chemical pathology of renal disease Flashcards
what are the functions of the kidney?
excretion and homeostatic functions:
- Excretion of metabolic waste products
- Fluid and electrolyte balance
- Acid base balance
- Removal of drugs and toxins
endocrine functions
- Renin angiotensin system
- Erythropoietin production
- Hydroxylation of vitamin D
what functions of the kidney are disturbed in AKI and CKD
The excretion and homeostasis function are disturbed early in AKI and late in CKD.
The endocrine functions are disturbed in CKD.
what are the stages of acute kidney injury?
stage 1
- creatinine rise of more than 26.5umol/l in 48 hours or 1.5-1.9 x from baseline
- urine output less than 0.5ml/kg/hr for 6-12 hours
stage 2
- creatinine rise 2-2.9 x from baseline
- urine output less than 0.5ml/kg/hr for more than 12 hours
stage 3
- creatinine rise more than 3 x from baseline or rise to more than 356.3umol/l or need for renal replacement regardless of serum creatinine
- urine output of less than 0.3ml/kg/hr for more than 24 hours or anuria for more than 12 hours
why do you need to catch AKI early?
It is important to catch acute kidney injury early (stage 1) because most of the causes are reversible but if they get to stage 2 there is a 33% mortality rate in hospital.
Hypovolemia and sepsis are the commonest causes of unrecognised AKI in hospitalised patients. These are treatable so it is important not to miss them.
what are the causes of AKI?
pre-renal causes (renal under perfusion of an otherwise normal kidney)
- Hypovolemia - Haemorrhage (trauma, GI bleed, ruptured aneurysm), dehydration
- Sepsis - causes vasodilation of the efferent arteriole
- Renal artery stenosis eg, caused by atherosclerosis
- Pump failure - heart
intrinsic renal failure
- Ischaemia
- Nephrotoxins - Drugs, Poisons, Myoglobin (rhabdomyolysis), Paraproteins (myeloma)
- Infection (pyelonephritis)
- Trauma
- Early stage of inflammatory causes of chronic kidney disease - Glomerulonephritis or Interstitial nephritis
Post-renal (obstruction to the renal tract)
- Stones
- Tumour
- Prostatic hypertrophy
- Beware of post obstructive diuresis - fluid replacement may be necessary
why do you need to differentiate between pre-renal and intrinsic causes of AKI?
the treatment is different
- pre-renal: fluid cures because it increases perfusion
- intrinsic: fluid kills because it will cause fluid overload
how do you differentiate between pre-renal and intrinsic causes of AKI?
good table summarising in notes
pre-renal causes
- low urine volume
- urine:plasma osmolality more than 2:1
- urine sodium concentration less than 15
- plasma sodium - high
- serum elevation of urea and creatinine - urea more than creatinine
intrinsic causes
- urine volume initially high
- urine:plasma osmolality less than 1:1
- urine sodium concentration more than 40
- plasma sodium - low
- serum elevation of urea and creatinine - urine = creatinine
urine sodium concentration will be the most specific test but is often forgotten about
what are the symptoms of AKI in the order of presentation?
Hyperkalemic metabolic acidosis
Malaise, nausea
Hyponatraemia - early sign of fluid retention
Fluid overload
what are the clinical and biochemical features of AKI?
Potentially life threatening biochemical changes due to disruption of homeostasis
- High potassium
- Acidosis
Clinical features will be nonspecific and present late. They result from failure to remove:
- Nitrogenous waste products (uraemia) - causes nausea, malaise, confusion but these are late features
- Fluid - retention of salt and water causing a reduced GFR which is usually hyponatremic (sodium loss +/- water retention)
- Electrolytes - potassium is life threatening once concentration is around 8mmol/L
- Acids - retention of acidic waste products of metabolism can be life threatening once plasma pH is less than 7
they will have no endocrine problems as they do not have long enough to develop
how is AKI managed?
step 1 - Distinguish between pre-renal, intrinsic and post renal causes
- Ask for senior review or refer to AKI team
- Identify underlying cause if possible
- stop/ avoid all offending drugs: ACE inhibitors, ARBs, NSAIDs, Other nephrotoxic medication
- Correct life threatening fluid, electrolyte and acid-base abnormalities
- Restore renal perfusion if prerenal by giving fluids (except in heart failure as it could cause fluid overload)
- Support renal function in life threatening intrinsic AKI (Haemofiltration, dialysis)
what is CKD?
chronic kidney disease - a gradual irreversible change in renal function
what are the commonest causes of CKD?
Diabetes mellitus Hypertension Polycystic kidney disease Recurrent pyelonephritis Recurrent reflux nephropathy Glomerulonephritis Interstitial nephritis Multisystem disease Drugs
how is CKD monitored?
Estimated GFR (eGFR) - MDRD formula calculation based on age, sex, plasma creatinine with a correction factor for ethnicity and paediatrics. This is universally quoted with U&E results - most wide used
GFR - requires 24 hour urine collection for protein - still used in paediatric practice
Creatinine clearance - calculation based on age, weight, plasma creatinine - old and not used as much anymore
Creatinine for end stage renal failure - in the early stages creatinine remains fairly normal so this is not effective. GFR is reduced by 50% before creatinine serum is increased. This is more useful in the late stage when eGFR is no longer useful (no longer decreasing).
Albumin: creatinine ratio
what are the stages of CKD?
stage 1 - eGFR more than 90mL/min
stage 2 - eGFR 60-90mL/min
stage 3a - eGFR 45-60mL/min, hypertension and increased CVD risk
stage 3b - eGFR 30-44mL/min, low calcium and secondary increased PTH
stage 4 - eGFR 15-30mL/min, anaemia, anorexia, high phosphate
stage 5 - eGFR less than 15mL/min, salt and water retention, acidosis, increased pottasium
stage 1-3a is monitored in GP and stage 3b onwards is monitored by a specialist
what biochemical changes occur in CKD stages 3-4?
- elevated creatinine
- reduced eGFR
- elevated ACR
- endocrine changes - Reduced 1 alpha hydroxylation of vitamin D which causes hypocalcemia and secondary hyperparathyroidism, reduced erythropoietin causing anemia
- Elevated cholesterol and triglyceride which causes increased risk of coronary heart disease
- impaired immune function
