renal function tests in practice

• Renal Function Tests

  Tests used to assess kidney function
• Acute kidney injury (AKI)

  Sudden episode of kidney failure or damage (reduction in renal function)
• Chronic kidney disease (CKD)

  Long terms condition - gradual decline in kidney function over a period of time
• 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
• Age related changes in renal function

  • Number of age-related changes can occur - structure and function
  • Decline in glomerular filtration rate (GFR) of approx. 6ml/min every 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 are also more common in older people
• Reasons to assess renal function

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

  
• Glomerular Filtration Rate (GFR)


  Total of the filtration rates of the functioning nephrons in the kidney

  
• Measured GFR most accurate measure of renal function

  
• Creatinine is a naturally occurring solute which is freely filtered by the kidneys - shows how well the kidneys are working

  
• 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

  
• Creatinine levels vary depending on factors including size, gender, diet, hydration and muscle mass - can increase the levels
• Diagnostic criteria for AKI

  • Rise in serum creatinine of 26 micromol/L within 48 hours
  • 50% or greater rise in serum creatinine known or presumed to have occurred within 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 of increase in serum creatinine or duration/extent of fall in urine output

  
• 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
• Estimated Glomerular Filtration Rate (eGFR)


  • Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) - uses serum creatinine, age, sex and adjusted for body surface area (in very small/large patients)
  • Modification of diet in Renal Disease (MDRD) Equation - also uses serum creatinine, age, sex and race

  
• MDRD 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

  Estimated GFR calculated using CKD-EPI or MDRD is normalised to a standard body surface area of 1.73m2. If using eGFR to calculate drug doses in patients at extremes of body weight or for drugs with a narrow therapeutic index correct eGFR to "actual GFR" using the equation: Actual GFR = (eGFR x BSA/1.73)

  
• Overestimates of eGFR

  • Elderly - can be higher than what their renal function actually is
  • Diet – low protein diet
  • Amputees
  • Low muscle mass/muscle wasting disorders
• Underestimates of eGFR

  • High muscle mass
  • Diet – high protein diet
  • Muscle breakdown e.g. after heavy exercise
• Urine dipstick

  Dipstick test for blood, protein, leucocytes, nitrates and glucose
• Albumin Creatinine Ratio (ACR)

  Ratio of albumin (mg) in the urine to creatinine (mmol) in the serum

  
• Protein Creatinine ratio (PCR)


  Ratio of protein (mg) in the urine to creatine (mmol) in the serum

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

  
• Urea

  Waste product produced by the liver, freely filtered in the kidneys and excreted in urine. Some reabsorption
• Potassium


  Levels controlled by aldosterone - excess potassium eliminated by kidneys
• Phosphate


  Can accumulate as kidney function declines
• High sodium – too little fluid/dehydration, Low sodium – too much fluid, oedema
• Why pharmacists need to know this

  • 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
• Labs will report renal function in adults based on eGFR and creatinine

  
• eGFR and eCrCl and not interchangeable
• For most drugs for most adult patients of average build and height – eGFR can be used to determine dose adjustments

  
• Most medicines – broad range of guidance for dose e.g. eGFR 30-50ml/min or CrCl 30-60ml/min
• When to use eCrCl rather than eGFR to determine renal dose adjustments

  • Creatinine clearance or absolute glomerular filtration rate should be used to adjust drug doses in patients with a BMI less than 18 kg/m2 or greater than 40 kg/m2
  • The Cockcroft and Gault formula is the preferred method for estimating renal function in elderly patients aged 75 years and over
  • The use of CKD-EPI may be appropriate in patients over 75 years, however muscle mass should be taken into consideration. Using CKD-EPI to calculate eGFR has the potential to overestimate renal function progressively as age increases, which can increase the risk of adverse effects due to higher than recommended doses being prescribed