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

Abstract

AimWe aim to study association serum creatinine(cr) variability and albuminuria progression. MethodsWe 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”). ResultsOver 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. ConclusionsCr variability independently predicts albuminuria onset. This is evident in patients with normoalbuminuria, suggesting that higher cr variability could herald albuminuria onset.