proteinuria and nephrotic syndrome Flashcards
what is proteinuria
excessive protein in the urine - >150mg/day
what proteins may be seen in the urine (4)
- albumin (mainly)
- beta2 microglobulin
- polypeptides
- RBP secreted proteins
what does the glomerular ultrafiltration barrier consist of
- endothelial cells (fenstrated capillaries)
- basement membrane
- podocyte food processes
how does heavy proteinuria present (2)
- frothy urine
- peripheral oedema
what kind of sample is required for a urine dipstick test
fresh, non-centrifuged morning sample
advantages of urine disptick test (3)
- simple bedside test in multiple settings
- rapid diagnosis
- inexpensive
main disadvantage of urine dipstick test
does not detect non-albumin proteinuria
what can dehydration lead to (urinanalysis)
false +ve for elevated protein
what does the urine albumin:creatinine ratio (ACR) show
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
what is the mgx for proteinuria with ACR >3 and protein:creatinine ratio >15
adequate to define CKD G1/G2 -> commence ACEi/ARB if diabetic
what is the mgx for proteinuria with ACR 30 and protein:creatinine ratio 50
give ACEi/ARB if hypertensive
what is the mgx for proteinuria with ACR 70 and protein:creatinine ratio 100
ACEi/ARB with stricter HTN limits, for non diabetic pts refer
what is proteinuria with ACR >250 and protein:creatinine ratio >300 defined as
“nephrotic range” -> if in the presence of oedema abd hypoalbuminemia
4 mechanisms for protienuria
- glomerular - disruption in filtration barrier e.g. loss of structural integrity
- tubular - inflammatory
- overflow - excess protein production that overwhelms the ability of the glomerulus to filter
- post-renal - inflammation in urinary tract post nephron
2 categories of proteinuria
- physiological/benign
- pathological
2 types of benign proteinuria
- orthostatic proteinuria - occurs when standing erect but not supine, often transient and in young pts
- transient proteinuria secondary to fver, heavy exercise, IV albumin etc.
2 types of pathological glomerular proteinuria
- primary glomerulonephritides
- secondary glomerulonephtitides
what is pathological glomerular proteinuria usually due to
disruption to the filtration barrier
what is usually the mechanism of nephrotic range proteinuria
glomerular cause
5 primary glomerulonephritides
- minimal change disease - most common for children
- primary focal segmental glomerulosclerosis
- idiopathic membranous nephropathy
- IgA nephropathy
- idiopathic membraneoproliferative glomerulonephiritis
6 secondary glomerulonephritides causes
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
what is the value of protein that is usually seen in tubular proteinuria
<1-2g/day
how can proximal tubule activity be assessed
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
causes of tubular proteinuria (3)
- tubulo-intestitial nephritis -> drugs e.g. abx, NSAIDs, PPIs
- autoimmine disease e.g crohn’s disease, sarcoidosis
- infections e.g. tuberculosis
what is overflow proetinuria and causes
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)
what non-renal organ system is proteinuria a risk factor for
cardiovascular
what renal condition is proteinuria a risk factor for
chronic kidney disease
4 key characteristics of nephrotic syndrome
- heavy proteinuria (>3.5 g/day)
- hypoalbuminaemia (<3g/dL)
- peripheral oedema
- hyperlipidemia
why does untreated nephrotic syndrome lead to high mortality (3)
- infection - loss of albumin + other immune modulating proteins -> immunocomprimise
- thrombosis - loss of anticoag proteins
- established renal failure
why is fluid retention characteristic in nephrotic syndrome
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
why are ACEi/ARBs given in nephrotic syndrome
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
what is the most common cause for nephrotic syndrome in children
minimal change disease
minimal change disease mgx
steroids (prednisolone) -> mgx is so good that most of the time investigations aren’t needed, if steroid don’t work consider other cause
what is thepathological change that occurs in minimal change disease
fusion of foot processes in the glomerular filter
mgx for primary/idiopathic focal segmental glomerulosclerosis
steroids and immunosuppression
mgx for secondary focal segmental glomerulosclerosis
diuretics, change in diet
causes for secodnary focal segmental glomerulosclerosis (4)
- obesity
- HTN
- HIV infection
- bisphosphonates
why might a focal segmental glomerulosclerosis kidney biopsy not show anything
due to the focal nature of the disease, the biospy may pick up an non-damaged part
what is the brief pathopsyiology of membranous nephropathy
immune deposits in the glomerular basement membrane -> spikes shown on basement membranes
what are kimmelstien wilson nodules
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
diabetic nephropathy mgx
- glycaemic control
- BP control
- RAAS inhibition
