Discovery and validation of serum creatinine variability as novel biomarker for predicting onset of albuminuria in Type 2 diabetes mellitus

Aim: We aim to study association serum creatinine(cr) variability and albuminuria progression.

Methods: We conducted a retrospective cohort study on patients with Type 2 Diabetes Mellitus at a Diabetes Centre in Singapore ("discovery cohort"). Outcome is worsening of urinary albumin-to-creatinine(ACR) across stages. Cr variability was expressed as adjusted cr-intrapersonal standard deviation(SD) and coefficient-of-variation(cr-CV). A separate cohort was used for validating association between cr variability and albuminuria progression ("validation cohort").

Results: Over median follow-up of 4.2 years, 38.4% of 636 patients had albuminuria progression in the discovery cohort. Increasing log-transformed adjusted cr-intrapersonal SD and cr-CV were significantly associated with albuminuria progression: HRs 1.43 (95%CI 1.11-1.85) and 1.44 (1.11-1.87) respectively in the discovery cohort, and HRs 1.94 (1.09-3.45) and 1.91 (1.05-3.45) respectively in the validation cohort. When stratified by baseline urinary ACR, higher cr variability was significantly associated with albuminuria progression in patients with normoalbuminuria but not microalbuminuria.

Conclusions: Cr variability independently predicts albuminuria onset. This is evident in patients with normoalbuminuria, suggesting that higher cr variability could herald albuminuria onset.