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