kidny function test

Kidney function test
5th class
Dr. Abdulhussien Aljebory
College of pharmacy
Babylon university
Why test renal function?
? To asses the functional capacity of kidney
? Early detection of possible renal impairment.
? Severity and progression of the impairment.
? Monitor response to treatment
? Monitor the safe and effective use of drugs which are excreted in the urine
• To identify renal dysfunction
• To diagnose renal disease
• To monitor disease progress
• To monitor response to treatment
• To assess changes in function that may impact on therapy (e.g. Digoxin, chemotherapy)




When should we assess renal function?
? Older age
? Family history of Chronic Kidney disease (CKD)
? Decreased renal mass
? Low birth weight
? Diabetes Mellitus (DM)
? Hypertension (HTN)
? Autoimmune disease
? Systemic infections
? Urinary tract infections (UTI)
? Nephrolithiasis
? Obstruction to the lower urinary tract
? Drug toxicity


Renal Functions
• Excretion of waste & production of urine
– Elimination of metabolic end products
– Elimination of foreign materials
• Control of volume & composition
– Water and electrolyte balance
– Acid/base status
• Endocrine Functions
– Renin
– Erythropoietin
– Calcitriol (activation of vitamin D)



Kidneys

• Located retroperitoneally on the posterior wall of the abdomen from T12-L3
• The average adult kidney weighs 4.5oz
• The right kidney sits lower in the abdomen due to liver placement
• An adrenal gland sits on top of each kidney
Kidney Anatomy
• Each kidney has two parts
• The renal medulla is the inner portion
– consists of renal pyramids which are collecting ducts that drain into renal pelvis
– Once urine leaves the renal pelvis the composition or amount of urine does not change
• The Cortex is the outer portion
– contains nephrons



Kidney Structure
Nephron
• Each kidney has approximately 1 million nephrons
• If the function is less than 20% replacement therapy is usually initiated
• The nephron is responsible for the initial formation of urine
Nephron
KIDNEY FUNCTIONS
• Urine formation
• Excretion of waste products
• Regulation of electrolytes
• Regulation of acid-base balance
• Control of water balance
• Control BP
• Regulation of RBC production
• Synthesis of vitamin D to active form
• Secretion of prostaglandins
• Regulation of calcium and phosphorus balance

What to examine???
Renal function tests are divided into the following:
? Urine analysis
? Blood examination
? Glomerular Function Test
? Tubular Function Test
Urine Formation
• Urine is formed in the nephrons in a three step process
– Glomerular filtration
– Tubular reabsorption
– Tubular secretion
• Glomerular Filtration produces ultrafiltrate which enters the tubules
• Selective reabsorption of H2O & solutes occurs in tubules
• Selective secretion of solutes occurs in tubules
• 99% of ultrafiltrate is reabsorbed into the bloodstream
• 1000-1500mL of urine is produced each day




Excretion of Waste Products


• The kidney is the body’s main excretory organ
• The major waste product of protein metabolism is urea
– 25-30g are produced and excreted daily
• Other waste products include:
– Creatinine
– Phosphates
– Sulfates
– Uric acid
– Drug metabolites
Regulation of Electrolytes
• In normally functioning kidneys the amount of electrolytes excreted per day is equal to the amount ingested
• Sodium
– Linked to blood volume and pressure
– Significant effects on osmotic pressure
– 90% of Na in ultrafiltrate is reabsorbed in the proximal tubules and loops of Henle
– Aldosterone causes kidneys to reabsorb sodium
• Potassium
– The kidneys excrete more than 90% of K intake to maintain a normal serum balance
– Aldosterone causes the kidneys to excrete potassium
Regulation of acid-base balance
• Normal serum pH is 7.35-7.45
• Normal urine pH is 4.6-8
• Kidneys 3rd line of defense in acid-base balance
– respiratory & other buffer systems respond more rapidly
– kidneys require several hours to a day or more to readjust balance
• Reabsorb bicarbonate from ultrafiltrate
• Excrete large quantities of acid in the urine (phosphoric and sulfuric acids) by buffering with ammonia



