proteinuria and nephrotic syndrome

Question 1

what is proteinuria

Answer 1

excessive protein in the urine - >150mg/day

Question 2

what proteins may be seen in the urine (4)

Answer 2

1. albumin (mainly)
2. beta2 microglobulin
3. polypeptides
4. RBP secreted proteins

Question 3

what does the glomerular ultrafiltration barrier consist of

Answer 3

1. endothelial cells (fenstrated capillaries)
2. basement membrane
3. podocyte food processes

Question 4

how does heavy proteinuria present (2)

Answer 4

1. frothy urine
2. peripheral oedema

Question 5

what kind of sample is required for a urine dipstick test

Answer 5

fresh, non-centrifuged morning sample

Question 6

advantages of urine disptick test (3)

Answer 6

1. simple bedside test in multiple settings
2. rapid diagnosis
3. inexpensive

Question 7

main disadvantage of urine dipstick test

Answer 7

does not detect non-albumin proteinuria

Question 8

what can dehydration lead to (urinanalysis)

Answer 8

false +ve for elevated protein

Question 9

what does the urine albumin:creatinine ratio (ACR) show

Answer 9

shows the amount of albumin in the urine removing the element of hydration that can otherwise affect results -> creatinine should be present in the urine while albumin should not be

it should be a spot urine sample

Question 10

what is the mgx for proteinuria with ACR >3 and protein:creatinine ratio >15

Answer 10

adequate to define CKD G1/G2 -> commence ACEi/ARB if diabetic

Question 11

what is the mgx for proteinuria with ACR 30 and protein:creatinine ratio 50

Answer 11

give ACEi/ARB if hypertensive

Question 12

what is the mgx for proteinuria with ACR 70 and protein:creatinine ratio 100

Answer 12

ACEi/ARB with stricter HTN limits, for non diabetic pts refer

Question 13

what is proteinuria with ACR >250 and protein:creatinine ratio >300 defined as

Answer 13

“nephrotic range” -> if in the presence of oedema abd hypoalbuminemia

Question 14

4 mechanisms for protienuria

Answer 14

1. glomerular - disruption in filtration barrier e.g. loss of structural integrity
2. tubular - inflammatory
3. overflow - excess protein production that overwhelms the ability of the glomerulus to filter
4. post-renal - inflammation in urinary tract post nephron

Question 15

2 categories of proteinuria

Answer 15

1. physiological/benign
2. pathological

Question 16

2 types of benign proteinuria

Answer 16

1. orthostatic proteinuria - occurs when standing erect but not supine, often transient and in young pts
2. transient proteinuria secondary to fver, heavy exercise, IV albumin etc.

Question 17

2 types of pathological glomerular proteinuria

Answer 17

1. primary glomerulonephritides
2. secondary glomerulonephtitides

Question 18

what is pathological glomerular proteinuria usually due to

Answer 18

disruption to the filtration barrier

Question 19

what is usually the mechanism of nephrotic range proteinuria

Answer 19

glomerular cause

Question 20

5 primary glomerulonephritides

Answer 20

1. minimal change disease - most common for children
2. primary focal segmental glomerulosclerosis
3. idiopathic membranous nephropathy
4. IgA nephropathy
5. idiopathic membraneoproliferative glomerulonephiritis

Question 21

6 secondary glomerulonephritides causes

Answer 21

systemic causes
1. diabetes mellitus
2. systemic amyloidosis
3. secondary focal segmental glomerulosclerosis e.g. obesity, HTN, HIV infection
4. autoimmune disease e.g SLE
5. secondary membranous nephropathy e.g. cancer drugs
6. idiopathic membraneoproliferative glomerulonephiritis - hep B/C

Question 22

what is the value of protein that is usually seen in tubular proteinuria

Answer 22

<1-2g/day

Question 23

how can proximal tubule activity be assessed

Answer 23

retinol-binding protein indicates -> Due to extensive tubular reabsorption, under normal conditions very little of the filtered retinol-binding protein appears in the final excreted urine. Therefore, an increase in the urinary excretion of retinol-binding protein indicates proximal tubule injury and/or impaired proximal tubular function

Question 24

causes of tubular proteinuria (3)

Answer 24

1. tubulo-intestitial nephritis -> drugs e.g. abx, NSAIDs, PPIs
2. autoimmine disease e.g crohn’s disease, sarcoidosis
3. infections e.g. tuberculosis

Question 25

what is overflow proetinuria and causes

Answer 25

excess production of low molecular weight poteirns exceeds capacity of tubules, all components function properly
causes:
1. myeloma (free light chains)
2. rhabdomyolisis (free myoglobin)
3. haemolysis (free haemoglobin)

Question 26

what non-renal organ system is proteinuria a risk factor for

Answer 26

cardiovascular

Question 27

what renal condition is proteinuria a risk factor for

Answer 27

chronic kidney disease

Question 28

4 key characteristics of nephrotic syndrome

Answer 28

1. heavy proteinuria (>3.5 g/day)
2. hypoalbuminaemia (<3g/dL)
3. peripheral oedema
4. hyperlipidemia

Question 29

why does untreated nephrotic syndrome lead to high mortality (3)

Answer 29

1. infection - loss of albumin + other immune modulating proteins -> immunocomprimise
2. thrombosis - loss of anticoag proteins
3. established renal failure

Question 30

why is fluid retention characteristic in nephrotic syndrome

Answer 30

loss of albumin = lower oncotic pressure -> leads to interstitial leakage of fluid and decreased circulating volume -> decreased circulating volume leads to renal hypoperfusion and activation of the renin-angiotensin-aldosterone system -> fluid retention

Question 31

why are ACEi/ARBs given in nephrotic syndrome

Answer 31

RAAS system activated in response to low fluid volume which results in angiotensin II causing vasocontriction and increased GFR -> inhibtion results in dilation of arteiroles and decreased GFR => decreases proteiuria

Question 32

what is the most common cause for nephrotic syndrome in children

Answer 32

minimal change disease

Question 33

minimal change disease mgx

Answer 33

steroids (prednisolone) -> mgx is so good that most of the time investigations aren’t needed, if steroid don’t work consider other cause

Question 34

what is thepathological change that occurs in minimal change disease

Answer 34

fusion of foot processes in the glomerular filter

Question 35

mgx for primary/idiopathic focal segmental glomerulosclerosis

Answer 35

steroids and immunosuppression

Question 36

mgx for secondary focal segmental glomerulosclerosis

Answer 36

diuretics, change in diet

Question 37

causes for secodnary focal segmental glomerulosclerosis (4)

Answer 37

1. obesity
2. HTN
3. HIV infection
4. bisphosphonates

Question 38

why might a focal segmental glomerulosclerosis kidney biopsy not show anything

Answer 38

due to the focal nature of the disease, the biospy may pick up an non-damaged part

Question 39

what is the brief pathopsyiology of membranous nephropathy

Answer 39

immune deposits in the glomerular basement membrane -> spikes shown on basement membranes

Question 40

what are kimmelstien wilson nodules

Answer 40

nodular glomerulosclerosis (the Kimmelstiel-Wilson lesion) of diabetes mellitus -> Nodules of pink hyaline material form in regions of glomerular capillary loops in the glomerulus, due to a marked increase in mesangial matrix from damage as a result of non-enzymatic glycosylation of proteins

Question 41

diabetic nephropathy mgx

Answer 41

1. glycaemic control
2. BP control
3. RAAS inhibition