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Excessive phosphate loading within the proximal tubular lumen has been proposed as a key mechanism driving progression of chronic kidney disease (CKD) through calcium phosphate microcrystallopathy. Researchers at the University of Tsukuba demonstrated that individuals with higher estimated proximal tubular fluid phosphate (ePTFp) concentration—a noninvasive index derived from blood and urine measurements—experience a more rapid age-related decline in kidney function. These findings suggest that ePTFp may serve as a useful marker for predicting CKD progression.

Tsukuba, Japan—In Japan's super-aging population, the burden of CKD continues to rise, underscoring the need for early prediction of individuals at risk and timely preventive strategies. Based on experimental evidence that high phosphate concentrations injure renal tubular cells, the investigators hypothesized that elevated phosphate concentrations in primary urine—reflected by increased ePTFp concentrations in the proximal tubule lumen—would be associated with an accelerated age-related decline in kidney function.

The study included 308 participants, comprising community-dwelling residents of Ibaraki Prefecture and patients with CKD. ePTFp concentrations were calculated using a validated formula based on serum creatinine, urinary creatinine, and urinary phosphate levels. Kidney function was assessed longitudinally over a 5-year period. Participants with higher baseline ePTFp concentrations exhibited a significantly steeper decline in kidney function over time. This association remained significant after adjusting for age, sex, baseline estimated glomerular filtration rate, comorbidities, and urinary markers of kidney injury, including albuminuria.

Notably, the association persisted even when serum phosphate concentrations were within the normal range, suggesting that intratubular phosphate exposure—rather than circulating phosphate alone—may contribute to accelerated age-related kidney function decline. These findings provide clinical support for mechanisms previously identified in cellular and animal studies and highlight a potentially under-recognized contributor to kidney aging. Assessing ePTFp concentrations may advance understanding of CKD pathophysiology, improve risk stratification, and inform strategies to prevent or slow CKD progression.

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This study was supported by a project grant from the Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology, the Cross-ministerial Strategic Innovation Promotion Program (grant no. 23gm1510012h0001), and the Japan Society for the Promotion of Science (grant nos. 23K24728 and 25K03003). Keisei Kosaki was supported by the MEXT Leading Initiative for Excellent Young Researchers (grant no. JPMXS0320200234).

Original Paper

Title of original paper:

Renal tubular calcium phosphate microcrystallopathy and age-related kidney function decline: the aging kidney study

Journal:

Clinical Kidney Journal

DOI:

10.1093/ckj/sfag085

Correspondence

Assistant Professor KOSAKI Keisei
Institute of Health and Sport Sciences, University of Tsukuba

Professor Emeritus KURO-O Makoto
Division of Mineral Metabolism, Center for Molecular Medicine, Jichi Medical University

Related Link

Institute of Health and Sport Sciences