Renal Function Test (RFT)

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

Original Editor - User Name

Top Contributors - Manisha Shrestha, Lucinda hampton and Joao Costa  

Introduction

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. 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

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

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

Components of RFT

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

Test to assess the kidney function

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

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)

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.

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:

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% . 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.

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

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 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

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).

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.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. 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.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

Serum parameters

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.

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

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

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.”