Control of water balance
• The human body is made up of 60% water
• Regulated by Antidiuretic hormone (ADH) or vasopressin
• Secreted by the posterior pituitary in response to serum osmolality
• ADH increases reabsorption of water to return serum osmolality to normal
• Decreased water intake stimulates ADH release
• ADH controls volume & concentration of urine by regulating permeability of distal tubule to H2O

Control BP
• The kidney secrets the hormone renin when there is a decrease in BP
• Renin converts angiotensinogen to angiotensin I
• Angiotensin I converts to angiotensin II
• Angiotensin II is a powerful vasoconstrictor and causes BP to increase
• Increase in BP stops the excretion of renin
• The adrenal cortex also releases aldosterone in response to increasing serum osmolality or poor perfusion to increase BP


• Regulation of RBC production
• The kidneys release erythropoietin when they sense a decrease in oxygen in the blood
• Erythropoietin stimulates the bone marrow to produce RBCs
• Vitamin D Synthesis
• The kidneys convert inactive vitamin D to 1,25-dihydroxycholecalciferol
• Vitamin D is necessary for calcium balance

Glomerular Filtration Rate (GFR) : The rate in ml/min at which small molecules are filtered through the kidney’s glomeruli. It is measure of the number of functioning nephrons.
Formation of urine
• Urine is formed by the help of nephrons
• About 1 million nephrones are present in one kidney
• Nephron contains bowmen’s capsule, proximal convoluted tubule, loop of henle, distal convoluted tubule and collecting tubule
• blood supply high-1200ml/min
• 120-125ml/min is filtered which is known as glomerular filtration rate (GFR)



Formation of urine
Process of urine formation basically involves two steps
• Glomerular filtration: formation of ultrafiltrate
– waste materials of plasma are filtered
• Tubular reabsorption: formation of pure urine
– retain water and most of the soluble constituents of the glomerular filtrate by reabsorption

• Renal threshold of a substance is the concentration in blood beyond which it is excreted in urine
• Renal threshold for glucose is 180mg/dL
• Tubular maximum (Tm): maximum capacity of the kidneys to absorb a particular substance
• Tm for glucose is 350 mg/min


Renal function tests
• Glomerular function tests: all the clearance tests (innulin, creatinine, urea)
• Tubular function test: urine concentration or dilution test or urine acidification test
• Analysis of blood/serum: blood urea, serum creatinine, protein and electrolytes
• Urine examination: simple routine examination of urine for volume, pH, proteins, blood, ketone bodies, glucose
Why Test Renal Function?
• To identify renal dysfunction.
• To diagnose renal disease.
• To monitor disease progress.
• To monitor response to treatment.
• To assess changes in function that may impact on therapy (e.g. Digoxin, chemotherapy).
Signs and Symptoms of Renal Failure
• Symptoms of Uraemia (nausea, vomiting, lethargy)
• Disorders of Micturation (frequency, nocturia, dysuria)
• Disorders of Urine volume (polyuria, oliguria, anuria)
• Alterations in urine composition (haematuria, proteinuria, bacteriuria, leukocytouria, calculi)
• Pain
• Oedema (hypoalbuminaemia, salt and water retention)
Biochemical Tests of Renal Function
• Urinalysis
– Appearance
– Specific gravity and osmolality
– pH
– Glucose
– Protein
– Urinary sediments?
• Measurement of GFR
– Clearance tests
– Plasma creatinine
• Tubular function tests
Role of Biochemical Testing
• Presentation of patients: -
• Routine urinalysis
• Symptom or physical sign
• Systemic disease with known renal component.
• Effective management of renal disease depends upon establishing a definitive diagnosis: -
• Detailed clinical history
• Diagnostic imaging and biopsy
• Role of biochemistry: -
• Rarely establishes the cause
• Screening for damage
• Monitoring progression.
Diagnostic Tests
• Blood Tests
– Serum Creatinine (0.5 – 1.2 mg/dl)
– Blood Urea Nitrogen (10-20 mg/dl)
– BUN/Creatinine Ratio (12:1 to 20:1 mass)
• Urine Tests
– Urinalysis
– Composite (e.g., 24hr) urine collections
– Creatinine Clearance Test
– Urine Electrolytes
– Osmolality (plasma; urine)
Diagnostic Tests (cont)
• Bedside sonography; Bladder scanners
• Radiographic Examinations
– Kidneys, Ureter, and Bladder X-ray
– Intravenous Urography
– Computed Tomography
– Cystography and Cystourethrography
• Other Renal Diagnostic Tests
– Renal Arteriography (Angiography)
– Renal Biopsy
– Renography (Kidney Scan)
– Ultrasonography
Urinalysis
• Color, odor, and turbidity
• Specific gravity
• pH
• Glucose
• Ketone bodies
• Protein
• Leukoesterase
• Cells, casts, crystals, and bacteria
Other Urine Tests
• Urine for culture and sensitivity
• Composite urine collections
• Creatinine clearance—best indication of overall kidney function
• Urine electrolytes
• Osmolarity, blood/plasma osmolarity, urine osmolarity

