Nephrotic vs nephritic syndrome Flashcards
Nephrotic syndrome [3]
Failure of glomerular filtration barrier, injury to podocytes or slit diaphragm.
Reduced GFR with microscopic haematuria or red cell casts.
Increased risk of venous thrombosis, loss of anticoagulant factors
Nephrotic syndrome - why is there the increased risk of venous thrombosis
Loss of anticoagulant factors like antithrombin II in urine, increased platelet aggregation and endothelial dysfunction
Causes of nephrotic syndrome [9]
- Minimal change disease.
- FSGS.
- Membranous nephropathy.
- Mesangiocapillary GN (mixed)
Secondary
* HIV-associated nephropathy.
* Renal amyloidosis.
* Light chain deposition disease.
* SLE with type 5 lupus nephritis.
* Diabetic glomerulosclerosis.
Diagnosis of nephrotic syndrome [4]
Nephrotic syndrome is defined by:
1. Proteinuria >3.5 g/24 hours (equivalent to urine protein/creatinine ratio >350 mg/mmol).
2. Hypoalbuminaemia (<35 g/L).
3. Oedema.
4. Hyperlipidaemia/hypercholesterolaemia.
Management of nephrotic syndrome [4]
- Salt and fluid restriction.
- Loop diuretics.
- Anti-proteinuric drugs: ACE inhibitors/angiotensin receptor blockers.
- Anticoagulation in selected patients.
Acute nephrotic syndrome - minimal change disease
Management
Relapse
90% of children below 6
Normal glomerular appearance on light microscopy
Diffuse effacement of podocytte foot processes on electron microscopy
Management
- Steroid treatment is responsive in up to 90% of adults within 12 weeks
- Rate of relapse 50-75%
FSGS
Presentation
Name some mutations which are associated with steroid resistant nephrotic syndrome
Primary FSGS commonly presents with nephrotic syndrome, nephrotic- or sub-nephrotic-range *protein- uria.
Renal impairment and progression to ESRD are common.
Mutations in some podocyte proteins are associated with steroid-resistant nephrotic syndrome and childhood-onset FSGS, including NPHS1 (nephrin), NPHS2 (podocin), ACTN4 (alpha-actinin 4) and TRPC6. Afro-Caribbean people also have increased susceptibility to FSGS, either alone or in association with hypertension or HIV infection.
Describe causes of secondary FSGS
Secondary FSGS results from various kidney insults leading to a common pattern of glomerular injury related to haemodynamic stress and glomerular hyperfiltration.
Infections: HIV, malaria, parvovirus, schistosomiasis
Drugs: adriamycin, heroin, interferon alpha, lithium, pamidronate
Malignancies: HL and NHL
Npehron loss from surgical ablation, reflux nephropathy
Treatment approaches of secondary FSGS [2]
General management of nephrotic syndrome
Try to induce remission and reduce proteinuria initally with course of steroids
Usually relapse on steroids so need additional agent, cyclosporin.
Membranous nephropathy (MN)
Idiopathic MN - autoantibody against antigen M-type phospholipase A2 receptor
Secondary MN
- Autoimmune causes
- Infectious diseases
- Drugs
- Malignancy
Secondary membranous nephropathy
- Autoimmune causes
SLE
RA
Sarcoidosis
Crohns disease - Infectious diseases
Hepatitis B and C
Syphilis
Fliariasis, hydatid cysts, schistosomiasis - Drugs
Gold, penicillamine
NSAIDs
Captopril - Malignancy
How is MN diagnosed on histology, light microscopy and electron microscopy?
Histologically immunoglobulin (usually IgG) and C3 deposition along the capillary walls or outer aspect of the GBM is evident.
Light microscopic features include thickening of the basement membrane and ‘spikes’ on silver staining
Sub-epithelial deposits are seen on electron microscopy.
Management of MN
Remission
Progression
Poor prognosticators
Management
Remission 30%
Progression 30%
Abnormal kidney function and heavy proteinuria (>10 g/ 24 hours), or persistent proteinuria >1 year after presentation
Treatment
- Immunosuppressive therapy - alternate steroids monthly and cyclophosphamide or chlorambucil
Mesangiocapillary GN or membranoproliferative GN
Conditions associated with a mesangiocapillary pattern of injury
1. Immune complex-mediated diseases
2. Complement mediated diseases
3. Conditions without immunoglobulin or complement deposition
Give 4 immune complex mediated diseases associated with mesangiocapillary pattern of injury
Chronic infections
Autoimmune diseases
Idiopathic
Paraprotein deposition diseases like light chain deposition or cryoglobulinemia
Give 4 complement mediated diseases associated with mesangiocapillary pattern of injury
- Dense deposit disease (MCGN type II).
- C3 glomerulopathy - partial lipodystrophy
- Atypical haemolytic uraemic syndrome (HUS).
Give 3 conditions without immunoglobulin or complement deposition that are associated with mesangiocapillary pattern of injury
- Chronic and healed thrombotic microangiopathies.
- Antiphospholipid syndrome.
