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== Introduction ==
== Introduction ==
[[File:KidneyAnatomy 01.png|right|frameless]]
Renal function tests (RFT)  are a group of tests that may be performed together to evaluate [[kidney]] (renal) function. The tests measure levels of various substances, including several minerals, electrolytes, proteins, and glucose (sugar), in the blood to determine the current health of the kidneys.
Renal function tests (RFT)  are a group of tests that may be performed together to evaluate [[kidney]] (renal) function. The tests measure levels of various substances, including several minerals, electrolytes, proteins, and glucose (sugar), in the blood to determine the current health of the kidneys.


If the kidneys are not functioning properly, waste products can accumulate in the blood and fluid levels can increase to dangerous volumes, causing damage to the body or a potentially life-threatening situation. Numerous conditions and diseases can result in damage to the kidneys. The most common causes of and main risk factors for kidney disease are [[diabetes]] and [[hypertension]]. <ref name=":2">Lab tests on line [https://www.labtestsonline.org.au/learning/test-index/kidney-function-tests Kidney function tests] Available:https://www.labtestsonline.org.au/learning/test-index/kidney-function-tests  (accessed 5.10.2021)</ref>
If the kidneys are not functioning properly, waste products can accumulate in the blood and fluid levels can increase to dangerous volumes, causing damage to the body or a potentially life-threatening situation. Numerous conditions and diseases can result in damage to the kidneys. The most common causes of and main risk factors for kidney disease are [[diabetes]] and [[hypertension]]. <ref name=":2">Lab tests on line [https://www.labtestsonline.org.au/learning/test-index/kidney-function-tests Kidney function tests] Available:https://www.labtestsonline.org.au/learning/test-index/kidney-function-tests  (accessed 5.10.2021)</ref>
== Indication ==
== Indication ==
Indications for the assessment of renal function are varied and range from acute emergency to chronic settings.  
Indications for the assessment of renal function are varied and range from acute emergency to chronic settings.  
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==== Glomerular Function- Clearance test ====
==== Glomerular Function- Clearance test ====
[[File:Nephron Anatomy.png|right|frameless|399x399px]]
Within the kidneys are about a million tiny blood filtering units called nephrons. In each nephron, blood is continually filtered through a cluster of looping blood vessels, called a glomerulus, which allows the passage of water and small molecules but retains blood cells, proteins such as albumin, and larger molecules.
The best test to assess glomerular function is Glomerular filtration rate (GFR), which is the rate in milliliters per minute at which substances in plasma are filtered through the glomerulus; in other words, the clearance of a substance from the blood. The normal GFR for an adult male is 90 to 120 mL per minute.  
The best test to assess glomerular function is Glomerular filtration rate (GFR), which is the rate in milliliters per minute at which substances in plasma are filtered through the glomerulus; in other words, the clearance of a substance from the blood. The normal GFR for an adult male is 90 to 120 mL per minute.  


GFR cannot be measured directly so various substances are used to assess GFR. There are various exogenous and endogenous substances that are used for clearance test. The characteristics of an ideal marker to measure GFR are as follows:
Testing for GFR can be a complicated and lengthy procedure, which is why doctors use a formula to estimate GFR or eGFR. The standard way to estimate GFR is with a simple blood test that measures creatinine levels. Creatinine is a waste product from the digestion of dietary protein and the normal breakdown of muscle tissue. Aside from [[Chronic Kidney Disease|chronic kidney disease]], creatinine levels can be affected by other factors, including diet, muscle mass, [[malnutrition]], and other [[Chronic Disease|chronic illnesses]].<ref>Kidney org. GFR Available:https://www.kidney.org/atoz/content/gfr (accessed 5.10.2021)</ref>  
 
* Constant rate of production (or for exogenous marker can be delivered intravenously at a constant rate)
* Freely filterable at the glomerulus (minimal protein binding)
* No tubular reabsorption
* No tubular secretion
* No extrarenal elimination or metabolism
* Availability of an accurate and reliable assay
* For exogenous marker: safe, convenient, readily available, inexpensive, and does not influence GFR (physiologically inert)<ref name=":0">Gounden V, Jialal I. [https://www.ncbi.nlm.nih.gov/books/NBK507821/ Renal Function Tests.][Updated 2020 Mar 31]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2020.</ref><ref name=":1">Rosner MH, Bolton WK. [https://www.ajkd.org/action/showPdf?pii=S0272-6386%2805%2901508-8 Renal function testing.] American Journal of Kidney Diseases. 2006 Jan 1;47(1):174-83.</ref>
 
