1. RENAL FUNCTION
Study Guide

2. Module Focus The kidney plays a major role in the maintenance of
fluid and electrolyte balance.
elimination of nitrogenous (nitrogen containing) waste products of protein catabolism (breakdown)
Urea or BUN (blood urea nitrogen)
Creatinine
The kidneys also synthesize and secrete certain hormones.

3. NEPHRON
Afferent arteriole: the kidney receives 1200 – 1500 ml of blood per minute

4. GLOMERULUS Function: Filters blood
First part of nephron
“glomus” means ball of yarn
Capillary tuft
Function:
Filters blood
Allows smaller subtances that are <70,000 MW to pass from blood to tubular filtrate
Filters 125 – 130 ml of plasma per minute “glomerular filtration rate” or GFR
Conserves most proteins or protein bound substances such as blood cells which are too large to be filtered
Filtrate = “cell-free fluid”

5. BOWMAN’S CAPSULE Extended end of renal tubule
Contains ultrafiltrate of plasma

6. PROXIMAL TUBULES
Reabsorbs or returns valuable substances back into blood
Returns 75-80% of H2O
Returns amino acids & vitamins
Ions such as sodium, potassium, chloride, bicarbonate, magnesium & calcium
Returns “renal threshold” substances such as glucose as long as the maximum concentration is not exceeded in the plasma (160 – 180 mg/dl) the excess the tubules cannot reabsorb will spill into the urine

7. PROXIMAL TUBULES Excretes waste products into tubular lumen (urine)
Urea (BUN)
Creatinine
Secretes waste products such as hydrogen ions and certain drugs from the blood into the tubular lumen (urine)

8. LOOP OF HENLE Concentrates filtrate and adjusts urine osmolality
Descending loop is permeable to water
Ascending loop is impermeable to water

9. DISTAL TUBULES
Small adjustments are made to achieve electrolyte and acid-base homeostasis
The hormone aldosterone is secreted by the adrenal cortex in response to a decreased blood flow
Aldosterone stimulates the reabsorption of sodium and the loss of potassium
 sodium levels in blood
 potassium and hydrogen levels in blood
Reabsorption of more water and bicarbonate also take place
Elimination of ammonia, hydrogen ions and uric acid

10. COLLECTING DUCTS Determines final urine osmolality or concentration
Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland in response to an increase in blood osmolality or decrease in blood volume.
ADH stimulates water reabsorption by making the walls permeable to water.

11. FUNCTIONS OF THE KIDNEY
Water balance maintained by:
Ingestion of water
Excretion & reabsorption of water in renal tubules under the influence of ADH
Electrolyte balance
Sodium, potassium, phosphate, calcium and magnesium
Maitained by tubule reabsorption under influence of aldosterone
Acid-Base balance
Conserve bicarbonate (HCO3-)
Excretes hydrogen ions (H+)

12. ELIMINATION OF NON-PROTEIN NITROGEN SUBSTANCES
NPN substances = compounds that contain nitrogen, but are not considered proteins
Urea (also known as blood urea nitrogen “BUN”)
Creatinine
Ammonia
Uric acid

13. SYNTHESIS OF HORMONES
Renin – which is a vasoconstrictor that aids in the regulation of sodium balance and blood pressure
Erythropoietin – which increases hemoglobin production by stimulating RBC production
1,25-dihydroxycholecalciferol, the active form of Vitamin D, which facilitates calcium absorption from the intestine
Prostaglandins – which affect renal blood flow

14. URINALYSIS Physical properties Chemical analysis pH Protein Glucose
Bilirubin
blood
Microscopic analysis
Cells
Crystals
Casts

15. CHEMISTRY TESTS Blood urea nitrogen (BUN)
Major waste product of protein breakdown
10 – 20 mg/dl
Creatinine
Waste product formed in muscle from creatine phosphate
Serum = 1.0 mg/dl & urine = 1 – 2 grams per day (constant amount)
BUN/Creatinine Ratio
Calculation or comparison
The ratio of BUN to serum creatinine
Normally = 10:1 to 20:1 ratio

16. CREATININE CLEARANCE
Measurement or calculation of the glomerular filtration rate (GFR)
Considered the most sensitive chemical test for assessing kidney function
Collect a 24 hour or timed urine specimen & a blood specimen from the patient
Measure the creatinine in the serum & urine specimen
Calculate the clearance

