Novel urinary biomarkers in pre-diabetic nephropathy

Renal involvement was thought to occur more than 10 years after onset of diabetes, but recent studies provide evidence that it starts even in the pre-diabetes stage. However, there is no sensitive marker to detect these changes at such early stages. Novel urinary biomarkers have showed promising results in detection of early nephropathy in pre-diabetics.

A total of 91 subjects (diabetes 61 and pre-diabetes 30) were enrolled into the study. Urinary biomarkers such as urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), urine Cystatin C and urine albumin-creatinine ratio (UACR) were estimated. Subjects were further divided in four groups on the basis of UACR: pre-diabetes with normoalbuminuria (21); pre-diabetes with microalbuminuria (9); diabetes with normoalbuminuria (37); and diabetes with microalbuminuria (24). The relationship of UACR, NGAL, and Cystatin C was estimated.

Urine levels of NGAL and Cystatin C were significantly higher in microalbuminuria group compared to normoalbuminuria. UACR was positively correlated to urine NGAL-creatinine ratio (UNCR) and urine Cystatin C-creatinine ratio (UCCR) in both diabetes and pre-diabetes. On logistic regression odds ratio of UNCR to predict microalbuminuria in diabetes and pre-diabetes was 1.070 (p = 0.000) and 1.138 (p = 0.010), respectively. Area under curve was determined by ROC analysis, and UNCR was found to be better than UCCR for estimating microalbuminuria.

Tubular damage may play major role in development of nephropathy in pre-diabetes. Newer markers like urine NGAL and Cystatin C are raised early in diabetes and pre-diabetes nephropathy.