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1
Q

What are 3 things that renal function testing provides info regarding and what does it require?

A

Renal blood flow
Glomerular filtration rate (GFR)
Tubular function

Requires: analysis of plasma/serum &/ urine samples

(slide 2)

2
Q

How is renal function testing imperfect (3)?

A
  • Various factors (besides renal parenchyma damage) can influence results
  • Localized & generalized damage
  • Temp. & permanent malfunction

(slide 2)

3
Q

Define renal disease?

A

Presence of histologic lesions in kidney, but does not specify any degree of renal dysfunction

(slide 3)

4
Q

Define renal failure?

A

75% of total nephron population has become non-functional, but does not necessarily imply underlying histologic lesions

(slide 4)

5
Q

What are some examples of renal function tests to evaluate clearance vs. tubular function?

A

Clearance tests: BUN, serum creatinine, creatinine clearance, albumin creatinine ratio

Tubular func.: fractional excretion of Na

(slide 5)

6
Q

What is the measurement of glomerular filtration rate (GFR) based on?

A

The concept of clearance: determination of the volume of plasma from which a substance is removed by glomerular filtration during it’s passage through the kidney

(slide 6)

7
Q

What is essential to renal function and the most frequently performed renal function?

A

GFR!

slide 6

8
Q

Describe the ideal substance to measure GFR (6)?

A
Freely filtered at the glomeruli
Not bound to plasma proteins or metabolized
Non-toxic & excreted only by the kidneys
Not reabsorbed/secreted by renal tubules
Stable in blood & urine
Easily measured

(slide 7)

9
Q

What does BUN stand for, what is it derived from, & what is its filtration/reabsorption/clearance rate(s)?

A

Blood urea nitrogen

Derived from protein catabolism via urea cycle in liver (AA -> NH3 -> Urea -> circulation)

Filtered by glomerulus (40% reabsorbed)
Clearance ~ 60% of true GFR

(slide 8)

10
Q

How would you test BUN and what does it measure (3)?

A

Serum/plasma testing (part of CMP or BMP)

Evaluates liver func., indirectly measures renal func., rough indicator of GFR & renal blood flow

(slide 10)

11
Q

What factors can interfere w/BUN (6)?

A
  • Protein intake
  • Muscle mass
  • Pregnancy (dec. due to hemodilution & inc. GFR)
  • Hydration level
  • Liver dx dec. production
  • Drugs

(slide 11)

12
Q

What is the normal adult level of BUN, the critical level, & causes for dec. BUN?

A

10-20 mg/dl (elderly higher)

Critical: >100 mg/dl (serious impairment of renal func.)

Dec. values: fluid overload, malnutrition, severe liver dx

(slide 12)

13
Q

What is azotemia? What could it indicate? What must you distinguish btwn?

A

Inc. concentration of non-protein nitrogenous waste produces in the blood (i.e. urea, creatinine, BUN)

Could indicate: renal dx or other conditions

Distinguish: pre-renal, renal, & post-renal azotemia

(slide 13)

14
Q

What are some pre-renal causes of inc. BUN (6)? What % of acute renal failure is this type?

A

55% = acute renal failure (sudden/severe drop in BP or interruption of blood flow to kidneys from injury/illness)

Low blood volume, shock, burns, dehydration
CHF, MI
GI bleed
Too much protein intake
High protein catabolism, starvation
Sepsis

(slide 14, 17)

15
Q

What are some renal causes of inc. BUN? What % of acute renal failure is this type?

A

40% of acute renal failure (direct damage to kidneys from inflamm., toxins, drugs, infx, dec. blood supply)

Renal dx (i.e. glomerulonephritis, pyelonephritis, acute tubular necrosis)
Nephrotoxic drugs

(Slide 15, 17)

16
Q

What are some post-renal causes of inc. BUN (2)? What % of acute renal failure is this type?

A

5% of acute renal failure (sudden obstruction of urine flow due to enlarged prostate, kidney stones, bladder tumor, injury)

Obstruction of ureters (i.e. stones, tumors, congenital)
Bladder outlet obstruction (i.e. prostatic hypertrophy, cancer, congenital)

(slide 16, 17)

17
Q

What is a more stable marker than BUN? What does its value depend on?

A

Serum creatinine (catabolic product of creatinine phosphate from skeletal mm)

Depends on: muscle mass, which fluctuates very little unless muscle-wasting pathology exists

(slide 18)

18
Q

What does the kidney do w/ serum creatinine?

A

Kidneys almost completely filter creatine, but its secreted by prox. tubule as well.

(slide 19)

19
Q

When do creatinine levels increase in relation to BUN levels? What do elevated levels suggest?
Who might normally have lower levels?