17. CLEARANCE CALCULATIONS
Urine creatinine mg/dl X Volume of Urine in ml/minute
Serum creatinine mg/dl
= Creatinine Clearance in ml per minute
Reference Ranges = approximately 125 ml/minute

19. URIC ACID Not typically used as a renal function test
Because it is a nonprotein nitrogen waste substance, it will be increased in serum if there is any type of renal dysfunction
Useful in the diagnosis of gout – arthritic condition where uric acid deposits in joints & also produces renal calculi

20. BLOOD UREA NITROGEN BUN OR UREA
Composition: O
NH2 – C – NH2
To convert BUN to Urea,
Multiply the BUN value by 2.14
Since 60 (urea) = 2.14
28 (BUN)
Molecular weight
N = 14 x 2 = 28
C = 12
O = 16
H = 1 x 4 = 4
Total = 60 gms

21. SOURCE OF UREA Major excretory product of protein catabolism.
Formed in the LIVER from carbon dioxide and ammonia through the urea cycle.
CO2 + NH3 = Urea
Excreted by the kidneys
Urea is a small molecule so it is filtered by the glomeruli
Approximately 40 – 70% is reabsorbed by the tubules (the amount reabsorbed is dependent upon the rate of urine flow)

22. UREASE METHOD
1. The enzyme urease hydrolyzes the urea in the patient specimen to form CO2 & ammonium (NH4) urease UREA NH4 + CO2
2. The ammonium is quantitated utilizing the enzyme glutamate dehydrogenase (GLDH) that reduces the coenzyme NADH to NAD with causes a decrease in absorbance that is measured at 340nm GLDH
NH4 + -ketoglutarate + NADH NAD + glutamic acid + H2O

23. REFERENCE RANGES BUN is approximately 10 – 20 mg/dl in serum
European labs correctly express BUN as Urea.
To convert, multiply BUN by 2.14
Example: BUN = 15mg/dl Urea = 15 x 2.14 =

24. CLINICAL INTERPRETATION
INCREASES
Prerenal Factors
Any condition that causes decreased renal perfusion (blood flow)
Congestive heart failure (CHF)
Renal Factors – any renal diseases or disorders
Postrenal Factors -Obstruction such as renal calculi
High protein diet “Dr. Atkin’s diet” will cause mild increases since urea comes from the breakdown of protein.
Cortisol therapy may also cause mild increases.

25. DECREASES IN BUN Decreases in BUN are rare & usually insignificant
Pregnancy
Starvation
Severe liver disease -  synthesis

26. CLINICAL INTERPRETATION
BUN is a more sensitive indicator or renal function because it rises earlier and more rapidly than creatinine.
However, it requires approximately 75% loss of nephron function before either BUN or creatinine serum values increase.
BUN is NOT specific because diet (high protein) and cortisol therapy may affect results and cause false increases.

27. CREATININE
SOURCE
Waste product formed in muscle from creatine phosphate
When needed for energy, creatine phosphate and ADP are converted to creatine & ATP
A small portion of creatine phosphate loses its phosphate and creatinine is formed.
Creatinine is excreted in the urine and is NOT usually reabsorbed
The amount of creatinine formed and excreted per day is a function of muscle mass. Typically normal individuals excrete 1 to 2 grams per day of creatinine.

28. METHODS Colorimetric: Jaffe Reaction NaOH
creatinine + picric acid alkaline picrate
(reddish-orange complex)
Noncreatinine chromagens (color-producing substances) such as glucose, ketones and vitamin C may interfere with this reaction
Jaffe KINETIC method modification was designed to monitor the rate of the reaction at selected time intervals to avoid picking up noncreatinine chromagens. (Typically 25 – 60 seconds)
Enzymatic: Creatinine aminohydrolase
A variety of coupled enzymatic methods are available.

29. REFERENCE RANGES Serum = 0.8 – 1.4 mg/dl Urine = 1 – 2 grams per day
FYI:
A serum creatinine value of 4mg/dl is equivalent to a reduction of GFR to 15 – 20% of normal.
An 8 mg/dl value = a reduction of GFR to 6 – 10% of normal.

