Glomerular Disease (Clinical) Flashcards
Glomerulonephritis:
- Immune-mediated disorders that affect the ________
- Responsible for around ___ of end-stage kidney disease
- Classified based on kidney _____ findings
glomeruli
15%
biopsy
What are podocytes?
Podocytes are cells in the Bowman’s capsule in the kidneys that wrap around capillaries of the glomerulus. Podocyte cells make up the epithelial lining of Bowman’s capsule, the third layer through which filtration of blood takes place
What are the features of glomerulonephritis?
- Haematuria (non-visible or visible)
- Proteinuria (low grade or nephrotic)
- Hypertension
- Renal impairment
What are the 2 different kinds of glomerulonephritis?
Nephritic state
Nephrotic syndrome
What is Nephritic state?
- Active urine sediment: haematuria, dysmorphic RBCs, cellular casts
- Hypertension
- Renal impairment
What is nephrotic syndrome?
- Oedema
- Nephrotic range proteinuria: >3.5g/day or 350mg/mmol creatinine
- Hypoalbuminemia: serum albumin <35g/L
- Dyslipidemia
name A
Nephrotic state
podocytes not there and wide spaces and albumin come out and not as much RBC come out
Name B
Nephritic state
an influx of white cells and it inflicts damage and destruction of endothelial membrane and this leads to leukocytes and a lot of RBCs to go out
what is A?
Proliferative
What is B?
Non-proliferative
What is the difference between a diffuse and focal pathology?
- Diffuse: >50% of glomeruli affected
- Focal: <50% of glomeruli affected
What is the difference between global and segmental pathology?
- Global: all the glomerulus affected
- Segmental: part of the glomerulus affected
(global top picture and segmental bottom)
name A
Nephrotic
name B
Nephritic
Is Nephrotic proliferative or non-proliferative?
Non-proliferative
Is Nephritic proliferative or non-proliferative?
Proliferative
What are examples of non-proliferative glomerulonephritis?
Minimal change disease
Membranous nephropathy
FSGS
What are examples of proliferative glomerulonephritis?
Mesangioproliferative GN
Membranoproliferative GN
Diffuse proliferative GN
Crescentic GN
Commonest cause of glomerulonephritis world-wide is what?
IgA nephropathy
Characterized by IgA deposition in the mesangium +mesangial proliferation
Most common in 2nd and 3rd decade of life with males more commonly affected
Up to 30% of cases can progress to end stage kidney disease or halving eGFR at 10 years
What is the presentation of IgA nephropathy?
- Microscopic haematuria
- Micoscopic haematuria + proteinuria
- Nephrotic syndrome
- IgA crescentic glomerulonephritis
(top is most common and bottom is leasT)
Case 1:
- 30 male referred to the renal clinic by GP for incidental microscopic haematuria
- BP 150/90 mmHg
- Creatinine 80 µmol/L, eGFR>60 ml/min/1.73m2
- Urine dip: RBC+++, Protein ++
- Urine protein creatinine ratio=180mg/mmol creatinine
- Renal US: normal kidney size with no structural abnormalities
What happens next?
- You decide to start ACE-I
- You also decide to perform a renal biopsy
- Renal biopsy confirms IgA nephropathy
Reduce proteinuria and tightly control BP
- At 5 years: serum creatinine 210 µmol/L and eGFR 32 ml/min/1.73m2
- 10 years later, serum creatinine 480 µmol/L and eGFR 14 ml/min/1.73m2
- Brother considered as kidney donor for living kidney transplantation
What is Post-streptococcal/Post Infectious glomerulonephritis
Follows 10-21 days after infection typically of throat or skin
Most commonly with Lancefield group A Streptococci
Genetic predisposition: HLA-DR, -DP, -DP
Case 2:
- Six-year-old boy brought to GP generally unwell, dark urine
- Puffy face, no rashes no oedema, BP 135/86mmHg
- Sore throat 2 weeks previously
- Presumptive diagnosis _________________
What investigations owuld be done and what treatments would be carried out?
post-streptococcal nephritis
investigations
- Hb 130g/L; WCC 11.3 x 109
- Urea 11.2mmol/L, creatinine 160mmol/L
- Urine microscopy RBC +++, casts +
- Complement: low C3
Treatment:
- Antibiotics for infection, debatable
- Loop diuretics such as frusemide for oedema
- Anti-hypertensives e.g. vasodilator drugs
What is Crescentic glomerulonephritis?
Crescentic glomerulonephritis is characterized by the presence of extensive glomerular crescents (usually greater than 50%) as the principal histologic finding. Because it often clinically presents with a rapid decline in kidney function, it is also known as rapidly progressive glomerulonephritis
What are the different types of crescentic glomerulonephritis?
Case 3:
- 60-year-old woman presents to GP with three-month history of increasing tiredness, anorexia and weight loss
- Physical examination revealed a rash on both ankles and lower legs, and bilateral basal crepitations: BP 150/85 mmHg
- Urine dipstick: protein+++ and blood++
- Serum creatinine 640 µmol/L, eGFR 8 ml/min/1.73m2
What is this and what is the treatment?
- Anti-neutrophil cytoplasmic antibodies positive with MPO-ANCA of >134 units/L
- Renal biopsy - Focal necrotizing glomerulonephritis
- Treatment:
- High dose steroids
- Cyclophosphamide
- Plasma exchange
What is Anti-GBM disease?
- Rare disease caused by circulating anti-GBM
- Around 10-20% of crescentic glomerulonephritis
Presents as:
- Nephritis (anti-GBM glomerulonephritis)
- Nephritis+ lung haemorrhage (Goodpasture’s syndrome)
- Two peaks: 3rd decade and 6th/7th decade
how doyu diagnose Anti-GBM disease?
