Lab5: Biochemistry in renal disase (2) Flashcards
What do we look at urine dipstick - signs of renal disease?
- Protein
- Blood (haematuria)
What’s normal amount of protein in the urine in 24 hr period?
<0.15 g/24hr
*more than 50% of the above is Tamm-Horsfall ( aka uromodulin) - momucoprotein (secreted by renal cells)
What is overflow proteinuria?
Large amount of urinary protein is being filtered - excess of protein goes through the kidney and through the urine
e.g. in Myeloma
What’s glomerular proteinuria?
Damage to glomerular membrane -> large molecular weight protein (not normally filtered through the membrane), but in that case they will be and they will come out in the urine
Main protein seen: albuminuria (as more abundant protein in the blood - so seen with damage)
What’s tubular proteinuria?
It’s when kidney tubules cannot reabsorb low molecular weight protein (e.g. beta 2) *
*low molecular weight protein are normally filtered through the glomerular membrane
What’s secreted proteinuria?
Excess of proteins that are normally secreted by renal cells
What do we test for when we want to test for glomerular proteinuria
- 24 hr total protein
- urine dipstic (0.3/L) protein -> 0.3/L upwards only detected by urine dipstic
- protein:creatinine ratio (PCR)
- Microalbumin
- Albumin:creatinine ratio (ACR)
What proteins would indicate glomerular proteinuria?
- Increase in high molecular weight proteins in the urine
- albumin is the main protein lost (most abundant in plasma)
- more severe glomerular damage - loss of larger proteins
What is detected via micro-albumin test?
Very low levels of albumin in the urine - early renal dysfunction
What to do if ACR (albumin: creatinine ratio) is between 3mg/mmol and 70 mg/mmol?
Confirm bu subsequent early morning sample
Condirmed ACR or >/= 3 mg/mmol = significant proteinuria
What is classified as significant proteinuria?
condirmed ACR or >/= 3 mg/mmol
Do we need to repeat ACR test for proteinuria if ACR is 70 mg/mmol or more?
No, this indicated significant proteinuria straight away
What tests to do for tubular proteinuria?
Tubular = low molecular weight protein in the urine
- 24 hr total protein
- Protein: creatinine ratio (PCR)
- specific proteins e.g. NAG, RBP, alpha 1 -microglobulin
* albumin: creatinine ratio normal (glomerular function intact)
High PCR (protein: creatinine ratio) and low ACR (albumin : creatinine ratio)
What does it indicate?
Increased low molecular weight protein -> possible tubular damage
*as Albumin gets through filtration membrane in glomerular damage; PCR will show microglobulins which are normally reabsorbed in the tubules
What proteins may be seen in overflow proteinuria?
Low molecular weight protein - examples:
- Myoglobin - serum creatinine kinase
- Bence-Jones protein
What are the urine casts?
Aggregation of molecular in distal/collecting duct -> damage to the nephrons / necrosis of renal tubules
e.g. Red cell casts, cellular debris, Tamm-Horsfall protein - hyaline, white cells
Look for it by MICROSCOPY
The most common types of stones
What are physiological inhibitors of stone growth?
mucopolysaccharides, citrate and pyrophosphate
What urine pH favours formation of renal stones
alkaline
What do we look at in the urine analysis when we suspect renal stones?
- calcium
- phosphate
- urate
- oxalate
- cysteine
- pH
- sodium
- magnesium
- citrate
- microbiology
What is diagnostic of CKD?
- abnormalities in kidney function or structure present for >/= 3 months
and/or
- GFR <60 ml/min/1.73 m2 on at least 2 occasions separated by a period of at least 90 days
CKD signs and symptoms
- early stages are asymptomatic
- uremic syndrome (weakness, fatigue, loss od appetite, nausea, vomiting, tremors, altered mental function)
- nocturia
- polyuria
- pain
- oedema
Reduced GFR -> what biochemical abnormality can be seen?
Increased serum urea/creatinine
What biochemical abnormality can be seen in reduced tubular function?
Hyponatremia
Reduced tubular function = sodium loss, inability to concentrate or dilute urine
What biochemical abnormality can reduced GFR lead to?
Hyperkalaemia
How can CKD lead to metabolic acidosis?
- Reduced GFR -> reduced H+ ion excretion and reduced PO4 excretion
- Reduced tubular function – bicarb reabsorption
Why hypocalcaemia is associated with CKD?
Reduced 1,25 –vitamin D (1alpha hydroxylase)
What test should be used for eGFR?
CKD-EPI creatinine equation
*advise people not to eat meat in 12 hours before having a blood test for creatinine/eGFR
What Ix should be used for proteinuria?
Urine ACR
What other /2nd line test to use to confirm/rule out CKD if eGFR with creatinine is borderline?
Cystatin C
*it is in the guidelines but not many places use it because of the cost and therefore not many labs offer it
What’s the aim of treatment of CKD?
- No cure
- Treatment to manage complications
- slow down the progression
- to reduce CVD risks
What findings would suggest the increased risk of progression of CKD?
What findings (in GFR) would indicate an increased risk of progression to end-stage kidney disease? (2)
- a sustained decrease in GFR of 25% or more over 12 months
OR
- a sustained decrease in GFR of 15 ml/min/1.73 m2 or more over 12 months
What’s ASSIST?
CKD from Renal Registry
- scheme aiming to increase early identification of CKD
Aim: to reduce the unplanned need for dialysis
*to look at eGFR over time and to alert the clinicians of significant changes
Pre-renal. What would increase more: creatinine or urea?
Urea > creatinine
pre renal -> less blood flow to the nephron -> slower filtrate flow through the nephrone -> filtrate spends longer in the nephron -> more time for the urea to be reabsorbed -> more urea reabsorbed -> more serum urea
A response of sodium and water to hypovolaemia in AKI in:
- pre-renal cause
- intrinsic
- pre- renal: sodium and water retention (tubule function initially is intact)
- intrinsic: sodium and water loss (tubular dysfunction so not able to reabsorb)
Management of AKI
- determine the cause and treat
- give fluids - if dehydrated
- stop nephrotoxic drugs
- treat metabolic complications - hyperkalaemia
- monitor (U&E, fluid balance chart)
- nephrology referral
- renal replacement therapy - if needed
