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Diabetic nephropathy pathophysiology, stages, diagnosis, treatment

It is not a glomerulonephritis but is considered to be a glomerulopathy.
• It is related to control of Diabetes and also to duration.
• It may be a part of Diabetic triopathy :
- Retinopathy
- Nephropathy
- Neuropathy
• Diabetic nephropathy is the commonest cause of end stage renal disease (ESRD).
• It occurs in 30-50% of IDDM (due to long natural history) and in 10- 15% of NIDDM.
• It is rare during the first 5 years of D.M, after which the incidence increases until it reaches a peak after 15 years of D.M.
• Diabetic nephropathy is characterized by persistent albuminuria (> 300 mg/24 hours), decline in GFR and hypertension.
• Renal biopsy had shown that a good percent of patients with NIDDM have nephropathy that is related to their diabetes.
Presence of RBCs casts or low levels of complement should lead to a search for other causes of renal disease in diabetics.
• Diabetic retinopathy is found in 90% of IODM, nearly one third of type 2 diabetes with proven diabetic nephropathy have no evidence .

Pathophysiology of Diabetic Nephropathy :

• Early there is renal hypertrophy associated with glomerular hyperfiltration (GFR >150ml/m this is related to glycaemic control).
• The afferent arteriole becomes vasodilated leading to increase of the intraglomerular filtration pressure ===> damage of glomerular capillaries ===> glomerular sclerosis.

Pathology of Diabetic Nephropathy

- Early, there is basement membrane thickening with mesangial expansion
- Later there is diffuse or nodular glomerulosclerosis, the latter is sometimes known as the Kimmelstiel -Wilson syndrome.

The presence of linear deposition of IgG along the capillary walls and deposition of IgM and C3 is a non specific passive trapping.

Stages of diabetic nephropathy

• Hyperfiltration (raised GFR above normal by 20-30%). This is related to glycemic control.
• Stage of microalbuminuria. (> 30 mg/d and < 300 mg/d)
• Gross proteinuria + nephrotic syndrome (1-5 years after onset of proteinuria).
• Renal impairment, then renal failure (GFR declines 1ml/min/month after the onset of gross proteinuria).

• End stage renal disease (ESRD).

Clinical Picture and diagnosis of diabetic nephropathy

• D.M. + nephrotic syndrome then CRF develops.
• Hypertension is common.
• Early diagnosis by appearance of micro albuminuria which is tested by radioimmunoassay or by using special dipsticks.
• Microscopic examination: There is thickening of basement membrane; also there is hyaline arteriosclerosis
of both afferent and efferent arterioles.
• Ultrasound examination: normal or large kidney size. No active urinary sediments.
* Diagnosis of diabetic nephropathy is usually not dependent on renal biopsy .

Treatment of diabetic nephropathy

• Restriction of dietary proteins.
• Control of blood sugar prevents the early hyperfiltration.
• Control of blood pressure.
• ACE inhibitors (must be used early e.g stage of micro-albuminuria)
Actions:
- Vasodilatation of efferent arteriole.
- Decreases  Intra glomerular pressure (antiprotelnuric effect).
- Decreases Process of glomerulosclerosis ===> inhibits the progression of renal disease.
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Tamer Mobarak

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