Week 3 Flashcards
Renal function tests that evaluate clearance include:
Renal function tests that evaluate Tubular function include:
CLEARANCE TESTS: Blood Urea Nitrogen (BUN) Serum Creatinine Creatinine clearance Albumin Creatinine Ratio
TUBULAR FUNCTION TESTS:
Fractional Excretion of Na+
The ideal substance to measure GFR would be…
100% filtered at the glomeruli easily measured not bound to plasma not metabolized non-toxic stable in blood Be excreted only by the kidneys Be neither reabsorbed nor secreted by the renal tubules
Blood Urea Nitrogen (BUN)
Derived from:
How much absorbed? Clearance?
Derived from protein catabolism via urea cycle in liver
AMino acids -> NH3 -> Urea -> circulation
Filtered by glomerulus -> 40% reabsorbed (b/c water follows it)
Urea clearance is about !60% of true GFR! under usual conditions
BUN can also be affected by:
The liver can cause abnormal Urea levels, so BUN isn’t specific for the kidneys filtration ability
BUN ; why is it considered a “rough indicator” of GFR and renal blood flow?
Serum/plasma testing- usually part of Comprehensive Metabolic Panel (CMP) or Basic Metabolic Panel (BMP)
Evaluates liver function
Indirect measurement of renal function
Rough indicator of GFR and renal blood flow
BUN
interfering factors:
Protein intake (diet) affects BUN Muscle mass pregnancy can decrease levels b/c hemodilution and incr. GFR Hydration levels liver dz decr. production drugs
BUN
Normal serum levels: (Adult)
Critical Value:
Causes for decreased values:
Normal serum levels
-Adult: 10-20 mg/dl (elderly may be slightly higher)
Critical Value: >100 mg/dl indicates serious impairment of renal function
Causes for decreased values:
- Fluid overload
- Malnutrition
- Severe liver disease
Azotemia
Azotemia = incr. concentration of non-protein nitrogenous waste products (ex: urea, creatinine) in the blood
- most renal dzs cause inadequate excretion of urea, so blood levels of urea increase
- Other conditions can cause incr. BUN, so you must distinguish between pre-renal azotemia, renal azotemia, and post-renal azotemia
!Patients with increased BUN have azotemia!
Prerenal causes of incr. BUN accounts for ___% of acute renal failures and includes the following conditions:
55% of acute renal failures
- Low blood volume, shock, burns, dehydration
- CHF, MI
- GI bleed
- Too much protein
- High protein metabolism, starvation
- sepsis
Sudden drop in blood pressure (shock) or interruption of blood flow to the kidneys from severe injury or illness
Renal causes of increased BUN account for ___% of acute renal failure and includes the following conditions:
40%
Renal disease, glomerulonephritis, pyelonephritis, acute tubular necrosis, nephrotoxic drugs
Direct damage to the kidneys by inflammation, toxins, drugs, infx, or reduced blood supply
Postrenal causes of incr. BUN account for ___% of acute renal failure and includes the following conditions:
5% of acute renal failure
- Obstruction of ureters (Stones, tumors, congenital)
- Bladder outlet obstruction (prostatic hypertrophy (BPH), Cancer, congenital)
Sudden obstruction of urine flow due to enlarged prostate, kidney stones, bladder tumor, or injury
Serum Creatinine Where does it come from? Levels depend on... Better or worse than BUN? \_\_% filtered by the kidneys
Superior to BUN!
- A catabolic product of creatinine phosphate from skeletal muscle
- Blood creatinine values depend on muscle mass, which fluctuates very little unless some muscle-wasting pathology exists or starvation
- More stable marker than BUN
!Creatinine is almost completely filtered by the kidneys! but is also secreted by the proximal tubule
Creatinine
increases before or after BUN?
Creatinine elevations suggest:
What populations generally have lower levels? Why?
increases later than BUN
Creatinine elevations suggest chronic dz process and parallel BUN increases
Elderly and young children generally have lower levels due to decreased muscle mass
Normal ranges for serum creatinine
Is it affected by liver function?