Clearance (C) is the rate at which an indicator substance is removed from plasma per unit concentration; specifies a volume from which all of a substance is removed per unit time. For a substance Z cleared by renal elimination:
 
Cz =UzxV ⁄ Pz
 
Where Cz is the clearance rate of Z substance, Uz is urinary concentration of z, Pz is plasma concentration of Z, and V is urine flow rate.
 
There are various exogenous and endogenous substances/markers that are used for clearance test and they are:
 
===== '''Inulin Clearance Test''' =====
Since there is no such endogenous marker currently exists, exogenous markers ( most commonly inulin, a polysaccharide- a fructose polymer) is  considered the reference method for the estimation of GFR.  First intravenous(IV) bolus of inulin is given then continuous infusion of inulin is given so that a constant inulin concentration is maintained in  body fluid.  Then samples of plasma and urine are taken and the rate of clearance of inulin is determined using clearance rate formula mentioned above.  
 
It is the best marker for clearance test as it is freely filtered  through from glomerulus, neither reabsorption nor secreted by renal tubules, and it is neither synthesized nor stored in body so it gives values near to the GFR i.e. about 125ml/minute.
{{#ev:youtube|rxrpN-mrwiQ}}<ref>Renal System 19 – Ultrafiltration – GFR (5-8) – Inulin Clearance Test | Dr. Prashant Sharma. Available from:https://www.youtube.com/watch?v=rxrpN-mrwiQ [lasted assessed: 1-6-2021]</ref>
 
===== '''Creatine Clearance test''' =====
Creatine phosphate is present in skeletal muscles which is continuously metabolized in to creatine with the wear and tear of muscles. Metabolism of creatinine:
 
* Generated in muscle by non-enzymatic conversion of creatine and phosphocreatinine
* Generation is proportional to muscle mass and is relatively constant
* Important role of liver in formation of creatinine through methylation of guanidine aminoacetic acid
 
Levels of creatine varies according to diurnal and menstrual variations, race, body surface area and diet (and method of meat preparation).As GFR increases in pregnancy, lower creatinine values are found in pregnancy.
 
Factors affecting serum creatine are:
{| class="wikitable sortable"
|Increase serum creatine
|Decrease serum creatine
|-
|Ketotic states
 
Hyperglycemia
 
Cephalosporins
 
Flucytosine (enzymatic method)
 
Cimetidine, trimethoprim (block secretion)
 
Vigorous exercise
 
Ingesting cooked meats ( 30% increase  after the ingestion of red meat)
|Dietary protein restriction
 
Muscle wasting, malnutrition
 
Bilirubin
 
Renal disease
 
Advanced age
 
Female sex
 
Advanced liver disease
|}
Not an ideal marker since it also is excreted by tubular secretion. Proportion of total creatinine clearance (Ccr) due to tubular secretion increases as GFR decreases and Ccr leads to GFR overestimation by approximately 10-20%<ref name=":1" /> <ref name=":0" />. However, it is the most commonly used endogenous marker for the assessment of glomerular function.
 
Serum creatinine is also utilized in GFR estimating equations such as the Modified Diet in Renal Disease (MDRD) and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. These eGFR equations are superior to serum creatinine alone since they include race, age, and gender variables. <ref name=":0" />
 
Formula to estimate creatine clearance via Cockcroft-Gault equation predicts Ccr as
 
Ccr=(140-age)  (weight)/(72 *SCr) (multiply by 0.85 if female)


