Kidney Function Assessment

What is a nephron?

the functional unit of kidney

How many nephrons are in each kidney?

approximately 1 million

What are the functions of the kidney?

filter blood through glomerulus, remove toxic substances (uremic toxins, drugs) from blood, concentrate urine with electrolytes, and maintain water balance

what are the excretory functions of the kidney?

waste products (BUN), water and salt (sodium balance)

what are the endocrine functions of the kidney?

renin secretion, erythropoietin production

what are the metabolic functions of the kidney?

vitamin D activation, CYP450 isoenzymes, metabolism of insulin and steroids, pH regulation

What is GFR?

glomerular filtration rate

eGFR

estimated glomerular filtration rate

eGFRcr

creatinine-based estimated glomerular filtration rate

eGFRcys

cystatin C-based estimated glomerular filtration rate

eGFRcr-cys

creatinine and cystatin C-based estimated glomerular filtration rate

mGFR

measured glomerular filtration rate

What is CrCl

creatinine clearance

eCrCl

estimated creatinine clearance

mCrCl

measured creatinine clearance

What are the methods to assess kidney function?

laboratory, urine output, urinalysis, estimation

laboratory assessment of kidney function

serum creatine (SCr), BUN, Cystatin C; measured GFR, measured CrCl

urine output assessment of kidney function

24-hour urine output in mL; oliguria: urine output < 400mL/ day

urinalysis assessment of kidney function

protein excretion, creatinine excretion

estimation assessment of kidney function

eGFR (CKD-EPI 2021), Cockcroft Gualt eCrCl

BUN normal range

8-20 mg/dL

What is BUN a marker of?

nitrogenous waste products in blood; renal function

When is BUN elevated?

when kidney does not properly excrete uremic toxins

Serum Creatinine normal range

0.5-1.5 mg/dL

What is serum creatinine a marker of?

glomerular filtration rate; renal function

Serum creatinine notes

product of normal muscle catabolism

Potassium normal range

3.5-5.0 mEq/L

Magnesium normal range

1.5-2.2 mEq/L

What is azotemia?

elevation of BUN > 20 mg/dL

What is uremia?

azotemia + symptoms

What symptoms are associated with uremia?

• nausea/vomiting/anorexia

• itching

• depression, mental status changes, insomnia

• muscle cramps, weakness

• fatigue, lethargy,

glomerular filtration rate normal range

90-120 mL/min

what is glomerular filtration rate?

amount of blood volume that is filtered by the glomeruli per unit time

what is creatinine?

an inert, endogenous compound that is freely filtered by the glomerulus, and therefore a useful biomarker of kidney function

what is the relationship of Scr to GFR?

curvilinear

BUN/Scr ratio normal range

10:1 to 20:1

what does an elevated Bun/Scr ratio mean?

decreased kidney perfusion; symptoms include dehydration, heart failure exacerbation, sepsis, pre-renal AKI

polyuria urine output

>3000 mL

normal urine output

1000 mL to 3000 mL

oliguria urine output

< 400 mL

anuria urine output

< 50 mL

What is a marker of glomerular damage?

proteinuria

what is proteinuria a prognostic indicator of?

• progression of diabetic nephropathy

• progression of CKD

• risk of cardiovascular disease

• risk of mortality

Proteinuria diagnosis

• 24 hour urine collection (gold standard)

• spot urine— protein to creatinine ratio (PCR) and albumin to creatinine ratio (ACR)

• dipstick method— Trace=10-20mg/dL; +1=30mg/dL,+2=100mg/dL,+3=300mg/dL, +4>1000mg/dL

Which proteinuria diagnosis methods need to be repeated?

spot and dipstick within 3-8 weeks

albuminuria

albumin in the urine

albumin normal range

< 30 mg/day (<30mg/g creatinine)

microalbuminuria (A2) range

30- 299 mg/day (30-299mg/g creatinine)

macroalbuminuria (A3) range

≥ 300 mg/day (): ≥300 mg/g creatinine); also just called albuminuria

what are the methods to assess creatinine clearance?

1. Cockcroft-Gault estimation of CrCl
2. Direct measurement via 12-hr or 24-hr urinary collection
3. Jelliffe eCrCl (better if acute changes in SCr)
4. Nankivell eCrCl (Kidney transplant patients)
5. Sanaka eCrCl (Elderly/muscle atrophy patients)
6. Salazar eCrCl (Obese patients)
7. Schwartz eCrCl (Pediatric patients)

Cockcroft Gualt eCrCl equation

eCrCl = [(140-Age) x ABW]/ (72 x SCr)

x(0.85 if female)

can also use IBW

Femal IBW Equation

45.5 + (2.3 x height in inches >60)

Male IBW Equation

50+ (2.3 x height in inches > 60)

How to mitigate limitations on the Cockcroft-Gualt eCrCl?

• compare with other GFR estimates

• compare with direct CrCl measurement

• utilize equations for special populations when necessary

• use best clinical judgement

how do you measure CrCl directly?

urine creatinine (mg/dL)/serum creatinine (mg/dL) x urine volume (mL)/time (min)

what is now the preferred equation to estimate GFR?

CKD EPI 2021

How is creatinine produced?

muscle catabolism

How is cystatin C produced?

all nucleated cells

what is creatinine affected by?

muscle mass, age, sex, weight/height, nutrition

what is cystatin C affected by?

age, sex, weight/height, cigarette smoking, steroid therapy, rheumatoid arthritis

creatinine in the kidneys

significant tubular secretion, especially in late CKD

cystatin C filtration

freely filtered by glomerulus

Indexed results

results automatically reported by lab with serum creatinine ; indexed to a “standard” body surface area

Non-indexed results

converted from indexed by multiplying result by patient-specific body surface area, then dividing by 1.73; patient specific

Limitations of eGFR

• underestimates true GFR, especially at higher GFR

• SCr must be stable

• Less reliable >70

Limitations of eCrCl

• overestimates true GFR

• SCr must be stable

• Less reliable < 30 mL/min

Clinical practice use of eGFR

CKD staging and drug dosing

Clinical practice use of eCrCl

drug doing; falling out of favor