Urinalysis 1
• Fresh sample = Valid sample.
• Appearance:
– Blood
– Colour (haemoglobin, myoglobin,)
– Turbidity (infection, nephrotic syndrome
• Specific gravity : -
– Normal is 1.0002-1.030
• pH:
– Normal =acidic, except after meal
Urinalysis 2
• Glucose
– Increased glucose
– Low renal threshold or other tubular disorders
• Proteinuria
– Normal < 200 mg/24h. Urine sticks (+)ve if ?300mg/L
– Causes:
• overflow (raised plasma Low MW Proteins, Bence Jones, myoglobin)
• glomerular leak
• decreased tubular reabsorption of protein (RBP, Albumin)
• protein renal origin
Causes of colouration in urine
Urinalysis 3
• Urine sediments
– Microscopic examination of sediment from freshly passed urine.
• Looking for cells, casts (Tamm-Horsfall protein), fat droplets
• Red Cell casts - haematuria - glomerular disease
• White cell cast + polymorphs + bacteriuria = pylonephrites
• Acute glomerulnephritis = haematuria, cells, casts

Measurement of Glomerular Filtration Rate (GFR)
• GFR is essential to renal function
• Most frequently performed test of renal function.
• Measurement is based on concept of clearance: -
“The determination of the volume of plasma from which a substance is removed by glomerular filtration during it’s passage through the kidney”
Plasma Creatinine Concentration
Difficulties: -
• Concentration depends on balance between input and output.
• Production determined by muscle mass which is related to age, sex and weight.
• High between subject variability but low within subject.
• Concentration inversely related to GFR.
– Small changes in creatinine within and around the reference limits = large changes in GFR.

? Serum creatinine
? Creatinine is a breakdown product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body depending on muscle mass
? Creatinine is filtered but not reabsorbed in kidney.
? Normal range is 0.8-1.3 mg/dl in men and 0.6-1 mg/dl in women.
? Not increased above normal until GFR<50 ml/min .
? The methods most widely used for serum creatinine are based on the Jaffe reaction. This reaction occurs between creatinine and the picrate ion formed in alkaline medium (sodium picrate); a red-orange solution develops which is read colorimetrically at 520 nm .

• Increased serum creatinine:
– Impaired renal function
– Very high protein diet
– Anabolic steroid users
– Vary large muscle mass: body
builders, giants, acromegaly patients
– Rhabdomyolysis/crush injury
– Athletes taking oral creatine.
– Drugs:
• Probenecid
• Cimetidine
• Triamterene
• Trimethoprim
• Amiloride


