Lecture 13 - Glomerular Diseases (clinical) Flashcards
What are glomerular diseases?
Inflammatory disorders of the kidney
What are glomerular diseases classified on? What investigation is necessary to differentiate them?
Morphology
Biopsy
What are the typical clinical features of a glomerulonephritis?
Haematuria
Proteinuria
Hypertension
Renal insufficiency
What are the types of haematuria?
Macroscopic/franks vs microscopic
Persistent vs transient
Define microscopic haematuria
5+ RBC per high power field
Is haematuria more typical of nephrotic or nephritic syndrome?
Nephritic
What can be the sources of blood in haematuria?
Kidney, ureter, bladder, urethra, prostate
What kind of haematuria do you tend to see in glomerulonephritis?
Persistent macroscopic haematuria (microscopy shoes dysmorphic RBCs)
Where abouts is the problem if you have proteinuria?
Glomerulus/tubules
How can you measure proteinuria?
Urine protein creatinine ratio
24 hour urine collection
What kind of proteinuria do you tend to see in glomerulonephritis?
Persistent proteinuria of more than 1g/mmol creatinine
Is hypertension more typical of nephritic or nephrotic syndrome?
Nephritic
What features are typical of nephritic syndrome?
Haematuria Mild/moderate proteinuria Hypertension Oliguria Red cell casts in the urine
What features are typical of nephrotic syndrome?
Oedema
Proteinuria >3.5g/day
Hypoalbuminaemia (<30g/L)
Hyperlipidaemia
What will you see on urinalysis of someone with nephrotic syndrome?
Proteinuria (protein ++++)
Frothy appearance
Why are individuals with nephrotic syndrome predisposed to thrombosis?
Loss of antithrombin III, proteins C and S and associated rise in fibrinogen levels
What are differential diagnoses for nephrotic syndrome and how could you differentiate them from nephrotic syndrome?
Congestive heart failure (JVP raised, normal albumin, minimal proteinuria)
Hepatic disease (abnormal LFTs, no proteinuria)
What are the aetiologies of glomerulonephritis?
Autoimmune
Infection
Malignancy
Drugs
NB same diseases can be caused by different things
What are the two subtypes of GNs?
Proliferative
Non-proliferative
What is a proliferative GN?
One in which there are excessive numbers of cells in glomeruli, incl infiltrating leucocytes
What is a non-proliferative GN?
Glomeruli appear normal or have areas of scarring
Normal number of cells
What is meant by a diffuse GN?
> 50% glomeruli affected
What is meant by a focal GN?
<50% of glomeruli affected
What is meant by a global GN?
All glomerulus affected
What is meant by a segmental GN?
Part of glomerulus affected
What GNs cause a nephrotic syndrome?
Minimal change disease
Membranous nephropathy
What GNs cause a nephritic state?
ANCA associated GN
Post-infectious GN
Crescentic GN
Diffuse proliferative GN
What GN largely just causes proteinuria and urinary sediment abnormalities?
IgA nephropathy
What GNs can cause nephrotic/nephritic state?
FSGS
Mesangioproliferative GN
List 4 of the proliferative GNs
Diffuse proliferative - post-infective nephritis
Focal proliferative - mesangial IgA
Focal necrotizing (crescentic) nephritis
Membrano-proliferative nephritis
What nodules do you see in post-infectious GN?
Kimmersteil-Wilson nodules
May also see IgA deposits
What is the natural history of post-strep GN?
Follows 10-21d post throat/skin infection
What organism most commonly causes post-strep GN?
Lancefield group A strep (usually strep pyogenes)
What alleles genetically predispose someone to getting post-strep GN?
HLA-DR, -DP
What causes post-strep GN?
Immune complexes (IgG, IgM, C3) deposition in the glomeruli
Who is most affected by post-strep GN?
Young children usually
What are the clinical features of post-strep GN?
Headache, malaise Haematuria Proteinuria HTN Low C3 Raised ASO titre 1-2w post URTI (more nephritic state, e.g. red cell casts etc)
How is post-strep GN treated?
Vasodilator drugs, e.g. amlodipine for HTN
Loop diuretics, e.g. frusemide if any oedema
What is the commonest GN worldwide?