Male: 0.6-1.2 mg/dl
Female: 0.5-1.1 mg/dl
Used to diagnose impaired renal function
Minimally affected by liver function (unlike BUN)
Creatinine and BUN are not good screening tests for overall renal function! Why?
What are they good for then?
You can lose 50% of both kidneys function and still have minimal changes in creatinine
-Large changes in “early” renal disease (50% loss of function) will cause very small changes in BUN and Creatinine
BUN and Creatinine are good for following the later stages of renal disease because: Small changes in GFR late in renal disease cause big changes in BUN or serum creatinine
Typical ratio btwn BUN:Creatinine in Prerenal Azotemia is:
Prerenal Axotemia = BUN:Creatinine of >20:1
- Decr. blood volume or renal circulation (shock, dehydration, MI, CHF)
- Incr. protein intake or catabolism (High protein tube feedings, GI hermorrhage, Starvation)
Renal Azotemia = BUN: Creatinine of 10-20:1
- Chronic diffuse bilateral kidney dz or damage
- Acute tubular necrosis
- Severe acute glomerular damage
How can you tell if your patient has Pre-renal dz or intrinsic Acute Renal Failure? (2 ways to tell)
Pre-renal => disproportionate rise in Urea (ratio = >20:1), protein in urine uncommon
Renal => tend to rise together (ratio = 10-20:1), protein in urine present on dipstick testing
Renal Function Tests
Provides info regarding:
renal blood flow, glomerular filtration rate (GFR), and tubular function
- Requires analysis of plasma/serum samples and/or urine samples
- Imperfect: other things other than damage to renal parenchyma can influence results; localized and general damage; temporary and permanent malfunction
Estimated Glomerular Filtration Rate (eGFR)
The ability of the kidneys to filter blood
As GFR goes down, serum creatinine goes up
A calculation using serum creatinine, the patient’s sex and age using the MDRD equation
Included whenever serum creatinine values are requested
eGFR is inaccurate when:
Vegetarian Pregnant Malnourished >70 or 60ml/min/1.73m^3 muscle disease When GFR by MDRD equation is >60 ml/min/1.73m^3
Creatinine Clearance; Blood and urine
Requires 24 hour urine collection and blood draw
Both samples are analyzed for creatinine
Provides a quantitative measure of the rate at which creatinine is removed from the blood, expressed in ml/min
Values are corrected for body surface are (BSA); must obtain patient height and weight
How to instruct a patient for a 24 hour urine sample:
On the 1st day of collection, first morning void goes into the toilet. Then all other subsequent urine is collected up to the next morning’s first morning void. After 24 hrs, stop collection.
Creatinine clearance norms:
Values decrease ___ ml/min for each decade of life after ___ yo due to…..
Males: 90-139 ml/min
Females: 80-125 ml/min
Values decrease 6.5 ml/min for each decade of life after 20 years due to decline in GFR
Cystatin C
normal range for adults:
gives a better estimate of GFR w/ one blood test; not the best for early detection
- filtered by the glomerular membrane and metabolized by proximal tubules
- estimates GFR independent of gender, age, race, muscle mass and cirrhosis, does not need to be corrected for height and weight.
- !Superior to serum creatinine!
- Normal range for adults: 0.54-1.55 mg/L
(this is a blood test! not a urine test)
Stages of Renal Failure
1: Kidney damage (protein in urine) w/ normal or elevated GFR [GFR = 90 or mo]
2: Kidney damage w/ [GFR = 60-89]
3: Kidney damage w/ [GFR = 30-59]
4: Kidney damage w/ [GFR = 15-29]
5: Kidney failure: end-stage renal dz (ESRD). Patients require dialysis or transplantation. [GFR
Acute vs. Chronic Renal Failure
ARF: Occurs over hours or days, pt has Hx of normal renal function, kidney size usually normal, anemia usually absent!, no broad casts in urine sediment
CRF: Fradual deterioration of renal function over time, pt. has Hx of incr. BUN and Cratinine, kidney size small, ANEMIC! often, broad casts present in urine sediment
pg. 37
Flow chart to look at
Pre-renal vs. Renal azotemia
How do your FENa levels differ in each case?
