Periostin as a Tissue and Urinary Biomarker of Renal Injury in Type 2 Diabetes Mellitus

<div><p>Background</p><p>Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated.</p><p>Methods</p><p>Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114), microalbuminuria (n=100) and macroalbuminuria (n=114). The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy.</p><p>Results</p><p>Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77) ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29) ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19) ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63) ng/mgCr] (P<0.01).Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86), 0.99 (95%CI, 0.98 to 1.00) and 0.95 (95%CI, 0.91 to 0.98), respectively).</p><p>Conclusion</p><p>The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.</p></div

Urine periostin levels in patients with diabetic nephropathy and in healthy controls.

<p>Significant differences were observed between the urine periostin values in the each stage of diabetic nephropathy (P<0.001) compared with healthy subjects. Data are presented as the median with interquartile range. Open and filled circles were defined as outlier data more than 1.5 times of upper quartile.</p

Baseline clinical characteristics.

<p>Data are mean ± SD, median with interquartile range and percentages;</p><p>^aP<0.05 versus normoalbuminuria,</p><p>^bP<0.05 versus microalbuminuria, RAAS;</p><p>renin—angiotensin—aldosterone system</p><p>Baseline clinical characteristics.</p

Renal periostin immunostaining in patients with diabetic nephropathy.

<p>Tissue sections were immunostained with a polyclonal rabbit anti-periostin antibody. Positive staining for periostin protein is shown in brown. All sections were counterstained with hematoxylin. Kidney tissues from patients with diabetic nephropathy display nodular glomerulosclerosis with arteriolar hyalinosis, interstitial fibrosis and tubular atrophy (A, B) and display diffuse periostin immunopositivity in glomerular and tubular compartments (C). Periostin staining was observed in the nodular sclerosis glomerulus with periglomerular and mesangial areas and also periostin staining in both atrophic and non-atrophic tubular epithelium (D). Periostin staining was found in the area of periglomerular fibrosis and collagen forming Bowman’s capsule within the ischemic type-change glomerulus (E). Global glomerulosclerosis showed periglomerular staining with periostin immunohistochemistry (F) (Original magnification: 400×).</p