Kidney function tests are a group of tests performed to evaluate the overall functioning of the kidneys. Assessment of renal function is important in the management of patients with kidney disease or pathologies affecting renal function.
The kidneys play a vital role in the excretion of waste products and toxins such as urea, creatinine and uric acid, regulation of extracellular fluid volume, serum osmolality and electrolyte concentrations, as well as the production of hormones like erythropoietin and 1,25 dihydroxy vitamin D and renin.
Derangement of any of these function would result in either decreased excretion of waste products and hence their accumulation in the body or loss of some vital nutrient from the body
Physiology of the kidneys
The functional unit of the kidney is called a nephron.
It consists of two main parts; the glomerulus and the tubular system.
The glomerulus is composed of a bowman’s capsule and a tuft of leaky blood vessels encapsulated by the bowman’s capsule.
The primary purpose of the glomerulus is filtrations.
The leaky vessels filter into the glomerulus almost all the water, electrolytes, small proteins, nutrients such as sugar, etc and excretory products such as urea, etc. The filtrations are dependent on the size and charge of the particles.
Also, the basement membrane carries a negative charge hence preventing negatively charged particles from passing through.
The Tubular system is responsible for reabsorption of most of the water, electrolytes, nutrients as well as excretion of the remaining nutrients by means of secretion into the tubules. These tubules are responsible for the concentration of urine.
The components of the Kidney function tests can be broadly divided into two
1.Tests that measure glomerular function
2.Tests that measure tubular function
The tests that are part of the Kidney Function tests panel are:
(a) Urine examination
(b) Serum Urea
(c) Serum creatinine
(d) Blood urea nitrogen (BUN)
(i) Creatinine clearance
(j) Urea clearance
(k) Inulin clearance
(l) Dilution and Concentration test
(l) Serum electrolyte levels
It provides excellent clues to the nature and location of the lesion in the renal system.
This examination consists of a physical examination where the
-Specific gravity etc of the urine is noted.
Examination of urine is done to rule out any pus cells, Rbc casts, Crystals.
Urea is the end product of protein catabolism produced from the amino group of the amino acids and is produced in the liver by means of the Urea cycle.
Urea undergoes filtrations at the glomerulus as well as secretion and reabsorption at the tubular level.
The rise in the level of serum urea is generally seen as a marker of renal dysfunction especially glomerular dysfunction.
Urea level only rises when the glomerular function is reduced below 50%.
The normal serum urea level is between 20-45 mg/dl. But the level may also be affected by diet as well as certain non-kidney-related disorders.
INCREASED in hypermetabolic conditions, starvation.
DECREASED in case of hepatic injury.
blood urea is not an excellent marker of renal dysfunction as it rises quite late in the dysfunction and its rise is also not exclusive to kidney dysfunction
Urea is measured in diagnostic labs either by the UV kinetic method using á ketoglutarate as an NH3+ acceptor in the presence of enzyme glutamate dehydrogenase. It is also measured calorimetrically by Berthelot’s endpoint method and is read in the visible range using a calorimeter.
Blood urea nitrogen (BUN)
Sometimes the Serum urea level is expressed as blood urea nitrogen.
The serum urea levels can be easily converted to BUN by multiplying it by 0.47.
Normal levels are 5-26mg/dl
DECREASED in fluid overload, malnutrition, severe liver disease, and SIADH.
INCREASED in intrinsic renal dysfunction, prerenal azotemia-CCF, shock, vomiting, and diarrhea,
postrenal azotemia-bilateral ureteral obstruction, bladder outlet obstruction, and bladder dysfunction
A rise in blood nitrogen levels is known as azotemia.
The Kidneys help control the amount of phosphate in the blood. Extra phosphate is filtered by the kidneys and passes out of the body in the urine.
High levels of phosphorus in blood only occur in people with severe kidney disease or severe dysfunction of their calcium regulation.
Excessively high levels of phosphorus in the blood, although rare, can combine with calcium to form deposits in soft tissues such as muscle.
