Renal medicine Flashcards
Granulomatosis with polyangitis biopsy findings:
Pauci-immune crescenteric glomerulonephritis (ANCA positive)
Anti-GBM disease biopsy findings:
Crescenteric glomerulonephritis with linear immunoglobulin G (IgG) deposition
Who presents with focal segmental glomerulosclerosis?
Diabetes, those on antiretrovirals, SLE, sickle cell disease
Membranous glomerulonephritis associations
Associated with SLE and polyarteritis nodosa
Minimal change association and treatment
Seen in the young
High dose pred. If contraindicated can think about tacrolimus + low dose steroids or rituximab for frequently relapsing disease
Difference nephrotic and nephritic
What types of glomerulonephritides are there?
General treatment approach to glomerulonephritis?
Non-proliferative vs proliferative
Non-proliferative glomerulonephritis is characterised by a lack of glomerular cell proliferation and typically presents with nephrotic syndrome.
Proliferative glomerulonephritis is characterised by increased numbers of cells in the glomerulus
It typically presents with nephritic syndrome
Non proliferative: Minimal change glomerulonephritis
Minimal change glomerulonephritis presents with nephrotic syndrome.
It accounts for 80% of all nephrotic syndrome in children and 20% of nephrotic syndrome in adults.
The underlying cause of minimal change glomerulonephritis is unknown.
Typical investigation findings
Urinalysis – proteinuria
Light microscopy – no visible abnormalities
Immunofluorescence – no immunoglobulins or complement deposits bound to the kidney tissue ¹
Electron microscopy – diffuse loss of visceral epithelial cells’ foot processes (i.e. podocyte effacement), vacuolation, and growth of microvilli on the visceral epithelial cells, allowing for excess protein loss in the urine ²
Management
Supportive care – nutritional support, salt and fluid restriction
Corticosteroids (first-line) – used in both adults and children (more data for efficacy in children) ¹
Other immunosuppressants (second-line – effectiveness unclear) – e.g. calcineurin inhibitor, mycophenolate mofetil, rituximab ¹
Non-proliferative: Focal segmental glomerulosclerosis (FSGS)
Typically presents with nephrotic syndrome(usually haematuria, hypertension and impaired renal function)
Aetiology:
Primary FSGS (i.e. genetic mutations)
Secondary FSGS (e.g. HIV, lupus, reflux nephropathy)
Typical investigation findings
Specific segments of certain glomeruli show segmental scarring in addition to foot process fusion
Management
Supportive care – salt restriction and fluid management
High-dose prednisolone (approximately 50% of patients respond – treatment can be up to 4 months in adults)
Additional cyclophosphamide or ciclosporin is used in some cases to reduce proteinuria.
Prognosis
Typically progresses to end-stage kidney disease over the course of several years in up to 50% of patients
Corticosteroids can halt progression in some cases
Non-proliferative: Membranous glomerulonephritis
Membranous glomerulonephritis typically presents with nephrotic syndrome
It is usually a slowly progressive disease primarily affecting individuals between the ages of 30-50
It is most commonly idiopathic but can be associated with hepatitis B, malaria and system lupus erythematosus (SLE)
Pathophysiology
Immune complex deposition, resulting in complement activation against glomerular basement membrane proteins
Typical investigation findings
Microscopic analysis shows thickened glomerular basement membrane (but not mesangium)
Immunofluorescence shows diffuse uptake of IgG
Management
- Prednisolone and cyclophophamide
- escalate to rituximab when necessary
Corticosteroids are often used to treat progressive disease
Prognosis
1/3 have chronic membranous glomerulonephritis
1/3 go into remission
1/3 progress to end-stage renal failure
Proliferative: IgA nephropathy
IgA nephropathy is also known as Berger’s disease
It is the most common type of GN in adults worldwide
It typically presents as nephritic syndrome (macroscopic haematuria) 24-48 hours after an upper respiratory tract infection
Typical investigation findings
Microscopically the disease is characterised by:
increased numbers of mesangial cells
increased matrix (the cellular scaffolding that holds everything together)
Immunohistochemistry reveals IgA deposition in the matrix.
Management
Some studies suggest that a course of high-dose prednisolone can reduce proteinuria and delay renal impairment
In patients with deteriorating renal function, immunosuppressive drugs are also often used
Prognosis
Prognosis is variable, with 20-30% of patients progressing to end-stage renal failure
Proliferative: Post-infectious glomerulonephritis
Post-infectious glomerulonephritis (PIGN) is an immunologically mediated glomerular injury triggered by an infection
PIGN is most commonly associated with streptococcal infections (referred to as post-streptococcal glomerulonephritis)
The disease typically presents approximately 2 weeks after infection with nephritic syndrome (i.e. gross haematuria, oliguria, oedema)
Typical investigation findings
Diffuse proliferative and exudative glomerular histology
Dominant C3 staining and subepithelial humps
Diagnosis
Diagnosis is typically based on the presence of:
Symptoms and signs of GN
History of recent infection (e.g. streptococcal)
Raised streptococcal titres
Management
Management is largely supportive, with careful monitoring of fluid balance
Prognosis
PIGN is usually a self-limited disease, especially in children, but long-term follow-up studies indicate persistent low-grade renal abnormalities in a significant proportion of patients
Proliferative: Membranoproliferative glomerulonephritis
Membranoproliferative glomerulonephritis is a group of immune-mediated disorders characterised histologically by glomerular basement membrane (GBM) thickening and proliferative changes on light microscopy.
It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.
