Arteriolar Hyalinosis Predicts the Onset of Both Macroalbuminuria and Impaired Renal Function in Patients with Type 2 Diabetes

Abstract

<b><i>Introduction:</i></b> Arteriolar hyalinosis (AH) has been shown to be associated with albuminuria and GFR. In this study, we investigated whether or not index of AH (IAH) is a predictor of the onset of macroalbuminuria and impaired renal function (eGFR &lt;60 mL/min/1.73 m² [eGFR &lt;60]) in type 2 diabetic patients with early diabetic nephropathy. <b><i>Methods:</i></b> The study population consisted of 35 patients with type 2 diabetes (25 men; age: 47 ± 9 years; eGFR: 92.7 ± 18.0 mL/min/1.73 m²) with normo- or microalbuminuria who underwent percutaneous renal biopsy. These patients were followed for at least 5 (18 ± 6, range: 6–28) years. The study endpoint was the onset of macroalbuminuria or eGFR &lt;60. Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate glomerular and interstitial structural changes. <b><i>Results:</i></b> During the observation period, 9 out of the 35 patients progressed to macroalbuminuria, and 15 out of the 35 patients developed eGFR &lt;60. The annual rate of eGFR decline was significantly correlated with IAH (<i>r</i> = −0.40, <i>p</i> = 0.016). Kaplan-Meier analysis demonstrated that AH was associated with a significantly higher risk of onset of macroalbuminuria and eGFR &lt;60, and microalbuminuria is associated with the onset of macroalbuminuria but not the onset of eGFR &lt;60. <b><i>Conclusions:</i></b> Aggravated AH is a histological risk factor which predicts the onset of macroalbuminuria and eGFR &lt;60 in patients with type 2 diabetes. These findings provide novel insights into the mechanism of progression of diabetic nephropathy.