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Next Lesson - Hyponatraemia
Core
There are a number of ways in which kidney function can be measured. One of these methods is through measurement of compounds filtered by the kidneys. The constituents of urine can also be analysed to check for underlying renal pathology. Imaging of the bladder, sphincter, and urethra can also be useful to check for their storage capability.
Kidney function is measured in terms of glomerular filtration rate (GFR). GFR defined as the amount of filtrate that is produced from the blood per unit time. The normal range of GFR is 90-120 mL/min/1.73m2 which means the normal amount of glomerular filtrate per day is between 140-180L. As it is impossible to get an actual measurement of GFR (as we cannot visualise the kidneys that closely), each measurement is only an estimate of GFR (known as eGFR) calculated from the presence of filtrates in the urine.
There are many factors which can cause temporary or permanent changes in GFR.
Men typically have a higher GFR than women.
In utero, nephron development is finished by the 35th-36th week of gestation, meaning premature and low birth weight infants have lower numbers of nephrons, meaning the GFR of these infants is lower. At birth, GFR is approximately 20/ml/min/1.73m2, but normal (adult) GFR is achieved by around 18 months of age.
GFR starts to decline again after the age of 30. The rate of decline after this point is roughly 6-7ml/min per decade. This is due primarily to the loss of functioning nephrons. In order to try and offset this decline, there is some compensatory hypertrophy of the renal medulla, but the capacity for hypertrophy also declines with age.
Larger people tend to have larger kidneys than smaller people, and larger kidneys contain more nephrons. Therefore, GFR in larger people is higher.
In pregnancy, GFR increases by around 50% to 130-180ml/min. This is associated with an increase in kidney size of about 1cm due to hypertrophy and increased plasma volume in pregnant women. The total nephron number stays the same. Normal pre-pregnancy levels will be reached after 6 months post-partum.
Due to the above factors, there is huge variability in the GFR between individuals. If the GFR declines it may be due to the decline in the number of nephrons, or the decline in the filtration ability within individual nephrons. When kidney function declines slowly, individual nephrons may hypertrophy so overall GFR may not fall until significant kidney damage has occurred.
We cannot measure the true GFR, therefore a surrogate marker is needed for measurement.
Renal clearance can be calculated with the following equation:
Where C = clearance, U = amount in urine, V = urine flow rate, Pa = arterial plasma concentration, and x = the substance we are measuring to calculate clearance.
In order to best measure GFR, the substance needs to have these four properties:
- Be freely produced at a constant rate.
- Be freely filtered across the glomerulus.
- Not be reabsorbed in the nephron.
- Not be secreted into the nephron.
If all four of these conditions are true, then the clearance rate will be equal to GFR.
Inulin is a polysaccharide which meets all of these conditions. However, it requires a continuous intravenous infusion to maintain a steady plasma concentration and requires a catheter and timed urine collections. For these reasons, it is not used in clinical practice. Please note this polysaccharide is inulin not insulin.
Creatinine is an endogenous substance which is the end product of muscle breakdown. It is freely filtered across the glomerulus and is not reabsorbed along the nephron. However, it is secreted into the nephron and the rate of production can change dependant on diet and exercise. For this reason it does not measure true GFR – but it is an estimate. However, due to the secretion into the nephron creatinine measurement tends to overestimate GFR. Creatinine clearance is measured by collecting urine over 24 hours – this is cumbersome and frequently inaccurate but it can be used in pregnancy.
51 Cr-EDTA is a radioactively labelled marker which is cleared exclusively by renal filtration. It has approximately a 10% lower clearance than inulin, meaning it slightly underestimates GFR. This can be used clinically to measure GFR in children or where a better indication of renal function is required e.g. in a kidney transplant or in a work-up to donate a kidney for transplant.
In clinical practice, GFR (eGFR) is derived from measurements of serum creatinine. This is very easy to measure but can vary greatly between individuals. In order to standardise the eGFR a bit, one of two calculations can be used which take into account other patient factors.
The MDRD calculation takes into account serum creatinine, age, sex, and ethnicity (black or Caucasian).
This calculation is inaccurate in:
- People without kidney disease – for example transplant donors
- Children
- Pregnancy
- Old age
- Ethnicity other than black or Caucasian
- Amputees or other patients with significantly reduced muscle mass
- Patients with kidney function above 60ml/min
- When true GFR changes quickly – like in AKI
For these reasons, the MDRD equation tends to underestimate the true GFR – leading to a risk of patients being inappropriately labelled as having chronic kidney disease.
The CKD-EPI equation uses the same variables as MDRD, however, the calculation is slightly different. This means it is equally as accurate as MDRD when GFR is below 60ml/min but more accurate when GFR is above 60ml/min – however, it is important to note it is still not a perfect calculation.
eGFR measurement is less accurate in patients with mild kidney disease. There are three reasons for this:
- A reduction in GFR (e.g. if the surface area of the glomerulus is decreased) leads to an increase in blood flow to the glomerulus, which naturally increases filtration.
- A reduced number of nephrons leads to nephron hypertrophy, which would increase filtration.
- Reduced filtration of creatinine due to reduced GFR results in increased serum creatinine which is actively excreted into the nephron in order to maintain a relatively constant plasma concentration.
These three factors mean that eGFR remains normal, despite there being some mild kidney damage.
Urinalysis is the term given to performing a dipstick test on a urine sample. Urinalysis allows practitioners to look for common microscopic abnormalities in a patient’s urine.
A urinalysis dipstick will give information on the following:
- Specific gravity (density)
- pH
- Leukocytes (white blood cells)
- Blood/Haemoglobin
- Nitrites
- Ketones
- Bilirubin
- Urobilinogen
- Protein
- Glucose
Common conditions have specific findings on a urinalysis strip which make them easier to diagnose:
- Urinary Tract Infection (UTI) – blood, nitrites, or leukocytes.
- Uncontrolled Diabetes – glucose and ketones.
- Nephrotic Syndrome – protein (with potentially small amounts of blood).
- Jaundice – bilirubin or urobilinogen.
These are just some of the conditions in which urinalysis is very helpful in making a diagnosis.
There are many advantages to performing a urinalysis. It is very cheap, requires little training to be able to do, can be done at the patient’s bedside or in clinic, and all results are back within two minutes. However, a urinalysis only shows a practitioner what is present in the urine and does not give any information as to the filtration function (GFR) on the kidney.
Urodynamics is an umbrella term for a group of more invasive tests which look directly at the function of the bladder, sphincters, and urethra.
Urodynamic tests include:
- Uroflowmetry – the measurement of urine speed and volume.
- Postvoid Residual Measurement – a measurement of the amount of urine left in the bladder after urination.
- Cystometric Testing – a measurement of how much the bladder can hold, how much pressure builds up inside the bladder as it stores urine, and how full the bladder is when the urge to void is felt.
- Leak Point Pressure Measurement – a measurement of the pressure at which leakage occurs in a patient with urinary incontinence during a cystometric test.
- Pressure Flow Studies – a study which looks at the pressure required in the bladder to void and the flow rate that a given pressure generates.
- Electromyography – sensors which are used to measure the electrical stimulation to the nerves and muscles around the bladder and sphincters. This is used when a neuromuscular cause of a urological problem is suspected.
- Video Urodynamic Tests – taking images (using x-ray or ultrasound) of the bladder during filling and voiding.
These tests provide the best look at the inner workings of the bladder, sphincters, and urethra. However, they are associated with significant discomfort and in some cases a risk of developing a UTI. The results of some tests are available instantly, while others like electromyography may take some days to come back.
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell
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