The disease is associated with hepatitis C and several autoimmune conditions including systemic lupus erythematosus (SLE).
Typical investigation results
Microscopy:
Thickened basement membrane
Thickened mesangium
“Tram tracking” appearance
Immunofluorescence:
Subendothelial deposition of IgG
Management
Children (with nephrotic-range proteinuria) – corticosteroids
Adults (dipyridamole and aspirin)
Kidney transplantation for patients with end-stage renal disease
Proliferative: Rapidly progressive glomerulonephritis (crescentic glomerulonephritis)
Rapidly progressive glomerulonephritis (RPGN) is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months.
RPGN is relatively uncommon, affecting 10 to 15% of patients with glomerulonephritis
It primarily occurs in patients aged 20 to 50 years
Proliferative: Anti-glomerular basement membrane antibody disease (Anti-GBM)
Anti-GBM disease is an immune-mediated pathology involving antibodies directed against glomerular basement membrane antigens (anti-GBM antibodies).
These antigens are located in the glomeruli and in the alveoli of the lungs.
A cell-mediated inflammatory response occurs as a result of the anti-GBM antibodies which can affect both the kidneys (nephritic syndrome) as well as the lungs (alveolar haemorrhage presenting with haemoptysis).
If the lungs and kidneys are involved the condition is known as Goodpasture’s syndrome.
Anti-GBM disease accounts for approximately 10% of RPGN.
Progression to renal failure is often rapid without medical intervention.
Typical investigation results
Immunohistochemistry –IgG deposits along the basement membrane of the glomerulus
Antibodies – anti-GBM antibodies
Management
High dose immunosuppression is required:
IV prednisolone
Cyclophosphamide
(azathioprine for long-term maintenance)
Plasmapheresis
Vasculitic: Granulomatosis with polyangiitis (Wegener’s)
Granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, is an extremely rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis)
It is a form of vasculitis that affects both small and medium-sized vessels in many organs (commonly the upper respiratory tract, lungs and kidneys)
Symptoms are highly variable, depending on which vessels are affected
GPA affecting the lungs, kidneys or heart can be life-threatening
The vasculitis is caused by anti-neutrophil cytoplasmic antibodies (c-ANCA)
Diagnosis
A history of unexplained symptoms
Positive c-ANCA test
Biopsy (e.g. of kidney or cutaneous tissue) – leukocytoclastic vasculitis with necrotic changes and granulomatous inflammation (clumps of typically arranged white blood cells) on microscopy
Management
Induction of remission – rituximab or cyclophosphamide in combination with high dose corticosteroids
Maintenance – methotrexate and corticosteroids
Vasculitic: Microscopic Polyangiitis
A systemic small-vessel vasculitis without clinical or pathological evidence of necrotising granulomatous inflammation
Clinical features can include weight loss, fevers, fatigue and renal failure
Ongoing inflammation is driven by anti-neutrophil cytoplasmic antibodies (p-ANCA)
Diagnosis
Raised ESR and CRP
Anaemia
p-ANCA is positive in almost all cases
Management
Long-term prednisolone and cyclophosphamide therapy (often cycled)
Plasmapheresis can be helpful acutely to remove p-ANCA antibodies
Peritoneal dialysis infection
Staph epidermidis, treated with vancomycin
What is thin basement renal membrane nephropathy?
Autosomal dominant disorder that runs in families. Similar to Alport syndrome but not progressive and no hearing loss
Treatment option for recurrent renal calcium stones?
Bendroflumethiazide as it reduces calciu secretion
Site of action of diuretics
Ascending limb of Henle is impermeable to water
Bronchiectasis effect on kidney
Chronic inflammation leads to systemic amyloidosis leading to deposition with progressively worsening protein leak
Eosinophilic pgranulomatosis with polyangiitis presentation (CHurg-Strauss)
Poorly controlled asthma, sinusitis, mononeuritis and peripheral blood eosinophilia.
30% are pANCA positive and biopsies show necrotising granuloma
Which drug do you use to slow renal progression in SLE?
Use mycophenolate mofetil before. using cyclophosphamide because of better side effect profile.
What are the renal cystic disorders?
ADPKD, ARPKD, vHL and tuberous sclerosis
vHL presentation
Tuberous sclerosis presentation
HAMARTOMAS: Hamartoma, Adenoma sebaceum, Mental retardation (now properly referred to as intellectual disability), Ash leaf spots, Rhabdomyoma, Tubers, Optic hamartomas (phakomas), Mitral regurgitation, Astrocytomas, Seizures
What structure overlies left renal hilum?
Tail of pancreas
What is Liddle Syndrome?
Autosomal Dominant Condition in epithelial sodium channel
Preentation: Early (teenage years) hypertension, hypokalemia, alkalosis,
Sign on US of unalateral renal artery stenosis
small kidney on affected side together with hypertension
Where is most phosphate reabsorbed?
Proximal tubule.
Liddle Syndrome
Congenital hypertension with hypokalaemic metabolic alkalosis.
Autosomal dominant.
Amiloride or triamterene interventions of choice
Bartter Syndrome
Normal blood pressure but hypokalaemic metabolic alkalsosis with increased urinary Ca excretion (mimics loop diuretic). SLC12A1 gene.
Gitelman syndrome
Normal blood pressure but hypokalaemic metabolic alkalsosis with decreased urinary Ca excretion (mimics thiazide diuretic). SLC12A3 gene.
Liddle vs Bartter vs Gitelman
Different types of RTA
Why is nephrotic syndrome pro-thrombotic?
