Renal Function Tests (RFT)

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.
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
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

1. RENAL FUNCTION TESTS MD ALTAMASH AHMAD ROLL-1850951001 PHARM D 4 TH YEAR

2. FUNCTIONS OF KIDNEY

3. Renal function tests (RFT) 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. 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 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

4. 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. Need of RFT

5. Urine analysis involves the assessment of urine by physical observation, chemical and microscopic examination. Physical examination- Normal urine output – 800-2000 ml/day Anuria and oliguria can be because of various conditions like, diminished perfusion of kidney due to diminished blood volume, renal diseases like tubular necrosis, pre-renal obstruction. Anuria - <100 ml/day Oliguria - <400 ml/day Polyuria - >2000 ml/day Polyuria can be caused by various conditions like glucosuria in diabetes mellitus, ADH deficiency in diabetes insipidus . To assess the Renal diseases Urinalysis (Urine Analysis)

6. Color of urine- Normally urine is Amber yellow in color. Hematuria or hemoglobinuria may result in dark brown colored urine. Pyuria , pale or turbid urine is due to infections. Dark yellow colored urine may be due to Jaundice, intake of B complex vitamins or reduced intake of water (less than 2 liters/day) pH of urine – It is usually acidic pH6 (4.5-8-pH ) specific gravity – Normally varies from 1.016 to 1.025 Osmolality – On average fluid intake, it ranges from 300 to 900 mosmol /kg Odour – Foul smell indicates bacterial infection

7. 2. 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.

8. Serum parameters - Normal values Parameter Normal range Blood urea 15-40 mg/dL Serum creatinine Male - 0.7 -1.4 mg/dL Female – 0.6-1.3 mg/dL Serum uric acid Male- 4-7 mg/dL Female- 3-6 mg/dl Sodium 135 -145 mmol /L Potassium 3.5 - 5.0 mmol /dL Chloride 96 - 106 mmol /dL Bicarbonate 23 - 27 mmol /dL Arterial blood pH 7.35 - 7.45 Arterial pCO2 35 - 45 mm of Hg Arterial pO2 80 - 100 mm of Hg

9. To assess Renal Function There are several clinical laboratory tests that are useful in investigating and evaluating kidney function. 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 ). Detectable amount of protein in urine indicates glomerular leak and is the first sign of glomerular injury . Normally the urinary excretion of albumin is lesser then 30 mg/24 hrs . When the excretion is between 30-299 mg/24 hrs , it is detected by special test called test for microalbuminuria or paucialbuminuria If it is more than 300 mg/24 hrs, it is called macroalbuminuria which can be detected by heat coagulation test or uristicks . In case of severe damage to glomerulus , hematuira also occurs.

10. GFR is the rate in millilitres 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 and they are: Inulin clearance test Creatinine clearance test Urea clearance test Glomerular Filtration Rate – Clearance test

11. Inulin Clearance Test Inulin , a polysaccharide- a fructose polymer is considered the reference method for the estimation of GFR in this method. 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, Where , C = inulin clearance in ml/min U = concentration of inulin in urine (mg/dl) P = plasma inulin concentration (mg/dl) V = volume of urine passed per minute =  

12. It is the best marker for clearance test as it is freely filtered through from glomerulus, neither reabsorption nor secreted by renal tubules. It is neither synthesized nor stored in body so it gives values near to the GFR i.e. about 125ml/minute .

13. Creatinine Clearance test Creatine phosphate is present in skeletal muscles which is continuously metabolized in to creatinine with the wear and tear of muscles . 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 . 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 . Where , C = creatinine clearance in ml/min U = concentration of creatinine in urine (mg/dl) P = plasma creatinine concentration (mg/dl) V = volume of urine passed per minute =  

14. Not an ideal marker since it also is excreted by tubular secretion . 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, Where, Ccr = total creatinine clearance SCr = serum creatinine Ccr = (multiply by 0.85 if female)  

15. 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 .

16. Clinical relevance of GFR- clearance test– Clearance test is useful in the early stages of renal disease It is decreased in renal dysfunction and indicates decreased glomerular filtration rate (GFR) Inulin clearance is exogenous compound and the blood level is maintained, It is neither secreted nor reabsorbed. It gives true GFR . Creatinine clearance is not an ideal marker since it also is excreted by tubular secretion . Urea clearance is poor marker of GFR as urea reabsorption occurs in proximal and distal nephron. In moderate impairment, blood urea, serum creatinine are elevated. That condition is known as azotemia or uremia

17. In adults, the normal eGFR number is more than 90. eGFR declines with age, even in people without kidney disease. Chart below shows average estimated eGFR based on age.

18. End-stage renal disease (ml/min/1.73 m 2 )

19. Albuminuria and Proteinuria Albuminuria refers to the abnormal presence of albumin in the urine. M icroalbumin , considered an obsolete term as there is no such biochemical molecule, is now referred to only as urine albumin. Albuminuria is used as a marker for the detection of incipient nephropathy in diabetics. It is an independent marker for the cardiovascular disease since it connotes increased endothelial permeability, and it is also a marker for chronic renal impairment . Urine albumin may be measured in 24-hour urine collections or early morning/random specimens as an albumin/creatinine ratio. The presence of albuminuria on two occasions with the exclusion of a urinary tract infection indicates glomerular dysfunction. The presence of albuminuria for three or more months is indicative of chronic kidney disease.