Pre-renal azotemia: FENa is 1%; decr. renal blood flow triggers renin-angiotensin pathway -> kidneys repson by conserving Na
Renal azotemia: FENa is >2% ; damaged tubules cannot effectively conserve Na
Pg. 40
Proteinuria is the !most important indicator of renal dz!
test is indicated if there is more than trace protein consistently found on routine UA
Normal adult range is less than 150 mg/24hr
Incr protein caused by either glomerular damage or diminished tubular catabolism of small molecular weight proteins
24 hr. urine protein
Functional range if asymptomatic:
if proteinuria ___________ mg/24hrs in adult (or ____ mg/kg/24hrs in child) indicates _________
If proteinuria ________ indicates __________
proteinuria 150-500 mg/24hrs can be functional if asymptomatic
if protenuira >2000 mg/24hrs in adult (or 40 mg/kg/24hrs in child) indicates !glomerular cause!
If proteinuria > 3500 mg/24hrs indicates !nephrotic Syndrome!
________ may cause proteinuria in the absence of structural abnormality.
Proteinuria can occur in non-renal diseases like:
CHF (Congestive Heart Failure)
Non-renal causes of proteinuria:
- CHF
- High serum protein (malignant etiology)
- Pre-eclampsia or eclampsia
- Hypertension
- Toxicity from heavy metals, solvents
Urine protein to Creatinine ratio
Used to monitor:
Which is more accurate (24 hr urine protein OR Urine protein to creatine ratio?)
Normal adult ratio:
Used to monitor persistent Proteinuria More accurate than 24 hr urine protein Use first morning void Normal adult ratio: 3.5 g protein/ 1g creatinine -Correlates with 3.5 g protein/day
Microalbuniuria
Test best for:
This is the most sensitive test to detect ____________ early!
Present in ~____% of type 1 and ~ ___% of type 2 DM with negative reagent test strips
Persistent proteinuria that is below the detection by routine reaggent strips but greater than normal
(Test best for: type II diabetes or hypertension OR type I diabetes for over 5 yrs)
Most Sensitive test to detect kidney disease early!
Present in ~25% of type 1 and ~ 35% of type 2 DM with negative reagent test strips
Albumin excretion
Normal: 300 mg/day
Urine to albumin to creatinine ratio
Used to detect…
Used to detect microalbuninuria (30-300 mg/day)
Diagnose and monitor kidney damage in patients with type 1 DM for 5 yrs or more or type 2 DM
Does not require 24 hr collection
-change may represent response to therapy or progression of disease
pg. 46,47
a graph and flow chart to look at
Kidney Stones
Also known as nephrolithiasis, urolithiasis or renal calculi Solid concretions (crystal aggregations) of dissolved minerals in urine Found inside the kidneys or ureters. They vary in size from as small as a grain of sand to as large as a grapefruit
Kidney Stones
Occur in ______ people at some time in their life
-Rare in _________
-For precipitation of crystals to occur, the urine must be _______________
occur in 1 in 20 people at some time in their life
-urolithiasis is rare in children. when present, it is often associated with specific metabolic disorders or anatomic abnormalities
For precipitation of crystals urine to occur, the urine must be “supersaturated” for the precipitating crystal
Kidney Stones
Stone formation secondary to infx and/or obstruction related to a congenital malformation of the urinary tract is often present before the age of ___.
Cystinuria, idiopathic calcium oxalate urolithiasis and primary hyperparathyroidism more often begin around:
Stone formation secondary to infx and /or obstruction related to a congenital malformation of the urinary tract often present befroe the age of 5
Cystinuria, idiopathic calcium oxalate urolithiasis and primary hyperparathyroidism more often begin around puberty or in the mid-teens
Stone formation
KIdney stones form when:
Form when:
- there is a high level of minerals; ie calcium (hypercalciuria), oxalate, or uric acid (hyperuricosuria) in the urine
- or a lack of citrate in the urine
- or insufficient water in the kidneys to dissolve waste products
Urine normally contains chemicals- citrate, magnesium, pyrophosphate- that prevent the formation of crystals
What to do after a first stone?
