Natural course (stages/evidence-based discussion)

Abstract

Studies during the 1960s to 1980s have led to characterization of the natural course of diabetic kidney disease (DKD), which occurs in series of five stages. DKD has historically been named diabetic nephropathy if there is macroalbuminuria or proteinuria. This chapter describes the five stages of DKD in Type 1 DM (T1DM) and Type 2 DM (T2DM) as well as their similarities and differences. Stage 1, the so-called hyperfiltration-hypertrophy phase, is detected at the diagnosis of DM. In stage 1 there is renal hypertrophy and elevated glomerular filtration rate (GFR). Stage 2 is named as the silent or normoalbuminuria stage as it is not detected clinically as urinary albumin excretion (UAE) remains within normal range and the GFR can be normal or elevated. However, there are significant structural changes such as thickening of the basement membrane and expansion of the mesangium. The third stage is termed microalbuminuria or incipient diabetic nephropathy and it is detected clinically as UAE is increased to microalbuminuria range (20-200 µg/min, 30-300 mg/24 h, or albumin-to-creatinine ratio (ACR) of 30-300 mg/g). GFR is usually preserved but can start declining in this stage. Untreated hypertension in this stage may worsen DKD. Stage 4 is called macroalbuminuria or overt diabetic nephropathy and has UAE in macroalbuminuria range (300 mg/24 h, >200 µg/min, or ACR >300 mg/g) or proteinuria. Although GFR can be within normal range early in this phase, it continues to decline as the stage progresses. Progression of kidney structural changes can be detected. Lastly, stage 5 is called end stage renal disease or uremia. It is due to advanced diabetic nephropathy and requires initiation of renal replacement therapy for survival.