Diabetic Nephropathy

Introduction

Diabetic nephropathy is one of the leading causes of ESRD and it is also a leading cause of DM-related morbidity and mortality. Proteinuria in individuals with DM is associated with markedly reduced survival and increased risk of cardiovascular disease. Individuals with diabetic nephropathy almost always have diabetic retinopathy.

Pathogenesis

Chronic hyperglycemia is the fundamental cause of diabetic nephropathy as in other microvascular complications. The mechanisms by which chronic hyperglycemia leads to end stage renal disease, though incompletely defined, involve the effects of soluble factors (growth factors, angiotensin II, endothelin, AGEs), hemodynamic alterations in the renal microcirculation (glomerular hyperfiltration or hyperperfusion, increased glomerular capillary pressure), and structural changes in the glomerulus (increased extracellular matrix, basement membrane thickening, mesangial expansion, fibrosis). Some of these effects may be mediated through angiotensin II receptors.

Clinical course

It is important to note that diabetic nephropathy is a multistage condition that takes several years to become clinically overt.

Microalbuminuria: the definition of diabetic nephropathy used to be dictated by the lower limit of detection of the assays for urinary albumin available at the time. Microalbuminuria is the first indication of diabetic nephropathy, and is defined as a persistent increase in urinary albumin excretion rate to 20–200 μg/minute (30–300 mg/ day).

Persistent albuminuria: an increase in albumin excretion to persistently more than 200 μg/minute (> 300 mg/day) marks the onset of clinically defined overt diabetic nephropathy.

Uraemia: persistent albuminuria is accompanied by a gradual decline in GFR. If untreated, this eventually leads to uraemia and death after an average of 7–10 years.

Diagnosis

Normally, there is little urinary albumin; normal ranges are:
1. urine albumin concentration < 20 mg/litre
2. albumin:creatinine ratio < 2.5 mg/mmol in men and < 3.5 mg/mmol in women
3. albumin excretion rate < 20 μg/minute.

Treatment

The optimal therapy for diabetic nephropathy is prevention. As part of comprehensive diabetes care, microalbuminuria should be detected at an early stage when effective therapies can be instituted. Interventions effective in slowing progression from Microalbuminuria to overt nephropathy include:

(1) Near normalization of glycemia,
(2) Strict blood pressure control, and
(3) Administration of ACE inhibitors or ARBs, and
(4) Treatment of dyslipidemia.