week 3: renal function tests Flashcards
• What info do you get from renal function testing? What is analyzed?
o Renal blood flow
o Glomerular filtration rate(GFR)
o Tubular function
o Plasma/serum or urine samples
• Why is renal function testing imperfect?
o various factors other than damage to renal parenchyma can influence results.
o Localized and generalized damage
o Temporary and permanent malfunction
• What is diff between renal dz and failure?
o Dz: presence of histologic lesions in the kidney but does not specify any degree of renal dysfunction
o Failure: 75% of the total nephron population has become non-functional but does not necessarily imply underlying histologic lesions
• What are the 2 types of renal function tests?
o Clearance: BUN, serum creatinine, creatinine clearance, albumin creatinine ratio
o Function: fractional excretion of Na+
• Why is measuring GRF important? Based on?
o It’s essential to renal function
o Most frequently performed test of renal function
o Based on clearance
• What is clearance?
o vol of plasma to clear a substance by glomerular filtration
• what characteristics of the ideal substance to measure GFR?
o Freely filtered at glomerulus o Not bound to plasma proteins o Not metabolized o Non-toxic o Excreted only by kidneys o Not reabsorbed nor secreted by renal tubules o Stable in blood and urine o Easily measured
• What is BUN?
o From protein catabolism in urea cycle in liver: amino acids -> NH3 -> Urea -> blood
o Filtered by glomerulus, 40% reabsorbed
o Urea clearance is 60% of true GFR
• Why/how is BUN used?
o Specimen types are serum, plasma: part of CMP or BMP
o Evaluates liver function; and indirect measure of renal function
o Rough indicator of GFR and renal blood flow
• What can interfere with BUN levels?
o Protein intake o Muscle mass o Pregnancy (increase) o Hydration o Liver dz (decrease) o Drugs…
• What are key BUN levels?
o Serum normal adults: 10-20 mg/dl (Elderly: may be slightly higher)
o Critical value: >100 mg/dl indicates serious impairment of renal function.
• What can cause decreased BUN?
o Fluid overload
o Malnutrition
o Severe liver dz
• What is increased BUN?
o Azotemia: Increased concentration of non-protein nitrogenous waste products (e.g. urea, creatinine) in the blood
• When does azotemia occur?
o Most renal dzs cause inadequate excretion of urea, so BUN rises
o Must distinguish b/w type: pre-renal, renal, post-renal
• What are pre-renal causes of azotemia?
o 55% of acute renal failures o Low blood volume, shock, burns, dehydration o CHF, MI o GI bleed o Too much protein intake o High protein catabolism, starvation o Sepsis
• What are renal causes of azotemia?
o 40% of acute renal failure
o Direct damage to kidneys by inflammation, infection, toxins, drugs, reduced blood supply
o Renal dz: GN, PN, acute tubular necrosis
o Nephrotoxic drugs
• What are post-renal causes of azotemia?
o 5% of acute renal failure
o Obstruction of ureters, e.g. stones, tumors, congenital
o Bladder outlet obstruction, e.g. prostatic hypertrophy (BPH), cancer, congenital
• What is serum creatinine?
o More stable marker than BUN
o catabolic product of creatine phosphate from skeletal muscle
o almost completely filtered by kidneys, but also secreted by proximal tubule
o values depend on muscle mass, which fluctuates very little unless some muscle-wasting pathology exists.
• When/what levels of creatinine would you see in dz?
o levels increase later than BUN
o elevations suggest chronic disease process & parallel BUN increases
o Elderly and young children normally have lower levels due to reduced muscle mass
• What is the effect of muscle mass on serum creatinine in normal and dzed kidneys?
o Increased muscle mass higher serum creatinine, but normal output
o Dzed kidney causes much lower output, and higher serum levels
• What are normal serum creatinine levels? Use?
o Male: 0.6-1.2 mg/dl
o Female 0.5-1.1 mg/dl
o diagnose impaired renal function
o Minimally affected by liver function (unlike BUN)
• What is relationship b/w BUN/Creatinine and % functional nephrons?
o Rectangular hyperbola
o Large changes in GFR “early” in renal disease cause small changes in BUN or creatinine
o Small changes in GFR late in renal disease cause big changes in BUN or serum creatinine
• What is BUN:Creatinine ratio?
o Prerenal azotemia: >20:1; disproportional rise in urea
o Renal: 10-20:1; tend to rise together; protein present on dipstick test
• What is estimated glomerular filtration rate (eGFR)?
o ability of the kidneys to filter blood
o GFR goes down, serum creatinine goes up
o A calculation using serum creatinine, the patient’s sex and age using the MDRD equation
o Included whenever serum creatinine values are requested
• When is eGFR inaccurate? Use what instead?
o Use creatinine clearance instead
o Vegetarian, pregnant, malnourished, elderly or infant, mm dz
o When GFR by MDRD eq is >60 mL/min/1.73m2
• How/why is creatinine clearance measured?
o Requires 24-hour urine collection & blood draw.
o quantitative measure of the rate at which creatinine is removed from the blood, expressed in ml/min.
o Values are corrected for body surface area (BSA); must obtain patient height and weight.