IgA nephropathy
What characterises IgA nephropathy?
IgA deposition in the mesangium + mesangial proliferation
Who most commonly gets IgA nephropathy?
20-30 yo males
What % of cases of IgA nephropathy progress to ESRD?
40%
How can IgA nephropathy present?
Microscopic haematuria (can be silent for a while)
Microscopic haematuria + proteinuria
Nephrotic syndrome
IgA crescentic GN
What is IgA nephropathy AKA?
Berger’s disease
How does IgA nephropathy classically present?
Macroscopic haematuria in young people following an URTI
typically nephritic syndrome!
What conditions are associated with IgA nephropathy?
Alcoholic cirrhosis
Coeliac disease/dermatitis herpetiformis
HSP
What do you see on histology in IgA nephropathy?
Mesengial hypercellularity
Positive immunofluorescence for IgA + C3
What is a marker of good prognosis in IgA nephropathy?
Frank haematuria
What is a marker of poor prognosis in IgA nephropathy?
Male grnder Proteinuria (esp >2g/day) HTN Smoking Hyperlipidaemia ACE genotype DD
What are the types of crescentic GN?
ANCA associated: microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis
Anti-GBM - e.g. anti-GBM nephritis or Goodpasture’s syndrome
Others - IgA vasculitis, post-infection GN, SLE
What is goodpastures syndrome?
A rare condition associated with pulmonary haemorrhage and rapidly progressive GN
What causes goodpastures syndrome?
Anti-glomerular basement membrane antibodies against type IV collagen
What HLA allele is associated with goodpastures syndrome?
HLA DR2
What factors in goodpastures syndrome increase the likelihood of pulmonary haemorrhage?
Smoking LRTI Pulmonary oedema Inhalation of hydrocarbons Young male
How do you investigate suspected goodpasture syndrome?
Renal biopsy (linear IgG deposits along the basement membrane)
What is involved in the management of goodpastures syndrome?
Plasmapheresis
Steroids
Cyclophosphamide
What causes anti-GBM disease?
Circulating anti-GBM antibodies
How can anti-GBM present?
Nephritis - anti-GBM glomerulonephritis
Nephritis + lung haemorrhage (Goodpastures)
How is anti-GBM disease treated?
Aggressive immunosuppression - steroids, plasma exchange, cyclophosphamide
How is crescentic GN managed?
Corticosteroids, plasma exchange, cyclophosphamide, B cell therapy (e.g. rituximab), complement inhibitors
What does 10-20% of anti-GBM disease progress to?
Crescentic GN
How do proliferative GNs present?
Nephritic syndrome
What are the main non-proliferative GNs?
Minimal change disease
Focal and segmental GN
Membranous nephropathy
How is nephrotic syndrome managed?
Treat oedema –> fluid + salt restriction, loop diuretics
HTN: RAAS blockade
Reduce risk thrombosis: heparin/warfarin
Reduce risk of infection e.g. pneumococcal vaccine
Treat dyslipidaemia, e.g. with statins
Who is minimal change disease the most common GN in?
Children
How does minimal change disease tend to present?
Sudden onset oedema (nephrotic syndrome)
How is minimal change disease treated?
Steroids (prednisolone 1mg/kg for up to 16w, taper over 6m once remission achieved)
What fraction of pts with minimal change disease relapse?
2/3rd
If someone has a relapse of minimal change disease how is this managed?
Cyclophosphamide Cyclosporin Tacrolimus Mycophenolate mofetil Rituximab
What is the prognosis of minimal change disease?
1/3 - just one episode
1/3 - infrequent episodes
1/3 - frequent episodes which stop before adulthood
Does minimal change disease present as a nephrotic or nephritic syndrome?
Nephrotic
What are the aetiologies for minimal change disease?
Usually idiopathic
Drugs: NSAIDs, rifampicin
Hodgkin’s lymphoma, thymoma
IM
What is the pathophysiology of minimal change disease?
T-cell and cytokine mediated damage to the glomerular basement membrane –> polyanion loss
Resultant reduction of electrostatic change –> increased glomerular permeability to albumin
What are the features of minimal change syndrome?
