ORIGINAL ARTICLE Novel urinary biomarkers in pre-diabetic nephropathy Vikas Garg • Manish Kumar • Himansu Sekhar Mahapatra • Anubhuti Chitkara • Adesh Kumar Gadpayle • Venketansan Sekhar Received: 17 September 2014 / Accepted: 14 January 2015 Ó Japanese Society of Nephrology 2015 Abstract Background 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-dia- betes stage. However, there is no sensitive marker to detect these changes at such early stages. Novel urinary bio- markers have showed promising results in detection of early nephropathy in pre-diabetics. Methods A total of 91 subjects (diabetes 61 and pre- diabetes 30) were enrolled into the study. Urinary bio- markers 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 rela- tionship of UACR, NGAL, and Cystatin C was estimated. Results Urine levels of NGAL and Cystatin C were sig- nificantly 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-dia- betes. 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. Conclusion 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. Keywords Pre-diabetes Á Diabetic nephropathy Á Cystatin C Á NGAL Introduction Pre-diabetes is characterized by plasma glucose levels higher than normal, but not high enough to be called dia- betes. It is associated with high risk for the future devel- opment of diabetes [1]. Microvascular changes viz. nephropathy which was previously thought to occur after long period of diabetes are now observed as early in the pre-diabetes stage. Hyper-filtration is the initially detected hemodynamic change occurring due to increased renal plasma flow and glomerular hypertension. It is more pro- nounced in newly diagnosed diabetes and progresses to microalbuminuria. Microalbuminuria is the earliest non- invasive marker of diabetic nephropathy (DN) that occurs as a consequence of diabetes-induced glomerular damage. Role of tubulo-interstitium has also been increasingly appreciated in progression of DN [2, 3]. Persistent albu- minuria in the range of 30–299 mg/24 h has been shown to be an early stage of DN in type 1 diabetes and a marker for development of DN in type 2 diabetes [4]. However, it is not very sensitive and specific marker of DN. Spontaneous remission of microalbuminuria may occur in 40 % of the diabetic subjects. In about 30–40 % cases of nephropathy, albumin levels of 30–299 mg/24 h do not progress to C300 mg/24 h over the next 5–10 years [5]. DN can pro- gress to low GFR without evidence of microalbuminuria. V. Garg Á M. Kumar Á H. S. Mahapatra (&) Á A. Chitkara Á A. K. Gadpayle Á V. Sekhar Room No 307, Admin Block, PGIMER, Dr RML Hospital, New Delhi, India e-mail: hsmnephro@gmail.com 123 Clin Exp Nephrol DOI 10.1007/s10157-015-1085-3