Determination of Clearance
• Clearance = (UxV)/P
Where, U is the urinary concentration of substance
V is the rate of urine formation (mL/min)
P is the plasma concentration of substance
• Units = volume/unit time (mL/min)
• If clearance = GFR then substance should have the properties:
– freely filtered by glomerulus
– glomerulus = sole route of excretion from the body (no tubular secretion or reabsorbtion)
– Non-toxic and easily measurable
Properties of Agents used to Determine GFR
What gets filtered in the glomerulus
At the proximal tubule
• Useful molecules (sugars, amino acids, bicarbonate, potassium) are reabsorbed from filtrate into blood
• Na+ is resorbed by active transport
• Cl- and water follow passively
• Urine is iso-osmotic to blood
Acute Renal Failure
Metabolic features:
• Retention of:
– Urea & creatinine
– Na & water
– potassium with hyper-kalaemia
– Acid with metabolic acidosis

Classification of Causes:
• Pre-renal
– reduced perfusion
• Renal
– inflammation
– infiltration
– toxicity
• Post-renal
– obstruction
Pre-renal versus intrinsic ARF





A tophus on the elbow of a middle aged man with chronic gout.

COMMON DISEASES IN RENAL
? Acute renal failure, a sudden loss of renal function
? Chronic kidney disease, declining renal function, usually with an inexorable rise in creatinine.
? Hematuria, blood loss in the urine
? Proteinuria, the loss of protein especially albumin in the urine
? Microalbuminuria, slight increase in urinary albumin excretion

? Electrolyte disorders or acid/base imbalance
? Kidney stones, usually only recurrent stone formers.
? Nephrosis, degeneration of renal tubular epithelium.
? Nephritis, inflammation of the kidneys
? Chronic or recurrent urinary tract infections
? Hypertension that has failed to respond to multiple forms of anti-hypertensive medication or could have a secondary cause
Acute Renal Failure
? Acute renal failure (ARF) is the rapid breakdown of renal (kidney) function that occurs when high levels of uremic toxins (waste products of the body s metabolism) accumulate in the blood.
? ARF occurs when the kidneys are unable to excrete (discharge) the daily load of toxins in the urine.
? Based on the amount of urine that is excreted over a 24-hour period, patients with ARF are separated into two groups: Oliguric: patients who excrete less than 500 mL/day. Nonoliguric: more than 500 mL/day

? In nonoliguric patients, the urine is of poor quality (i.e., contains little waste) because the blood is not well filtered, despite the fact that an adequate volume of urine is excreted.
? Both kidneys are failing when ARF occurs. One normally functioning kidney can maintain adequate blood filtering.
Incidence
? ARF affects approximately 1% of patients on admission to the hospital, 2-5% during the hospital stay, and 4-15% after cardiopulmonary bypass surgery.
CAUSES
Pre-renal (causes in the blood supply):
? hypovolemia (decreased blood volume), usually from shock or dehydration and fluid loss or excessive diuretics use.
? hepatorenal syndrome in which renal perfusion is compromised in liver failure
? vascular problems, such as atheroembolic disease and renal vein thrombosis (which can occur as a complication of the nephrotic syndrome)
? infection usually sepsis, systemic inflammation due to infection

Renal (damage to the kidney itself):
? toxins or medication (e.g. some NSAIDs, aminoglycoside antibiotics, iodinated contrast, lithium)
? rhabdomyolysis (breakdown of muscle tissue) - the resultant release of myoglobin in the blood affects the kidney; it can be caused by injury (especially crush injury and extensive blunt trauma), statins, stimulants and some other drugs

? hemolysis (breakdown of red blood cells) - the hemoglobin damages the tubules; it may be caused by various conditions such as sickle-cell disease, and lupus erythematosus
? multiple myeloma, either due to hypercalcemia or "cast nephropathy" (multiple myeloma can also cause chronic renal failure by a different mechanism)
? acute glomerulonephritis which may be due to a variety of causes, such as anti glomerular basement membrane disease/Goodpasture s syndrome, Wegener s granulomatosis or acute lupus nephritis with systemic lupus erythematosus

Post-renal (obstructive causes in the urinary tract) due to:
? medication interfering with normal bladder emptying.
? benign prostatic hypertrophy or prostate cancer.
? kidney stones.
? due to abdominal malignancy (e.g. ovarian cancer, colorectal cancer).
? obstructed urinary catheter.