Studies show medical evaluation and prophylaxis is not cost effective in:
Some believe patients with first stone do not need detailed metabolic evaluation
Studies show medical evaluation and prophylaxis is not cost effective in:
-1st time presenters
-those who form stones
Limited Evaluation
Chemistry panel may help identify:
Chemistry panel may help identify:
- Calcium: look for hyperCz on two occasions to r/o primary hyperparathyroidism
- Bicarb: low may be suggestive of Type 1 RTA or chronic diarrhea
PTH (parathyroid hormone), if elevated serum Ca
UA, including pH and urine culture
Limited evaluation cont…
Urinalysis
-pH (what stones form at what pH?)
Sediment should be examined for crystalluria or stones. Some findings might be:
- what are the constituents of struvite stones?
- what crystals may be found in individuals without stone disease?
pH
>7.5 compatible with struvite or calcium phosphate
Complete evaluation
Two 24- hour urine collections should be obtained in outpatient setting when patient is on his regular diet, at least 2-3 months after stone event
24-hr urine Calcium
Measures urinary excretion of calcium over 24 hours. Used to support diagnosis of hypercalciuria causing recurrent renal calculi.
Hypercalciuria is defined as 24 hr urinary calcium excretion >300mg in men & >250mg in women
Normal findings: vary with dietary intake “Normal” diet: 100-400 mg/day Low-calcium diet: 50-150 mg/day
Blood calcium used more often in routine work-ups
What do each cases indicate when found in a 24 hr Ca Urine collection?
Increased levels of Urine Calcium:
Decreased levels:
Increased Ca in Urine:
Primary hyperparathyroidism
Vitamin D excess
Corticosteroid treatment
PTH-producing tumor, e.g. lung
Cushing’s syndrome Sarcoidosis, tuberculosis Osteoporosis
Metastatic tumors to bone Renal tubular acidosis
Decreased Ca in Urine:
Hypoparathyroidism Vitamin D deficiency Calcium malabsorption Renal failure
24 hr urine ca is useful for
Useful to Determine:
• Primary hyperparathyroidism
• Cause of recurrent nephrolithiasis
24 hr Urine Oxalate
Oxalate may be derived from:
• Dietary intake: 10%
• Metabolism of ascorbic acid: 35-50%
• Glycine metabolism: 40%
Patients with a tendency to calcium oxalate nephrolithiasis appear to absorb and excrete a high proportion of dietary oxalate in the urine
Hyperoxaluria may also result from a low calcium diet
Calcium oxalate indications:
Indications
• Patients with surgical loss of distal ileum,esp.those with Crohn’s disease
• Nephrolithiasis occurs in 3-10%ofpatientswithIBS • Jejunal bypass for morbid obesity oftenleadsto
hyperoxaluria & stone formation
(Excess enteric fat binds dietary calcium and allows free oxalate to be more readily absorbed in the colon)
Urine Oxalate normal values
Normal values:
Males: 7-44 mg/24 hours
Female: 4-31 mg/24 hours
Children: 13-38 mg/24 hours
Renal Function Testing provides information regarding:
Renal blood flow
Glomerular filtration rate (GFR)
Tubular function
Requires analysis of plasma/serum samples and/or urine samples(Which is why you may need a blood sample)
Renal disease implies the presence of:
Renal dz implies the presence of histologic lesions in the kidney but does not specify any degree of renal dysfunction
Renal Failure implies:
Renal failure implies that 75% of the total nephron population has become non-functional but does not necessarily imply underlying histologic lesions
What exactly does “clearance” mean:
Clearance: the rate at which a substance is removed by glomerular filtration during it’s passage through the kidney
Creatinine Clearance eqx =
Provides good estimate of _____, but tends to over estimate it by ___% due to…..
CC = (urine Creat)/(serum creat) x (24hrs/1440min) x (m^2)/(1.73m^2) x Volume (ml)
Provides a relatively good estimate of GFR
BUT it tends to over-estimate it by about 10% due to tubular secretion of creatinine
When GFR decrs. to
When GFR decrs. to
Creatinine Clearance
Interfering factors:
Interfering factors:
- Exercise amy incr. serum creatinine values
- Pregnancy incr. urinary creatinine
- Incomplete urine collection gives false low value
- Drugs
A patient presents with signs and symptoms of kidney failure. List some of these symptoms:
Loss of appetite Nausea/vomiting Edema Low back pain Decr. urine output Fatigue
Tubular FUnction Test
Fractional Excretion of Sodium (what’s the equation?)
