2019A06 Outline the clinical laboratory tests of renal function. What are the limitations of each?

 

List:

·       Intro

·       Plasma markers

·       GFR estimation

·       GFR measurement

 

Intro:

Renal function

·  Kidneys excrete metabolic waste

·  Rate of removal ∝ glomerular filtration rate

·  Substances that accumulate in renal impairment can be used as tracers

·  GFR = (urine concentration / plasma concentration)  x urine output

Ideal tracer

·  Freely filtered, not reabsorbed or secreted or metabolized

·  Inert, non-toxic

·  Does not affect renal function

·  Clearance of this substance = GFR

 

Plasma markers:

Urea

What is it:

·  End-product of amino acid deamination and ornithine cycle

·  Accumulates in renal impairment -> encephalopathy, platelet dysfunction etc.

Renal handling:

·  Freely filtered, 50% reabsorbed at proximal tubule

·  Same 50% secreted into thin descending loop of Henle

·  Same 50% reabsorbed at medullary collecting duct (i.e. urea recycling)

Problems:

·  ↑Protein metabolism (incl GIT bleed)-> ↑[Urea] -> underestimate GFR

·  ↓Protein metabolism -> ↓[Urea] -> overestimate GFR

·  [Urea] ∝ 1/ hydration

Creatinine

What is it:

·  Metabolite of sarcoplasmic creatine kinase

Renal handling:

·  Freely filtered

·  10% secreted in health

·  Not reabsorbed

Problems:

·  Sarcopaenia -> ↓SCr -> overestimate GFR

·  Renal failure -> ↑secreted fraction -> overestimation of GFR

Urea : Creatinine

·  Normal: 40-100:1

·  Pre-renal failure: ↑

·  Intra-renal failure: ↓

·  Post-renal failure: ↔

Graph

·  Interpretation: >50% decrease in GFR before significant increase in creatinine or urea

 

GFR estimation:

Cockroft-Gault equation

·  eGFR = [(140 – age) x LBW] / (72 x SCr)    ( x 0.85 if female)

o Lean body weight in kg

o Serum creatinine in mg/dL

MDRD

·  eGFR = 175 x SCr-1.154 x age-0.203   ( x 0.742 if female)   (x 1.21 if black)

CKD-Epi

·  eGFR = (SCr/A)B x 0.993age x C

o A: dependent upon sex

o B: dependent upon sex and SCr

o C: dependent upon race

Problems

·  Estimations only

·  Multiple variables

·  Accuracy limited if height, weight not included

·  Renal failure -> ↑secreted fraction -> overestimation of GFR

 

GFR measurement:

Inulin

Ideal properties = Gold standard

·  Freely filtered

·  Not secreted

·  Not reabsorbed

·  Inert

·  Non-toxic

Method:

·  IV infusion until steady state

·  Measure urine volume and [inulin] via IDC

·  Gold standard

Problems:

·  Invasive

·  Cumbersome

Creatinine

Method:

·  24 hour urine collection

·  Measure urine volume and [creatinine]

Problems:

·  Inconvenient

·  Accuracy limited as above

·  SCr may not be constant (e.g. stress, exercise)

Radioisotope renography

·  e.g. mercaptoacetyltriglycine (MAG3) with 99mTc

Method:

·  Tracer injected IV

·  Renal excretion observed with gamma camera

Problems:

·  Ionizing radiation

·  Expensive

·  Time-consuming