Definition

 • CKD caused by diabetes mellitus.

Epidemiology

 • Common cause of CKD.

Aetiology

 • Type 1 or type 2 diabetes mellitus.

• Only 30– 40% of diabetics develop nephropathy. This is largely dependant on glycaemic control; however other factors are involved, as the severity of renal involvement is variable from patient to patient.

 Pathogenesis

• Complex and multifactorial.

• High glucose levels are thought to be directly injurious, at least partly through abnormal glycosylation of extracellular proteins, oxidative stress, and enhanced production of TGF- β, which promotes fibrosis.

 Presentation

• Onset of proteinuria in a patient with diabetes mellitus.

 • Typically, this starts as microalbuminuria but progresses to overt proteinuria, which may be heavy enough to cause the nephrotic syndrome.

 • Hypertension is often present.

Histopathology

 • Glomerular changes develop progressively and are classified by severity, from early to late lesions:

- Class I: thickening of the glomerular basement membranes on electron microscopy only (light microscopy normal or near normal);

- Class II: increase in mesangial matrix, without nodules (IIa, mild; IIb, severe);

- Class III: nodular glomerulosclerosis/ Kimmelstiel– Wilson lesion (Fig. 1);

- Class IV: advanced diabetic glomerulosclerosis (many globally sclerosed glomeruli).

• Hyalinization of arterioles, typically affecting both afferent and efferent arterioles.

 • Tubulointerstitial fibrosis proportional to the degree of glomerular damage.

 * Note that a renal biopsy is not necessary to confirm a diagnosis of diabetic nephropathy, provided the clinical picture is typical. Biopsy is usually reserved for atypical cases where an alternative or additional diagnosis is suspected (e.g. new- onset of nephrotic- range proteinuria without ante cedent proteinuria).

Immunofluorescence

 • Linear enhancement of glomerular and tubular basement membranes with IgG may be seen.

Fig1. Nodular diabetic glomerulosclerosis (periodic acid– Schiff stain). The mesangial matrix is expanded by nodules of matrix referred to as Kimmelstiel– Wilson nodules (see Plate 20).

Electron microscopy

• Diffuse glomerular basement membrane thickening and increase of mesangial matrix.

• No electron- dense deposits are present.

 Prognosis

• Patients with poor glycaemic control, hypertension, and proteinuria show gradual deterioration in renal function, which may result in the need for renal replacement therapy.

 • Control of blood pressure and glycaemic control can slow disease progression.