Renal function tests

Question 1

Name some kidney functions?

Answer 1

• Extracellular fluid volume.
• H⁺ homeostasis.
• Excretion of urea.
• Erythropoietin production
• Vitamin D metabolism.

Question 2

Name some components of the glomerulus?

Answer 2

a) Basement membrane.
b) Capillary lumen.
c) Urinary space.

Question 3

Describe aldosterone

Answer 3

• Secreted from adrenal cortex.
• Acts on principal (P) cells in distal tubule and collecting duct.
• Increases sodium reabsorption.
• Modifies sodium channels.
• Promotes expression of new channels and ATPases.

Question 4

What is vasopressin (ADH)

Answer 4

• Released from posterior pituitary.
• Acts on collecting duct cells to promote insertion of aquaporin-2 water channels into luminal membrane.
• Increases water permeability.
• Increased water reabsorption.

Question 5

What is glomerular filtration rate used to assess?

Answer 5

• Used to assess glomerular function.
• Creatinine formed from creatine in muscle - an end product of nitrogen metabolism.
• Plasma concentration depends on muscle mass and therefore lower values may be found in wasting diseases and in children.
• Decreased in pregnancy and mildly increased by high meat intake or vigorous exercise.

Question 6

Glomerular filtration rate: Urine collection

Answer 6

• 8.00 am empty bladder and void.
• Start collecting.
• 8.00 am next day empty bladder, collect urine and stop.
• Incorrect performance a major source of error in GFR measurement.
• Creatinine concentration is relatively static over time.

Not a great biomarker!

Question 7

GFR or plasma creatine?

Answer 7

• GFR changes substantially before change in plasma creatinine is detectable.
• Therefore GFR is a more sensitive indicator of potential renal damage.

However:

• Measurement of plasma creatinine concentration is more precise than of GFR.
• Plasma creatinine is easier to measure than the GFR.
• Plasma creatinine is entirely satisfactory to follow the course of renal disease or to detect rejection after renal transplantation.

Question 8

What are the causes of elevated creatinine in plasma?

Answer 8

• Impaired renal perfusion.
• Due to decreased blood pressure, reduced blood volume or narrowing of the renal artery.
• Loss of functioning nephrons.
• e.g. glomerulonephritis which is associated with antibody mediated damage or deposition of immune complexes in glomeruli.
• Increased pressure on tubular side of nephron
• e.g. prostatic enlargement or a kidney stone (most commonly consisting of calcium oxalate or calcium oxalate and phosphate).

Question 9

Describe the interpretation of plasma urea measurements

Answer 9

• Wide normal range 2.5 - 6.6 mmol/l limits use.
• High protein diet, or increased protein catabolism after trauma, will increase plasma urea without kidney involvement.
• Liver failure, low protein diet or water retention will decrease plasma urea without renal involvement.
• As with creatinine, decreased perfusion of the kidney, renal disease and obstruction of urine outflow will elevate plasma urea.

Question 10

Kidney structure

Answer 10

Question 11

Proximal tubular function: Glucosuria

Answer 11

• Glucose in urine with a normal blood glucose could indicate malabsorption of glucose in the proximal tubule.
• In diabetes mellitus blood glucose is elevated and swamps the reabsorption.

Question 12

Distal tubular function

Answer 12

• Assessed by urine concentration tests.

Measure:

• Specific gravity (ratio of mass of 1ml of urine : 1 ml H₂O).
• No good if protein in urine.
• Osmolality (related to number of solute particles).
• the concentration of a solution expressed as the total number of solute particles per kilogram.
• 285 mmol/kg in serum.
• Normal early morning tests:
• Osmolality > 800 mmol/kg; SG > 1.02.
• If you deviate from these numbers there can be a problem in the distal tubule.

Question 13

Distal tubular function: Testing

Answer 13

• Inject synthetic analogue of vasopressin intramuscularly and collect samples hourly for the next 3 hours.
• Osmolality of urine should increase.

Question 14

Protein and renal function

Answer 14

• Albumin (normal < 30mg/24h).

Microalbuminuria:

• 30-300 mg/24h.
• Detectable with immunoassay stick and analyser.
• Found in diabetic nephropathy.

Macroalbuminuria:

• > 300 mg/24h.
• Colourimetric dipstick.

Question 15

Proteinuria

Answer 15

Question 16

Dipsticks for urine tests

Answer 16

Question 16

Dipsticks for urine tests

Answer 16

Question 17

Acute kidney injury

Answer 17

• Always retention of urea, creatinine and H⁺.
• Usually oligouria (<400 ml/24h) and hyperkalaemia (elevated plasma K⁺).
• Uncomplicated AKI has a mortality rate of 5-10%.
• Elderly and critically ill.
• Serious more complicated forms of the disorder require immediate medical attention.
• Dialysis

Question 18

Marker for AKI

Answer 18

• Rise in plasma creatinine can be delayed.
• High mortality – early biomarker would be useful.
• Neutrophil gelatinase-associated lipocalin is one of the most highly induced proteins in kidney after ischaemic or nephrotoxic damage.
• Released into urine within 2h of AKI – promising.

Question 19

Course of AKI

Answer 19

Diuretic phase – GFR increases but still below normal; tubules still non-functional

Question 20

Chronic kidney disease occurs in:

Answer 20

• Glomerulonephritis, diabetes mellitus, pyelonephritis (subclinical repeated infection of kidney) and polycystic renal disease (genetic origin).
• Decreased number of functioning nephrons.
• Patients may be asymptomatic until GFR< 15 ml/min which requires immediate referral.
• Reduced GFR.
• Retention of urea, creatinine and phosphate and potassium (concentration in plasma goes up).

Question 21

Chronic kidney disease: Classified by GFR

Answer 21

• MDRD equation is ok for stages 3-5.
• Stages 1-2 require additional evidence e.g. clinical proteinuria or haematuria

Question 22

Chronic kidney disease: Graph of reciprocal of serum creatinine concentration vs time

Answer 22

Graph of reciprocal of serum creatinine concentration vs time is often a straight line which allows prediction of when renal replacement will be required.