glomerulonephritis And DM Flashcards
What is GN and what are the 4 structures that can be damaged
• ‘inflammation of glomeruli’ 4 structures in glomerulus that can be damaged: • Capillary endothelium • Glomerular basement membrane • Mesangial cells • Podocytes • Often involves the immune system
What are the types of damage that can occur to the nephron
Too many mesangium cell,s fusion of podocytes, subepithelial innume complexes, narrowed lumen,
How can GN be classified
- Clinical presentation (e.g. nephrotic)
- Histological appearance (e.g. minimal change disease)
- Diagnosis (e.g. lupus)
- Primary / Secondary
What is teh clinical presentation of GN
- Asymptomatic haematuria & / or proteinuria
- Chronic glomerulonephritis
- Acute glomerulonephritis - weeks-months
- Rapidly progressive glomerulonephritis. Matter of days
- Nephrotic syndrome
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Compare nephrotic and nephritic syndrome
NEphrotic - podocytes damage leading t glomerular charge-barrier disruption - proteinuria - bigger molecules liek albumin can get out
Nephritic - inflammation disrupting glomerular basement membrane - haematuria
What is nephrotic syndrome
A triad of :
• Proteinuria > 350 mg/ mmol (or 3.5 g in 24 hours)
• Hypoalbuminaemia - Losing protein faster than liver cn make it
• Oedema
• Usually accompanied by high cholesterol
Other features:
• BP often normal (can be low or high)
• Creatinine may be normal
• Proteinuria > 350 mg/ mmol alone = nephrotic range proteinuria
What are the causes of nephrotic syndrome
Primary Renal Disease
• Minimal change disease • Membranous nephropathy
• Focal segmental glomerulosclerosis (FSGS)
Secondary Renal Disease
• Diabetes Most common cause
• SLE (lupus)
• Amyloid
(Amyloid and dm - Nephrotic syndrome but not GN)
What si the management for nephrotic syndrome
Oedema
– Diuretics, need large doses and may need to be i.v. if gut oedema
– Salt and fluid restriction
ACE-Inhibitor (if by ok)
– Anti-proteinuric but caution if intravascularly deplete or if renal function deteriorating acutely
Hypercholesterolaemia
– Atherogenic if long-term nephrotic
(dont give statin if cholesterol is high)
Treat underlying condition
– e.g. steroids for MCD, underlying cause of disease (e.g. amyloid)
Dont give steroid to diabetic
What is nephritic syndrome
A triad of:
• Haematuria - doesn’t need to be visible but has to be present on dippstick
• Reduction in GFR (renal impairment / oliguria)
• Hypertension
Other features
• Often some proteinuria but less than nephrotic syndrome
• Disruption of the endothelium results in inflammatory response & damage to the glomerulus
• Onset may be acute or rapidly progressive (RPGN)
• Rapidly Progressive / Crescentic GN - a fulminant form of nephritic syndrome
What are common causes of nephritic syndrome
- Anti-GBM disease (Goodpasture’s)
- ANCA-associated vasculitis
- IgA / Henoch-Schönlein purpura*
- Post-infectious*
- Lupus*
• Associated with immune disease
*can also present as nephrotic
What is the management for nephritic syndrome
Blood pressure control / reduction of proteinuria
– ACE-I or AIIR first line if renal function allows
– Salt restrict
Treatment of oedema
– As for nephrotic syndrome if adequate renal function
Disease specific treatments
– Generally immunosuppressants
– e.g. RPGN
– prednisolone, cyclophosphamide +/- plasma exchange
Cardiovascular risk management
– Stop smoking, statin etc
Dialysis (often short-term)
Wat is ANCA associated vasculitis
- Granulomatosis with polyangiitis (Wegener’s) & microscopic polyangiitis
- Affect small arterioles
- Often kidneys and lungs
- ‘pulmonary-renal syndrome’
- Often systemic symptoms (inflammatory condition)
- Fatigue, arthralgia, myalgia, weight loss
- No immune deposits in kidney – circulating antibodies to white cells
- cause Endothelial damage
What is anti gbm disease
Anti-GBM Disease (Goodpasture’s disease)
• Caused by anti-bodies to α3 chain of type 4 collagen in glomerular basement membrane
• Can also affect α3 chain of type 4 collagen in alveolar basement
membrane but harder for anti-bodies to get here.
• Pulmonary haemorrhage more likely with pre-existing damage to alveolar endothelium e.g. smokers, infection
• Always causes RPGN
Present very acutely - goes from being nothing to being renal failure within days. Kidney failure - need dialysis sits.
