Role of Clinical Biochemistry in Renal Disease Flashcards
Key Analyses
U&E request gives serum concentrations of:
- Creatinine – Reference Interval higher in males than females
- Urea
- Sodium
- Potassium
- e-GFR calculated using serum creatinine concentration
Urine:
- Albumin:Creatinine ratio (ACR)
- Protein:Creatinine ratio (PCR)
Measurement of glomerular filtration
GFR = (U x V)/S = ml/min U = urine concentration V = urine flow rate S = serum concentration Requires: a substance that is filtered and then neither absorbed or secreted and 24 hr urine collection and a venous blood sample
Why creatinine
Derived from creatine in muscle
Serum concentrations relatively stable
24 h urine output is also stable day to day
No absorption and very little secretion
Simple to measure
But variation in serum concentrations and 24hr urine output by: Age, Sex – male > female, Lean body mass – ethnic origin, Effect of diet
Overcoming GFR variations with creatinine
GFR related to body SA – so standardise to a given body surface area
This allows: Comparison against a general standard; Staging of renal disease; Monitoring of change in renal filtration – individual or cohort; Chosen standard: 1.73m2
MDRD (modification of diet in renal disease)
This allows for variation by age, sex and ethnic origin
What does this data tell us about renal function
Failure of glucose metabolism leads to keto-acidosis – 3-OH butyrate
Acidosis – plasma 3-OH butyrate and bicarbonate – lead to increased serum concentrations of potassium and phosphate
Renal impairment – leads to potassium and phosphate accumulation and enhances the acidosis
Dehydration
Dehydration is very likely if the serum urea:creatinine ratio is greater than 100 mol/l
Mechanism is the passive reabsorption of urea in the nephron (esp at low flow rates)
Serum protein concentrations may also be elevated
Acute kidney injury
a rise in serum creatinine of 26 µmol/L or greater within 48h,
a 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days,
a fall in urine output to less than 0.5 mL/kg/hr for more than 6 hours for adults and more than 8 hours in children or young people,
a 25% or greater fall in eGFR in children and young people < 18y
Causes of AKI
Poor perfusion - loss of isotonic fluids Sepsis - any severe infection Toxins - drugs eg NSAIDS Obstruction - renal calculus, prostatic enlargement Parenchymal - glomerulonephritis
Causes of CKD
Hypertension
Diabetes – T2DM>T1DM
Hyperlipidaemia
Recurrent renal infections
Chronic glomerulonephritis – IgA nephritis
Systemic disease – systemic lupus, multiple myeloma
Genetic - polycystic kidney, Alport syndrome
Chronic obstruction – prostatic hypertrophy, renal calculi, reflux
Medication – NSAIDs, lithium
ACR - Albumin: Creatinine ratio
Proteinuria is a common finding in renal disease
A small amount of albumin is normally filtered but metabolised in the proximal tubule, but at larger loads due to glomerular damage more albumin escapes into urine
Measurement as a ratio with creatinine allows use of a random urine sample rather than a timed collection
Metabolic features of CKD
Stage 2: E elevated
serum urea
and creatinine concentrations:
some increase in serum parathyroid hormone (PTH) concentration
Stage 3: Calcium absorption decreased, Lipoprotein lipase decreased, Malnutrition, Anaemia – erythropoietin decreased
Stage 4: Elevated serum triglyceride concentration, Elevated serum phosphate concentration, Metabolic acidosis, Hyperkalaemia – elevated serum potassium
Stage 5: Marked elevation of serum creatinine and urea concentrations, Much more marked other features above
Role of lab in finding causes of renal disease
AKI - Plasma lactate – prognostic indicator - Infection – serum procalcitonin, CRP, WBC, blood culture - Autoimmune causes CKD - Serum and urine light chains – myeloma - Glycated Hb – diabetic control - Antibody tests – ANA, ANCA, anti-GBM - Biopsy - histology
Monitoring Renal Dialysis
Pre and post dialysis samples to: Show the effectiveness of dialysis, Indicate the required frequency of dialysis, Determine the need for other interventions:
- Diet, supplements, phosphate binders, calcimimetic drugs, lipid lowering agents, iron supplements/erythropoietin
Monitoring renal transplant patients
Serum creatinine – transplant function e-GFR ACR or PCR – potential damage to the transplanted kidney Measuring anti-rejection drugs o Ciclosporin o Tacrolimus, Sirolimus Checking for any tubular dysfunction Monitoring as for CKD 3
When an individual’s GFR is required
- Remember MDRD and CKD-Epi are linked to a standard body surface area.
- The real GFR of an individual is required
o To determine the dose of renally excreted drugs that are potentially toxic
o Monitoring dialysis and transplant patients - Here the Cockroft and Gault calculation is used
Cockroft and Gault calculation - GFR ml/min = ((140 – Age) x (Weight x Constant)) / Serum creatinine
- Constant = 1.23 in males and 1.04 in females
- This is an individual measurement and used in calculating drug dosage.