According to the Kidney Disease Improving Global Outcomes (KDIGO), The stages of chronic kidney disease (CKD):
According to the Kidney Disease Improving Global Outcomes (KDIGO), The stages of chronic kidney disease (CKD):
* Stage 1 GFR greater than 90 ml/min/1.73 m²  
* Stage 1 GFR greater than 90 ml/min/1.73 m²  
* Stage 2 GFR-between 60 to 89 ml/min/1.73 m²
* Stage 2 GFR-between 60 to 89 ml/min/1.73 m²
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* Stage 5-GFR less than 15 ml/min/1.73 m² (end-stage renal disease)
* Stage 5-GFR less than 15 ml/min/1.73 m² (end-stage renal disease)


===== Urea Clearance test =====
== Typical Tests Performed ==
Urea or Blood urea nitrogen (BUN)  is a nitrogen-containing compound formed in the liver as the end product of protein metabolism and the urea cycle. About 85% of urea is eliminated via kidneys; the rest is excreted via the [[gastrointestinal (GI) tract]]. It is freely filtered but reabsorbed in proximal and distal nephron (urea clearance is less than GFR); urea reabsorption is substantial in states of decreased renal perfusion. Thus, it is the poor marker for GFR.
The individual tests included in a kidney function panel can vary by laboratory, but the tests typically performed include:  
 
Serum urea levels increase in conditions where renal clearance decreases. Other factors affecting serum urea <ref name=":1" />are:
{| class="wikitable"
|Increase serum urea
|Decrease serum urea
|-
|Dehydration
 
Reduced renal perfusion (heart  failure)
 
Increased dietary protein
 
Catabolic states:
 
·          Fever
 
·          Trauma
 
·          GI bleeding
 
·          Tetracyclines
 
·          Corticosteroids
|Volume expansion
 
Pregnancy
 
SIADH (Syndrome of inappropriate secretion of antidiuretic hormone)
 
Restriction of dietary protein
 
Liver disease
 
Advanced renal disease
 
Starvation
|}
 
==== Glomerular permeability ====
Kidneys retain or reabsorb the filtered proteins and return them to the circulating blood while removing wastes by excreting them in the urine. Whenever the kidney is compromised, their ability to filter the blood by differentiating protein from the waste, or retaining the filtered protein then returning which back to the body, is damaged. Albumin is a protein produced by the liver which makes up roughly 50%-60% of the proteins in the blood. Due to this, the concentration of albumin in urine is a sensitive test for the kidney disease.
 
Glomerular permeability helps in the detection of protein in urine. Proteinuria is the presence of excess proteins in the urine. Screening for proteinuria can be accomplished with either standard urine dipsticks (total proteinuria) or albumin-specific dipsticks. Urine protein may be measured using either a 24-hour urine collection or random urine protein: creatinine ratio (early morning sample is preferred since it is a near representative of the 24-hour sample).<ref name=":0" /><ref name=":1" />
 
==== Tubular function ====
The renal tubules play a vital role in the reabsorption of electrolytes, water, and maintaining acid-base balance. Measurement of urine osmolality allows for assessment of concentrating ability of urine tubules.<ref name=":0" />There two types of  test: concentration and dilution test.
 
Specific gravity is an indicator of the renal concentrating ability, which can be measured using refractometry or chemically by the use of urine dipstick. The physiological range for specific gravity is 1.003 to 1.030. Specific gravity is increased in concentrated urine and decreased in dilute urine. <ref name=":0" />In general, urine osmolality of 50 mOsm/kg (mmol/kg) is approximately equivalent to a specific gravity of 1.000; 300 mOsm/kg, a specific gravity of 1.010; 800 mOsm/kg, a specific gravity of 1.020.<ref name=":1" />The normal specific gravity of urine, range from 1.0101-1.025.
 
===== Concentration test =====
It helps to identify the ability of kidney to concentrate the urine measuring specific gravity of the urine. It is conducted under the restricted of intake of fluid. Normal water deprivation for 18 to 24 hours leads to urine osmolality >900 mOsm/kg in most healthy persons. In this, overnight water deprivation is done and 2 samples at the interval of 1 hour is taken in the morning.  At least one of the sample should have specific gravity of more than 1.025.
 
===== Dilution test =====
It helps to identify the ability of kidney to dilute the urine when fluid intake is loaded. Specifity gravity is used as a measure. In this 1200ml of water is loaded over the period of 30 mins and 4 samples are taken at the interval of 1 hour and one of the sample should have specific gravity of less than 1.010.