30. CLINICAL INTERPRETATION
INCREASES
Any renal factors
Creatinine is NOT affected by diet
Creatinine is NOT typically reabsorbed by the tubules
Creatinine levels reflect the glomerular filtration rate (GFR)

31. DECREASES
No medical significance

32. CLINICAL INTERPRETATION
Creatinine is more specific than BUN since it is not affected by nonrenal factors.
Creatinine is not as sensitive as BUN since serum creatinine levels rise slower than BUN levels.
Remember: Creatinine serum levels are not above normal until ½ to ¾ of kidney function is lost.

33. BUN-CREATININE RATIO Purpose:
Calculation/comparison that compares the patient’s BUN to their creatinine value
Quality control purposes
Differential diagnosis

34. EXAMPLE
If a patient’s BUN is approximately 10 – 15 mg/dl, their creatinine should be approximately 1.0mg/dl.
This would be equivalent to a 10:1 to 15:1 ratio.

35. REFERENCE VALUES 10:1 to 15:1 ratio is considered normal
Normal ratios are usually observed in renal diseases.
Example: If a patient’s BUN is mg/dl, their creatinine would be approximately 5.0 mg/dl.

36. CLINICAL INTERPRETATION
INCREASES:
A 20:1 to 30:1 ratio is often due to prerenal factors
Decreased renal perfusion (blood flow to the kidneys) such as:
Congestive heart failure
Shock, etc.
Causes a >40% reabsorption of urea occurs, but NOT creatinine

37. CREATININE CLEARANCE
Estimates the Glomerular Filtration Rate (GFR) by measuring the serum/plasma creatinine level and its rate of excretion into the urine.
Clearance indicates the number of milliliters of plasma from which the kidney can remove all of a given substance in one minute.
The normal GFR is approximately 125 ml/minute.

38. CLEARANCE REQUIREMENTS
Substance must be filtered through the glomeruli
Essentially no absorbance or secretion must take place in the tubules.
Substance must exist in the same form in the blood and the urine.
Ideally, an endogenous (body-made) substance should be utilized.

39. PROCEDURE
Collect a timed urine specimen (usually a 24 hour) from the patient.
Record the time period of the collection
Measure and record the total volume of the urine specimen
Collect a blood specimen during the time of the urine collection period.
Measure the urine and serum creatinine in mg/dl.
Calculate the clearance.

40. Calculate the rate of urine flow or “VOLUME” in ml/minute
Divide the total volume of the urine specimen by the number of MINUTES in the collection period.
Example:
The total volume of a 24hr urine specimen was 1500ml
The number of minutes in a 24hr period would be 24 x 60 = 1440 minutes
Divide 1500ml by 1440 minutes
Volume = 1.04 ml/minute

41. Clearance Calculations
Urine creatinine (mg/dl) X Volume (ml/min)
Serum creatinine (mg/dl)
Example: A patient’s serum creatinine was 1.0
mg/dl and their urine creatinine was 100 mg/dl. The volume of the 24 hr urine specimen was 1500 ml or 1.04 ml/minute.
Clearance =
100 mg/dl X ml/min = 104 ml/minute
1.0 mg/dl

42. REFERENCE VALUES Serum creatinine = 0.8 – 1.4 mg/dl
Urine creatinine = 1- 2 grams per day or 100 mg/100 ml
Total volume = 1000 – 2000 ml/day
Creatinine Clearance
Males: 75 – 140 ml/minute
Females: 70 – 130 ml/minute

43. CLINICAL INTERPRETATION
Remember: You are looking for increased serum values due to the failure of the kidneys to excrete creatinine. This will cause a decrease in urine creatinine as well as a decreased clearance values.
DECREASED CLEARANCE VALUES
Acute or chronic damage to the glomeruli
Creatinine clearance is the MOST SENSITIVE chemical indicator of assessing renal function. (more sensitive than serum BUN or serum creatinine)

44. SOURCES OF ERROR Error in collection of urine specimen Calculations
If clearance values are decreased, but the patient’s serum creatinine is normal, check:
Clearance calculations
Urine volume and timing
Incomplete voiding
Incomplete timing
Loss of some urine specimen
Incorrect volume measurement
Urine & serum creatinine values

