Clinical Characteristics of Biopsy-Confirmed Kidney Disease in Patients with Type 2 Diabetes

Background: In patients with type 2 diabetes mellitus (T2D), differentiating diabetic nephropathy (DN) from non-diabetic nephropathy (NDN) is essential for appropriate management. Although kidney biopsy is the gold standard for diagnosis, it is an invasive procedure and often reserved for cases with atypical features. Nevertheless, DN may still be diagnosed histologically even when clinical suspicion points toward NDN. Identifying clinical indicators that increase the likelihood of DN or NDN may improve patient selection and reduce unnecessary biopsies. This study aimed to investigate clinical differences among DN, NDN, and mixed forms, with a focus on identifying potential noninvasive markers that could assist in differentiating renal pathologies prior to kidney biopsy. Methods: We retrospectively analyzed 263 patients with T2D who underwent kidney biopsy. Patients were categorized into pure DN (n=118), NDN (n=120), and mixed forms (DN+NDN, n=25) groups based on histopathological findings. Subgroup analyses were conducted based on the presence of diabetic retinopathy (DR) in both DN and NDN±DN groups. Results: Patients with DN were younger, had higher blood pressure and heart rate, larger kidneys, and more frequent diabetic neuropathy, retinopathy, hypertension, and peripheral edema compared to those with NDN±DN (all p<0.05). In the NDN±DN group, mixed DN+NDN patients had longer diabetes duration (p=0.033), larger kidneys (p=0.002), higher HbA1c levels (p=0.043), and significantly more frequent DR (56.0% vs 12.5%, p<0.001) compared to NDN group without DN. Among pure DN patients, those with DR had more severe kidney injury, including higher proteinuria, lower eGFR, and elevated potassium and cystatin C levels compared to those without DR (all p<0.05). Within NDN±DN, patients with DR had longer diabetes duration, higher proteinuria, more peripheral edema, and increased serum C4 levels compared to those without DR (all p<0.05). Conclusion: Clinical features such as diabetic retinopathy, diabetes duration, and kidney size may help predict the underlying renal pathology in T2D patients with proteinuria. These indicators could assist clinicians in selecting appropriate candidates for kidney biopsy by stratifying the likelihood of DN versus NDN.