A

Creatinine increases later than BUN
Elevations suggest chronic dx process & parallel BUN inc.
Elderly & young children have norm. low lvls (reduced muscle mass)

(slide 20)

20
Q

What is the norm. serum creatinine range? What are they used to diagnose?

A

Norm. male: 0.6-1.2 mg/dl
Norm female: 0.5-1.1 mg/dl
Diagnose impaired renal func. (minimally affected by liver func., unlike BUN)

(slide 22)

21
Q

What is the relationship btwn BUN, creatinine, & % of functional nephrons? What does that mean about it’s screening test ability?

A

Rectangular hyperbola:
Lrg. changes in GFR ‘early’ in renal dx cause sml. changes in BUN/Creatinine
Sml. changes in GFR late in renal dx cause BIG changes in BUN/Creatinine

*Not a good screening test

(slide 23)

22
Q

What dx processes could be wrong if the BUN/Creatinine ratio is 10-20:1 (in renal azotemia) (3)?

A
  1. chronic diffuse bilat. kidney dx or damage
  2. acute tubular necrosis
  3. Severe acute glomerular damage

(slide 24)

23
Q

What dx processes could be wrong if the BUN/Creatinine ratio is >20:1 (in pre-renal azotemia) (6)?

A

If… dec. blood volume or renal circulation
then… shock, dehydration, MI/CHF

If… inc. protein intake or catabolism
then… high protein tube feedings, GI hemorrhage, starvation

(slide 24)

24
Q

What is the association btwn urea/creatinine & protein in urine?

A

Pre-renal:
Disproportionate rise in Urea
Protein uncommon in urine

Renal:
Urea/creatinine rise together
Protein present on dipstick test

(slide 25)

25
Q

What is the eGFR?

A

estimated GFR: ability to kidneys to filter blood, calculated using creatinine, pts sex, & age (MDRD equation)

GFR goes down, creatinine goes up

(slide 26)

26
Q

When could the eGFR be inaccurate?

A

Vegetarian, pregnant, malnourished, >70 or 60 ml/min/1.73 m^3

(slide 27)

27
Q

What would you use instead of eGFR for a more accurate estimate of glomerular filtration?

A

Creatinine clearance

slide 27

28
Q

What does creatinine clearance require? What info does it provide? What are values corrected for?

A

Requires: 24/hr urine collection & blood draw (both samples analyzed for creatinine)

Provides: quantitative measure of rate at which creatinine is removed from blood (ml/min)

Corrected for: body surface area (BSA), need pts height/weight

(slide 28)

29
Q

Be able to instruct a pt how to do a 24 hr urine sample?

A

See slide 29 for instructions :-)

30
Q

What does creatinine clearance provide a good estimate of? When can it be incorrect?

A

Estimates GFR

Over-estimates by 10% due to tubular secretion of creatinine.

If GFR dec. to <30% of norm, CC = invalid (secreted fraction is larger proportion of total urinary creatinine)

(slide 30)

31
Q

What is a normal value for creatinine clearance?

A

Male: 90-138 ml/min
Female: 80-125 ml/min
*values dec. 6.5 ml/min each decade of life after 20 yrs (decline in GFR)

(slide 31)

32
Q

What are interfering factors with creatinine clearance (4)?

A

Exercise (inc. serum creat.)
Pregnancy (inc. urinary creat.)
Incomplete urine collection gives false low value
Drugs

(slide 32)

33
Q

What is cystatin C? What does it estimate? What is its normal range?

A

Filtered by glomerular memb. & metabolized by prox. tubules.

Estimates: GFR independent of gender, age, race, muscle mass, cirrhosis (no height/weight correction)
*better than serum creatinine

Normal: 0.54-1.55 mg/L

(slide 33)

34
Q

What are SSx of kidney failure?

A

Loss of appetite, N/V, edema, low back (flank) pain, dec. urine output, fatigue

(Slide 34)

35
Q

How do you tell the diff. btwn acute vs. chronic renal failure?

A

ARF: occurs over hrs-days, pt has hx of norm. renal func., kidney size norm., no anemia, no broad casts in urine sediment

CRF: gradual deterioration of renal func. over time, pt hx of inc. BUN & creatinine, kidney size sml, anemia present, broad casts present in urine sediment

(slide 35)

36
Q

What is the tubular function test? What does it differentiate? What does it require?

A

Fractional excretion of Na (FENa)

Differentiates: pre-renal azotemia from renal azotemia (tubular necrosis) - both common causes of ARF

Requires: Na in plasma & urine AND creatinine in plasma & urine

(slide 37)

37
Q

What result from a FENa test would you expect for pre-renal azotemia? What about renal azotemia?