45. Increased Clearance Values
No medical significance
Suspect error in collection of urine specimen

46. Correction of Clearance for Body Surface Area
Purpose: Since creatinine is a function of muscle mass, correction is essential if a patient is unusually large or small such as a pediatric patient.
Procedure:
Obtain the height & weight of the patient.
Use a nomogram such as the one in your text or study guide to obtain the body surface area of the patient in square meters.
The body surface area of the average patient is assumed to be 1.73 square meters.
Use the following formula to obtain the corrected clearance:
Clearance (before correction) X M2
Body surface area of patient in M2

47. URIC ACID Source: Breakdown of nucleic acids such as RNA & DNA
End product of purine metabolism.
Purines = nitrogen containing constituents of certain coenzymes and nucleic acids.
Derived from endogenous (body made) and exogenous (dietary) nucleoproteins.
Liver, kidneys & shellfish are rich in nucleoproteins.

48. URIC ACID METABOLISM
Uric acid is synthesized in the liver from the breakdown of nucleic acids.
90 – 95% is filtered through the glomeruli.
Uric acid is relatively insoluble and will precipitate out of solution if concentration in plasma is > 6.5 mg/dl forming deposits in joints as well as renal calculi (kidney stones).
Mammals other than man are usually capable of oxidizing uric acid to allantoin, which is a more soluble compound.

49. Methods of Measurement
Phosphotungstic method – outdated
Uricase – enzymatic method is the most widely utilized
URICASE
Uric acid + O2 + H2O Allantoin + H2O2 + CO2
Uric acid is oxidized to allantoin and hydrogen peroxide (H2O2) is formed.
A coupled enzymatic reaction, utilizing the enzyme peroxidase, is typically used to quantitate the amount of hydrogen peroxide produced.

50. Reference Ranges
Males: 3.5 – 7.2 mg/dl
Females: 2.6 – 6.0 mg/dl

51. Clinical Interpretation
Miscellaneous Increases
Increased tissue breakdown as seen in chemotherapy and radiation treatment.
Increased dietary intake of foods rich in purines.
Decreased excretion of uric acid will cause an increase in serum levles, as seen in renal diseases. However, uric acid is not typically utilized as a renal function test.
INCREASES
GOUT: overproduction of uric acid which is relatively insoluble and depositis in joints causing “GOUTY ARTHRITIS”
 in plasma uric acid may also cause renal calculi to form.

52. OSMOLALITY
Purpose: useful in the evaluation of fluid & electrolyte balance
Provides an assessment of the hydration status of a patient.
Sodium ions account for 90% of osmotic pressure.
Osmolality is actually a
measurement of the TOTAL
NUMBER of dissolved
particles per kilogram of
water.
The molecular weight, size or type of particle does not matter.
Osmolality is a more accurate reflection of the total number of dissolved particles in a solution than the specific gravity.

53. OSMOMETRY Any substance dissolved in a solution will do the following:
Increase the osmotic pressure of the solution
Elevate the boiling point (Have you ever made fudge?)
Decrease the vapor pressure
Lower/depress the freezing point (Have you ever made popsicles or frozen daiquiris?) They take longer to freeze than ice cubes or water.

54. FREEZING POINT DEPRESSION METHOD
The more particles in a solution (the more concentrated), the LOWER will be its freezing point.
The osmometer actually superfreezes urine or serum belong its freezing point and then brings it back to its actual freezing point.
One mole of each ionic or nonionic particle/kilogram of water lowers the freezing point by 1.86C.

55. REFERENCE VALUES Serum: 275 – 300 mOsm/kg
24hr urine: 300 – 900 mOsm/kg
Random urine: 40 – 1350 mOsm/kg
The ratio of urine osmolality to serum osmolality:
Urine should be at least as concnetrated as serum if not 3X as concentrated.
Ratio = 1.0 – 3.0
Example: urine = Ratio = 3.0
serum = 300

56. CLINICAL INTERPRETATION
Increased values
Dehydration
Hypernatremia ( sodium in plasma)
Hyperglycemia, azotemia ( BUN & creatinine), alcohol ingestion
Decreased values
Overhydration
Hyponatremia ( sodium in plasma)

57. CALCULATED OSMOLALITY
If an osmometer is not available, the osmolality can be calculated if the serum sodium, glucose & BUN results are available.
Osmol Gap:
The difference between the calculated osmolality and the measured osmolality.
If the gap is >0, may indicate the presence of a volatile substance such as ethanol, methanol or ethylene glycol (antifreeze).