6. Nephritic and nephrotic conditions Flashcards
How can glomerular diseases be classified
Heridtary
Primary: disease process originates from the glomerulus
Secondary to systemic disease: systemic lupus erythematosus, diabetes mellitus, bacterial endocarditis
What do glomerular diseases result in?
inflammation of glomerulus - Glomerulonephritis
What 4 clinical structures within glomerulus are prone to damage?
- Capillary endothelial cell lining
- Glomerular basement membrane
- Mesangium supporting the capillaries
- Podocytes on the outer surface of the capillary
What if glomerular disease is long lasting or left untreated?
Progresses to CKD
What is characteristic of nephrotic syndrome?
Proteinuria (> 3.5g/day)
What are the secondary effects of proteinuria in nephrotic syndrome? Why do these occur?
Hypoalbuminaemia causing:
- Oedema: lower capillary oncotic pressure
- Hyperlipidaemia: due to increased hepatic lipoprotein synthesis, secondary to protein loss
What allows proteinuria in nephrotic syndrome?
Podocyte damage, leading to increased pore size and a disruption of glomerular basement membrane charge barrier, hence allowing albumin to exit
How is nephrotic syndrome managed?
• Oedema
– Diuretics, need large doses and may need to be i.v. if gut oedema
– Salt and fluid restriction
• ACE-Inhibitor
– Anti-proteinuric but caution if intravascularly deplete or if renal function deteriorating acutely
• Hypercholesterolaemia
– Atherogenic if long-term nephrotic
• Treat underlying condition
– e.g. steroids for MCD, underlying cause of disease (e.g.amyloid)
• Blood pressure control
• Anticoagulation if hypercoaguable (risk of thrombosis increases as albumin decreases)
Why may anticoagulation be required for management of nephrotic syndrome?
As albumin decreases, the risk of thrombosis increases
What is the triad of nephrotic syndrome?
- Proteinuria
- Hypoalbuminaemia
- Oedema
What is nephritic syndrome usually accompanied by nephrotic syndrome and why?
high cholesterol as liver tries to compensate for hypalbuminaemia by producing more albumin and cholesterol made as a by product
What other features may be present with nephrotic syndrome>
- BP often normal (can be low or high)
- Creatinine may be normal
- Proteinuria > 350 mg/ mmol alone = nephrotic range proteinuria
Which types of primary renal disease can cause nephrotic syndrome?
- Minimal change disease
- Membranous glomerulonephritis
- Focal segmental glomerulosclerosis
Which types of secondary renal disease can cause nephrotic syndrome?
- Systemic lupus erythematous
Causing nephrotic syndrome but not glomerulonephritis: - Diabetes - most common cause
- Amyloid
What is minimal change disease?
Most common cause of nephrotic syndrome in children under 6, resulting in damage and effacement of foot processes of podocytes
How does minimal change disease present?
Foamy urine facial and Periorbital swelling peripheral and Pitting oedema ascites Possibly abdominal pain because of oedema in the gut mucosa (esp in children)
What causes nephrotic syndrome
podocyte damage leading to glomerular charge barrier disruption
How can you see the renal changes in minimal change disease?
Only on electron microscope, no significant changes visible under light microscope
How is minimal change disease treated?
- Diuretics e.g. furosemide to help manage oedema
- High-dose oral corticosteroids to reduce inflammation
- May require additional supplements of vitamin das corticosteroids can reduce calcium absorption
How is the prognosis of minimal change disease?
Good in children, but many relapse after treatment
Variable w/ adults
What investigation can be done to confirm minimal change glomerulonephritis?
only way to confirm is renal biopsy but in children with nephrotic syndrome, minimal change is most likely diagnosis so risks of biopsy are generally considered to outweigh the potential diagnostic benefit.
What is membranous glomerulonephritis?
Subepithelial deposition of immune complexes causes thickening of the basement membrane and subsequently larger fenestrations/filtration slits
Causes of membranous glomerulonephritis
Most idiopathic Primary type - immune complexes Infections - syphilis, malaria, hep B Tumours Drugs - heroin, mercury SLE
How is membranous glomerulonephritis treated?
