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 filtrate 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

·   End-product of amino acid deamination and ornithine cycle

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

·   Renal handling:

o Freely filtered, 50% reabsorbed at proximal tubule

o Same 50% secreted into thin descending loop of Henle

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

·   Problems:

o Dehydration or high protein intake -> ↑[urea] -> underestimation of GFR

o GFR can decrease by 50% before significant ↑[urea]

Creatinine

·   Metabolite of sarcoplasmic creatine kinase

·   Freely filtered, 10% secreted in health, not reabsorbed

·   Problems:

o GFR can decrease by 50% before significant ↑[creatinine]

o Sarcopaenia -> ↓SCr -> overestimation of GFR

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

Graph

 

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 tracer: freely filtered, not secreted, not reabsorbed, inert, non-toxic

·   Method: insert urine catheter, IV infusion until steady state, measure concentrations and urine volume

·   Gold standard

·   Problems

o Invasive

o Cumbersome

Creatinine

·   Method: 24 hour urine collection, measure concentrations and volume

·   Problems:

o Inconvenient

o Accuracy limited as above

o 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:

o Small dose of ionizing radiation

o Expensive

o Time-consuming

 

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