• What is eq for creatinine clearance?
o CC= urine creat/serum creat x 24 hrs/1440 min x m2/1.73m2 x vol (mL)
• Is creatinine clearance a good measure of GFR? When not?
o Provides relatively good estimate of GFR.
o BUT it tends to over-estimate it by about 10% due to tubular secretion of creatinine.
o When GFR decreases to < 30% of normal, CC is invalid because the secreted faction becomes a much larger proportion of the total urinary creatinine.
• What are normal values for creatinine clearance?
o Male: 90-139 ml/minute
o Female: 80-125 ml/minute
o Values decrease 6.5 ml/minute for each decade of life after 20 years due to decline in GFR.
• What can interfere with CC?
o May be increased by exercise
o Pregnancy can increase urinary level
o Incomplete urine collection=false low value
o Drugs…
• What are ssx of kidney failure?
o Loss of appetite o Nausea/vomiting o Edema o Low back (flank) pain o Decreased urine output o fatigue
• what is diff b/w acute and chronic renal failure?
o 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.
o CRF: Gradual deterioration of renal function over time, pt. has hx of increased BUN & Creatinine, kidney size usually small, anemia usually present, broad casts present in urine sediment
• What is Cystatin C?
o Filtered by the glomerular membrane and metabolized by proximal tubules
o Estimates GFR independent of gender, age race, muscle mass and cirrhosis, does not need to be corrected for height and weight.
o Superior to serum creatinine
o Normal Range for adults 0.54-1.55 mg/L
• What is fractional excretion of Na+?
o Useful to differentiate Pre-renal azotemia from Renal azotemia
o Requires both Na+ and Creatinine in both plasma and urine
o FENa= UNa x PC / PNa x UC x 100%
• What are pre and renal azotemia FENa levels?
o Pre: kidneys respond by conserving Na
o Renal: 2%; Damaged tubules cannot effectively conserve Na.
• What is the most important indicator of renal dz? Bad levels? Why does it occur?
o Proteinuria
o Proteinuria >2000mg/24 hours in adult (or 40 mg//kg/24 hours in child) indicates glomerular cause
o Proteinuria >3500 mg/24 hours indicates nephrotic syndrome
o Increased protein caused by either glomerular damage or diminished tubular catabolism of small molecular weight proteins
• What is test for proteinuria? Normal range?
o Test (24-hr urine protein) is indicated if there is more than trace protein consistently found on routine UA o Normal adult range is less than 150 mg/24 hours
• When can proteinuria occur?
o Transient: exercise, acute illness, fever, CHF (may cause proteinuria in the absence of structural abnormality)
o Persistent/asymptomatic: orthostatic, overflow, tubular, glomerular
o Symptomatic: overflow with ARF, systemic dz, renal dz w/ sub-nephrotic proteinuria, nephrotic syndrome
o Non-renal dzs: high serum protein (malignant etiology); pre-eclampsia or eclampsia, HTN, toxicity from heavy metals, solvents
• What is the urine protein to creatinine ratio?
o Used to monitor persistent Proteinuria
o More accurate than 24 hr urine protein: Use first morning void
o Normal adult ratio: 3.5 ; (correlates with 3.5 g protein a day)
• What is microalbuminuria?
o Persistent proteinuria that is below the detection by routine reagent strips but greater than normal.
o Used in patients with DM and/or HTN for early detection of kidney disease
o Present in ~25% of type 1 & ~36% of type 2 DM with negative reagent test strips
• What are the normal and albuminuria levels?
o Normal: 300 mg/day
• What is the urine albumin to creatinine ratio?
o Used to detect microalbuminuria (30-300mg/day)
o Diagnose and monitor kidney damage in patients with type 1 DM for 5 years or more or type 2 DM
o Does not require 24 hr collection
o Change may represent response to therapy or progression of disease
• What are the stages of renal failure (with GFR mL/min)?
o 1, 90+, kidney damage (proteinuria) w/ normal or elevated GFR
o 2, 60-89, kidney damage w/ mildly decreased GFR
o 3, 30-59, moderate
o 4, 15-29, severe
o 5, <15, kidney failure: end-stage renal dz; require dialysis or transplantation
• What are kidney stones?
o Crystal aggregate of dissolved mineral in urine
o In kidneys or ureters; small as grain of sand to large as grapefruit
o Occur in 1 in 20 ppl, rare in children
• Why do kidney stones form?
o Often assoc with metabolic d/o or anatomic abnormality (often present before age 5)
o Urine must be supersaturated to precipitate crystal (calcium, oxalate, uric acid)
o Puberty: Cystinuria, idiopathic calcium oxalate urolithiasis, primary hyperparathyroidism
o Lack of citrate in urine, dehydration, to dissolve waste products
• What does urine normally have to prevent crystal formation?
