Nephrotic Syndrome + Glomerulonephritis

Question 1

Proteinuria

Answer 1

Represents abnormal glomerular filtration barrier function (as this is what is supposed to keep proteins out of urine)

Question 2

Normal proteinuria

Answer 2

<150mg/day (around 30mg is albumin)

Question 3

Microalbuminuria

Answer 3

30-300mg/day

ACR= 3-30mg/mmol

Question 4

Macroalbuminuria

Answer 4

> 300mg/day

ACR= >30mg/mmol

Question 5

Asymptomatic proteinuria

Answer 5

<3g/day

Question 6

Nephrotic range proteinuria

Answer 6

> 3g/day

Question 7

Proteinuria measurement- Urine Dipstick

Answer 7

Trace= 15-30mg/dL
1+= 30-100mg/dL
2+= 100-300mg/dL
3+= 300-1000mg/dL
4+= >1000mg/dL
Will show up +ve if protein >300mg/day
Convenient and easy
Protein excretion not consistent throughout day
Only albumin detected
False negatives in multiple myeloma (protein component not albumin)

Question 8

Proteinuria measurement- ACR/PCR

Answer 8

Daily creatinine excretion almost constant 910mmol/day)
Therefore ACR/PCR corrects for changes in urine conc. throughout day
First morning specimen most accurate
Can multiply PCR/ACR x 10 to obtain approx. value for 24hr excretion
Limitations- extremes of muscle mass, collection timing

Question 9

24 hour urine collection- proteinuria

Answer 9

Gold standard
Impractical + difficult
Figure precise but often not necessary

Question 10

Different causes of oedema- pathophysiological mechanisms

Answer 10

Increased hydrostatic pressure
Decreased oncotic pressure
Increased capillary permeability
Lymphatic blockage

Question 11

Oedema- underfill hypothesis

Answer 11

Decrease in intravascular colloid oncotic pressure due to hypoalbuminuria
Leads to intravascular vol. depletions
Results in overactivation RAAS–> salt and water retention

Question 12

Oedema- overfill hypothesis

Answer 12

Primary mechanism in nephrotic syndrome
Sodium retention is primary event due to increased Na/K ATPase activity in collecting duct
Leads to expansion of intravascular volume that increases hydrostatic pressure to force more fluid into interstitial space

Question 13

Nephrotic syndrome

Answer 13

Clinical syndrome arising from failure of glomerular filtration barrier to restrict passage of proteins into Bowman’s space
Proteinuria (>3g/day) associated with hypoalbuminuria (<30g/L), generalised oedema, hyperlipidaemia + thrombotic tendency

Question 14

Nephritic syndrome

Answer 14

Clinical syndrome associated with underlying glomerulonephritis (inflammation of glomerulus)
Haematuria, mild proteinuria, hypertension, impaired renal function, oliguria + mild oedema

Question 15

Nephrotic syndrome diagnostic criteria

Answer 15

Proteinuria >3g/day
Hypoalbuminuria <30g/L
Generalised oedema
Hypercholesterolaemia

Question 16

Nephrotic syndrome clinical history

Answer 16

Generalised oedema
Frothy urine
Collateral history- previous history, OTC NSAIDS, fam history renal disease, weight loss etc

Question 17

Nephrotic syndrome Investigations

Answer 17

Exam- peripheral + sacral oedema, periorbital oedema, ascites, pleural effusions
BP- can be normal, low or raised
Urine dipstick- protein 4+, blood may be + or -

Question 18

Nephrotic syndrome differential diagnoses

Answer 18

Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Amyloidosis
Diabetic nephropathy

Question 19

Minimal change disease- nephrotic syndrome

Answer 19

Most common cause nephrotic syndrome in children
Idiopathic
Secondary to- recent resp. infection, immunisation, NSAIDs, haematological malignancy
Massive oedema- facial + periorbital swelling, ascites, pleural + pericardial effusions
Absence of microscopic haematuria
BP= low/normal
Light microscopy= normal
Electron microscopy= effacement of podocyte end-feet
Treatment= corticosteroids

Question 20

Focal segmental glomerulosclerosis- nephrotic syndrome

Answer 20

Most common cause in Hispanic + African American adults
Idiopathic
Secondary to- longstanding hypertension, any chronic kidney condition, HIV, heroin, obesity
Microscopic haematuria often present
BP often raised
Light microscopy- segmental sclerosis + hyalinosis
Electron microscopy- effacement of podocyte end-feet
Treatment- immunosuppression

Question 21

Nephrotic syndrome- membranous nephropathy

Answer 21

Most common cause primary nephrotic syndrome in Caucasian adults
Most commonly idiopathic
Secondary to- drugs (gold, NSAIDs, penicillamine), infections (HBV, HCV, syphilis), SLE, solid tumours
Microscopic haematuria common
BP often raised
VTE common
Light microscopy- diffuse capillary + GMB thickening
Immunostaining- positive IgG staining
Electron microscopy- subendothelial deposit humps in GBM
Treatment- immunosuppression

Question 22

Nephrotic syndrome- amyloidosis

Answer 22

Associated with chronic conditions that predispose amyloid deposition
e.g. AA amyloid in IV drug users

Question 23

Nephrotic syndrome- diabetic nephropathy

Answer 23

Light microscopy- mesangial expansion, GBM thickening, Kimmelstein-Wilson nodules
Electron microscopy= GBM thickening

