Where do we stand on human diabetic nephropathy?

The prevalence of type 2 diabetes is rising rapidly in Asian populations due to lifestyle changes and increased life expectancy. With the rapidly increasing number of patients with diabetes worldwide, diabetic nephropathy (DN) is becoming one of the most common causes of renal disease. Indeed, approximately 20–40% of diabetic patients develop DN [1]. The diagnosis of DN is based primarily on clinical features such as lengthy duration of diabetes and presence of target organ damage, especially proteinuria usually preceding decreased renal function. Although validation of this clinical approach is well established in type 1 diabetes, it is much more difficult in patients with type 2 diabetes because of the unknown duration of the disease [2]. The characteristic pathological features of DN are diffuse or nodular mesangial sclerosis, glomerular basement membrane thickening accompanied by chronic interstitial fibrosis and tubular atrophy usually observed in advanced glomerulosclerosis, and hyaline changes in both afferent and efferent arterioles. However, nondiabetic renal disease (NDRD) occurs in patients with type 2 diabetes, and can be either isolated or superimposed on underlying diabetic glomerulosclerosis. Interestingly, NDRD is associated with a broad spectrum of symptoms [3–5]. The ability to clearly differentiate between renal lesions associated with DN and NDRD in diabetic patients is critical for making appropriate treatment decisions, and thus numerous research efforts are focused on how to identify DN in patients with diabetes. Recently, Liang et al [5] performed a meta-analysis of 26 relevant studies comprising 2,322 patients and suggested that the absence of diabetic retinopathy (DR), shorter duration of diabetes, lower HbA1C, and lower BP may help to distinguish NDRD from DN in patients with diabetes [5]. In this issue of Kidney Research and Clinical Practice, Kim et al [6] retrospectively analyzed renal pathological findings including the incidence of NDRD in 75 diabetic patients who underwent renal biopsy for clinically suspected NDRD. They also analyzed the clinical characteristics and renal prognosis of patients with DN and NDRD. They found that 10 patients (13.3%) had only DN, 11 patients (14.7%) had DN with superimposed NDRD, and 54 patients (72%) had only NDRD. The most common pathological findings of NDRD were membranous nephropathy (23.1%), IgA nephropathy (21.5%), and acute tubulointerstitial nephritis (15.4%). Compared with DN and NDRD superimposed on DN, the clinical characteristics of NDRD consisted of a short duration of diabetes and less severe DR. Conversely, patients with combined DN and NDRD exhibited the lowest baseline