- Evidence
- Studies in people · animals · lab
- Summarised from
- Full text
- Cite
- Shiizaki K, Tsubouchi A, Miura Y, et al (2021). Calcium phosphate microcrystals in the renal tubular fluid accelerate chronic kidney disease progression. The Journal of clinical investigation. doi:10.1172/JCI145693Free full textPubMed 34185705DOI
Summary written 30 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error