Diagnosed by demonstrating anti-GBM antibodies in serum and kidney
What si the treatment of Anti-GBM disease?
aggressive immunesuppression: steroid, plasma exchange, and cyclophosphamide
Summary - Proliferative glomerulonephritides
- Present with _______ state - Haematuria + variable proteinuria + hypertension +/- renal impairment
- Can cause rapid decline in renal function leading to _______
- Early diagnosis is necessary to save ________ - _______ _______+ __________ ______ + _____ _______
nephritic
dialysis
nephrons
Clinical suspicion + immunology screen + renal biopsy
onto Non-proliferative
what is seen in Non-proliferative Glomerulonephritis?
- Minimal Change Disease
- Focal and segmental glomerulonephritis
- Membranous Nephropathy
WHat are the 2 types of Nephrotic syndrome management?
general measrues
specific therpay
What are some general measures for Nephrotic syndrome management?
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
nephrotic syndrome management - Specific therapy towards cause of the ______________
non-proliferative glomerulonephritis
What is Minimal Change Disease and what does it cause?
- Commonest form in children
- Sudden onset of oedema – days
- Complete loss of proteinuria with steroids
- Relapse occurs in two thirds of patients
a kidney disease in which large amounts of protein is lost in the urine. It is one of the most common causes of the Nephrotic Syndrome (see below) worldwide
what is the treatment of 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 of minimal change disease?
Despite relapsing behaviour, prognosis is favourable
Risk of end stage kidney disease is low
Steroids toxicity as multiple exposure
Case 4:
- 22-year-old woman presents with bilateral leg oedema which has developed suddenly over a week
- She also describes breathless and chest pain
- Urine dip ++++ protein
what investigations would be carried out?
Urine protein creatinine ration 400mg/mmol.
Creatinine 60 mmol/l and eGFR of >60 ml/min/1.73m2
Serum Albumin 15 g/L
Haemoglobin 154 g/L
Cholesterol 9.2 mmol/l
Pregnancy test negative
What is the treamtent and prognosis of case 4?
- Salt and fluid restrictions
- Daily weights
- Loop diuretic e.g. Furosemide
- Thromboprophylaxis e.g. low molecular weight heparin
- Prednisolone 60 mg per day
- Achieved remission after 8 weeks of treatment
- Diuretics and thromboprophylaxis stopped
- Prednisolone dose tapered over 6 months
What is Focal and segmental glomerulonephritis?
Is not a single disease, rather a syndrome with multiple causes
Presents with nephrotic syndrome
Pathology reveals focal and segmental sclerosis with distinctive patterns e.g.
tip lesion, collapsing, cellular, perihilar, and not otherwise specified
FSGS can be caused by what 2 main ways?
Primary (idiopathic) or secondary
FSGS is resistant to what type of treatment?
Generally steroid resistant
FSGS has a high chance of progression to what?
High chance of progression to end stage kidney disease
What is the treatment of FSGS?
General measures, as previously described
Trail of steroids, positive response , even partial remission, carries better prognosis
Alternative options: cyclosporin, cyclophosphamide, and Rituximab
Case 5:
- 34-year-old man presented with severe oedema which developed over 3 weeks
- Investigations:
- Urine PCR 560mg/mmol creatinine
- Serum albumin 18 g/L
- Serum creatinine 130 µmol/L, eGFR 56 ml/min/1.73m2
•Renal biopsy showed FSGS
What is the treatment and prognosis?
- Diuretics helped to reduce oedema
- Prednisolone - no response
- Trial of cyclosporin – progressively rising serum creatinine
- Serum creatinine at 280 µmol/L and eGFR 26 ml/min/1.73m2 at 8 months from presentation
- At 18 months serum creatinine 540 µmol/l and eGFR 11 ml/min/1.73m2
- Pre-emptive renal transplantation from brother, early recurrence post-transplant
- Plasma exchange and Rituximab
- Remission at 3 months post-transplant with serum creatinine 80µmol/L and normal serum albumin
What is Membranous Nephropathy?
deposition of immune complexes on the glomerular basement membrane (GBM) with GBM thickening
Commonest cause of nephrotic syndrome in adults
Membranous Nephropathy is mainly caused by what?
Majority of cases occur in isolation (idiopathic)
What are serological markers for Membranous Nephropathy?
- Anti-phospholipase A2 receptor (PLA2R) antibody positive in 70% of idiopathic cases
- Thrombospondin type 1 domain containing 7A (THSD7A) in ~2%
What are secondary causes of Membranous Nephropathy?
Secondary causes include:
- Malignancies
- SLE
- Rheumatoid arthritis
- Drugs: NSAIDs, gold, penicillamine
WHat is Membranous nephropathy-treatment
- 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
- Tacrolimus
- Rituximab
What is Membranous nephropathy
Prognosis?
- 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
Case 6:
- 66-year old man presented with cough, breathlessness, and peripheral oedema
- He smokes 20 cpd
- Urine dip: Proteinuria ++++
- Urine protein creatinine ration 580mg/mmol
- Serum albumin 20 g/L
- Serum creatinine 135mmol/l
- Renal biopsy: confirms ____________________
what happens next?
confirms membranous nephropathy
- CT chest/abdomen/pelvis: suggestive of lung cancer
- Bronchoscopy and biopsy confirm squamous cell carcinoma
- General measures for nephrotic syndrome
- No immunesuppression
- At 3 months: partial remission following radiotherapy
Summary - Non-proliferative glomerulonephritis:
- Present with ________ syndrome
- Renal ______ is key investigation
- Identify _____, if possible
- _______ measures are important in all cases
- ________ treatment as appropriate
nephrotic
biopsy
cause
General
Specific
