Assessment of proteinuria in patients with chronic kidney disease stage 3: albuminuria and non-albumin proteinuria.

Background and Objective: Proteinuria assessment is key in investigating chronic kidney disease (CKD) but uncertainty exists regarding optimal methods. Albuminuria, reflecting glomerular damage, is usually measured, but non-albumin proteinuria (NAP), reflecting tubular damage, may be important. This study investigated the prevalence and associations of albuminuria and NAP, and the optimum number of urine specimens required.
Methods: 1,741 patients with CKD stage 3, recruited from primary care, underwent medical history, clinical assessment, blood sampling, and submitted three early morning urine samples for albumin to creatinine ratio (uACR) and protein to creatinine ratios (uPCR). Albuminuria was defined as uACR ≥ 3 mg/mmol in at least two of three samples. Isolated NAP was defined as uPCR ≥ 17 mg/mmol in two of three samples and uACR <3 mg/mmol in all three. Prevalence and associations of albuminuria and NAP, degree of agreement between single uACR and average of three uACRs, and urine albumin to protein ratio (uAPR  =  uACR/uPCR) were identified.
Results: Albuminuria prevalence was 16% and NAP 6%. Using a <1 mg/mmol threshold for uACR reduced NAP prevalence to 3.6%. Independent associations of albuminuria were: males (OR 3.06 (95% CI, 2.23-4.19)), diabetes (OR 2.14 (1.53-3.00)), lower estimated glomerular filtration rate ((OR 2.06 (1.48-2.85) 30-44 vs 45-59), and high sensitivity CRP ((OR 1.70 (1.25-2.32)). NAP was independently associated with females (OR 6.79 (3.48-13.26)), age (OR 1.62 (1.02-2.56) 80 s vs 70-79) and high sensitivity CRP ((OR 1.74 (1.14-2.66)). Of those with uPCR ≥ 17 mg/mmol, 62% had uAPR<0.4. Sensitivity of single uACR was 95%, specificity 98%, PPV 90%. Bland Altman plot one vs average of three uACRs showed: mean difference 0.0064 mg/mmol (SD 4.69, limits of agreement -9.19 to +9.20, absolute mean difference 0.837).
Conclusions: In CKD stage 3, albuminuria has associations distinct from those of isolated NAP (except for inflammatory markers). Single uACR categorised albuminuria but average of three performed better for quantification.