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

Abstract Background and Hypothesis Elevated phosphate concentration in proximal tubular fluid promotes calcium phosphate microcrystallopathy, thereby accelerating the progression of chronic kidney disease (CKD). However, the clinical significance of proximal tubular phosphate exposure in humans remains uncertain. We aimed to determine whether estimated proximal tubular fluid phosphate concentration (ePTFp) is independently associated with age-related kidney function decline in adults with and without CKD. Methods We conducted a 5-year prospective cohort study involving 308 adults with and without CKD. ePTFp—a novel, noninvasive index—and serum fibroblast growth factor 23 (FGF23) concentrations were derived from blood and urine measurements. Kidney function decline, expressed as estimated glomerular filtration rate (eGFR) slope, was modeled using linear mixed-effects analysis. Associations of ePTFp and serum FGF23 with eGFR slope were examined using multivariable regression analysis, adjusting for potential covariates at baseline, including age, sex, several comorbidities, current smoking status, eGFR, and urinary glomerular and tubular injury markers. Results Over 5 years, eGFR declined in participants with and without CKD, with a steeper decline in those with CKD. Higher baseline ePTFp and serum FGF23 were inversely correlated with eGFR slope. In multiple adjusted models, elevated ePTFp remained independently associated with faster eGFR decline, whereas the serum FGF23 association was attenuated after covariate adjustment. Conclusions Elevated ePTFp was independently linked to accelerated kidney function decline, underscoring the clinical relevance of calcium phosphate microcrystallopathy. ePTFp may represent a practical biomarker with implications for prevention and treatment strategies targeting the aging kidney with proximal tubular phosphate exposure.