Glomerular Disease (clinical) Flashcards
in basic terms what is glomerular disease
Inflammatory disorders of the kidney.
Responsible for almost 30% of end-stage kidney disease.
Classified based on morphology.
Majority are attributed to autoimmune aetiologies
what are features of glomerulonephritis
haematuria
proteinuria
hypertension
renal insufficiency
what are the two types of haematuria and how are they classified
macroscopic - tea or cola coloured ruin or frank blood
microscopic - >5 RBC per high power field
what is the difference between nephrotic and nephritic syndromes
nephrotic
- disease of the kidneys
- loss of protein
nephritic
- disease of the glomeruli
- loss of protein AND whole RBC
how is haematuria seen in glomerulonephritis
persistent microscopic haematuria
miroscopy shows dysmorphic RBC (mickey mouse like)
what are the aspects of haematuria
Macroscopic or Microscopic,
Transient or persistent
Nephritic>nephrotic
Source: kidney, ureter, bladder, prostate, urethra
how is proteinuria seen in glomerulonephritis
persistent, proteinuria of more than 1 gram /mmol creatinine
what are the aspects of hypertension
> 140/80 mmHg
Nephritis > nephrotic
Renal insufficiency i.e. rising creatinine
- Nephritic > nephrotic
- Mild or severe
- Slow or rapid deterioration
what comprises the nephritic state
Active urine sediment: haematuria, dysmorphic RBCs, cellular casts
Hypertension
Renal impairment
what comprises nephrotic syndrome
Oedema
Proteinuria >3.5 g/day
Hypoalbuminemia
Hyperlipidemia
Can be caused by primary (idiopathic) glomerular disease or secondary glomerular diseases
how would you make a differential diagnosis of nephrotic syndrome
Congestive Heart Failure (JVP raised, normal albumin, minimal proteinuria)
Hepatic Disease (abnormal LFTs, no proteinuria)
what three ways is glomerulonephritis classified
- Aetiology: autoimmune, infection, malignancy, drugs, others
- Primary versus secondary i.e. kidney alone or part of multisystem disease.
- Morphological
what are the 2 types of glomerulonephritis
proliferative and non-proliferative
what happens in proliferative glomerulonephritis
Excessive numbers of cells in glomeruli - these include infiltrating leucocytes
what happens in non-proliferative glomerulonephritis
Glomeruli look normal or have areas of scarring - they have normal numbers of cells
what does diffuse indicate in terms of the disease
Diffuse: >50% of glomeruli affected
what does focal indicate in terms of the disease
Focal: <50% of glomeruli affected
what does global indicate in terms of the disease
Global: all the glomerulus affected
what does segmental indicate in terms of the disease
Segmental: part of the glomerulus affected
what would be seen in IgA nephropathy
urinary sediment abnormalities
proteinuria
what would be seen in nephrotic syndrome
membraneous nephropathy - minimal change disease
what would be seen in a nephritic state
Anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis
Post-infection glomerulonephritis
what are the 4 types of proliferative glomerulonephritides
- diffuse proliferative - post infective
- focal proliferative - mesangial IgA disease
- focal necrotizing (cresentic) nephritis
- membrano-proliferati e
what happens in post-streptococcal glomerulonephritis
follows 10-21 days after infection typically of the throat or skin
most commonly Lancefield group A streptococci
genetic predisposition - HLA-DR, -DP
CASE 1: Six year old boy brought to GP generally unwell, dark urine
Puffy face, no rashes no oedema, BP 135/86mmHg
Had had a sore throat 2 weeks previously
What is the presumptive diagnosis
post-streptococcal nephritis
CASE 1: what investigations should be taken
Blood counts
urins sample
Hb 130g/L; WCC 11.3 x 109
Urea 11.2mmol/L, creatinine 160mmol/L
Urine microscopy RBC +++, casts +
Complement: low C3
CASE 1: what treatments should he be given
Antibiotics for infection, debatable.
Loop diuretics such as frusemide for oedema
Vasodilator drugs (e.g. amlodipine) for hypertension
what is the most common cause of glomerulonephritis world-wide
IgA nephropathy
- most common in 2nd and 3rd decade of life
- males more commonly affected
how is IgA nephropathy characterised
by IgA deposition in the mesangium as well as mesangial proliferation
how does IgA nephropathy present
Microscopic haematuria.
Microscopic haematuria + proteinuria
Nephrotic syndrome
IgA crescentic glomerulonephritis
CASE 2: 30 male referred to the renal clinic by GP for incidental microscopic haematuria.
BP 150/90 mmHg.
Creatinine 80 µmol/L.
Urine dip: RBC+++, Protein ++.
Renal US: normal kidney size with no structural abnormalities
what is your differential diagnosis
IgA nephropathy
CASE 2: what treatment could this man be started on straight away
ACE-I and antihypertensives for better BP control
CASE 2: what investigation could be done to confirm the diagnosis of IgA nephropathy
renal biopsy
CASE 2: what could you expect this man to need 10 years down the line
kidney transplant
CASE 3: how could focal necrotising glomerulonephritis present clinically
increasing tiredness, anorexia, weight loss, rash on ankles and lower legs, bilateral basal crepitations
BP 150/85
CASE 3: what would her urine dipstick show and what could her serum creatinine be
protein +++
blood ++
creatinine 640 micromol/L
CASE 3: renal biopsy shows focal necrotising glomerulonephritis - what would the treatment be
High dose steroids, Cyclophosphamide,
plasma exchange
what are the three types of crescentic glomerulonephritis
- anti-neutrophil cytoplasmic antibody (ANCA)-associated
- anti-glomerular basement membrane (anti-GBM) eg goodpastures syndrome
- others - IgA vasculitis, post-infectiom GN, SLE (lupus nephritis)
what is anti-GBM disease and how is it diagnosed
rare disease caused by circulating anti-GBM
diagnosed by demonstrating anti-GBM antibodies in serum and kidney
how does anti-GBM disease present
presents as nephritis
= anti-GBM glomerulonephritis
presents as nephritis AND lung haemorrhage
= goodpastures syndrome
when does presentation of anti-GBM disease peak
Two peaks: 3rd decade and 6th/7th decade.