A

FENa = kidneys respond by conserving Na

FENa = >2%
Damaged tubules CANNOT effectively conserve Na

(slide 38)

38
Q

What is the most important indicator of renal disease?

A

Proteinuria

slide 39

39
Q

When is the 24-hr urine protein test indicated? What is the normal range?

A

Indicated: more than trace protein consistently found on routine UA

Normal: <150 mg/24 hrs

(slide 39)

40
Q

If you get a 24 hr urine protein test btwn 150-500 mg/24 hrs what does that mean?
What about >2000 mg/24 hrs in an adult?
40 mg//kg/24 hrs in a child?
>3500 mg/24 hrs in an adult?

A

Can be functional if asymptomatic
Glomerular cause
Glomerular cause
Nephrotic syndrome

(slide 40)

41
Q

What may cause proteinuria in the absence of structural abnormality?
What are some non-renal disease that can cause proteinuria?

A

CHF

High serum protein (malignant etiology), pre-eclampsia/eclampsia, HTN, toxicity from heavy metals/solvents

(slide 41)

42
Q

What is the urine protein to creatinine ratio used for?
Is it more accurate than 24 hr urine protein?
What is the normal ratio & nephrotic ratio?

A

Used to monitor persistent proteinuria (use 1st morning void)
Yes
Norm adult: 3.5:1

(slide 42)

43
Q

What is microalbuniuria?
When would you use it?
What is the range?

A

Persistent proteinuria that’s below detection by routine reagent strips, but greater than norm.
Pts w/ DM or HTN (early detection of kidney dx)
Norm: 300 mg/day

(slide 43)

44
Q

What is the urine albumin:creatinine ratio used for?

A
Detect microalbuminuria (30-300mg/day)
Diagnose & monitor kidney damage in pts w/type 1 DM for 5+ yrs or type 2 DM

(slide 44)

45
Q

What are the 5 stages of renal failure (include GFR range)?

A

1: kidney damage (proteinuria) w/norm. or elevated GFR (90+ ml/min)
2: kidney damage, dec. GFR (60-89 ml/min)
3: kidney damage, dec. GFR (30-59 ml/min)
4: kidney damage, dec. GFR (15-29 ml/min)
5: Kidney failure: end-stage renal dx (ESRD), dialysis/transplant to survive (<15 ml/min)

(slide 47)

46
Q

What is nephrolithiasis?

A

Urolithiasis or renal calculi or KIDNEY STONES!

Solid concentrations (crystal aggregations) of dissolved minerals in urine found inside kidney/ureter (size range: grain of sand - grapefruit)

(slide 52)

47
Q

What is the epidemiology of kidney stones?

A

1 in 20 ppl at sometime in their life
Rare in children (associated w/metabolic disorders or anatomic abnormalities)

(slide 53)

48
Q

Why do kidney stones form?

A
High level of mineral(s) (i.e. Ca, oxalate, uric acid) in urine
OR
Lack of citrate in urine
OR
Insufficient water in kidneys

(slide 55)

49
Q

What do you do with a pt after they have their first kidney stone?

A

Medical evaluation & prophylaxis not cost effective in 1st time presenters & ppl who form stones < every 3 yrs

(slide 56)

50
Q

What does the limited evaluation for kidney stone producers entail?

A

Chemistry panel:
Hyper Ca on 2 occasions (r/o primary hyperparathyroidism) & Low bicarb m/b type 1 RTA or chronic diarrhea

PTH: if inc. serum Ca

UA:
Including pH: >7.5 (struvite or calcium phosphate); <5.5 (uric acid, cystine stones); *Ca oxalate stones not pH dependent

Urine culture: crystalluira/stones (calcium phosphate; cystine crystals; Mg ammonium phosphate & Ca carbonate-apatite - struvite; Ca oxalate crystals & uric acid crystals - w/o stone dx

(slide 58)

51
Q

What does the complete evaluation for kidney stone producers entail? Including what are values of Ca, uric acid, oxalate, and citrate that would be of concern for men & women?

A

2 24 hr urine collections obtain in outpt setting w/pt on regular diet (2-3 months after stone event)
Ca M: <320 mg

(slide 59)

52
Q

What does 24 hr urine Ca measure?
What is normal range, low-ca diet range, hypercalciuria?
What is used more often in routine work-ups?

A

Measures: urinary excretion of Ca over 24 hrs (support diagnosis of hypercalcemia causing recurrent kidney stones)

Norm: 100-400 mg/day
LowCaDiet: 50-150 mg/day
Hyper: M: >300 mg; F: >250 mg

Blood Ca

(slide 60)

53
Q

What does 24 hr urine Ca determine?

