Renal Function Test (RFT)

Original Editor - Manisha Shrestha Top Contributors - Manisha Shrestha and Lucinda hampton

Original Editor - User Name

Top Contributors - Manisha Shrestha and Lucinda hampton  

Introduction[edit | edit source]

The kidneys are responsible for the urinary excretion of uremic toxins and the regulation of several body systems such as intra and extracellular volume status, and acid-base status. They adapt quantitative and qualitative composition of the urine to keep these systems in balance. [1]Along with that kidneys helps in the production of

  • erythropoietin which stimulates the production of red blood cell.
  • renin for blood pressure regulation
  • carries out the conversion of vitamin D to its active form, ultimately helps in calcium absorption.

Renal function test (RFT), also known as kidney function test is a group of tests used to assess the functions of kidney. It is used screen for, detect, evaluate and monitor acute and chronic kidney diseases. These are simple blood and urine tests that are used identify kidneys problems.

Need of RFT[edit | edit source]

RFT is ordered, if your doctor

  • thinks your kidneys may not be working properly which is known from signs and symptoms
  • and if you have other conditions that can harm the kidneys, such as diabetes or high blood pressure


Signs and symptoms related to kidney problems are:

  • Blood in urine (reddish urine)
  • Lethargy and weakness
  • Dry and itching skin
  • Increase urge to urinate (specially at night)
  • Foamy urine (due to presence of protein in urine)
  • Persistent puffiness of body ( especially around eyes)
  • Poor appetite
  • Muscles cramping
  • Discomfort during urination[2]

Co-morbidities such as diabetes and hypertension usually cause chronic kidney diseases in long term so to screen the kidney function, RFT plays a vital role.

Tests of renal function have utility in

  • Identifying the presence of renal disease
  • Monitoring the response of kidneys to treatment
  • Determining the progression of renal disease[3]

Components of RFT[edit | edit source]

It is divided into two main types based on it's aim:

Aim To assess the renal diseases To assess the kidney function
1. Serum parameters

·         Serum urea

·         Creatinine

·         Electrolytes ( Na+, K+)

Glomerular function

·         Clearance test

2. Urine analysis Glomerular permeability

·         Proteins

3. Tubular function

·         Concentration test

·         Dilution test

[4]

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]

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:

  • 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)[3][5]

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[edit | edit source]

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.

[6]

Creatine Clearance test[edit | edit source]

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:

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%[5] [3]. 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. [3]

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):

  • 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)
Urea Clearance test[edit | edit source]

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.

Serum urea levels increase in conditions where renal clearance decreases. Other factors affecting serum urea [5]are:

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[edit | edit source]

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).[3][5]

Tubular function[edit | edit source]

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.[3]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. [3]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.[5]The normal specific gravity of urine, range from 1.0101-1.025.

Concentration test[edit | edit source]

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[edit | edit source]

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[edit | edit source]

Serum parameters[edit | edit source]

These are routinely done test to rule out kidney problems. It include: urea, creatinine, sodium and potassium.

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.[7]

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.

Normal range of sodium:135-150mmol/L

Normal range of potassium:3.5 -5 mmol/L

Urine Analysis[edit | edit source]

Urine analysis involves the assessment of urine by physical observation, chemical and microscopic examination.

Physical characteristics includes:

  • Volume
  • 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- Benedict's test (Glucose is not detected in healthy patients but may be seen in diabetes mellitus, pregnancy, and renal glycosuria)
  • 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.

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.”[8]

References[edit | edit source]

  1. Gueutin V, Deray G, Isnard-Bagnis C. Renal physiology. Bulletin du cancer. 2012 Mar 1;99(3):237-49.
  2. National Kidney Foundation. 10 Signs You May Have Kidney Disease. [Internet]. Available from: https://www.kidney.org/news/ekidney/august14/10_Signs_You_May_Have_Kidney_Disease [Lasted accessed: 31 May 2021]
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Gounden V, Jialal I. Renal Function Tests.[Updated 2020 Mar 31]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2020.
  4. Kidney function tests and Interpretation of Results. Available from:https://www.youtube.com/watch?v=aa_syowyGvg [Lasted accessed: 1-6-2021]
  5. 5.0 5.1 5.2 5.3 5.4 Rosner MH, Bolton WK. Renal function testing. American Journal of Kidney Diseases. 2006 Jan 1;47(1):174-83.
  6. 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]
  7. Urea. Available from:https://www.eurodiagnostics.in/uploads/products/20170608095849_Urea%20Berthelot%20insert%20final.pdf
  8. 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.