Nephrotic syndrome
Highly selective proteinuria (only medium sized proteins, e.g. albumin + transferrin)
What do you see on renal biopsy in minimal change disease?
Normal glomeruli on light microscopy
Electron microscopy shows fusion of podocytes + effacement of foot processes
What % of minimal change disease is steroid responsive?
80%
Cyclophosphamide next step for steroid resistant cases
What is focal and segmental GN?
A syndrome with multiple causes
Does focal and segmental GN present with a nephritic or nephrotic syndrome?
Nephrotic
What do you see on histology in focal and segmental GN?
Focal + segmental sclerosis with distinctive patterns, e.g. tip lesion, collapsing, cellular etc.
Can focal and segmental GN be treated with steroids?
No - usually v. steroid resistant
What is the prognosis of focal and segmental GN?
High chance of progression to ESRD
How is focal and segmental GN managed?
General measures for nephrotic syndrome, e.g. treat oedema, HTN etc.
Trial steroids, even if partial remission
Alt options: cyclophosphamide, cyclosporin, rituximab
What is focal and segmental GN aka?
Focal segmental glomerulosclerosis
Who does FSGS normally present in?
Young adults
What are causes of FSGS?
Idiopathic 2 to other renal pathology, e.g. IgA nepropathy, reflux nephropathy HIV Heroin Alport's syndrome Sickle-cell
What is the recurrence rate of FSGS like post-transplant?
V. high
What do you see on renal biopsy in FSGS?
Focal + segmental sclerosis + hyalinosis on light microscopy
Effacement of foot processes on electron microscopy
What is the commonest cause of nephrotic syndrome in adults?
Membranous nephropathy (usually idiopathic)
What antibody is present in 70% cases of membranous nephropathy?
Anti-phospholipase A2 receptor antibody
What are secondary causes of membranous nephropathy?
Malignancies - lung cancer, lymphoma, leukaemia SLE RA Infections - hep B, malaria, syphillis Drugs - NSAIDs, gold, penicillamine
What other marker is screened for in membranous nephropathy (apart from PLA2R)?
Thrombospondin type 1 domain containing 7A
What can you see on electromicroscopy in membranous nephropathy?
Basement membrane is thickened with subepithelial electron dense deposits - creates a spike and dome appearance
How is membranous nephropathy managed?
ACEi/ARB
General measures for at least 6m
Immunosupression if severe/progressive disease
Corticosteroids tend to be used in combo with another agent, e.g. cyclophosphamide
Anticoagulation for high risk pts
What is the prognosis of membranous nephropathy?
1/3rd: spontaneous remission
1/3rd remain proteinuric
1/3rd develop ESRD
What is membranoproliferative GN AKA?
Mesangiocapillary GN
How can membranoproliferative GN present?
Nephrotic syndrome, haematuria or proteinuria
What is the prognosis of membranoproliferative GN?
Poor
What the different types of membranoproliferative GN?
Type 1
Type 2
Type 3
What is the most common type of membranoproliferative GN?
Type 1 (90%)
What are the causes of type 1 membranoproliferative GN?
Cryoglobinaemia
Hepatitis C
What do you see on electromicroscopy on membranoproliferative GN?
Subendothelial and mesangium immune desposits of electron dense material –> tram track appearance
What is type 2 membranoproliferative GN?
Dense deposit disease
Caused by persistent activation of alternative complement pathway
Causes - partial lipodystrophy, factor H deficiency
What blood result abnormality do you see in patients with type 2 membranoproliferative GN?
Low circulating levels of C3
What do you see on electron microscopy in type 2 membranoproliferative GN?
Intramembranous immune complex deposits with dense deposits
What are causes of type 3 membranoproliferative GN?
Hep B and C
How can membranoproliferative GN be treated?
Steroids may be effective
What is rapidly progressive GN?
Term used to describe a rapid loss of renal function assoc. w formation of epithelial crescents in the majority of glomeruli
What are causes of rapidly progressive GN?
Goodpastures syndrome
Wegner’s granulomatosis
SLE, microscopic polyarteritis
What are features of rapidly progressive GN?
Nephritic syndrome + features specific to underlying cause, e.g. vasculitis rash and sinusitis with Wegners
