W9 L2 - Renal function tests in practice

Question 1

2 Categories of renal dysfunction

Answer 1

• AKI (acute kidney injury)
• CKD (chronic kidney disease)

Question 2

Acute kidney injury (AKI)

Answer 2

• Sudden episode of kidney failure or damage (reduction in renal function)
• Happens within a few hours or days
• Can result in failure to maintain fluid balance, electrolyte level disturbances and acid-based imbalances
• most AKI starts in community (primary care)

Question 3

Chronic kidney disease (CKD)

Answer 3

• Long terms condition - gradual decline in kidney function over a period of time
• Abnormal kidney function and/or structure that has been present for more than three months
• Those with CKD have a substantially increased mortality
• Commonly leads to cardiovascular disease and other complications such as anaemia, disordered bone mineral metabolism and calcification of blood vessels ​
• Can result in end-stage kidney failure​

Question 4

Age-related changes in renal function

Answer 4

• Number of age-related changes can occur - structure and function
• Declinein glomerular filtration rate (GFR) of approx. 6ml/minevery 10 years
• Includes nephrosclerosis - changes (hardening) of the blood vessels in the kidneys
• Results in decline in the number of functional nephrons
• Common causes of chronic kidney disease e.g. hypertension arealso more common in older people

Question 5

Assessing renal function - Why

Answer 5

• Routine screening/baseline bloods
• Those at risk of kidney disease
• Signs and symptoms of kidney disease
• Progression of kidney disease

Question 6

Assessing renal function - How

Answer 6

• Glomerular Filtration Rate (GFR)
  Measured GFR most accurate measure of renal function
  Clearance of an external filtration marker during 24-hour urine collection
  Time-consuming and difficult to do in practice
• Creatinine
  Naturally occurring solute which is freely filtered by the kidneys
  Can measure levels in blood and urine
• Estimated Creatinine Clearance (CrCl)
  Cockcroft and Gault formula – single blood level of creatinine put into mathematical formula
• Estimated Glomerular Filtration Rate (eGFR)
  Different formulas available to calculate this, again uses single blood level of creatinine

Question 7

Assessing renal function - Creatinine

Answer 7

• Creatinine = breakdown product of muscle (metabolic by-product muscle metabolism)
• Formed at relatively constant rate
• Cleared by kidneys (freely filtered at the glomerulus)
• Only reabsorbed and secreted in small amount
• Measure levels in blood and urine
• Usual range (blood) approx. 59 – 104 micromol/L
  Limitation
• Creatinine levels vary depending on factors including size, gender, diet, hydration and muscle mass
• Acute kidney injury (AKI) - measureserum creatinineand compare tobaseline

Question 8

diagnostic criteria for AKI

Answer 8

• Rise in serum creatinine of 26micromol/L within 48 hours
  50% or greater rise in serum creatinine known or presumed to haveoccurredwithin past 7 days
• Fall in urine output to less than 0.5ml/kg/hr for > 6 hours (catheter)
• Can also assess stage (severity) of AKI (graded 1 –3) by looking at extent ofincrease in serum creatinine or duration/extent of fall in urine output
• Note - eGFR result doesn’t help determine severity (unlike with CKD)

Question 9

Assessing renal function -eCrCl

Answer 9

• creatinine clearance equation
  CrCl = (140 – age(yrs)) x weight (kg)/ Plasma creatinine (micromol/l) X 1.04 (female) or 1.23 (male)
• Some debate over what weight to use in obese patients and those who are very frail
• In these cases, may need to calculate using actual, ideal and adjusted body weight (i.e. get three values) and then compare results
• Creatinine level must be at steady state (stable from day to day) to provide most accurate estimate
• Accuracy issues for some people including:
  Pregnancy
  Amputees
  Severely malnourished
  Extremes of age
  Rapidly changing or very elevated creatinine
• Doesn’t take into account variations between different ethnicities

Question 10

Assessing renal function -eGFR

Answer 10

1. Chronic Kidney Disease Epidemiology Collaborationequation (CKD-EPI)
   - Uses serum creatinine, age, sex and adjusted for body surface area (in very small/large patients)
   - Recommended first-line method for estimating GFR in most patients
   - Normal GFR > 90ml/min/1.73m2
   - Most labs use CKD-EPI to report eGFR
2. Modification of diet in Renal Disease (MDRD) Equation
   Also uses serum creatinine, age, sex and race
   Has been found to be less accurate than the CKD-EPI formula when eGFR is greater than 60 mL/min/1.73 m2

“Actual GFR”
If person is at extreme of body weight or for certain medicines can calculate “actual GFR”:
Actual eGFR = eGFR x Body Surface Area/1.73

Question 11

Overestimates of eGFR

Answer 11

• eGFR may appear better than it is in the following:
• Elderly
• Diet – low protein diet
• Amputees
• Low muscle mass/muscle wasting disorders

Question 12

underestimates of eGFR

Answer 12

eGFR may appear worse that it is in the following:
- High muscle mass
- Diet – high protein diet
- Muscle breakdown e.g. after heavy exercise

Question 13

Assessing renal function -Urinalysis

Answer 13

• Urine dipstick
  Dipstick test for blood, protein, leucocytes, nitrates and glucose
  Can help to identify potential cause of renal dysfunction
  Good initial “screen”
• Albumin Creatinine Ratio (ACR)
  Ratio of albumin (mg) in the urine to creatinine (mmol) in the serum
• Protein Creatinine ratio (PCR) - less sensitive than ACR
  Ratio of protein (mg) in the urine to creatine (mmol) in the serum
• Urine output
  24-hour urine collection- urine creatinine clearance

Question 14

Assessing renal function - CKD

Answer 14

Chronic kidney disease (CKD) is classified using a combination of eGFR and albumin:creatinine ratio (ACR)

Question 15

Assessing renal function – other blood tests

Answer 15

• Urea (usual range approx. 2.5 - 7.8 mmol/L)
  Waste product produced by the liver
  Freely filtered in the kidneys and excretedin urine. Some reabsorption
  In dehydration – reabsorption increases therefore high urea could be due to dehydration or reduced eGFR
• Potassium (usual range 3.5 - 5.3 mmol/L)
  Levels controlled by aldosterone - excess potassiumeliminated by kidneys
  Renal dysfunction (both acute and chronic)- can get high levels (hyperkalaemia)
  Phosphate (usual range 0.8 - 1.4 mmol/L)
• Phosphate can accumulate as kidney function declines
• Sodium (usual range 135 – 145 mmol/L)
  A number ofmechanisms regulate sodium and water balance
  High sodium – too little fluid/dehydration,Low sodium – too much fluid, oedema

Question 16

Safe Medicine Use in Renal Impairment

Answer 16

• Some medicines can cause kidney problems/damage – often referred to as nephrotoxic medicines
• The use of medicines in patients with reduced renal function (AKI or CKD) can also give rise to problems for a number of reasons including:​
• pharmacokinetic (ADME) changes including reduced renal excretion of a drug or its metabolites which may cause toxicity​
• sensitivity to some drugs is increased even if elimination is unimpaired​
• many side-effects are tolerated poorly by patients with renal impairment​
• some drugs are not effective when renal function is reduced​

Question 17

What will I need to do

Answer 17

• Identify medicines which might require dose adjustment in renal impairment
• Identify medicines that may require additional monitoring in renal impairment
• Know about medicines which can cause or exacerbate renal impairment (nephrotoxic medicines)
• Advise/make dose adjustments as appropriate:
  total daily maintenance dose may need to be reduced
  reduce the size oftheindividual dosesor increase the interval between doses
  considerformulations available