=== Test to assess the renal diseases ===
# Electrolytes – electrically charged chemicals that are vital to normal body processes, such as nerve and muscle function; among other things, they help regulate the amount of fluid in the body and maintain the acid-base balance. Electrolytes include:


==== Serum parameters ====
* Sodium
These are routinely done test to rule out kidney problems. It include: urea, creatinine, sodium and potassium.
* Potassium
* Chloride
* Bicarbonate (Total CO2)


Urea can be measured by using Urea GLDH or Urease  Berthelot method. In renal diseases urea concentrations are elevated when the glomerular filtration rate is markedly reduce and when the protein intake is higher than 200g/day. There are three causes that cause increase in serum urea. They are: pre-renal (burn, dehydration, vomiting, infection), renal (glomerunephritis, renal failur, nephrotic syndrome, pyelonephritis) and post-renal(tumor, stone, tuberculosis of ureter, urethra and bladder). Reference value of serum urea is 14 – 40 mg/dL.<ref>Urea. Available from:https://www.eurodiagnostics.in/uploads/products/20170608095849_Urea%20Berthelot%20insert%20final.pdf</ref>
2. Minerals


Creatine is most sensitive than urea to assess renal function. Normal range for male is 0.7- 1.4mg/dl and for female: 0.6-1.3mg/dl.
* Phosphorus – a mineral that is vital for energy production, muscle and nerve function, and bone growth; it also plays an important role as a buffer, helping to maintain the body's acid-base balance.
* Calcium – one of the most important minerals in the body; it essential for the proper functioning of muscles, nerves, and the heart and is required in blood clotting and in the formation of bones.


Normal range of sodium:135-150mmol/L
3. Protein


Normal range of potassium:3.5 -5 mmol/L
* Albumin – a protein that makes up about 60% of protein in the blood and has many roles such as keeping fluid from leaking out of blood vessels and transporting hormones, vitamins, drugs, and ions like calcium throughout the body.


==== Urine Analysis ====
4. Waste products
Urine analysis involves the assessment of urine by physical  observation, chemical and microscopic examination.  


'''Physical characteristics''' includes:
* Urea – urea is a nitrogen-containing waste product that forms from the metabolism of protein; it is released by the liver into the blood and is carried to the kidneys, where it is filtered out of the blood and eliminated in the urine.
* Creatinine – another waste product that is produced by the body's muscles; almost all creatinine is eliminated by the kidneys.


* Volume
5. Energy Source
* Color: The normal urine is straw-colored, while in the presence of dehydration, urine is darker in color. Red urine may indicate hematuria or porphyria or could represent the dietary intake of food like beets. Cloudy urine may be seen in the presence of pyuria due to urinary tract infection.
* Odour
* Specific gravity: The physiological range for specific gravity is 1.003 to 1.030.
* pH
* Total solid
* Pus cells


'''Chemical Characteristics'''
* Glucose – supplies energy for the body; a steady amount must be available for use, and a relatively constant level of glucose must be maintained in the blood.


* Glucose- Benedict's test (Glucose is not detected in healthy patients but may be seen in diabetes mellitus, pregnancy, and renal glycosuria)
=='''Clinical Significance'''==
* Protein- Heat coagulation test
* Blood- Benzidine test(Blood may be present after renal tract injury or infection, with ascorbic acid causing a falsely negative result.)
* Bile salt: Hays test
* Bile pigment: Fouchet test
* Ketone bodies: Rothera's test (Ketones are present in fasting, severe vomiting, and diabetic ketoacidosis)


Dipstick method: Urine dipstick provides qualitative analysis of different analytes in urine using chemical analysis. It uses dry chemistry methods to detect the presence of protein, glucose, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocyte esterase.  
* Creatinine: Serum creatinine is elevated when there is a significant reduction in the glomerular filtration rate or when urine elimination is obstructed.  About 50%  of kidney function must be lost before a rise in serum creatinine can be detected. Thus serum creatinine is a late marker of acute kidney injury.
* BUN : Serum urea/BUN level increases in acute and chronic renal disease.
* eGFR equations are used to determine the presence of renal disease, stage of CKD, and to monitor response to treatment.


