Urine Albumin-Creatinine Ratio Variability in People With Type 2 Diabetes: Clinical and Research Implications

Rationale & Objective While evidence has demonstrated that albuminuria is a key diagnostic and prognostic marker of diabetic chronic kidney disease, the impact of its day-to-day variability has not been adequately considered. This study sought to quantify within-individual variability of albuminuria in people with type 2 diabetes to inform clinical albuminuria monitoring. Study Design Descriptive cross-sectional analysis. Setting & Participants: People with type 2 diabetes (n=826, 67.1[60.3-72.4] years, 64.9% male) participating in the PRogrEssion of DIabetic ComplicaTions (PREDICT) cohort study. Exposure Four spot urine collections for measurement of urinary albumin-creatinine ratio (UACR), within four weeks. Outcomes Variability of UACR. Analytical Approach We characterized within-individual variability (coefficient of variation [CV], 95% limits of random variation, intraclass correlation coefficient [ICC]) and developed a nomogram displaying probabilities that any observed difference between a pair of UACR values truly exceeded a 30% difference and estimated the ranges of diagnostic uncertainty to inform need for additional UACR collections to exclude or confirm albuminuria. Multiple linear regression sought factors influencing UACR variability. Results We observed high within-individual variability (CV=48.8%; 95% limits of random variation showed a repeated UACR to be as high/low as 3.78/0.26 times the first). If a single-collection UACR increased from 2 to 5 mg/mmol, the probability that UACR actually increased by at least 30% was only 50%, rising to 97% when two collections were obtained at each time point. Ranges of diagnostic uncertainty were 2.0-4.0 mg/mmol after an initial UACR test, narrowing to 2.4-3.2 and 2.7-2.9 mg/mmol for the mean of two and three collections, respectively. Some factors correlated with higher (female sex; moderately increased albuminuria) or lower within-individual UACR variability (reduced eGFR and SGLT2i/ACE/ARB treatment). Limitations Reliance on the mean of four UACR collections as the reference standard for albuminuria. Conclusions UACR demonstrates a high degree of within-individual variability among individuals with type 2 diabetes. Multiple urine collections for UACR may improve capacity to monitor changes over time in clinical and research settings but may not be necessary for the diagnosis of albuminuria.