o Citrate, magnesium, pyrophosphate
• What should you do after a first kidney stone?
o Some say don’t need detailed metabolic evaluation; not cost effective in first time, or those who get stones < every 3 yrs
• What does a limited evaluation after kidney stone include?
o Chemistry: calcium, bicarb o PTH (if high Ca) o UA- pH and urine culture (>7.5=struvite, CaPO4; <5.5=uric acid, cysteine)
• What is a complete evaluation after kidney stones?
o 24-hr urine
• What is 24-hr urine calcium? Hypercalciuria? Normal?
o Used to support diagnosis of hypercalcemia causing recurrent renal calculi.
o 24-hr hyper: >300mg in men & >250mg in women
o “Normal” diet: 100-400 mg/day; Low-calcium diet: 50-150 mg/day
• What is urine calcium used for?
o To determine primary hyperparathyroidism; cause of recurrent nephrolithiasis
o Increased levels: hyper pth, vit d excess, corticosteroid, cushing’s, sarcoidosis, osteoporosis, bone tumor, renal tubular acidosis
o Decreased: hypo pth, vit D def, Ca malabsorption, renal failure
• What are constituents of most kidney stones?
o Calcium oxalate: low urine vol
o calcium phosphate: alkaline urine
• When is 24 hr oxalate indicated?
o Surgical loss of distal ileum, esp crohn’s
o IBS
o Jejunal bypass
o Excess enteric fat
• What are normal 24 hr oxalate values?
o Males: 7-44 mg
o Female: 4-31
o Child: 13-38
• What causes increased/decreased oxalate?
o Increased: ethylene glycol, genetic (hyperoxaluria), pancreas dz, liver cirrhosis, pyridoxine def (B6), sarcoidosis, celiac
o Decreased: renal failure, high urinary Ca
• What is hypocitraturia?
o 24 hr urine: <400-500 (F and M)
o Decreased by: IBD, intestinal malabsorption, renal tubular acidosis
o High protein diet cause decreased citrate
o Citrate normally inhibits Ca crystals
• What is 24 hr urine uric acid?
o Normal: 25-750 mg
o From purine metabolism; made in liver
o 75% in blood excreted by kidneys, rest by GI
o Elevated= gout
o Stones in urine with very low pH (10-15% of stones)
• What can cause increased and decreased urine uric acid?
o Uricosuria: gout, cancer, myeloma, leukemia, chemo, high purine diet, lead
o Decreased: renal dz, eclampsia, alcoholism
• What are triple phosphate crystals?
o Mg NH4 PO4; alkaline urine
o More common in women; UTIs from bacteria
o Form struvite stones (10-15% of stones)
• What is 24 hr vanillylmandelic and homovanilic acid?
o End products of catecholamines
o Dx pheochromocytoma, neuroblastoma, ganglioneuroma
• Instructions for 24 hr urine collection?
o Urinate in morning, start time, collect next 24 hrs
o Keep refrigerated
• What is deoxypyridinoline and bone turnover?
o Cross-link of collagen- tensile strength to bone matrix
o In blood from bone resorption, into urine
o Also found in dentin, be very careful not to contaminate
o 2nd morning void best
• What causes increased deoxypyridinoline?
o Osteoporosis, bone cancer, hyperthyroid, children, hyper PTH, myeloma, steroids, cushings
• What is N-telopeptides (ntx) in bone turnover?
o Decreases with age; cross links in collagen
o Similar to deoxypyridinoline
• What is urinary human chorionic gonadotropin (HCG)
o Pregnancy dx, and some cancers (germ cell tumors)
o Serum levels increase first, 10 days after conception to see in urine
• Increased HCG?
o Hydratidiform mole: abnormal pregnancy
o Choriocarcinoma: malignant placental epithelium
• When is drug testing done clinically?
o Before prescribing a medication/controlled substance
o Before increasing dose
o Before referring to pain or addiction specialist
• What are 2 main types of urine drug test?
o Immunoassay: Abs, rapid results, cheap, preferred, high PPV for pot and cocaine; low PPV for opiates and amphetamines
o GC/MS: molecules separated, expensive, more accurate (used in forensics)
• How long can immunoassay detect drugs?
o Most are1-3 days
o Pot is increased with increased use
• What gives false negs for immunoassay?
o Dilute urine o Past time detection of use o Lab’s established threshold limits o Sample tampering o Neg result doesn’t exclude occasional or even daily use
• What gives false pos with immunoassay?
o Welbutrin, Prozac, pseudephedrine, Ritalin, benadryl, poppy seeds, ibuprofen, Demerol, NSAIDs, PPIs
• Criteria for drug urine test? Adulteration?
o At least 30 mL
o 90-100 F
o Ph=4.5-8.5
o Tamper: nitrite >500 mg/dL, unusual appearance, very low sp grav