20. Frank proteinuria is defined as greater than 300 mg per day of protein. Normal urine protein is up to 150 mg per day (30% albumin; 30% globulins; 40% Tamm Horsfall protein). 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). The KDIGO classification defines three stages of albuminuria: A1: Less than 30 mg/g creatinine A2: 30 to 300 mg/g creatinine A3: Greater than 300 mg/g creatinine In nephrotic syndrome, urine protein excretion exceeds 3.5 g per day and is associated with edema , hypoalbuminemia, and hypercholesterolemia.

21. Blood Urea Nitrogen (BUN) Urea or 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. Serum urea levels increase in conditions where renal clearance decreases (in acute and chronic renal failure/impairment). Serum creatinine is a more accurate assessment of renal function than urea; however, urea is increased earlier in renal disease. The ratio of BUN: creatinine can be useful to differentiate pre-renal from renal causes when the BUN is increased. In pre-renal disease, the ratio is close to 20:1, while in intrinsic renal disease, it is closer to 10:1. Upper GI bleeding can be associated with a very high BUN to creatinine ratio (sometimes >30:1).

22. Cystatin C 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). In other words, high values indicate low GFRs, while lower values indicate higher GFRs, similar to creatinine. The renal handling of cystatin C differs from creatinine. While glomeruli freely filter both, once cystatin C is filtered, it is reabsorbed and metabolized by proximal renal tubules, unlike creatinine.  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.

23. 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- eGFR equations are used to determine the presence of renal disease, stage of CKD, and to monitor response to treatment . Cystatin C- It is more reliable marker of GFR than creatinine, particularly in early renal impairment because it is not affected by age, muscle bulk, or diet.

24. Urine concentration (or) fluid deprivation test- After 15 hrs of withholding fluid intake, the first urine sample collected should have osmolality more than 850 mosm /kg or specific gravity more than 1.025. If it is lesser then these values, it could be due to, 1 . Renal tubular defect (nephrogenic diabetes insipidus) 2 . ADH deficiency (diabetes insipidus ) On ADH stimulation test, if it becomes normal then it is due to ADH deficiency and not due to tubular defect. Tubular function tests

25. In dilution test, after emptying the bladder , 1200 ml of water is given. Urinary specific gravity should fall to 1.005 or an osmolality lesser the 100 mosml /kg Urine specimens are collected hourly for next four hours In renal tubular disease, there will be a fixed specific gravity Urine dilution tests

26. Urine acidification tests To assess the ability of kidney to reabsorb bicarbonate and excrete hydrogen ions. Ammonium chloride (100 mg/kg) in gelatin capsule is given. Urine is collected hourly for eight hours. pH of urine normally falls between 4.6 and 5.0 But in renal tubular acidosis, it does not fall below 5.3

27. Phenolsulphthalein (PSP) test Patient is given 600 ml water initially. Phenolsulphthalein test dye 6 mg in 1 ml saline is given intravenously and urine Urine samples are collected at 15, 30, 60, 120 minutes. If the 15 minute urine contains 25% or more, the test is normal. If it is lesser than 25%, it indicates impaired renal excretory function.

28. Significance of Renal function tests (RFT)- 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. The functional unit of the kidney is the nephron, which consists of the glomerulus, proximal and distal tubules, and collecting duct. Assessment of renal function is important in the management of patients with kidney disease or pathologies affecting renal function . Tests of renal function have utility in identify ing the presence of renal disease , monitoring the response of kidneys to treatment , and determining the progression of renal disease . According to the National Institutes of Health, the overall prevalence of chronic kidney disease (CKD) is approximately 14%. Worldwide, the most common causes of CKD are hypertension and diabetes.

29. Acute renal impairment or acute kidney injury (AKI) refers to the sudden onset of kidney injury within a period of a few hours or days. Chronic kidney disease (CKD) is caused by long-term diseases such as hypertension and diabetes. Causes of acute kidney injury can be divided into The following: Causes that result in decreased blood flow to the kidneys ( pre-renal causes ), for example, hypotensive and cardiogenic shock, dehydration, and blood loss from major trauma Causes that result in direct damage to the kidneys ( renal /intrinsic causes ) such as damage to kidneys by nephrotoxic medications and other toxins, sepsis, cancers such as myeloma, autoimmune diseases or conditions that cause inflammation, or damage to the kidney tubules Causes that result in blockage of the urinary tract such as bladder, prostate, or cervical cancer, large kidney stones, and blood clots in the urinary tract ( post-renal causes )

30. It is important to note that pre-renal kidney injury may progress to acute tubular necrosis (ATN) and cause intrinsic renal injury . Other laboratory investigations apart from serum creatinine play a vital role in the diagnosis of AKI and assist in differentiating between different types of acute kidney injury. This is important, as it will determine the appropriate patient management, with patients that have pre-renal causes being treated with fluid replacement. In contrast, those with renal and post-renal causes would be given fluids more conservatively . Investigations that assist in determining if the renal injury is pre-renal, renal, or post-renal include the measurement of urine specific gravity, which is increased (greater than 1.020) in dehydration and pre-renal causes. The presence of white and red blood cells, tubular epithelial cells, casts, or crystals in the urinary sediment under light microscopy can assist in the differential diagnosis .

31. Fractional excretion of sodium ( FeNa ) is useful in distinguishing acute tubular necrosis from pre-renal uremia . It requires the measurement of serum creatinine and sodium and measurement of creatinine and sodium in spot urine specimens. Fractional excretion is calculated using the following formula: FeNa = 100  x ( urinary sodium x serum creatinine) / (serum sodium x urinary creatinine). A value of less than 1% indicates a pre-renal cause, and values greater than 2% indicate intrinsic causes. A urine osmolality of greater than 500 mOsm /Kg is associated with pre-renal causes, while an osmolality similar to serum (approximately 300 mOsm /kg) reflects an intrinsic cause.

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