S8) Diabetes and Other Systemic Conditions Affecting the Kidney Flashcards
Describe the structure of the glomerular capillary wall
What is the commonest cause of ESRD (end stage renal disease)?
Diabetic nephropathy
Identify 5 pathological processes which occur in diabetic nephropathy
- Hyperfiltration / capillary hypertension (occurs first)
- GBM thickening (increases pore size)
- Mesangial expansion
- Podocyte injury
- Glomerular sclerosis / arteriolosclerosis
What causes afferent vasodilation in Diabetes?
- Hyperglycaemia
- Low NaCl delivery to macula densa
- High blood amino acid levels
What causes the arteriolosclerosis observed in diabetic nephropathy and what impact does this have?
Hyalinosis of arterioles which causes tissue ischaemia
The clinical signs and symptoms observed in diabetic nephropathy can be arranged into 5 stages.
Identify them
- Hyperfiltration & hypertrophy
- Latent stage
- Microalbuminuria (moderately increased albuminuria)
- Overt proteinuria (severely increased albuminuria)
- ESRD
What is observed in the latent stage of diabetic nephropathy?
- Normal albuminuria
- GBM thickening
- Mesangial expansion
What is observed in the third stage of diabetic nephropathy (microalbuminuria)?
- Variable mesangial expansion / sclerosis
- Increased GBM thickening
- Podocyte changes
- GFR normal
What is observed in the fourth stage of diabetic nephropathy (overt proteinuria)?
- Diffuse glomerular histopathological changes
- Worsening systemic hypertension
- Falling GFR
- Microvascular changes (hyalinosis of arterioles)
What is the first clinical sign of diabetic nephropathy?
Microalbuminuria (assuming isotope GFR not measured)
Overt proteinuria in the third stage of diabetes is detectable on conventional dipstick.
What is the expected value in a woman?
Proteinuria > 30 mg/mmol Cr (0–3.5mg/mmol Cr)
Overt proteinuria in the third stage of diabetes is detectable on conventional dipstick.
What is the expected value in a man?
Proteinuria > 30 mg/mmol Cr (0–2.5mg/mmol Cr)
What is the clinical significance of overt proteinuria?
- Average decline in GFR 12mls / min/ year (2 – 20 mls)
- Most patients reach end-stage kidney disease in 3-7 years
Identify 5 risk factors for diabetic nephropathy
- Genetic susceptibility
- Race
- Hypertension
- Hyperglycaemia
- Increasing age
Describe the primary prevention of diabetic nephropathy
- Tight blood glucose control < 48 mmol/mol (<6.5%)
- Tight blood pressure control
Tight glycaemic control involves multiple injections or insulin pump to achieve a near normal blood glucose.
Describe 4 effects of this
- Can reverse initial hyperfiltration
- Can delay microalbuminuria
- Can reduce microalbuminuria over 2 years treatment period
- Doesn’t slow GFR loss once overt proteinuria develops
Referring to 5 options, describe the managment of microalbuminuria and proteinuria
- Inhibition of RAAS
- Tight blood pressure control < 130/75 mmHg
- Statin therapy
- CV risk management (exercise, diet, stop smoking)
- Moderate protein intake
Angiotensin II is released following renin release.
Identify 4 effects of this substance on the kidney
- Increases glomerular permeability to proteins
- Mesangial cell proliferation
- Increases mesangial matrix
- Constricts efferent glomerular arteriole
- Increases glomerular pressure
State 2 effects of RAAS inhibition in the management of diabetic nephropahty
- Reduces glomerular hyperfiltration (efferent > afferent arterioles)
- Reduces proteinuria & slows progression at stages 2 - 4 of diabetic nephropathy
What is the first renal sign of hypertensive renal disease / nephrosclerosis?
Microalbuminuria
Describe the general diagnosis of hypertensive nephrosclerosis
- Hypertension precedes proteinuria
- Long-term decline in GFR
- Often, left ventricular hypertrophy and hypertensive eye disease before developing kidney disease
How does the clinical presentation of renal artery stenosis differ from hypertensive nephrosclerosis?
- More acute hypertension
- More rapid decline in GFR
- Evidence of atherosclerosis elsewhere
- Acute worsening with RAAS-blockade
Describe the vascular changes of hypertensive nephrosclerosis
Vascular changes to renal arteries & arterioles:
- Fibroelastic intimal thickening → narrowing of lumen
- Hyalinosis of afferent arteriolar walls
Describe the glomerular changes of hypertensive nephrosclerosis
Glomerular changes secondary to ischaemia from vascular changes:
- Wrinkling of glomerular tuft
- Glomerulosclerosis (patchy)
Briefly, describe how hypertensive disease in young black patients is probably different than that in older Caucasian patients
The managment of hypertension in hypertensive nephrosclerosis slows the overall progression of the disease.
Describe the management
Good BP control:
- ACE-Inhibitors
- Angiotensin-receptor blockers (if there is albuminuria)
Hypertensive emergency involves an acute large increase in BP with target organ damage.
Describe how this presents
- Damage to endothelium (haematuria)
- Fibrinoid necrosis of arterioles (ischaemia – activation of RAAS)
- Shearing of blood cells (haemolytic anaemia)
- AKI
Identify the 3 characteristic features of Nephrotic Syndrome
- Proteinuria > 350 mg/mmol
- Hyperalbuminuria
- Oedema
Identify 3 other serum measurements which often accompany Nephrotic Syndrome
- High cholesterol
- Normal BP often (can be low or high)
- Creatinine may be normal
Identify 3 primary and secondary causes of Nephrotic Syndrome
- Primary: minimal change disease, FSGS, membranous nephropathy
- Secondary: diabetes, amyloidosis, SLE
Describe the management of Nephrotic Syndrome
- Diuretics (large doses) – oedema
- ACE-Inhibitor – proteinuria
- Atherogenic – hypercholesterolaemia (if long-term nephrotic)
- Treat underlying condition
Identify 4 clinical features of Nephritic Syndrome
- Haematuria
- Reduction in GFR (renal impairment / oliguria)
- Hypertension
- Non-nephrotic proteinuria
What is occurring in Nephritic Syndrome?
In Nephritic syndrome, the disruption of the endothelium results in inflammatory response and damage to the glomerulus
Onset of Nephritic Syndrome may be insidious or rapidly progressive.
What is Rapidly Progressive / Crescentic GN?
Rapidly Progressive / Crescentic GN is a fulminant form of nephritic syndrome caused by crescent formation
Identify 5 common causes of Nephritic Syndrome
- Goodpastures Syndrome
- ANCA-associated vasculitis
- IgA / Henoch-Schönlein purpura*
- Post-infectious*
- SLE*
*can also present as nephrotic
Describe the management of Nephritic Syndrome
- Proteinuria – blood pressure control (ACE-I/AIIR)
- Oedema – diuretics (large doses)
- Disease specific treatments – generally immunosuppressants
- CV risk management – stop smoking, statin, etc.
What is Systemic Lupus Erythematosus?
- SLE is an auto-immune systemic disease which can affect multiple systems and has many different patterns of renal disease
- It can cause nephritic or nephrotic syndrome
What is ANCA vasculitis?
- ANCA vasculitis is a type of autoimmune swelling caused by autoantibodies which affects small arterioles often in the kidneys and lungs
- It offten presents with systemic symptoms: fatigue, arthralgia, myalgia, weight loss