Immunosuppressants
Treating underlying cause
What causes primary FSGS?
Idiopathic
What causes secondary FSGS?
Sickle cell disease
HIV
Heroin abuse
Kidney hyperfusion
How is FSGS treated?
Steroids
What is focal segmental glomerulosclerosis?
Sclerosis of segments of some but not all glomeruli
Briefly describe the pathophysiology of FSGS
Podocytes damaged
Proteins build up in glomerulus
Hyalinosis
Sclerosis
What type of condition is diabetic nephropathy?
nephrotic condition
Describe the pathophysiology of diabetic nephropathy
- Excess glucose in blood binds to proteins. Especially at efferent arteriole.
- Hyaline atherosclerosis – obstructs blood flow
- Initially ↑GFR
- Over time mesangial cells secrete more structural matrix
- Thickening of BM
- ↓GFR
What is the treatment of diabetic nephropathy?
Hypertension, good glycemic control, ACE inhibitors, angiotensin receptor blockers
What is nephritic syndrome?
inflammation disrupting glomerular basement membrane
What is nephritic syndrome characterized by?
Triad of haematuria(microscopic or macroscopic), reduced GFR (so oliguria) and hypertension
What are some other features of nephritic syndrome, other than the classic triad?
- 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
- Fluid retention – seen as facial oedema
- Uraemia
- Patients may also complain of loin pain, headaches and general malaise
What are some common causes of nephritic syndrome?
- Goodpasture’s (Anti GMB)
- Rapidly progressive GN
- IgA Nephropathy (Berger’s Disease)
- Post-streptococcal GN
What is Berger’s disease?
IgA deposited in the mesangium, causing sclerosis of the damaged segment
What is the most common primary glomerular disease which causes recurrent haematuria?
IgA Nephropathy/Berger’s disease
What will be raised in berger’s disease
Hypertension and IgA levels raised
How is Berger’s disease treated?
Controlling BP
Antihypertensives
Steroids
What will 20% of patients with Berger’s disease go onto develop?
Advanced CKD
What is rapidly progressive glomerulonephritis?
AKA crescentric glomerulonephritis
Inflammation in the glomerulus, leading to loss of renal function within days to weeks
Describe the pathology in rapidly progressive glomerulonephritis
Severe glomerular injury, leading to leakage of fibrin and macrophages, and the proliferation of epithelial cells into crescent shaped masses which reduced the glomerular blood supply
How is rapidly progressive glomerulonephritis treated? Give examples of the medications required
High dose steroids e.g. prednisolone
Immunosuppressants e.g. cyclophosphamide, rituximab
Plasma exchange - removing immune complexe
What is post-streptococcal glomerulonephritis?
Nephrotic syndrome arising 1-3 weeks following the group A beta-haemolytic streptococcal infection of tonsils, pharynx or skin
How is post-streptococcal glomerulonephritis treated?
Antibiotics for remaining infection
What is the prognosis for post-streptococcal glomerulonephritis?
Excellent in children
60% of adults recover completely, rest develop hypertension or renal impairment
What is Goodpasture’s syndrome?
Inflammation due to antibodies against type IV collagen in glomerular basement membrane, resulting in progressive glomerulonephritis, acute renal failure and lung haemorrhage
Why is the lung affected in Goodpasture’s syndrome?
Has similar type of collagen to which the antibodies are against
What is the treatment of Goodpasture’s syndrome? What is the prognosis like without treatment?
Treated with plasma exchange to remove antibodies and corticosteroids for the inflammation
Poor prognosis without treatment
What can be a sign of proteinuria? Is this always a sign of it?
Frothy urine
Can be frothy for other reasons e.g. high volume of urine expelled quickly
How is nephritic syndrome managed?
• 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 or rituximab +/- plasma exchange
• Cardiovascular risk management
– Stop smoking, statin etc
• Dialysis (often short-term)