Protein in urine is noticeably increased in a renal disease of any etiology, except obstruction, and is, therefore, a very sensitive, general screening test for renal disease, though not specific.
The extent of proteinuria also provides useful information.
The greatest degree of proteinuria is found in the nephrotic syndrome (> 3 – 4 g/day).
In renal disease with the nephritic syndrome, the urinary protein excretion rate is usually about 1 – 2 g/day.
In tubulointerstitial disease, urine protein is generally less than 1 g/day.
Only in the nephrotic syndrome is the urine protein loss sufficiently great to result in hypoproteinemia.
Serum Creatinine levels
Creatine is a small tripeptide found in the muscles. It stays in its phosphorylated form and releases energy for any burst of muscular activity and released from the muscles during regular wear and tear and is converted to creatinine.
It is to be remembered that unlike urea, creatinine is not toxic waste. It is simply used as a marker of renal function.
Creatinine is freely filtered at the glomerulus and is also to a very small extent secreted into the tubules. So any problem with glomerular filtrations has a significant effect on the excretion of creatinine resulting in a much substantial rise in serum creatinine level.
Creatinine levels are lower in pregnant women and a value of more than 0.8 mg/dl is abnormal
Decreased in reduced muscle mass.
Elevated by drugs such as trimethoprim and cimetidine, in hypothyroidism and decreased in hyperthyroidism.
Normal serum creatinine level is 0.6 to 1.5 mg/dl.
Serum creatinine is a better indicator of renal function and more specifically glomerular function than urea. For a particular individual, the creatinine level is dependent on the muscle mass and muscle wear and tear.
Creatinine is measured in laboratories calorimetrically by Jaffe’s method.
Creatinine clearance rate
Creatinine is filtered at the glomerulus and its reabsorption at the tubular level is insignificant.
Because of this creatinine clearance can be used to measure GFR.
It is measured over a period of 24 hrs. This urine is collected over a 24 hour period and a blood sample is also collected.
The concentration of creatinine is measured both in the urine as well as the serum sample.
Creatinine clearance is then calculated using the equation:
- C = (U x V) / P
C = clearance, U = urinary concentration, V = urinary flow rate (volume/time ie ml/min), and P = plasma concentration
The normal range of creatinine clearance is:
Males : 100 – 120 ml/ min
Females : 95 – 105 ml/min
This is very close to the glomerular filtration rate
GFR is the ability of the kidneys to filter blood.
Normal is 125ml/min/1.73m2 in male
100ml/min/1.73m2 in female
Urea clearance is the hypothetical amount of blood from which the kidney clears urea in one minute.
This is measured by measuring the concentration of urea in blood, concentration of urea in urine and amount of urine excreted over a one-hour interval.
Urea clearance is less than its glomerular filtration as some of the areas that is filtered at the glomerulus is reabsorbed at the tubules.
To measure urea clearance first the patient is made to void urine and then the made to drink two glasses of water. Then the urine is collected after an hour and a blood specimen is also collected at the same time. Then the patient’s urine sample is collected after another hour. The urea level in the two urine samples and the blood sample is measured.
Maximum urea clearance of an average individual or body surface area of 1.73 sq m is 75 ml/ min and a standard urea clearance is 54 ml/min.
A urea clearance below 60% of a standard is considered impaired.
Cystatin C is a low-molecular-weight protein that functions as a protease inhibitor produced by all nucleated cells in the body. It is formed at a constant rate and freely filtered by the kidneys. Serum levels of cystatin C are inversely correlated with the glomerular filtration rate (GFR).
High values indicate low GFRs, while lower values indicate higher GFRs, similar to creatinine. The renal handling of cystatin C differs from creatinine. While both are freely filtered by glomeruli, once cystatin C is filtered, it is reabsorbed and metabolized by proximal renal tubules, unlike creatinine. Thus, under normal conditions, cystatin C does not enter the final excreted urine to any significant degree.
Cystatin C is measured in serum and urine. The advantages of cystatin C over creatinine are that it is not affected by age, muscle bulk, or diet, and various reports have indicated that it is a more reliable marker of GFR than creatinine particularly in early renal impairment.