Most causes of ARF are ________ and __________. How do you differentiate from these two?
Most common causes of ARF are pre-renal and tubular necrosis.
Useful to differentiate Pre-renal azotemia from Renal azotemia (tubular necrosis). How do you do this?
Requires Na+ AND creatinine levels in plasma and urine
FENa= (Urine Na) x (plasma creatinine) / (Plasma Na x Urine Creatinine) x 100%
____________ is the most important indicator of renal disease.
Proteinuria
When is the 24 hr Urine protein test indicated?
Normal adult range:
Incr. protein is caused by either _______________ or _______________
Test is indicated if there is more than trace protein consistently found on routine UA.
Norm Adult: 150 mg/24hrs
Increased protein caused by either glomerular damage or diminished tubular catabolism of small molecular weight proteins
_____________ and _____________ comprise 70-80% of all kidney stones.
Calcium Oxalate and Calcium Phosphate
Calcium oxalate:
- low urine volume
- high conc. of Ca and Oxalate
Calcium Phosphate:
- alkaline urine
- high urine Ca conc.
24 hr Urine Ca
What do elevated Ca levels indicate? Decreased Ca levels?
Increased levels: Primary hyperparathyroidism Vit D excess Corticosteroid treatment PTH-producing tumor Cushing's syndrome Sarcoidosis, tuberculosis Osteoporosis Metastatic tumors to bone Renal tubular acidosis
Decreased levels: Hypoparathyroidism Vit D deficiency Ca malabsorption Renal Failure
24 hr urine oxalate
Incr. values indicate:
Increased values:
- Ethylene glycol ingestion
- Genetic disorder
- Pancreatic dz
- Liver cirrhosis
- Pyridoxine deficiency (B6)
- Sarcoidosis
- Celiac dz
Decr. Values
-Renal Failure
Hypocitraturia
Women levels:
Men levels:
Decrease commonly seen in conditions that cause chronic metabolic acidosis:
____________ plays an important role in inhibiting Ca crystal formation and preventing stones.
What type of diet tends to increase acidosis? How does this increase the likelihood of stone formation?
24hour urine citrate excretion
24 hour Uric acid findings
Normal Findings:
Normal findings: 250-750 mg/24 hours •Breakdown product of purine metabolism •Uric acid is produced in the liver •75% of blood uric acid is excreted by kidneys, remainder via GI tract •Elevated levels may indicate gout
Uric acid stones
Form in urine with a ____ pH and ____________.
Incrs. risk in _________
Form in urine with an unusually low pH and hyperuricosuria. Increase risk in the obese Metabolic syndrome May be linked to insulin resistance
24 hr urine Uric Acid
Increased levels:
Decreased levels:
Increased levels = Uricosuria •Gout •Metastatic cancer •Multiple myeloma •Leukemia •Cancer chemotherapy •High purine diet •Lead toxicity
Decreased levels
•Renal disease
•Eclampsia
•Chronic alcoholism
Triple phosphate crystals
make up ____% of kidney stones
10-15% of kidney stones Composed of magnesium ammonium phosphate •Typically seen an alkaline urine •More common in women •Commonly seen in patients with UTI caused by urea splitting organisms such as proteus •Form Struvite stones
Describe a diagnostic workup of nephrolithiasis:
Stone analysis Serum and blood tests -Calcium, parathyroid hormone, Vit D, electrolytes Urine dip and microscopic examination -pH, sediment Culture 24 urine collection -volume, creatinine, calcium oxalate, sodium, citrate, uric acid, cystine Helical CT without contrast
24hr urine for Vanillylmandelic Acid and Homovanilic Acid
- Catcholamines: epinephrine, norepinephrine & dopamine.
