Renal Disease Flashcards
What are the functions of the kidneys?
- Excretory - Excrete waste products and drugs
- Need to assess impairment, adjust doses, hold/stop nephrotoxins - Regulatory - fluid volume and composition, bp, pH
- Endocrine - Erythropoetin production, renin production, prostaglandin production
- Metabolism - Vitamin D metabolism
What routine tests are done to assess renal function?
- Plasma:
- Creatinine levels (by product of protein metabolism)
- Urea
- eGFR - Urine:
- Albumin : Creatinine ratio (ACR)
- Osmolarity - High particle concentration = High osmolarity
- Specific gravity - solute concentration, higher gravity = more solutes
Proteinuria/Microalbuminuria
- Haematuria - Blood in the urine
- Mid-stream urine - UTI
How is Creatinine Clearance calculated?
GFR (Glomerular filtration rate) = CrCl (creatinine clearance)
24-hour urine collection:
CrCl (ml/min) =
Urine Cr (umol/l) x Volume (ml) / Plasma Cr (umol) x Time
- Time delays and suspect accuracy of urine collection
What is the Cockcroft and Gault equation and what are the limitations of using it?
CrCl (ml/min) =
(140-age) x wt x F* / Plasma Cr (umol/l)
(F* = 1.23 males and 1.04 females)
Limitations:
- Assumes average population data
- Unsuitable for children and pregnancy
- Renal function must be stable
Traditionally “normal” Cr= 55-125umol/l and “normal” CrCl = 120ml/min
How is eGFR calculated?
eGFR is calculated either using:
- MDRD - 4-variable Modification of Diet in Renal Disease equation:
- Serum Cr, age, sex, ethnic origin
- Less accurate when >60ml/min/1.73m2 and overestimates for elderly patients - CKI-EPI - Chronic Kidney Disease Epidemiology Collaboration Formula
- Same limitations as CrCl
- eGFR can be calculated using and on-line calculator
What is Stage 1 (Normal) eGFR value?
> 90 ml/min/1.73m^2
What is Stage 2 (Mild impairment) eGFR value?
60-89 ml/min/1.73m^2
What is Stage 3A (Mild to Moderate) eGFR value?
45-59 ml/min/1.73m^2
What is Stage 3B (Moderate to Severe) eGFR value?
30-44 ml/min/1.73m^2
What is Stage 4 (Severe impairment) eGFR value?
15-29 ml/min/1.73m^2
What is Stage 5 (Established/End Stage) eGFR value?
<15
What is urea?
Urea is the breakdown product of protein metabolism
> 15mmol/l = Uraemia (range: 1-7 - 6.7 mmol/l)
Urea can also be raised by:
- Dehydration
- Muscle injury
- Infection
- Haemorrhage
- Excess protein intake
What is proteinuria / ACR?
The predictor of renal disease development and adverse outcomes.
Albumin - protein found in the blood, should NOT be in the urine
Albumin : Creatinine Ratio (ACR)
- Divide albumin (mg) by creatinine (g)
- >70mg/mmol in non-diabetics
- >2.5mg/mmol (Males) and >3.5 (Females) diabetics due to increased risk of developing renal disease.
What does ADME stand for and what does each factor indicate?
ABSORPTION
- Uraemia reduces drug absorption via: D&V, GI oedema
- Reduced calcium absorption (less vitamin D activation)
- Hyperphosphatemia - phosphate binder treatment reduces some drugs absorption
DISTRIBUTION
- Less protein binding (e.g. Phenytoin due to hypoalbuminemia & urea competition)
- Less tissue binding (e.g. Digoxin, increased concentrations)
METABOLISM
- Less vitamin D metabolism (less calcitriol production) = Less calcium absorption from gut and kidneys
- Less insulin metabolism
- Less elimination of pharmacologically active metabolites e.g. nor-pethidine
EXCRETION
- Less excretion
- Dose adjustments: Lower dose and/or increased dose interval
- NO adjustment to LOADING DOSES
What characteristics would the ideal drugs have in renal impairment?
- A wide therapeutic index
- Cleared by the liver
- Drugs not affected by fluid balance, protein binding or tissue binding
- Not nephrotoxic
Can be essential to use a nephrotoxic drug:
- Monitor renal function and toxicity
- In end-stage renal failure - no further renal function damage or decline. Monitor for toxic accumulation side effects.
What are the 3 classifications (cause types) of renal disease?
- Pre-renal
- Intrinsic
- Post-renal
What is pre-renal failure?
Reduced renal perfusion
For example:
- Hypovolaemia (burns, dehydration, haemorrhage)
- Reduced cardiac output - heart failure, MI
- Infection
- Liver disease - chronic, blood flow through the liver reduces, lack of blood supply ongoing to the kidney
- Medications causing impaired renal regulation - ACEIs, NSAIDs, Ciclosporin, Tacrolimus - Diuretics, Laxative abuse or D&V side effects
Explain the pharmacology of pre-renal failure.
What is intrinsic renal failure?
Damage to renal tissue.
Can be secondary from pre-renal failure and prolonged reduced perfusion.
For example:
- Glomerular
- Tubular
- Renovascular
- Infection
- Nephrotoxicity - NSAIDs, Contrast media
- Metabolic (e.g. Hypercalcaemia, hyperuricaemia)
- Congenital
Nephrotoxicity:
1. Hypersensitivity reactions (unpredictable)
- Glomerulonephritis - Phenytoin, Pencillins
- Interstitial damage - Penicillins, Cephalosporins, Allopurinol, Azathioprine
- Directly toxic (more predictable)
- Aminoglycosides, amphotericin, cyclosporin
- Can occur from a single dose
What is post-renal failure?
Obstruction to urinary flow
For Example:
- Stones blocking ureter (e.g. calcium oxalate)
- Structural (e.g. tumour, stricture)
- Nephrotoxicity (e.g. cytotoxic medication, high dose sulphonamides)
- Outside urinary tract (e.g. Ovarian tumour, prostatitis, BPH)
What does AKI stand for?
Acute kidney injury
What does CKD stand for?
Chronic kidney disease
What is acute kidney injury (AKI)?
Rapid decline (hours/days) in someone’s usual level of kidney function, which has an up to 90% mortality rate if not identified and treated.
How is acute kidney injury diagnosed?
- Serum creatinine rises by over 26.5umol/L within 48hrs
OR - Serum creatinine rises by >1.5 fold from their baseline value, which is known or presumed to have occurred within the last 7 days
OR - Urine output is < 0.5ml/kg/hr for 6 hours
