ChemPath: Assessment of Renal Function 2 Flashcards
Distinguish between AKI and CKD
AKI
* Abrupt decline in GFR
* Defined and staged using serum creatinine and urine output
* Potentially reversible
* Tx targetted to precise dx + reversal of disease
CKD
* Longstsanding decline in GFR
* Defined and graded using GFR
* Irreverisble
* Tx targeted to prevent complications and limit progression
Define AKI.
Rapid reduction in kidney function, leading to inability to maintain electrolyte, acid-base and fluid homeostasis.
It is a medical emergency
What are the three stages of AKI?
Stage 1: increase in serum creatinine by 1.5-1.9 times baseline
Stage 2: increase in serum creatinine by 2-2.9 times baseline
Stage 3: increase in serum creatinine by >3 times baseline
What are the biochemical definitions of AKI?
- Increase in serum creatinine > 26.5µmol/L within 48 hours
- Increase in serum creatinine > 1.5 times baseline within the previous 7 days
- Urine volume < 0.5 ml/kg/hr for 6 hours
3 broad causes of AKI
Pre-renal (commonest)
Renal
Post-renal
What is pre-renal AKI?
AKI caused by reduced renal perfusion (either by generalised reduction in tissue perfusion OR selective renal ischaemia) WITH NO structural abnormality
AKI occurs when normal adaptive mechanisms of kidneys fail. Note that kidneys are good at maintainig adequate profusion even as pressure lowers due to RAAS + activation of sympathic nervous sytem. However when pressure lowers so much these adaptive mechanisms no longer compensate ==> pre-renal AKI!
Describe the normal renal response to reduced circulating volume.
- Activation of central baroreceptors and renin-angiotensin system
- Release of vasopressin
- Activation of sympathetic system
- Results in vasoconstriction, increased cardiac output and renal sodium retention
List some causes of pre-renal AKI.
- True volume depletion (severe dehydration)
- Hypotension (e.g. blood loss = generalised low tissue perfusion)
- Oedematous state (e.g. heart failure where fluid is stuck in wrong place hence low perfusion)
- Selective renal ischaemia (e.g. renal artery stenosis)
- Drugs affecting renal blood flow
List how common drugs (ACEi/ARBs, NSAIDs, Diuretics, CalcineurinI) may cause a pre-renal AKI.
- ACE inhibitors - reduce efferent arteriolar dilatation
- NSAIDs - decreased afferent arteriolar constriction
- Calcineurin inhibitors - decrease afferent arteriolar constriction
- Diuretics - affect tubular funciton and decrease preload
Broad treatment regime for AKI
Responds well to restoration of normal circulating volume and perfusion to kidney.
What is a consequence of prolonged pre-renal insult?
Acute tubular necrosis (ATN)
= ischaemia results in renal necrosis and no longer responds to restoration of circulating volume
ATN is NOT a type of pre-renal AKI as it involves structural abnormalities (necrosis) in kidney.
What might be seen on urine microscopy in a patient with ATN?
Epithelial cell casts
List the possible sites of disease in renal AKI.
- Vascular (e.g. vasculitis)
- Glomerular (e.g. glomerulonephritis)
- Tubular (e.g. ATN)
- Interstitial (e.g. AIN)
List the 3 main pathophysiological pathways resulting in renal AKI
- Direct tubular injury
- Immune dysfunction causing renal impairment
- Infiltration of abnormal protein deposits
What can cause direct tubular injury in renal AKI?
- Ischaemia (MOST COMMON)
- Endoengous toxins (e.g. myoglobin in rhabdomyolisis, immunoglobulin in myeloma)
- Exogenous toxins (e.g. aminoglycosides, aciclovir)
Diseases that can cause renal AKI through immune dysfunction
Glomerulonephritis
Vasculitis (rash + AKI!)
Which diseases can cause renal AKI due to infiltration/abnormal protein deposition?
- Amyloidosis (associated with nephrotic syndrome)
- Lymphoma (plasma cell infiltration)
- Myeloma (plasma cell infiltration - note that myeloma can cause renal AKi in two diff ways)
What causes post-renal AKI?
Physical obstruction of urine flow
List some sites of urine obstruction.
- Intra-renal (stones in PUJ)
- Ureteric (stones - unilateral usually)
- Prostatic/urethral (bilateral changes seen)
- Blocked urinary catheter
Outline the pathophysiology of post-renal AKI.
- GFR is dependent on a hydraulic pressure gradient (high pressure in blood but low in filtrate)
- Obstruction results in increased tubular pressure (increased pressure in filtrate)
- This results in an immediated decline in GFR and rise in serum creatinine
What happens to GFR in cases where there is immediate removal of obstruction
GFR returns to normal with NO structural damange to kidneys
What are some consequences of prolonged renal obstruction?
- Glomerular ischaemia
- Tubular damage
- Long-term interstitial scarring
List the possible outcomes of AKI.
- Partial recovery of renal function
- Discharged with increased serum creatinine
- Discharged requiring chronic dialysis
- Death
Why do some AKIs solve and others do not and result in renal damage
Some patients have a pathological response to AKI characterised by imbalance between scarring and remodelling. Replacement of renal tissue by scar tissue therefore leads to chronic disease.