A

Primary hyperparathyrodism
Recurrent kidney stones

(slide 61)

54
Q

What 2 compounds comprise 70-80% of all kidney stones?

How would you tell the difference between the 2?

A

Calcium oxalate:
low urine volume
high concentrations of Ca & oxalate

Calcium phosphate:
Alkaline urine
High urine Ca concentrations

(slide 62)

55
Q

What are some conditions that could lead to inc or dec levls of Ca in a 24/hr urine Ca test?

A

Inc: primary hyperparathyroidism, Vit D excess, corticosteroid tx, PTH-producing tumor (i.e. lung), cushing’s syndrome, sarcoidosis, TB, osteoporosis, metastatic tumors to bone, renal tubular acidosis

Dec: hypoparathyroidism, Vit D deficiency, Ca malabsorption, renal failure

(slide 63)

56
Q

Where may oxalate be derived from?

A

10% diet
35-50% metabolism of ascorbic acid
40% glycine metabolism

(slide 64)

57
Q

Patient’s w/ a tendency to Ca oxalate kidney stones appear to _____ & _____ a high proportion of dietary oxalate in the urine.

A

absorb, excrete

slide 64

58
Q

When is it indicated to do a 24/hr urine oxalate?

A

Pts w/surgical loss of distal ileum, esp. those w/crohn’s dx
Nephrolithiasis occurs in 3-10% of pts w/IBS
Jejunal bypass for morbid obesity -> hyperoxaluria & stone formation

(slide 65)

59
Q

What are normal values for 24/hr urine oxalate?

A

M: 7-44 mg/24 hrs
F: 4-31 mg/24 hrs
Children: 13-38 mg/24 hrs

(slide 66)

60
Q

What are some reasons for an inc or dec 24/hr urine oxalate?

A

Inc: ethylene glycol ingestion, genetic disorder (primary hyperoxaluria), pancreatic dx, liver cirrhosis, pyridoxine deficiency (B6), sarcoidosis, celiac dx

Dec: renal failure, high urinary Ca

(slide 67)

61
Q

What role does citrate play involving kidney stones?

A

It inhibits Ca crystal formation & preventing stones

slide 68

62
Q

What is the low cutoff for 24 hr urine citrate excretion?

A

<434 in men

slide 68

63
Q

What are some things that could cause a dec. level of citrate in the urine?

A

Conditions that cause chronic metabolic acidosis (IBD, intestinal malabsorbtion, renal tubular acidosis)

(slide 68)

64
Q

How could high protein diets lead to kidney stone formation?

A

Inc. acidosis -> releases Ca from bone into urine & dec. release of citrate in urine to buffer acidosis -> inc. stone formation

(slide 68)

65
Q

What are the normal findings of 24/hr urine uric acid?
Where does it come from?
What might elevated levels indicate?

A

250-750 mg/24 hrs
It is a breakdown product of purine metabolism, produced in the liver. 75% of blood uric acid is excreted by kidneys (remainder via GI tract).
Elevated ~ gout

(slide 69)

66
Q

How are uric acid stones formed? What is their incidence of total kidney stones? What populations have increase risk?

A

Form in urine w/unusually low pH & hyperuricosuria
10-15% of kidney stones
Increase risk in obese (potentially linked to those w/ metabolic syndrome or insulin resistance)

(slide 70)

67
Q

What do inc. or dec. levels of uric acid from a 24 hr urine uric acid test mean?

A

Inc: uricosuira (gout, metastatic cancer, multiple myeloma, leukemia, cancer chemotherapy, high purine diet, lead toxicity)

Dec: (renal dx, eclampsia, chronic alcoholism)

(slide 71)

68
Q

What are triple phosphate crystals? What is their incidence of kidney stones? What population is at inc. risk?

A

Composed of Mg ammonium phosphate, seen in alkaline urine, & form Struvite stones.
10-15% of kidney stones
More common in women, pts w/UTI caused by urea splitting organisms (proteus)

(slide 72)

69
Q

What is the diagnostic workup of nephrolithiasis (6)?

A
  1. stone analysis
  2. serum & blood tests (Ca, parathyroid hormone, Vit D, electrolytes)
  3. urine dip & microscopic exam (pH, sediment)
  4. culture
  5. 24 hr urine collection (volume, creatinine, Ca oxalate, Na, citrate, uric acid, cystine)
  6. helical CT w/o contrast

(slide 73)

70
Q

What is the 24 hr UR for Vanillylmadelic & Homovanilic acid? What does it measure? What is it used to diagnose?

