assessment of kidney function

what are the conventional markers of kidney function?

• serum creatinine (SCr)

• serum or blood urea nitrogen (BUN)

• Urine output (UO)

• fractional excretion of sodium (FeNa)

• fractional excretion of urea (FeUrea)

Serum creatinine is formed via the cleavage of creatine during ___________ metabolism and release into the plasma at a relatively constant rate

muscle

Which biomarker is most widely used for kidney disease detection?

SCr (serum creatinine)

How is serum creatinine (SCr) primary eliminated?

through glomerular filtration

For serum creatinine (SCr), as GFR ________, the SCr will ____________

decreases, increase

What are some limitations of SCr?

•Undergoes tubular secretion (10-15%)

•SCr “lag time” (Increase not usually seen until after kidney dysfunction has already developed)

•Many factors influence levels

what factors can falsely increase SCr?

• increase in muscle mass

what factors can falsely decrease SCr?

What medications can cause a “false” SCr increase by inhibiting the secretion of creatinine?

• TMP and Sulfamethoxazole/TMP

• Cimetidine and Famotidine

• Dolutegravir and Cobicistat

• Dronedarone

What medications can cause a “false” SCr increase by interfering with lab assay?

• Dobutamine

• Flucytosine

How is BUN eliminated?

via glomerular filtration (50% still reabsorbed in proximal tubule

BUN is a byproduct of _____ _______

protein metabolism

Why could BUN following H2O reabsorption be a problem?

excretion of BUN decreases in conditions that necessitate water conversions

describe azotemia

elevated levels of nitrogen (BUN) in the blood

describe uremia

Clinical syndrome resulting from elevated levels of BUN (waste) in the blood

_______________ can be an indication for emergent kidney replacement therapy (eg, hemodialysis)

elevated BUN

Uremia typically does not present until BUN > _____________

80-100 mg/dL

what are the initial symptoms of uremia

• fatigue

• N/V

• itching

• altered mental status

list complications of uremia

• impact lung

• liver

• brain

• death

what are some limitations of BUN?

•50% reabsorbed in tubules / urea clearance not constant

•BUN “lag time” (Increase not usually seen until after kidney dysfunction has already developed)

•Many factors influence levels

what factors can falsely increase BUN?

• high protein diets ( increase in dietary protein)

• GI bleeding

• critical illness (eg. fever, burns, trauma, sepsis)

what factors can falsely decrease BUN?

• liver disease

• protein restricted diets/ malnutrition

when is it most useful to use urine output

during continuous monitoring

list limitations of urine output

• lack sensitivity and specificity

• dependent on fluid intake

Patients can have normal urine output and still have renal dysfunction. T/F

T

Abnormal urine output means that patients must have renal dysfunction. T/F

F

Describe Urinalysis

physical and chemical composition data of urine

What is used to detect presence of hemoglobin or myoglobin in urine?

urinalysis

What is urinalysis a helpful tool for?

differentiating various aspects of kidney disease

is urinalysis helpful in assessing AKI?

not really

what are the most useful components for assessing AKI?

• specific gravity (not useful alone but can help point to type of AKI

• urinary sediment (eg. casts, crystals, cells)

• Nitrite, LE, WBCs (as markers for UTI as a contributing factor for AKI)

what is the most useful component for assessing CKD?

What is the FENa equation?

FENa= [(UNa/SNa)/(UCr/SCr)] * 100

When the kidney perceives decreased perfusion, sodium reabsorption ___________in the renal tubules and excretion __________

increases, decreases

For FENa, water will follow in order to ____________ intravascular volume and aid in perfusing the kidney

increase

When the kidney views itself as “dry” or not being perfused/ receiving blood flow → FENa will ________

decrease

What are some useful tools in diagnosing type of acute kidney injury?

• Prerenal AKI= FENa< 1%

• Intrinsic AKI or postrenal AKI= FeNa> 1%

What kind of drug can falsely increase FENa?

diuretics (loops specifically)

limitations of FENa

• FENa < 1% can also be found in other types of renal failure

• diuretics can falsely increase FENa

describe the mechanism of how diuretics can falsely increase FENa

diuretics inhibit sodium reabsorption ( increase urine sodium excretion)

If FENa < 1%, what does this mean?

• FENa is accurate

• can be used for assessment of prerenal AKI if diuretic given prior to measurement

If FENa >1%, what does this mean

• FENa is inaccurate

• cannot be used for assessment of prerenal AKI if diuretic given prior to measurement

• Use FeUrea instead

FEurea equation

FEUrea= [(Ur urea nitrogen/BUN)/(UCr/SCr)] *100

what is the single best indicator of kidney function?

GFR

describe glomerular filtration rate

volume of plasma filter across the glomerulus per unit of time

How is GFR determined?

by measuring clearance of substance that is freely filtered by glomerulus with additional tubular secretion

list assumptions about creatinine

• constant daily production and conversion

• freely filtered by tubules

• collection and measurement is accurate

describe ClCr

24 hour urine collection of creatinine with calculation

why do you think the direct measurements of GFR and ClCR are not done on a regular basis?

takes too long

list limitations of GFR

• Technically difficult – administration of agents,

accurate collection of serum and urine samples

• Limited utility in some disease states due to limits with

accurate urine output (i.e. benign prostatic hypertrophy,

neurogenic bladder, etc.)

• Cost $$$

list limitations of ClCr

• Proper collection of serum and urine samples needed for accuracy

• Poor patient adherence

• 10-15% of SCr cleared by renal tubules

MDRD is used for AKI and most medication dosage adjustments. T/F

F

MDRD is not used for AKI and is not used for most medication dosage adjustments. T/F

T

what is MDRD based on?

Based on creatinine, age, sex, and race

What is CKD- EPI based on?

SCr, cysC, and age

What is considered a “race-free" equation endorsed by the NKF-ASN Task Force and recommended by 2024 FDA guidance over Cockcroft-Gault to characterize kidney impairment in pharmacokinetic studies?

CKD EPI

Is there enough evidence for CKD- EPI to support routine use in dose adjustments of historic medications?

No

what are the limitations of Cockcroft-Gault (CG) Equation?

• Factors that influence accuracy of SCr

• Variations in which weight to use

• Race and gender biases (originally studied in ~250 white males)

• Cannot use calculation as sole estimate in patients with AKI

What special populations should you consider?

• unstable renal function -AKI

• Elderly

• Paraplegia, quadriplegia, wheelchair and/or bed bound

• liver disease

• malnutrition

• pregnancy

• pediatrics