Diabetic Nephropathy Flashcards
What is diabetic nephropathy characterised by?
Gradual increase in urinary albumin excretion
Blood pressure of GFR falling insidiously towards end-stage renal disease.
Pathophysiology of diabetic nephropathy.
Renal hypertrophy due to increased GFR. (Related to hyperglycaemia)
As the kidneys become damaged the afferent arteriole becomes vasodilated to a greater extent than intraglomerular filtration pressure. This damages the glomerular capillaries.
Raised intraglomerular pressure leads to increased local shearing forces. This is likely to contribute to the mesangial cell hypertrophy and increased extracellular mesangial matrix.
Kimmelstiel-Wilson nodules
This will eventually lead to glomerular sclerosis.
What is the initial structural lesion in the glomerulus?
Thickening of the basement membrane.
What does thickening of the basement membrane lead to?
Disruption of protein cross-linkages.
Which leads to leakage of proteins into the urine.
Light microscopic changes in diabetic nephropathy.
Diffuse and nodular glomerulosclerosis.
Nodular glomerulosclerosis is also called Kimmelstiel-Wilson lesions.
At late stages the glomerulus will be replaced by hyaline material.
What is the hallmark of classical diabetic nephropathy?
Gradually increasing urinary albumin excretion.
What is the earliest evidence of albuminuria called?
Microalbuminuria.
Why is it called microalbuminuria?
Because the amounts of urinary albumin are too small to be detected on standard dipsticks.
What is microalbuminuria?
When urine dipstick is negative for protein but the urine albumin:creatinine ratio (UA:CR) is 3mg/mmol or more.
This reflects early renal disease and increased vascular risk.
Plasma creatinine levels at persistent proteinuria.
Normal.
However once this stage has been reached end-stage kidney disease ensues within 5-10 years. It is no longer reversible.
The rising plasma creatinine is a late feature
What might happen as the proteinuria becomes very heavy?
Transient nephrotic syndrome with peripheral oedema and hypoalbuminaemia.
Other features of diabetic nephropathy.
Normochromic normocytic anaemia
Raised eryhtrocyte sedimentation rate
Raised CRP
Hypertension
Screening for diabetic nephropathy.
Urine is checked at the very least anually for presence of microalbuminuria.
The albumin:creatinine ratio is checked.
The ratio is less than 2.5mg/mmol in healthy men and less than 3.5 mg/mmol in healthy women.
If microalbuminuria is detected it should be repeated twice due to false-positive being common.
Investigations of diabetic nephropathy.
Albuminuria
Proteinuria
Plasma creatinine levels
eGFR
Diagnosis of diabetic nephropathy.
When urine dipstick is negative but the urine albumin:creatinine ratio is >3.0 mg/mmol - 30 mg/mmol
Other causes needs to be excluded.
The diagnosis is strengthened by diabetic retinopathy and neuropathy.