A

HVA & VMA secreted in urine as primary end product of catecholamine metab.
Measures catcholamines (Epi, Norepi, dopamine)
Diagnoses: pheochromocytoma, neuroblastoma, ganglioneuroma, ganglioneuroblastoma, rare adrenal tumors

(slide 74)

71
Q

What is measured to assess bone turnover?

A

Deoxypyridinoline (cross-link of type 1 collagen - provides tensile strength to collagen matrix of bone)
It’s released into circulation during bone resorption & excreted unchanged into urine

(slide 77)

72
Q

What are 2 things to note regarding deoxypyridinoline measurements?

A

Lvls fluctuate throughout the day so 2nd morning void is the sample to use.
Be careful that no other tissue/body fluid contaminates the sample

(slide 77)

73
Q

What could cause inc. levels of deoxypyridinoline & N-Telopeptides (NTX)?

A

Osteoporosis, osteolytic metastatic CA, hyperthyroidism, children, osteomalacia, hyperparathyroidism, multiple myeloma, paget’s disease, long-term steroid therapy, Cushing’s syndrome

(slide 78)

74
Q

What is the reference range for N-Telopeptides (NTX)?

A

Men 18-29 yo: 12-99 units
Men 30-59 yo: 9-60 units
Women (premenopausal): 4-64 units

(slide 79)

75
Q

What is N-telopeptide, what is it used to detect, & how do you check levels?

A

Unique AA sequence at cross-links in type I collagen

Bone turnover. Correlated inversely w/BMD T-scores. Early marker/predictor to therapeutic response, response determined w/in 3-6 mo vs. 1-2 yrs.

Use 2nd morning void

(slide 79)

76
Q

What is urinary human chorionic gonadotropin (HCG) used to diagnose/predict?

A

Pregnancy (produced by placental trophoblast, serum values inc. first, takes 10 days after conception to see inc. in urine)
CA (some, germ cell tumors)

1st morning void

(slide 81)

77
Q

What do inc. levels of HCG mean?

A

Normal/ectopic pregnancy
Germ cell tumors of testes/ovaries
Hydatidiform Mole (abnormal preg. due to proliferation of epithelial covering of chorionic villi -> mass of cysts resembling bunch of grapes)
Choriocarcinoma (abnormal malignant proliferation of placental cuboidal epithelium)

(slide 82)

78
Q

When might you use a urine drug test?

A
  • Employers before a new hire
  • Deciding on appropriateness of prescribing a controlled substance for a pt
  • Before increasing dose of analgesic meds
  • Before referring to pain/addiction specialist

(slide 83)

79
Q

What are the 2 main types of urine drug screening?

A
Immunoassay testing (use antibodies to detect presence of drugs)
Gas chromatography/Mass spectroscopy (GC/MS) (molecules are separated & analyzed)

(slide 84, 85)

80
Q

What is the preferred initial test for drug screening?

A

Immunoassay test (rapid results, inexpensive)

slide 84

81
Q

What drug screening test has a high predictive value for marijuana & cocaine, but a low predictive value for opiates & amphetamines?

A

Immunoassay test

slide 84

82
Q

What drug screening test has more accurate results, but is used for a confirmatory test?

A

GC/MS (more expensive & time consuming)
Forensic criterion standard

(slide 85)

83
Q

What are reasons for FN with immunoassay drug screens?

A

Dilute urine
Time from use has exceeded test duration
Labs established limits
Sample tampering

(slide 87)

84
Q

What are reasons for FP with immunoassay drug screens?

A

Many other drugs/substances: welbutrin, prozac, nasal decongestants, ritalin, zantac, zoloft, benadryl, poppy seeds, verapamil, ibuprofen, demerol, effexor, NSAIDS, PPIs

(slide 88)

85
Q

What are the criteria for assessment of drug screening?

A

Sample at least 30 ml, temp btwn 90-100 F, specific gravity >1.0010 but <1.0030, pH of 4.5-8.5

(slide 89)

86
Q

What are signs of adulteration in a drug screen?

A

Nitrate concentration >500 mg/dL
Unusual appearance

(slide 89)

87
Q

What are the duration of detectability for some commonly measured substances in a immunoassay drug screen (amphetamines, benzos, cocaine, opiates, phencyclidine, tetrahydrocannabinol)?

A

Amp: 2-3 days
Benzos: 3 days short acting, up to 30 days long acting
Cocaine/Opiates: 1-3 days
Phencyclidine: 7-14 days
Cannabinol: 3 days w/single use, 5-7 days w/4x week use, 10-15 days w/daily use, >30 days w/long term use

(slide 86)