- HVA & VMA secreted in urine as the primary end-product of catecholamine metabolism
- Used to dx pheochromocytoma, neuroblastoma, ganglioneuroma, ganglioneuroblastoma, & rare adrenal tumors.
pg 75 and 76 have good charts for tyrosine to epinephrine conversion
and Bone turnover
look at it
Bone Turnover - Deoxypyridinoline
A cross-link of Type I collagen – provides tensile strength to collagen matrix of bone
•Released into circulation during bone resorption & excreted unchanged into urine
•Is labile and also found in dentin
•Fluctuates throughout the day so 2nd morning void is sample used.
•Must be careful that no other tissue or body fluid contaminates sample
Bone Turnover- Deoxypyridinoline
Increased Levels:
Increased levels: •Osteoporosis •Osteolytic metastatic cancers •Hyperthyroidism •Children •Osteomalacia •Hyperparathyroidism Multiple Myeloma •Paget’s Disease •Long-term steroid therapy •Cushing’s Syndrome
Bone Turnover:
N-Telopeptides, NTX
Reference range: Men: 18-29yo 12-99 units 30-59yo 9-60 units Women: 4-64 units (premenopausal)
Unique amino acid sequence at cross-links in Type I collagen
•Has been correlated inversely with BMD T-scores.
•Early marker or predictor to therapeutic response.
•Response can be determined within 3-6 months rather than 1-2 years.
•Use 2nd morning void
•Increased levels associated with same conditions as increased deoxypryidinoline
(better marker than deoxypryidinoline for bone turnover detection; both together is best
Urinary Human Chorianic Gonadotropin (HCG)
Urinary Human Chorionic Gonadotropin (HCG)
•Dx Pregnancy: Produced by placental trophoblast
•Dx some Cancers: Germ cell tumors
•Serum values increase first – usually takes about 10 days after conception to see increased values in urine
•The first morning urine sample is the best specimen
Increased levels of HCG are not specific for pregnancy. Incr. levels could also be caused by:
Urinary Human Chorionic Gonadotropin (HCG)
Increased levels:
•Normal pregnancy
•Ectopic pregnancy
•Germ cell tumors of testes or ovaries
•Hydatidiform Mole – abnormal pregnancy due to proliferation of epithelial covering of chorionic villi mass of cysts resembling bunch of grapes
•Choriocarcinoma – abnormal malignant proliferation of placental cuboidal epithelium
Drug Testing (urine testing)
Drug testing
•Common screening test performed on urine samples.
•Some employers require testing before a new hire.
•Can be used when deciding on the appropriateness of prescribing a controlled substance for a patient. (any relevant drug abuse)
•Can be used before increasing dose of analgesic medications
Or before referring to a pain or addiction specialist
Urine Drug screening (2 main types)
Urine drug screening
(2 main types)
•Immunoassay testing (1st type)
–Use antibodies to detect the presence of drugs
–Rapid results
–Inexpensive
–Preferred initial test for screening
–High predictive value for marijuana & cocaine
–Low predictive value for opiates & amphetamines
Type 2: Gas Chromatography/Mass Spectroscopy (GC/MS) Molecules are separated and analyzed –Used as confirmatory testing –More expensive & time consuming –More accurate results (forensic criterion standard)
Immunoassay Duration of detectability for drug tests
Amphetamines: 2-3 days
Benzodiazepines: 3 days for short acting
Up to 30 days for long acting
Cocaine: 1-3 days
Opiates: 1-3 days
Phencyclidine: 7-14 days
Tetrahydrocannabinol: 3 days with single use
5-7 days with use around 4x /week
10-15 days with daily use
>30 days with long term or heavy use
False negatives for immunoassay drug testing:
False negatives
–Dilute urine
–Time from use has exceeded test duration
–Laboratory’s established threshold limits
–Sample tampering
–A negative result does not exclude occasional or even daily drug use
-Many other drugs, and substances including:
•Welbutrin, Prozac, nasal decongestants, Ritalin, Zantac, Zoloft, Benadryl, poppy seeds, Verapamil, Ibuprofen, Demerol, Effexor, NSAIDS, PPIs,
Methods and criteria for assessing drug screen viability
Sample must be at least 30ml
•Temp between 90°F - 100°F
•Specific gravity >1.0010 but 500 mg/dL
unusual appearance
