Center for Biomedical Research of the Canary Islands (CIBICAN), University of La Laguna, Tenerife, Spain.
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Lancet Diabetes Endocrinol. 2015 May;3(5):382-91. doi: 10.1016/S2213-8587(15)00094-7.
Largely on the basis of data from patients with type 1 diabetes, the natural history of diabetic renal disease has been classified as a sequence of three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Progressive decline of glomerular filtration rate (GFR) was thought to parallel the onset of macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was deemed a hallmark of early disease. However, researchers have since shown that albuminuria is a continuum and that GFR can start to decline before progression to overt nephropathy. In addition to proteinuria, other risk factors might contribute to GFR deterioration including female sex, obesity, dyslipidaemia (in particular hypertriglyceridaemia), hypertension, and glomerular hyperfiltration, at least in a subgroup of patients. This phenomenon could explain why patients with type 2 diabetes can have renal insufficiency even before the onset of overt nephropathy, and might also suggest why the heterogeneous phenotype of type 2 diabetic renal disease does not necessarily associate with typical histological lesions of diabetic renal disease, unlike in type 1 diabetic renal disease. Patients with renal insufficiency but without albuminuria are usually excluded from randomised clinical trials in overt nephropathy, thus optimum treatment for this group of patients is unknown. The wide inter-patient variability of the disease probably needs individually tailored intervention.
主要基于 1 型糖尿病患者的数据，糖尿病肾病的自然病程被分为三个阶段：正常白蛋白尿、微量白蛋白尿和大量白蛋白尿。肾小球滤过率（GFR）的逐渐下降被认为与大量白蛋白尿（显性肾病）的发生平行，而肾小球高滤过被认为是早期疾病的标志。然而，研究人员后来表明，白蛋白尿是一个连续体，在进展到显性肾病之前，GFR 就可以开始下降。除蛋白尿外，其他危险因素如女性、肥胖、血脂异常（特别是高甘油三酯血症）、高血压和肾小球高滤过，至少在一部分患者中，可能导致 GFR 恶化。这种现象可以解释为什么 2 型糖尿病患者在发生显性肾病之前就可能出现肾功能不全，也可能解释为什么 2 型糖尿病肾病的异质性表型不一定与 1 型糖尿病肾病的典型组织学病变相关。肾功能不全但无白蛋白尿的患者通常被排除在显性肾病的随机临床试验之外，因此，这组患者的最佳治疗方法尚不清楚。该疾病的患者间变异性很大，可能需要个体化干预。