Signs and Symptoms: ARF does not produce a classic set of symptoms. The most common symptom is decreased urine output, which occurs in 70% of patients.

Diagnosis: ARF is most easily diagnosed by an increase in blood levels of creatinine and blood urea nitrogen (BUN). The blood level of creatinine typically increases by 0.5 milligrams per tenth of a liter (mg/dL) every day.
Chronic Renal Failure
? Chronic renal failure (CRF) is the progressive loss of kidney function.
? The kidneys attempt to compensate for renal damage by hyperfiltration (excessive straining of the blood) within the remaining functional nephrons (filtering units that consist of a glomerulus and corresponding tubule).
? Over time, hyperfiltration causes further loss of function.

? Chronic loss of function causes generalized wasting (shrinking in size) and progressive scarring within all parts of the kidneys.
? In time, overall scarring obscures the site of the initial damage.
? Yet, it is not until over 70% of the normal combined function of both kidneys is lost that most patients begin to experience symptoms of kidney failure.
CAUSES
? The cause for CRF sometimes can be determined by a detailed medical history, a comprehensive physical examination, and laboratory studies.
? More often than not, determining the cause of CRF is difficult if not impossible.
? Even a kidney biopsy may be inconclusive, because all forms of kidney failure eventually progress to diffuse scarring and look the same on kidney biopsy.
? The most common causes for CRF are diabetes and hypertension.

Pre-Renal CRF
? Some medical conditions cause continuous hypoperfusion (low blood flow) of the kidneys, leading to kidney atrophy (shrinking), loss of nephron function, and chronic renal failure (CRF).
? These conditions include poor cardiac function, chronic liver failure, and atherosclerosis ("hardening") of the renal arteries.
? Each of these conditions can induce ischemic nephropathy.

Post-Renal CRF
? Interference with the normal flow of urine can produce backpressure within the kidneys, can damage nephrons, and lead to obstructive uropathy, a disease of the urinary tract.

Abnormalities that may hamper urine flow and cause post-renal CRF include the following:
? Bladder outlet obstruction due to an enlarged prostate gland or bladder stone
? Neurogenic bladder, an overdistended bladder caused by impaired communicator nerve fibers from the bladder to the spinal cord
? Kidney stones in both ureters, the tubes that pass urine from each kidney to the bladder

? Obstruction of the tubules, the end channels of the renal nephrons
? Retroperitoneal fibrosis, the formation of fiberlike tissue behind the peritoneum, the membrane that lines the abdominal cavity
? Vesicoureteral reflux (VUR), the backward flow of urine from the bladder into a ureter

Renal CRF : Chronic renal failure caused by changes within the kidneys, is called renal CRF.
? Diabetic nephropathy, kidney disease associated with diabetes; the most common cause of CRF
? Hypertension nephrosclerosis, a condition that occurs with increased frequency in African Americans; the second leading cause of CRF
? Chronic glomerular nephritis, a condition caused by diseases that affect the glomeruli and bring about progressive dysfunction.

? Chronic interstitial nephritis, a condition caused by disorders that ultimately lead to progressive scarring of the interstitium
? Renal vascular CRF, large vessel abnormalities such as renal artery stenosis (narrowing of the large arteries that supply the kidneys)
? Vasculitis, inflammation of the small blood vessels
? Cystic kidney disease, kidney disease distinguished by multiple cysts (lined cavities or sacs)
? Hereditary diseases of the kidney, such as Alport s syndrome (hereditary nephritis)
Signs & Symptoms
? Chronic renal failure (CRF) usually produces symptoms when renal function – which is measured as the glomerular filtration rate (GFR) – falls below 30 milliliters per minute (<30 mL/min). This is approximately 30% of the normal value.
? When the glomerular filtration rate (GFR) slows to below 30 mL/min, signs of uremia (high blood level of protein by-products, such as urea) may become noticeable. When the GFR falls below 15 mL/min most people become increasingly symptomatic.

