Albuminuric and non-albuminuric pathways to renal impairment in diabetes

Abstract

Traditionally, microvascular disease resulting in a glomerulopathy and an increase in albumin excretion rate (AER) is believed to be the only significant mechanism by which diabetic renal disease develops. However, recent results have challenged the concept that a decline in renal function in patients with diabetes is always accompanied by an increased AER. This has led to the concept that subjects with diabetes, especially those with type 2 diabetes, can progress to renal impairment via either an albuminuric or non-albuminuric pathway. The natural history, renal morphological changes and exaggerated cardiovascular risk associated with the albuminuric-pathway to renal impairment have been well documented. Interventions to attenuate the progression of this pathway, especially inhibition of the renin-angiotensin system (RAS), are also a routine part of clinical practice. Subjects who follow the albuminuric pathway are detected by screening for the presence of microalbuminuria. The finding of microalbuminuria in this setting should provoke an intensified modification of the common risk factors for renal and cardiovascular disease, i.e. hyperglycemia, hypertension, dyslipidemia and smoking. In contrast, little is known about the natural history and structural basis of the non-albuminuric pathway to renal impairment and the best way to retard its progression is also not known. The prevalence of impaired renal function and normoalbuminuria is relatively common and in subjects with type 2 diabetes is at least 20% after accounting for the use of RAS inhibitors. It is therefore recommended that screening for diabetic renal disease should include an estimation of glomerular filtration rate (GFR) in addition to measuring AER. This will allow the detection of subjects following either an albuminuric or non-albuminuric pathway to renal impairment.