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What are the main functions of the kidneys?
Produce urine: filter blood, allowing removal of waste products, excess water, salt etc; and retention of proteins
Make important proteins: erythropoietin (epo), active vitamin D, renin
Regulate blood pressure and acid-base: regulate salt & water, produce renin, buffer H+ etc.
What is proteinuria a cardinal sign of?
When should you test for proteinuria?
Any routine medical consultation should include dipstick (test is cheap, non-invasive, reliable and alters management)
In oedema (including periorbital -usually children- , sacral if recumbent); unexplained ascites or pleural effusions
As part of the care of patients with hypertension, diabetes mellitus etc
If a systemic disease is possible
How can you tell if there is protein in the urine without a dipstick? (not used any more)
Urine with protein becomes frothy when shaken. When boiled, protein precipitates.
What combination of signs is kidney disease until proven otherwise?
Proteinuria and haematuria.
What may trace or 1+ proteinuria mean?
Can be normal, especially after exercise/standing upright.
What does 2+ proteinuria mean?
2+ or more implies intrinsic renal disease and very unlikely to be explained by asymptomatic infection
How can you quantify proteinuria?
albumin/creatinine ratio - timed collection rarely helpful
What must you test if you find proteinuria?
Test kidney renal function, consider systemic diseases
NEVER ignore/dismiss it
What type of sample is the albumin/creatinine ratio (mg/mmol) tested on?
Small urine sample taken at any time of day.
What do you multiply ACR by to get the mg/24hrs albumin?
What is the albumin / 24hrs threshold that indicates high likelihood of kidney disease with bad prognosis?
1g / 24hrs.
What is a normal ACR range?
Less than 3.5
What is the ACR range for microalbuminuria?
What is the ACR range for (macro)albuminuria?
How can excretory renal function be measured?
plasma/serum creatinine (serum = plasma without clotting factors)
estimated GFR: MDRD formula (sex, age, race, creatinine)
isotope GFR (usually 51Cr EDTA) - when assessing kidney donor etc, expensive and invasive
Cystatin C measurement is more expensive than creatinine
Why can you get atheroma around the origin of the renal arteries?
Due to turbulent blood flow - arise at 90 degrees.
What is the basic functional unit of the kidney?
Which substances are filtered across the slit membrane and which are not? What is the threshold molecular weight?
- RBCs, WBCs + platelets
- beta-2 microglobulin and Cystatin C
- urea, sodium, potassium, hydrogen
RBCs, WBCs, and platelets remain in the capillary
A tiny amount of albumin goes through and is reabsorbed in the proximal tubule
IgG doesn't go through - except in kidney disease
Beta-2 microglobulin and cystatin C go through freely
Creatinine is freely filtered = plasma creatinine. A bit is secreted into the tubule by cells.
Urea, sodium, potassium and hydrogen are freely filtered and reabsorbed
Glucose is freely filtered and is resorbed - has a threshold, so in diabetes acts as an osmole.
Threshold is lower in pregnancy.
50 kilodaltons is the size threshold for filtration.
What is congenital nephrotic syndrome?
Due to mutation in podocyte-specific gene eg nephrin. Disrupts the normal filter and causes albumin to leak out.
What does the presence of blood and protein in the urine indicate? What should you test and consider?
Implies glomerular disease and an urgent need to test excretory kidney function, consider systemic diseases such (eg vasculitis, lupus).
What is the earliest clinical feature of diabetic nephropathy in diabetes mellitus?
Microalbuminuria - may initially be intermittent.
What does albuminuria in hypertension suggest?
A primary renal cause.
What type of prognostic significance does albuminuria carry?
Increased cardiovascular risk. Aggressive management indicated.
What is the definition of nephrotic syndrome?
Clinical syndrome comprising oedema, heavy proteinuria, hypoalbuminaemia.
What features are clinically significant in nephrotic syndrome but not included in the definition?
Thrombotic risk, propensity to infection and (often severe) hyperlipidaemia.
How may nephrotic syndrome be associated with excretory kidney function?
May be impaired.
What are the dominant symptoms of nephrotic syndrome?
Severe lethargy, reduced exercise tolerance, nausea, loss of appetite.
What are the causes of nephrotic syndrome?
Glomerulonephritis, diabetes, infections (hepatitis B/C, malaria, HIV), amyloid depositions.
In which diseases is the glomerulus damaged and so may present with proteinuria/haematuria?
Anything that damages blood vessels
Rare genetic/developmental disorders
Inflammation of blood vessels - vasculitis, isolated or systemic disease
Glomerular inflammation - glomerulonephritis
Deposition diseases eg amyloid
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