Diabetic Nephropathy Flashcards
What are the stages in the pathological change in diabetic nephropathy
Hyperfiltration/capillary hypertension
Glomerular basement membrane thickening - due to increased glucose
Mesangial expasion
Podocyte injury - due to increased protein filtration caused by high intraglomerular pressure causing gaps to form in GBM
Glomerular sclerosis/arteriolosclerosis
Describe how diabetes causes hyperfiltration/capillary hypertension
Increased glucose in filtrate is reabsorbed by SLGT2
Increased glucose reuptake by SLGT2 increases Na reuptake (also causes increased water reabsorption)
Increased Na reuptake means there is decreased Na at the macula densa so the body believes it is hypovolaemic so stimulates dilation of afferent arterioles and constriction of efferent arterioles
This results in hyperfiltration due to the increased intraglomerular pressure
What are the clinical stages in diabetic nephropathy
Hyperfiltration and hypertrophy - have increased GFR, normal renal histology
Latent stage
Microalbuminuria
Over proteinuria
ESRD
Describe the latent stage of diabetic nephropathy
Normal albuminuria
GBM thickening and mesangial expansion
Describe the microalbuminuria stage of diabetic nephropathy
Moderately increased albuminuria
Variable mesangial expansion/sclerosis
Increased GBM thickening
Normal GFR
Will not be picked up by a dipstick - requires special test
Potentially reversible
Describe the over proteinuria stage of diabetic nephropathy
Severely increased albuminuria
Diffuse glomerular histopathological changes
Systemic worsening hypertension
Microvascular changes causing tissue ischaemia
Decline to ESRD in 3-7yrs - can be slowed with treatment
GFR normal initially -> drops in linear pattern gradually
Mesangial expansion/sclerosis
Detectable on conventional dipstick
Name some risk factors of diabetic nephropathy
Genetic susceptibility
Race - caucasians more likely
Hypertension
Hyperglycaemia
High level of hyperfiltration
Increasing age
Duration of diabetes
Smoking
How do you prevent diabetic nephropathy
Tight glucose control - injections/insulin pump to get normal glucose. Can reverse initial hyperfiltration and delay microalbuminuria. Can reduce microalbuminuria. Doesn’t slow GFR loss once overt proteinuria develops
Tight BP control
Stop smoking and statin therapy - CV risk
SLGT-2 inhibitors
What is the management of microalbuminuria and proteinuria
Inhibition of RAAS - decreased hyperfiltration, has an anti-proteinuria effect, slows progression of diabetic nephropathy
Tight BP control
Statin therapy and CV risk management
Moderate protein intake
Tight blood glucose control
ACE-inhibitors - prevent protein-creatinine ratio from doubling
How do you figure out a patients protein loss
Look at the ratio of protein to creatinine/albumin in the urine over 24hrs
What effects does angiotensin II have that can lead to proteinuria
Increased glomerular permeability to proteins
Mesangial cell proliferation
Increased mesangial matrix
Efferent glomerular constriction causing increased glomerular pressure
What nodules can form in diabetic nephropathy and where do they form
Kimmelstiel-Wilson nodules can form - hyaline nodules
Form in regions of glomerular filtration loops in the glomerulus
(Diffuse nodular glomerulosclerosis)
