Relative circadian disruption in urinary excretion associates with renal function in biopsy-proven primary glomerular diseases: a cross-sectional study using the novel CRDI metric

The circadian rhythmicity of urinary solute excretion is a hallmark of intact renal physiology, yet its disruption in chronic kidney disease (CKD) lacks a practical quantitative tool. We developed the novel Circadian Rhythm Disruption Index (CRDI) to objectively quantify this disruption from routine clinical data and investigated its association with estimated glomerular filtration rate (eGFR) in primary glomerular diseases. This cross-sectional study prospectively enrolled 81 inpatients with biopsy-confirmed primary glomerular diseases under standardized hospital protocols. All spontaneous urine samples over 24-hours were collected. The presence of circadian rhythms in urinary excretion was validated by cosinor analysis. CRDI metrics were defined and developed to calculate protein, creatinine, and volume. Multivariable linear regression was used to examine the CRDI-eGFR relationship, adjusting for demographics, pathology, and medications. Clinical utility was assessed using ROC and decision curve analysis. Significant circadian rhythms were confirmed for all biomarkers. The CRDI for creatinine (CRDIcr) demonstrated the strongest independent inverse association with eGFR after full adjustment (β = -4. 45 mL/min/1. 73m2 per unit, p = 0. 008). A key finding was the pathological specificity of this relationship; it was most pronounced in IgA nephropathy. Incorporating CRDIcr into a clinical model improved the AUC for identifying eGFR ≤60 mL/min/1. 73m2 from 0. 748 to 0. 800 and yielded a significant net reclassification improvement (NRI = 0. 237). The CRDI effectively quantifies relative circadian disruption. CRDIcr is independently associated with renal function in a pathology-specific manner, highlighting its potential as a novel biomarker for refined risk stratification in specific glomerular diseases, particularly IgA nephropathy.