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 (CRDI_cr) 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 CRDI_cr 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. CRDI_cr 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.
What was known:
Circadian rhythm disruption is implicated in the pathogenesis and progression of chronic kidney disease (CKD).
The gold-standard 24-hour urine collection condenses dynamic excretory patterns into a single aggregate value, failing to capture clinically meaningful diurnal variations.
A simple, quantitative tool to assess the extent of urinary excretory rhythm disruption in clinical practice was lacking.

Circadian rhythm disruption is implicated in the pathogenesis and progression of chronic kidney disease (CKD).
The gold-standard 24-hour urine collection condenses dynamic excretory patterns into a single aggregate value, failing to capture clinically meaningful diurnal variations.
A simple, quantitative tool to assess the extent of urinary excretory rhythm disruption in clinical practice was lacking.
This study adds:
We introduce the Circadian Rhythm Disruption Index (CRDI), a novel quantitative metric to objectively assess rhythm disturbances in urinary protein, creatinine, and volume excretion patterns from routine clinical data.
We demonstrate that CRDI for creatinine (CRDI_cr) shows the strongest independent association with estimated glomerular filtration rate (eGFR) in patients with primary glomerular diseases, with notable pathological specificity particularly in IgA nephropathy.
We provide evidence that incorporating CRDI_cr into clinical models improves the identification of patients with moderate renal impairment (eGFR ≤ 60 mL/min/1.73m2) and offers context-dependent clinical utility.

We introduce the Circadian Rhythm Disruption Index (CRDI), a novel quantitative metric to objectively assess rhythm disturbances in urinary protein, creatinine, and volume excretion patterns from routine clinical data.
We demonstrate that CRDI for creatinine (CRDI_cr) shows the strongest independent association with estimated glomerular filtration rate (eGFR) in patients with primary glomerular diseases, with notable pathological specificity particularly in IgA nephropathy.
We provide evidence that incorporating CRDI_cr into clinical models improves the identification of patients with moderate renal impairment (eGFR ≤ 60 mL/min/1.73m2) and offers context-dependent clinical utility.
Potential impact:
The CRDI provides clinicians with a practical, noninvasive tool to dynamically monitor circadian renal health in specific glomerular diseases, potentially enhancing risk stratification and personalized management.
By quantifying a novel dimension of glomerular disease pathophysiology, the CRDI opens new avenues for research into the mechanisms linking circadian dysregulation to renal functional decline.
If validated in longitudinal studies, the CRDI could serve as a functional biomarker to track disease progression and evaluate interventions aimed at restoring circadian rhythmicity in targeted patient populations.

The CRDI provides clinicians with a practical, noninvasive tool to dynamically monitor circadian renal health in specific glomerular diseases, potentially enhancing risk stratification and personalized management.
By quantifying a novel dimension of glomerular disease pathophysiology, the CRDI opens new avenues for research into the mechanisms linking circadian dysregulation to renal functional decline.
If validated in longitudinal studies, the CRDI could serve as a functional biomarker to track disease progression and evaluate interventions aimed at restoring circadian rhythmicity in targeted patient populations.