Clinical Characteristics of Nodular Lesions in Patients with Diabetic Kidney Disease

Background: Nodular lesions are recognized as typical renal pathology findings in patients with diabetic kidney disease (DKD), although many cases without nodular lesions have also been documented. In diabetic animal models, maintaining a hyperglycemic state alone rarely results in nodular lesions, suggesting the involvement of other contributing factors. However, the pathogenesis remains unclear. This study investigates nodular lesions' clinical features in patients with DKD. Methods: We conducted a retrospective study of 163 patients diagnosed with DKD via renal biopsy at our institution from 2008 to 2023. The patients were divided into two groups: those with nodular lesions and those without. We examined clinical and laboratory examinations, as well as renal pathology findings. Results: Comparing the groups with and without nodular lesions, there were no significant differences in renal function (eGFR 34.2 ml/min/1.73m2 vs. 36.4 ml/min/1.73m2, p=0.92) or HbA1c (6.9% vs. 6.9%, p=0.43) at the time of biopsy. However, the group with nodular lesions was younger (56 years vs. 70 years, p<0.01) and had a shorter duration of type 2 diabetes (13 years vs. 18 years, p<0.02). Despite these factors, this group exhibited higher systolic blood pressure (152mmHg vs. 137mmHg, p<0.01), higher rates of hematuria (23% vs. 10%, p<0.03), and higher levels of proteinuria (6.2 g/gCr vs. 2.8 g/gCr, p<0.01). Additionally, the group with nodular lesions had higher rates of retinopathy (79% vs. 52%, p<0.01) and dialysis initiation (60% vs. 36%, p<0.01), as well as a shorter duration from biopsy to dialysis (4 years vs. 10 years, p<0.01). Light microscopy findings revealed that the group with nodular lesions had greater intimal thickening in interlobular arteries (p<0.01) and a higher incidence of exudative lesions (80% vs. 61%, p<0.02) and mesangiolysis (62% vs. 21%, p<0.01). Conclusion: If hyperglycemia were the primary factor in the formation of nodular lesions, an increase in nodular lesions would be expected in older patients with a longer history of diabetes. However, our study found that the group with nodular lesions was younger with a shorter duration of diabetes. This group also exhibited higher blood pressure, more exudative lesions, and mesangiolysis, suggesting that endothelial cell injury plays a crucial role in the formation of nodular lesions.