What is systemic lupus erythematosus
• Auto-immune systemic disease. Can affect multiple systems
• Has many different patterns of renal disease
• Can cause nephritic or nephrotic syndrome
• Prognosis depends on type of lesion, activity and amount of kidney
involved
• Treatment also varies according to pattern of lupus nephritis
Wha is diabetic nephropathy
• Commonest cause of ESRD • Historically quoted that 30-40% all types of diabetes eventually get ESRD • It is a glomerulopathy - NOT a gomerulonephritis
What are the pathological changes in diabetic nephropathy
- Hyperfiltration / capillary hypertension
• Happens before all other changes - Glomerular basement membrane thickening
- Mesangial expansion
- Podocyte injury
- Glomerular sclerosis / arteriolosclerosis
What happens in the early course of diabetic nephropathy
Hyperfiltration & hypertrophy
• Occurs early in course of
disease • Related to hyperglycaemia • Glomerular hypertension
• ↑ GFR
What are the structural and functional relationships in gfr in diabetic hyerfiltratiob
Reabsorbing more glucose tiem each sodium - more water and salt held in the body. Delivering less to macula dense - sensory TGF feedback to dilate AA, - renin secreted - raas - constricts EA - increase pressure
Describe teh glomerular filtration barrier in diabetic nephropathy
Damage to podocytes
Thickened GBM increases pore size
Mesangial expansion
High intraglomerular pressure
Describe the histology in diabetic nephropathy
Ss
What are teh clinical signs as diabetic nephropathy progresses
- Hyperfiltration & hypertrophy
• Increased GFR
Normal histology - Latent stage
• Normal albuminuria
• GBM thickening & mesangial expansion - Microalbuminuria (aka moderately increased albuminuria)
• Variable mesangial expansion / sclerosis
• Increased GBM thickening
• Podocyte changes
• GFR normal - Overt proteinuria (aka severely increased albuminuria)
• Diffuse glomerular histopathological changes
• Systemic hypertension
• Falling GFR - ESRD - end stage renal disease
Describe microalbuminuria
• First clinical sign (assuming isotope GFR not measured) • GBM thickening & mesangial expansion
• Albuminuria Potentially • 30 – 300 mg/day reversible at this stage
• ‘Albustix’
UHL spot sample • 0 – 3.5 mg / mmol Cr in women • 0 – 2.5 mg / mmol Cr in men
What is overt proteinuria
• Previously associated with inexorable decline to ESRD in 3 – 7 years
• GFR normal initially (i.e. dropped from hyperfiltration) then generally drops in linear pattern
• mesangial expansion / sclerosis → reduced surface area for filtration
• Detectable on conventional dipstick Not
• Proteinuria > 30 mg/mmol Cr reversible – can be
• Frequently increases to nephrotic range proteinuria slowed
• Worsening systemic hypertension
• Microvascular changes (hyalinosis of arterioles)
– Causes tissue ischaemia
Wat is the significance of overt proteinuri
• Normal GFR and proteinuria < 100 mg mmol = mild kidney disease - not likely to get to esrd
- EXCEPT in diabetes - oath to decline
• Average decline in GFR 12mls / min/ year (2 – 20 mls)
• Most patients reach end-stage kidney disease in 3-7 years
Wha ar are the risk factors for diabetic nephropathy
• Genetic susceptibility DM type 1 with 1st degree relative with DN = 83% risk1
DM type 1 with 1st degree relative with DM type 1 but no nephropathy = 17% risk
• Race (aucasian less likely than Mexican, Caribbean, African saeAsian etc)
• Hypertension
• Hyperglycaemia
• High level of hyperfiltration
• Increasing age
• Duration of diabetes • Smoking
What is teh primary prevention of diabetic neproathy
• Tight blood glucose control
– < 48 mmol/mol (<6.5%)
• Tight blood pressure control
– No particular agent shown to be better with normal albuminuria
- ? SGLT-2 inhibitors
- ? Not smoking
- ? Statin therapy
Describe tyight glycaemic control
- Multiple injections or insulin pump → near normal blood glucose
- Can reverse initial hyperfiltration and delay microalbuminuria
- Can reduce microalbuminuria over 2 years treatment period
- Doesn’t slow GFR loss once overt proteinuria develops
What os the management of microalbuminuria and proteinuria
• Inhibition of RAAS • Tight blood pressure control – <130/80 mmHg • Statin therapy • CV risk management (exercise, diet, stop smoking) • Moderate protein intake • Tight blood glucose control (does not affect progression once overt proteinuria develops)
What does raas blockade do
• Reduces glomerular hyperfiltration
• Efferent > afferent arterioles
• Anti-proteinuric effect more than BP reduction alone
• Reduces proteinuria & slows progression at stages 2 - 4 of diabetic
nephropathy
• Hyperkalaemia limits use with advanced CKD
What is thr principal of salt inhibition
If you cn block salut 2 reabsorption 0 glucoseuria - sodium delivered here- not triggering tgf feedback - pressure doesn’t increase
