9/15- GFR in Health and Disease Flashcards
What is the relationship between CKD and HTN?
CKD causes HTN and HTN causes CKD
What is the best estimate of kidney function?
GFR- glomerular filtration rate (or change in urine output)
T/F: Acute kidney disease (AKD) is fairly common in sick patients
True
- Up to 20% of all hospitalized pts
- Over 45% of pts in critical care setting
What is AKD?
Syndrome with many different causes which all result in abrupt decrease in kidney function
What is the line between acute and chronic kidney disease?
- CKD is kidney damage for > 3 mo
- AKD is kidney damage for < 3 mo
What are common markers of kidney injury?
- Urinalysis
- Imaging
- Lab Analysis
Urinalysis:
- Protein
- Blood
- Cells
Imaging:
- Size of kidneys
- Absence of kidney
Lab Analysis:
- Creatinine and Blood Urea Nitrogen (BUN)
- Creatinine clearance (CrCl)
- Glomerular Filtration Rate (GFR)
What is creatinine? Limitations?
Creatinine clearance used to measure kidney function/injury
Limitations:
- Late marker of injury
- Best evaluated in steady state
What are relatively new markers (“renal troponins”) of renal damage?
- NGAL: neutrophil gelatinase-associated lipocalin
- KIM-1: Kidney Injury Molecule-1
- TIMP-2: Urine tissue inhibitor of metalloproteinases-2
- IGFBP7: Urine insulin-like growth factor binding protein-7
- CD80: Marker for podocyte injury
What is clearance? Equation?
Clearance- the volume of blood that is COMPLETELY cleared of solute per unit of time (mL/min)
- Allows generalization across classes of solutes
Px x RPFa = (Pxv x RPFv) + (Ux x V)
Where RPFa = 0 and (Pxv x RPFv) = 0
Thus, Clearance = (Ux x V)/Px
T/F: Clearance is independent of concentration
True
What is the ideal solute for renal clearance (describe)?
In steady state, solute has same value day to day… thus
- Solute production = solute elimination
- Rate at which solute is produced = rate at which it disappears from blood plasma = rate at which kidneys excrete solute into urine
What are the relative clearance of solutes:
- Na, Cl, K, P
- Glucose
- Creatinine
- Inulin
- Glucose = 0 (almost all reabsorbed)
- Na < Cl < K < P
- Inulin = 125
- Creatinine = 140
(Higher numbers suggest secretion)
Creatinine is an ____ (endogenous/exogenous) marker
Creatinine is an ENDOgenous marker
How is creatinine typically measured? How do we account for limitations?
Typically 24 hour urine collection
- Best results involve collecting urine urea and creatinine
- Average the two for a true GFR
Limitations of urine collection lead to:
- Estimating formulas for GFR have been developed based on serum creatinine value:
- Cockroft-Gault equation
- MDRD study equation
- CKD-EPI equation
- Since 2006, estimated GFR (MDRD) is reported with serum creatinine
What is the Cockroft-Gault equation?
(App- don’t need to memorize)
What is the modified MDRD equation?
( App- don’t need to memorize)
Case)
- 50 yo, 60 kg African American male
- Serum creatinine 1.3 mg/dL
- Pt is emaciated and has very little muscle mass
Suspect that creatinine clearance (true GFR) will be what compared to estimated GFR (eGFR) by the MDRD equation?
A. Lower
B. Higher
C. Came
Real GFR will be lower (A)
- Creatinine comes from muscle mass; decreased muscle mass in this patient, so actual value will be lower than expected
- Key: USE OF CREATININE TO ESTIMATE KIDNEY DZ MUST BE INTERPRETED IN CONTEXT OF MUSCLE MASS
How can a serum creatinine of 1.0 represent either a GFR of 60 or 100?
Serum creatinine varies with:
- Age
- Muscle mass
- Tubular secretion
(It is not an ideal marker)
How does GFR change from fetus -> young adult?
- 1 wk preterm = 15
- 2-8 wks preterm = 29
- 5-7 d = 50
- 9-12 mo = 88
- 2-12 yrs = 130
How does GFR change with age?
Decreases 10 mL/decade after 35-40 yo
When could CrCl be better (more ideal)?
Pt’s basal creatinine generation is abnormal
- Extreme body size or muscle mass (obese, severely malnourished, amputees, paraplegics, or other muscle-wasting diseases)
- Unusual dietary intake (vegetarian, creatinine supplements)
Relationship between creatinine, creatine, and phosphocreatine?
Case)
- Mr S is a 40 yo white male with cirrhosis who needs a liver transplant
- Chronically ill with reduced muscle mass
- 10 yr Hx of HTN
- Serum creatinine is 2.0
- Listed for dual organ transplant if GFR is under 30 mL/min
- By MDRD equation, eGFR is 40 mL/min
What are your options?
Measured GFR (mGFR)- gold standard
- Relies on urinary or plasma clearance of exogenous filtration markers (ex: inulin)
- Common Nuclear Tracers
- Iothalamate (cold)
- Tc-99m-DTPA; 125I-iothalamate; 51Cr-EDTA (radiolabeled)
Other options:
- 24 hr urine collection (creatinine and urea)
- Kidney biopsy (% fibrosis and glomerulosclerosis)
- Results will help guide the team for dual organ listing
What are characteristics of the ideal mcl to measure GFR?