Cystatin C has also be incorporated into eGFR equations such as the combined creatinine-cystatin KDIGO CKD-EPI equation.
Cystatin C concentration may be affected by the presence of cancer, thyroid disease, and smoking
Inulin is a small polysaccharide of low molecular weight made up of fructose.
To measure glomerular filtrate the substance used should have the following qualities:
(a) It should be nontoxic.
(b) Should not be metabolized in the body.
(c) Should be completely filtered at the glomerulus.
(d) Should neither be secreted or reabsorbed at the tubules.
Inulin meets all these criteria and hence makes for a suitable candidate to measure GFR.
Inulin clearance hence equals to GFR.
To measure Inulin clearance first Inulin is introduced in the blood by means of a slow continuous infusion to maintain a steady concentration of Inulin in the blood.
This is done by first infusing 30 ml of 10% inulin in 250 ml of normal saline infused at a rate of 20 ml/ min to achieve the desired concentration.
Then 70 ml of 10% inulin in 500 ml saline is infused at a rate of 4 ml/ min to maintain the desired concentration.
The patient is asked to micturate 20 minutes after the second infusion and the urine in discarded and the time noted. After exactly 60 minutes, take another sample of urine and blood is collected. Measure the volume of urine and the concentration of inulin in both the serum and urine.
Normal inulin clearance is 120 to 130 ml/minute for an average person with a body surface area of 1.73 sq m. This is a close approximation of the GFR.
A below-normal inulin clearance shows an impaired glomerular function.
In the case of a water shortage in the body, the kidney is able to concentrate urine and conserve water.
This is done by increasing the reabsorption of water from the glomerular filtrate at the tubular level.
The measure of the ability of the kidney to conserve water and concentrate urine is a measure of tubular function.
For this test, the patient is not allowed to take any food or water after the evening meal.
The first three urine samples passed in the morning are collected and their specific gravity measured.
In a normal person, the specific gravity of at least one of the samples should be above 1.025 or above.
If the specific gravity remains below 1.025 then it is a sign of tubular dysfunction.
Like the concentration test, the dilution test is also a measure of the functioning of the tubules.
In cases of fluid overload of our body, the tubules reabsorb lesser amounts of water resulting in excretion of diluted urine.
For this test, the subject is put on overnight fast and then in the morning, the subject is made to drink 1200 ml of water over a time period of 30 minutes.
Then the urine samples are collected every hour for 4 hours.
The specific gravity of the samples is measured and at least one of the samples should have a specific gravity of 1.003 or less.
If none of the samples have the specific gravity of 1.003 or less this is a sign of tubular dysfunction
The purpose of the kidney is not just water balance and excretion but also to maintain the electrolyte balance of our body. Kidneys actively reabsorb or excrete electrolytes.
This test measures the amount of Calcium in your blood, not the calcium in your bones.
The body needs it to build and fix bones and teeth, help nerves work, make muscles contraction, help blood clots, and help the heart to work.
The Calcium test screens for problems with the parathyroid glands or kidneys, certain types of cancers and bone problems, pancreatitis and kidney stones.
Normal Results: 8.5 to 10.2 mg/dl.
Indications for kidney function tests
Indications for the assessment of renal function are varied and range from acute emergency to chronic settings.
Primarily kidney function tests are performed to identify the renal disease to determine appropriate patient management and prevent further deterioration of renal function.
Further indications in patients in whom the renal disease has been identified are to stage level or type of renal disease and to monitor the progression of renal disease to ensure that optimal management occurs timeously and to monitor response to interventions.
In other scenarios, kidney function tests may be required to establish and monitor renal function where a known or possibly nephrotoxic therapeutic agent is initiated for patient management.
Renal function tests are also indicated in those individuals who are transplant donors to assess the initial donor suitability, and after that, to detect any significant deterioration of renal function post-donation.
Tests of renal function can also be utilized to identify which area of the functional unit of the kidney (nephron) is affected, for example, glomerular versus tubular disease.