s the Modified Diet in Renal Disease (MDRD) and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. These eGFR equations are superior to serum creatinine alone since they include race, age, and
== Significance ==
== Significance ==
Chronic kidney disease is not only a major risk factor for dialysis but also increases the risk of cardiovascular diseases and is closely related to lifestyle-related diseases such as diabetes and hypertension. In addition, dialysis patients develop complications including cardiovascular diseases, infections, and malignant neoplasms and have a very poor prognosis as the mortality 3 years after the initiation of dialysis exceeds 30%.  
Chronic kidney disease is not only a major risk factor for dialysis but also increases the risk of cardiovascular diseases and is closely related to lifestyle-related diseases such as diabetes and hypertension. In addition, dialysis patients develop complications including cardiovascular diseases, infections, and malignant neoplasms and have a very poor prognosis as the mortality 3 years after the initiation of dialysis exceeds 30%.  

Revision as of 02:45, 5 October 2021

Original Editor - Manisha Shrestha Top Contributors - Manisha Shrestha, Lucinda hampton and Joao Costa

Introduction[edit | edit source]

KidneyAnatomy 01.png

Renal function tests (RFT) are a group of tests that may be performed together to evaluate kidney (renal) function. The tests measure levels of various substances, including several minerals, electrolytes, proteins, and glucose (sugar), in the blood to determine the current health of the kidneys.

If the kidneys are not functioning properly, waste products can accumulate in the blood and fluid levels can increase to dangerous volumes, causing damage to the body or a potentially life-threatening situation. Numerous conditions and diseases can result in damage to the kidneys. The most common causes of and main risk factors for kidney disease are diabetes and hypertension. [1]

Indication[edit | edit source]

Indications for the assessment of renal function are varied and range from acute emergency to chronic settings.

  1. Primarily, renal function tests are performed to identify the renal disease to determine appropriate patient management and prevent further deterioration of renal function.
  2. 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 and to monitor response to interventions[2].

Components of RFT[edit | edit source]

RFT, a group of tests that may be performed together, evaluate kidney (renal) function. The tests measure levels of various substances, including several minerals, electrolytes, proteins, and glucose (sugar), in the blood to determine the current health of the kidneys[1].

Clinically, the most practical tests to assess renal function is to get an estimate of the glomerular filtration rate (GFR) and to check for proteinuria (albuminuria).[2]

[3]

Test to assess the kidney function[edit | edit source]

It is very essential to know the function of kidney and also the process of urine formation to know the rational behind these test and also to interpret the result of these test.

Glomerular Function- Clearance test[edit | edit source]

Nephron Anatomy.png

Within the kidneys are about a million tiny blood filtering units called nephrons. In each nephron, blood is continually filtered through a cluster of looping blood vessels, called a glomerulus, which allows the passage of water and small molecules but retains blood cells, proteins such as albumin, and larger molecules.

The best test to assess glomerular function is Glomerular filtration rate (GFR), which is the rate in milliliters per minute at which substances in plasma are filtered through the glomerulus; in other words, the clearance of a substance from the blood. The normal GFR for an adult male is 90 to 120 mL per minute.

Testing for GFR can be a complicated and lengthy procedure, which is why doctors use a formula to estimate GFR or eGFR. The standard way to estimate GFR is with a simple blood test that measures creatinine levels. Creatinine is a waste product from the digestion of dietary protein and the normal breakdown of muscle tissue. Aside from chronic kidney disease, creatinine levels can be affected by other factors, including diet, muscle mass, malnutrition, and other chronic illnesses.[4]

According to the Kidney Disease Improving Global Outcomes (KDIGO), The stages of chronic kidney disease (CKD):

  • Stage 1 GFR greater than 90 ml/min/1.73 m²  
  • Stage 2 GFR-between 60 to 89 ml/min/1.73 m²
  • Stage 3a  GFR 45 to 59 ml/min/1.73 m²
  • Stage 3b GFR 30 to 44 ml/min/1.73 m²
  • Stage 4 GFR of 15 to 29 ml/min/1.73 m²
  • Stage 5-GFR less than 15 ml/min/1.73 m² (end-stage renal disease)