Uremic symptoms can affect every organ system:
? Neurological system–cognitive impairment, personality change, asterixis (motor disturbance that affects groups of muscles), seizures (rare)
? Gastrointestinal system–nausea, vomiting, food distaste (often described as bland, metallic, "like cardboard")
? Blood-forming system–anemia due to erythropoetin deficiency, easy bruising and bleeding due to abnormal platelets

? Pulmonary system–fluid in the lungs, with breathing difficulties
? Cardiovascular system –chest pain due to inflammation of the sac surrounding the heart (pericarditis) and pericardial effusion (fluid accumulation around the heart)
? Skin –generalized itching
Diagnosis
? CRF is diagnosed by the observation of a combination of symptoms and elevated BUN & creatinine levels.
? Anemia (< red blood cell count)
? High level of parathyroid hormone
? Hypocalcemia (< blood level of calcium)
? Hyperphosphatemia (> blood level of phosphate)
? Hyperkalemia (> blood level of potassium)
? Hyponatremia (< blood level of sodium)
? Low blood level of bicarbonate
? Low plasma pH (blood acidity)
Hematuria
? Hematuria is the presence of blood, specifically red blood cells, in the urine.
? Whether the blood is visible only under a microscope or visible to the naked eye, hematuria is a sign that something is causing bleeding in the genitourinary tract: the kidneys, the tubes that carry urine from the kidneys to the bladder (ureters), the prostate gland (in men), the bladder, or the tube that carries urine from the bladder out of the body (urethra).

? Bleeding may happen once or it may be recurrent.
? It can indicate different problems in men and women.
? Causes of this condition range from non-life threatening (e.g., urinary tract infection) to serious (e.g., cancer, kidney disease).
? Therefore, a physician should be consulted as soon as possible.
Proteinuria & Microalbuminuria
? Proteinuria is an abnormally high amount of protein in the urine.
? Proteins in the blood, like albumin and immunoglobulin, help coagulation (clotting), balance bodily fluids, and fight infection.
? The kidneys remove wastes from protein-rich blood through millions of tiny filtering screens called glomeruli.
? Most proteins are too large to pass through the glomeruli into the urine.

? The glomeruli are negatively charged, so they repel the negatively charged proteins.
? Thus, a size and charge barrier keeps protein molecules from entering the urine.
? But when the glomeruli are damaged, proteins of various sizes pass through them and are excreted in the urine.
Electrolyte Imbalance
? Electrolytes are salts that conduct electricity and are found in the body fluid, tissue, and blood.
? Examples are chloride, calcium, magnesium, sodium, and potassium. Sodium (Na+) is concentrated in the extracellular fluid (ECF) and potassium (K+) is concentrated in the intracellular fluid (ICF).
? Proper balance is essential for muscle coordination, heart function, fluid absorption and excretion, nerve function, and concentration.

? The kidneys regulate fluid absorption and excretion and maintain a narrow range of electrolyte fluctuation.
? Normally, sodium and potassium are filtered and excreted in the urine and feces according to the body s needs.
? Too much or too little sodium or potassium, caused by poor diet, dehydration, medication, and disease, results in an imbalance.
? Too much sodium is called hypernatremia; too little is called hyponatremia.
? Too much potassium is called hyperkalemia; too little is called hypokalemia.
Kidney Stones
? Kidney stones (calculi) are hardened mineral deposits that form in the kidney.
? They originate as microscopic particles and develop into stones over time.
? The medical term for this condition is nephrolithiasis, or renal stone disease.
? The kidneys filter waste products from the blood and add them to the urine that the kidneys produce.

? When waste materials in the urine do not dissolve completely, crystals and kidney stones are likely to form.
? Small stones can cause some discomfort as they pass out of the body.
? Regardless of size, stones may pass out of the kidney, become lodged in the tube that carries urine from the kidney to the bladder (ureter), and cause severe pain that begins in the lower back and radiates to the side or groin.

? A lodged stone can block the flow of urine, causing pressure to build in the affected ureter and kidney.
? Increased pressure results in stretching and spasm, which cause severe pain.