Question 24

Nephrotic syndrome- Treatment of oedema

Answer 24

Restrict salt <2g/day
Fluid restriction <1l/day
Loop diuretics to decrease fluid retention

Question 25

Nephrotic syndrome- Reduction proteinuria

Answer 25

Will reduce aggravation of tubulointerstitial fibrosis which will reduce progression to functional decline ACEI or ARB for anti-proteinuria effects BP <125/70 Protein intake 0.8g/kg/day

Question 26

Nephrotic syndrome- Anticoagulation

Answer 26

NS risk factor for thrombosis | Anti-coagulate with SC heparin or warfarin for duration

Question 27

Nephrotic syndrome- Infection

Answer 27

Low IgG predisposes to infection Treat infection promptly Vaccinate against pneumococcus

Question 28

Nephrotic syndrome- Dyslipidaemia

Answer 28

Dietary restrictions | Statins

Question 29

Nephrotic syndrome- Immunosuppression, minimal change

Answer 29

1st line= corticosteroids 2nd line= CNI 3rd line= cyclophosphamide 4th line= rituximab

Question 30

Nephrotic syndrome- Immunosuppression, FSGS

Answer 30

1st line= corticosteroid 2nd line= CNI 3rd line= cyclophosphamide 4th line- MMF

Question 31

Nephrotic syndrome- Membranous

Answer 31

1st line= corticosteroid + calcineurin inhibitor 2nd line= cyclophosphamide 3rd line= MMF 4th line= Rituximab

Question 32

Nephritic syndrome (Glomerulonephritis) diagnostic criteria

Answer 32

Haematuria (urine dip +++) Red cell casts on urinary microscopy Mild proteinuria (<1-1.5g/day) With progression --> hypertension, oedema, AKI

Question 33

Glomerulonephritis- immune mediated

Answer 33

IgA nephropathy (berger disease)--> most common cause GN worldwide Small vessel vasculitis- Wegener's granulomatosis, microscopic polyangiitis Systemic lupus Anti-GBM disease Cryoglubinaemia

Question 34

Glomerulonephritis- infections

Answer 34

Viral --> hep B, hep C, HIV Post-streptococcal Subacute bacterial endocarditis

Question 35

Glomerulonephritis malignancy

Answer 35

Myeloma | Lymphoma

Question 36

Glomerulonephritis- IgA nephropathy

Answer 36

Episodic gross haematuria that occurs concurrently with resp/GI infections Mesangial proliferation Young adults Purpuric skin rash Arthritis Abdo pain Worse prognosis if increased BP, male, proteiuria

Question 37

Glomerulonephritis- Anti-GBM (Goodpasture's disease)

Answer 37

Isolated renal and pulmonary effects Anti-GBM in circulation/kidney Treat- plasma exchange, steroids, cytotoxics

Question 38

Glomerulonephritis- Wegener's (granulomatosis with polyangitis)

Answer 38

``` Vasculitis rash Sinusitis Epistaxis Haemoptysis Eye redness ```

Question 39

Glomerulonephritis- microscopic polyangitis

Answer 39

``` Vasculitis rash Haemoptysis Eye redness Diarrhoea + abdo pain Neuropathy ```

Question 40

Glomerulonephritis- SLE

Answer 40

Butterfly malar rash Painful + swollen joints Fever Chest pain

Question 41

Glomerulonephritis- Myeloma

Answer 41

``` Bone pain Fractures Anaemia Repeated infections Easy bleeding ```

Question 42

Glomerulonephritis- Post-streptococcal

Answer 42

``` Occurs around 2 weeks after infection Oedema Headache Oliguria Fever Malaise Nausea ```

Question 43

Glomerulonephritis Investigations- bloods

Answer 43

``` FBC U+Es LFTs CRP Nephritic screen ```

Question 44

Rapidly Progressive Glomerulonephritis

Answer 44

Term used to describe rapid loss of renal function (50% GFR decline in 3 months) associated with formation of epithelial crescents in majority of glomeruli Increased creatinine and decreased GFR secondary to GN

Question 45

Rapidly Progressive Glomerulonephritis- biopsy

Answer 45

Crescent moon shape consisting of fibrin + plasma proteins (e.g. C3b) with glomerular parietal cells, monocytes, macrophages

Question 46

Rapidly Progressive Glomerulonephritis- types

Answer 46

Immune complex RPGN Pauci-Immune RPGN- 80-90% are ANCA positive Anti-GBM

Question 47

Rapidly Progressive Glomerulonephritis- treatment

Answer 47

Corticosteroids | Cyclophosphamide

Question 48

Pulmonary renal syndrome

Answer 48

Pulmonary haemorrhage occurring simultaneously with GN Dyspnoea, cough, fever, haemoptysis, peripheral oedema, haematuria Treatment= corticosteroids, cyclophosphamide, plasma exchange

Question 49

Glomerulonephritis treatment- oedema

Answer 49

Limit salt <5g Limit fluid <1L Diuretics (loop)

Question 50

Glomerulonephritis treatment- proteinuria

Answer 50

ACEI/ARB

Question 51

Glomerulonephritis treatment- BP

Answer 51

``` <130/80 Diruretics BB CCBs ACEI/ArB ```

Question 52

Glomerulonephritis treatment- immunosuppression

Answer 52

``` Corticosteroids Cyclophosphamide Calcineurin inhibitors Azathioprine Mycophenoate Rituximab ```

Question 53

Factors that indicate poor prognosis with any glomerulonephritis

Answer 53

Heavy proteinuria Sever hypertension Significant elevations creatinine