Typical Tests Performed[edit | edit source]

The individual tests included in a kidney function panel can vary by laboratory, but the tests typically performed include:

  1. Electrolytes – electrically charged chemicals that are vital to normal body processes, such as nerve and muscle function; among other things, they help regulate the amount of fluid in the body and maintain the acid-base balance. Electrolytes include:
  • Sodium
  • Potassium
  • Chloride
  • Bicarbonate (Total CO2)

2. Minerals

  • Phosphorus – a mineral that is vital for energy production, muscle and nerve function, and bone growth; it also plays an important role as a buffer, helping to maintain the body's acid-base balance.
  • Calcium – one of the most important minerals in the body; it essential for the proper functioning of muscles, nerves, and the heart and is required in blood clotting and in the formation of bones.

3. Protein

  • Albumin – a protein that makes up about 60% of protein in the blood and has many roles such as keeping fluid from leaking out of blood vessels and transporting hormones, vitamins, drugs, and ions like calcium throughout the body.

4. Waste products

  • Urea – urea is a nitrogen-containing waste product that forms from the metabolism of protein; it is released by the liver into the blood and is carried to the kidneys, where it is filtered out of the blood and eliminated in the urine.
  • Creatinine – another waste product that is produced by the body's muscles; almost all creatinine is eliminated by the kidneys.

5. Energy Source

  • Glucose – supplies energy for the body; a steady amount must be available for use, and a relatively constant level of glucose must be maintained in the blood.

Clinical Significance[edit | edit source]

  • Creatinine: Serum creatinine is elevated when there is a significant reduction in the glomerular filtration rate or when urine elimination is obstructed.  About 50%  of kidney function must be lost before a rise in serum creatinine can be detected. Thus serum creatinine is a late marker of acute kidney injury.
  • BUN : Serum urea/BUN level increases in acute and chronic renal disease.
  • eGFR equations are used to determine the presence of renal disease, stage of CKD, and to monitor response to treatment.

s the Modified Diet in Renal Disease (MDRD) and the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. These eGFR equations are superior to serum creatinine alone since they include race, age, and

Significance[edit | edit source]

Chronic kidney disease is not only a major risk factor for dialysis but also increases the risk of cardiovascular diseases and is closely related to lifestyle-related diseases such as diabetes and hypertension. In addition, dialysis patients develop complications including cardiovascular diseases, infections, and malignant neoplasms and have a very poor prognosis as the mortality 3 years after the initiation of dialysis exceeds 30%.

Since it is a chronic disease, a multidisciplinary treatment approach and patient centered treatment will be very beneficial. Renal rehabilitation was defined as “a long-term comprehensive program consisting of exercise therapy, diet therapy and water management, drug therapy, education, psychological/mental support, etc., to alleviate physical/mental effects based on kidney disease and dialysis therapy, prolong the life expectancy, and improve psychosocial and occupational circumstances.”[5]

References[edit | edit source]

  1. 1.0 1.1 Lab tests on line Kidney function tests Available:https://www.labtestsonline.org.au/learning/test-index/kidney-function-tests (accessed 5.10.2021)
  2. 2.0 2.1 Gounden V, Jialal I. Renal function tests. Available:https://www.ncbi.nlm.nih.gov/books/NBK507821/ (accessed 5.10.2021)
  3. Kidney function tests and Interpretation of Results. Available from:https://www.youtube.com/watch?v=aa_syowyGvg [Lasted accessed: 1-6-2021]
  4. Kidney org. GFR Available:https://www.kidney.org/atoz/content/gfr (accessed 5.10.2021)
  5. Yamagata K, Hoshino J, Sugiyama H, Hanafusa N, Shibagaki Y, Komatsu Y, Konta T, Fujii N, Kanda E, Sofue T, Ishizuka K. Clinical practice guideline for renal rehabilitation: systematic reviews and recommendations of exercise therapies in patients with kidney diseases. Renal Replacement Therapy. 2019 Dec;5(1):1-9.