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)

9/15- GFR in Health and Disease Flashcards by Kathryn Kudlaty

What is the relationship between CKD and HTN?

CKD causes HTN and HTN causes CKD

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What is the best estimate of kidney function?

GFR- glomerular filtration rate (or change in urine output)

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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

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What is AKD?

Syndrome with many different causes which all result in abrupt decrease in kidney function

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What is the line between acute and chronic kidney disease?

CKD is kidney damage for > 3 mo
AKD is kidney damage for < 3 mo

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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)

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What is creatinine? Limitations?

Creatinine clearance used to measure kidney function/injury

Limitations:

Late marker of injury
Best evaluated in steady state

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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

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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

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T/F: Clearance is independent of concentration

True

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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

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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)

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Creatinine is an ____ (endogenous/exogenous) marker

Creatinine is an ENDOgenous marker

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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

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What is the Cockroft-Gault equation?

(App- don’t need to memorize)

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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...