what is the treatment for anti-GBM disease
aggressive immunesuppression
steroid,
plasma exchange, cyclophosphamide
what is the general management plan for crescentic glomerulonephritis
IMMUNOSUPPRESSION Corticosteroids Plasma exchange Cytotoxic e.g. Cyclophosphamide B-cell therapy e.g. Rituximab Complement inhibitors
PROLIFERATIVE GN SUMMARY:
how does it present
what would a dipstick show
what can rapid decline lead to
nephritic syndrome
blood, variable proteinuria
rapid loss of renal function and dialysis
what are the three types of non-proliferative GN
minimal change disease
focal and segmental GN
membranous nephropathy
what is the management of nephrotic syndrome
GENERAL
Treat oedema: salt and fluid restriction and loop diuretics.
Hypertension: use Renin-Angiotensin-Aldosterone-blockade.
Reduce risk of thrombosis: Heparin or Warfarin.
Reduce risk of infection e.g. pneumococcal vaccine.
Treat dyslipidemia e.g. statins.
SPECIFIC
specific therapy towards cause of non-proliferative GN
how does minimal change nephrotic syndrome present
commonest in children
sudden onset fo oedema (days)
complete loss of proteinuria with steroids
what is the treatment for minimal change disease
Prednisolone – 1mg/kg for up to 16 weeks.
Once remission achieved , slow taper over 6 months.
Initial relapse treated with further steroid course.
Subsequent relapses treated with
- Cyclophosphamide
- Cyclosporin
- Tacrolimus
- Mycophenolate mofetil
- Rituximab
what is the prognosis for minimal change disease
Despite relapsing behaviour, prognosis is favourable.
Risk of end stage kidney disease is low.
BUT risk of steroids toxicity as multiple exposure
CASE 4: 22 year old woman presented with severe oedema which had developed suddenly over a week.
she was breathless and had left sided chest pain
urine dip ++++ protein
what is your differential diagnosis
minimal change disease (non-proliferative GN)
CASE 4: what investigations would you want to do
Urine protein creatinine ration Creatinine Serum Albumin Haemoglobin Cholesterol Pregnancy test
CASE 4: investigation results-
Urine protein creatinine ration 400mg/mmol.
Creatinine 110 mmol/l (<110)
Serum Albumin 15 g/L (>35)
Haemoglobin 154 g/L
Cholesterol 9.2 mmol/l
Pregnancy test negative
what are general measures you may want to take
Salt and fluid restrictions.
Daily weights.
Loop diuretic e.g. Furosemide.
Thromboprophylaxis e.g. low molecular weight heparin.
CASE 4: what is a typical treatment plan
Prednisolone 60 mg per day
Achieved remission after 8 weeks of treatment.
Diuretics and thromboprophylaxis stopped.
Prednisolone dose tapered over 6 months.
what is the pathology of focal and segmental GLomerulosclerosis
focal and segmental sclerosis with distinctive patterns e.g.
tip lesion, collapsing, cellular, perihilar, and not otherwise specified
how does focal and segmental GS present
nephrotic syndrome - not a single disease but a syndrome with multiple causes
can be primary (idiopathic) or secondary
how does FSGS respond to steroids
steroid resistant
what is the treatment for FSGS
General measures, as previously described.
Trial of steroids, positive response , even partial remission, carries better prognosis.
**Alternative options: cyclosporin, cyclophosphamide
Rituximab
CASE 5: 34 year old man presented with severe oedema which developed over 3 weeks
Investigations - severe nephrotic syndrome
what might a renal biopsy show
focal and segmental glomerulo sclerosis
what is the commonest case of nephrotic syndrome in adults
membranous nephropathy
what are serological markers of membranous nephropathy
Anti-phospholipase A2 receptor (PLA2R) antibody positive in 70% of idiopathic cases
Thrombospondin type 1 domain containing 7A (THSD7A).
most cases of membranous nephropathy are idiopathic - what are some secondary causes
Malignancies
SLE
Rheumatoid arthritis.
Drugs: NSAIDs, gold, penicillamine
what is the treatment for membranous nephropathy
General measures for at least 6 months.
Immunesuppression if symptomatic nephrotic syndrome, rising proteinuria or deteriorating renal function.
Cyclophosphamide and steroids (alternate months) for 6 months.
Cyclosporine.
Rituximab.
what is the prognosis for membraneous nephropathy
Resolves spontaneously in a third.
Prognosis good in treated patients whose proteinuria resolves
About 25% are on dialysis at 10 years
Can recur in renal transplants
NON-PROLIFERATIVE GN SUMMARY:
how does it present
what is the key investigation
what are the broad treatment guidelines
nephrotic syndrom
renal biopsy
general measures important in all cases - then specific treatment as appropriate
