Diabetic nephropathy - Complications of diabetes

Diabetic nephropathy

Definition

Diabetic nephropathy is a microvascular disease of type 1 and 2 diabetes.

Incidence

Patient individual risk is falling however due to increasing rates of diabetes the overall prevalence of diabetic nephropathy is rising.

Age

Increases with age.

Aetiology

Associated with hypertension, smoking and poor glycaemic control.

Pathophysiology

In addition to the other microvascular mechanisms hypertension can accelerate nephropathy by causing further thickening of the capillary walls and reduced glomerular filtration rate. This further increases hypertension.

Glomerular basement membrane (GBM) thickening and glomerulosclerosis due to an increase in the mesangial matrix. It leads to diffuse sclerosis of the glomerulus, which later condenses into nodular lesions, called Kimmelstiel-Wilson lesions. The thickening of the base-ment membrane increases its permeability to albumin. As the disease progresses, the amount of protein lost increases.

The glomerular filtration rate is initially normal, but falls with progressive renal damage and chronic renal failure occurs around 5–7 years after macroalbuminuria occurs.

Clinical features

The condition is asymptomatic until chronic renal failure or nephrotic syndrome develops. Patients should be screened annually for all diabetic complications and hypertension.

Microscopy

The GBM is thickened (can be seen on electron microscopy). There are exudative lesions on the surface of the glomerulus, which are masses of red-staining fibrin protein. The mesangial matrix is expanded and there are round hyaline areas in the glomeruli (Kimmelstiel-Wilson nodules).

Investigations

Annual screening of urine for microalbuminuria. Amount of albumin lost per 24 hours:

30–300 mg/24 hours      Microalbuminuria

>300 mg/24 hours         Proteinuria

>3.6 g/24 hours   Hypoalbuminaemia and Nephrotic syndrome

Diabetic patients may have other causes for proteinuria and renal failure, so particularly if there are atypical features such as haematuria, rapid onset or absent retinopathy further investigation must be carried out to look for another cause.

Management

Microalbuminuria and proteinuria require aggressive treatment of hypertension (<130/75), better glycaemic control and cessation of smoking. ACE inhibitors and angiotensin II blockers appear to be most effective in reducing protein loss and delaying progression.

End-stage renal failure is treated as for non-diabetics. Haemodialysis may be more complicated because of increased cardiovascular disease and autonomic neuropathy which exacerbates postural hypotension. Hypoglycaemia may occur because insulin and sulphonylureas accumulate in renal failure.

Renal transplantation is the preferred option in younger patients, and pancreatic-renal transplants may be of value in reducing diabetic complications.