- Freely filtered at glomerulus
- Neither reabsorbed nor excreted
- Neither synthesized or metabolized
- Does not alter kidney function
Use of tracers and infusions of exogenous markers: more costly, time consuming, potential side effects
How do you perform a creatinine clearance (CrCl)?
- Should the pt collect or flush urine at time 0? 24 hr?
- Performed only if creatinine is stable from one day to the next; pt must be able to keep urine
- Flush at 0 hr, but collect at 24 hr
- Need 24 hr rather than 6 hr, because there is variable secretion of creatinine
Calculate clearance for:
[UrCr] = 20 mg/dL
[PCr] = 2.0 mg/dL
Urine volume = 1000 mL
Units must be mL/min!
C = UV/P x 1.73/A
- A = body surface are in m2 (varies by height and weight)
Clearance = 7 mL/min
Case)
- 25 yo male victim of MVA
- Severe bladder injury and currently anuric
- Serum creatinine on admission (within 1 hr of accident) is 6.5 mg/dL
- His family states he was healthy but had never seen a doctor before
- His weight is 70 kg Is he healthy?
(Calculate this pts expected creatinine generation)
Creatinine production
- Males = [28 - 0.2(age)] x weight = (28 - 0.2(25)) x 70 = 1400 mg (per kg/day)
Body fluid in dL = 420 (60% x 70 kg) ~ 42 L
- Max rise in creatinine = 1400 mg/420 ~ 3 mg/dL
- Thus he is not healthy; he came in with kidney disease
What is typical creatinine generation (mg/day)?
Males = [28 - 0.2(age)] x weight
Females = [23.8 - 0.17(age)] x weight
Case)
- 60 yo African American male pt with Acute Kidney Injury
- Creatinine was 1.9 mg/dL yesterday and 2.6 today
- eGFR is 30 mL/min by MDRD equation
- Can you dose his ABx to a GFR of 30 mL/min?
No
- Creatinine is only useful as a marker for GFR when in steady state
Case)
- You know that creatinine is imprecise due to tubular secretion of the drug
- You decide to give the pt a drug to block secretion of the drug
- What can you give (Rx) to make CrCl resemble GFR during a collection?
A. Cimetidine 400 mg bid
B. Lasix 40 mg bid
C. Inulin 1 g/min infusion
- What can you give (Rx) to make CrCl resemble GFR during a collection?
A. Cimetidine 400 mg bid
B. Lasix 40 mg bid
C. Inulin 1 g/min infusion
What is Cystatin C?
- Renal handling characteristics
- Response to injury
LMW protein produced at a constant rate by all nucleated cells in body
- Freely filtered, not secreted, totally reabsorbed by tubules
- Virtually none in urine
Blood levels rise in response to injury
“Better estimate in early disease since independent of age, gender. But not shown to be superior to formula-adjusted estimations of kidney function”
What are some conditions with reduced GFR
(don’t memorize by rote)?
- Metabolic Acidosis
- Hyperphosphatemia
- Hyperkalemia
- Hypertension
- Volume overload
- Hyponatremia
And others…
What are some pathologies with normal GFR?
(don’t memorize by rote)
- Renal Tubular Acidosis
- Metabolic Acidosis / Alkalosis
- Volume Overload
- Hyper- / Hypo- Natremia
- Hyper- / Hypo- Kalemia
- Certain glomerular diseases
And others…
What is fractional excretion? Equation?
Answers the question: “Of the percentage of X that is filtered, what is secreted by the kidney”
What should be measured to determine volume status?
FeNa (fractional excretion of sodium)
- Lower percentage means sodium is absorbed
- FeNa < 1% equates to sodium retention by kidney (pre-renal state)
FeUrea
What should be measured to determine Ca or Mg disorders?
- FeCa
- FeMg
What is the protein-creatinine ratio (g/g)?
- Why is it useful
- Process?
- Glomerular disease is quantified by amount of protein excreted
- A 24 hr urine can be cumbersome and inaccurate A SPOT protein-creatinine ratio is easy to do
- Assumption: 1 g creatinine production/day
- 10-20 mg/kg creatinine generated per day
Summary
- Clearance is ______
- The best measure of clearance and “kidney function” is ____
- Creatinine is an __-genous marker to use for calculated ___ and estimated ____
- Exogenous markers are often necessary to measure GFR
- Low GFR (CKD or AKD) is bad
- Clearance is how we measure the kidney’s ability to remove wastes
- The best measure of clearance and “kidney function” is glomerular filtration rate (GFR)
- Creatinine is an ENDO-genous marker to use for calculated clearance and estimated GFR
- Exogenous markers are often necessary to measure GFR
- Low GFR (CKD or AKD) is bad
What to measure for:
- Elimination of toxic metabolites
- Homeostasis
- Endocrine related
Eliminate toxic metabolites
- Urea
- Creatinine
- Toxins
Homeostasis
- Na, K, P, Ca
- Water
- Acid (H)
Endocrine related
- Activated Vit D (25 to 1,25)
- EPO
- Metabolize insulin…