- Radiation nephritis.
IgA nephropathy
IgA nephropathy is the commonest primary glomerulonephritis in the world. Peak incidence is in the sec- ond and third decades of life.
Tissue injury is caused by deposition of ab- normally glycosylated IgA immune complexes in the mesangium, subsequent mesangial cell activation, and cytokine and growth factor production.
Associations: liver cirrhosis, coeliac disease, IBD, rheumatic conditions, HSP
IgA nephropathy
Presentation [4]
- Asymptomatic microscopic haematuria ± mild proteinuria.
- Recurrent macroscopic haematuria, typically within 1–3 days of an upper respiratory tract infection (‘sympharyngitic haematuria’).
- CKD from longstanding undiagnosed disease.
- Rarely, AKI with oliguria, which may be associated with a crescentic pattern of injury on biopsy.
IgA nephropathy
Prognosis - risk of progression, predictors of esrd
Management [2]
Prognosis
* Most patients with isolated haematuria and no proteinuria have low risk of progression, while those with renal impairment at presentation, heavy proteinuria, or tubulo-interstitial fibrosis or glomerulosclerosis on biopsy are at risk of progressive renal impairment.
* Persistent proteinuria of >1 g/24 hours and/or hypertension carries a 50% risk of ESRD at 10 years.
Management
Supportive measures for all patients: * BP management.
* Renin-angiotensin system blockade with ACE-I or ARBs.
Tubulo-interstitial kidney disease
Acute interstitial nephritis
Chronic tubule-interstitial kidney disease
Common causes of AIN [4]
- Drugs: antibiotics, NSAIDs, PPI, allopurinol, anti-retroviral
- Infections: asending pyelonephritis, TB, leptospirosis, Hanta virus
- Autoimmune disease
- Idiopathic
In AIN, what is TINU syndrome
Tubulointerstitial nephritis + Uveitis
AIN presentation
Biopsy in AIN will show
Treatment
AIN- fever, arthralgia, rash, eosinophilia, hypertension.
Investigations
sterile pyuria
white cell casts
If biopsied, characteristic features include an inflammatory cell infiltrate in the interstitium, which may be eosinophil-rich and include granulomata.
Treatment of drug-induced AIN is withdrawal of the likely agent, plus corticosteroid therapy if the AIN is severe (dialysis-dependent AKI) or if no improvement is seen 10 days after withdrawal of the inciting agent.
Chronic tubule-interstitial kidney disease- how does it develop?
Untreated AIN, or prolonged exposure to the causative agent, can progress to chronic tubulo-interstitial disease. Histologically this is characterised by varying tubular atrophy, interstitial fibrosis and inflammation.
Renovascular disease
Aetiology [2]
Presentation [4]
Ix [4]
50% of those atherosclerosis have renal artery stenosis
5% - caused by fibromuscular dysplasia
Hypokalaemia
Resistant to tx HTN
Progressive CKD - ischaemic nephropathy
Recurrent flash pulmonary oedema
Ix
Doppler
MAG3 (nuclear imaging) with captopril
CT/MR angio
Gold standard - DSA
Management of renal artery stenosis
Management of cardiovascular risk factors
Definitive - angioplasty
Stenting may not improve BP control or preserve kidney function because atherosclerosis is a systemic process
Endovascular intervention is indicated in those with refractory HTN or rapidly declining kidney function
Nephritic syndrome
Rapidly progressive glomerulonephritis - name 3 types
Also known as crescentic GN
- Type 1 linear
- Type 2 granular - immune complex mediated
- Type 3 pauci immune
Name Type 1 RPGN
- Goodpasture- Anti-GBM disease
Name Type 2 Immune complex mediated RGPN
- Post-streptococcal
- Lupus class V
- IgA nephropathy
- Henoch schonlein purpura
Name Type 3 RGPN (pauci-immune)
- ANCA positive usually but non immune complex mediated, non anti-GBM
- cANCA - Wegener
- pANCA - eGPA
Distinguish between Post-streptococcal and IgA nephropathy
SLE nephritis
Describe 6 stages
WHO classification
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis
class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis
Summary
Describe the 6 stages of lupus nephritis
Which one is the most common form?
WHO classification
class I: normal kidney
class II: mesangial glomerulonephritis
class III: focal (and segmental) proliferative glomerulonephritis
**class IV: diffuse proliferative glomerulonephritis - most common!
**class V: diffuse membranous glomerulonephritis
class VI: sclerosing glomerulonephritis
Lupus nephritis
Describe diffuse proliferative glomerulonephritis biopsy
Renal biopsy characteristically shows the following findings:
glomeruli shows endothelial and mesangial proliferation, ‘wire-loop’ appearance
if severe, the capillary wall may be thickened secondary to immune complex deposition
electron microscopy shows subendothelial immune complex deposits
granular appearance on immunofluorescence
Pulmonary stenosis vs aortic stenosis murmur
Pulmonary stenosis
* ejection systolic murmur, loudest in inspiration
Aortic stenosis
* same murmur but louder on expiration
