AKI Flashcards
What are the diagnostic criteria for AKI stage I?
Creatinine increase ≥ 25 umol/L or 1.5-2x
UO 6 hrs less than 0.5 mL/kg/hr
Why is creatinine used as a surrogate measure of GFR?
Predominantly excreted by glomerular filtration (only very small amount secreted)
What is the gold standard substance for assessing renal clearance?
Inulin (only used in research setting)
What are the diagnostic criteria for AKI stage II?
Creatinine increase ≥200-300%
UO 12 hrs less than 0.5 mL/kg/hr
What are the diagnostic criteria for AKI stage III?
Creatinine increase ≥300% or creatinine ≥350umol/L after a rise of at least 50 umol/L or RRT
UO 24 hrs less than 0.3 mL/kg/hr, or anuria for 12 hrs
What is the main cause of community-acquired AKI?
Hypoperfusion
List 4 broad causes of intrinsic AKI. Which of these are common? Which are uncommon?
Tubular injury (common) Interstitial nephritis (common) Glomerular disease (uncommon) Vascular disease (uncommon)
What processes occur on a cellular level with ATN?
Ischaemic depletion of ATP, release of ROS and apoptosis
Cell desquamation, obstructive cast, and back-leak of tubular fluid (pathological absorption of metabolic wastes)
What is the main risk factor for AKI?
Background of CKD
List 7 risk factors for AKI
Elderly CKD HF Liver disease DM Vascular disease Nephrotoxic medications
Give 4 examples of acute insults which may tip a person with risk factors into AKI
STOP: Sepsis and hypoperfusion Toxicity Obstruction Parenchymal disease (e.g. acute GN, myeloma)
What are the 4 main physiological roles of the normal kidney?
Fluid balance
Acid-base balance
Excretion of wastes and solutes
Endocrine function
What hormones are produced by the kidneys?
Activation of 25-OH vitamin D to 1,25-OH (active) vitamin D
EPO
What disturbances to normal function occur with kidney disease?
Na+/H2O imbalance (failure of conservation or excretion)
Accumulation of acids
Accumulation of solutes and waste products
Abnormalities of endocrine function
What specific abnormalities of endocrine function may be expected in kidney disease?
Anaemia
Disordered bone metabolism
Of the 4 main disturbances resulting from acute kidney disease, which are the most easily measured and recognisable indicators of loss of function? Which of these may be immediately abnormal and which are time-dependent?
Na+/H2O imbalance (immediately abnormal)
Accumulation of acids (time-dependent)
Accumulation of solutes and waste products (time-dependent)
RRT
Renal replacement therapy (e.g. haemodialysis)
How is AKI defined in the research setting?
Acute elevation in serum creatinine
Oliguria
How is AKI defined pathophysiologically?
Any or all of: Decreased GFR Oliguria or polyuria Acidosis Hyperkalaemia Abnormal urinary contents (electrolyte abnormalities, glycuria) Inflammation leading to malnutrition or systemic injury Anaemia Disordered bone metabolism
What phenomena commonly cause a delay in AKI diagnosis?
Injury evolution time (delay between injury and drop in GFR)
Delayed actual rise (between drop in GFR and rise in sCr)
Why is it difficult to recognise an increased sCr?
Baseline, true and current sCr may be difficult to assess
Why is it difficult to assess the baseline sCr?
Interperson variability relating to the influence of age, sex and race on muscle mass
Why is it difficult to assess the true sCr?
Analytical variability (~10 uM)
Why may it be difficult to assess the current sCr?
Infrequent sampling
Give 3 examples of AKI biomarkers likely to be incorporated into the diagnostic criteria
RIFLE R (AKIN-1) RIFLE I (AKIN-2) RIFLE F (AKIN-3) (In order of increasing levels of damage)
Is community-acquired AKI usually a result of pre-renal, renal or post-renal causes? What is the 2nd most common cause?
Pre-renal in 70% of cases
2nd most common cause is obstruction
What proportion of cases of community-acquired AKI are superimposed on pre-existing CKD?
About half
What is the main cause of AKI in hospitalised patients? What is the predicted mortality in these cases?
ATN (renal cause) in >75% of cases
Mortality >70% in these cases
What is the adaptive physiological response to low renal perfusion? What is the effect of this response on urinary concentration capacity?
BP: maintained by SNS and RAAS
Na+/H2O: retention mediated by ADH and aldosterone
Urinary concentration capacity is intact, corresponds to stage I-II early AKI
What occurs with decompensation following prolonged renal hypoperfusion?
Excessive SNS and RAAS results in ischaemic injury
What medications may exacerbate the dysautoregulation that occurs in prolonged renal hypoperfusion?
NSAIDs
ACEIs
Give 2 causes of tubular injury in AKI (i.e. ATN)
Ischaemia/prolonged hypoperfusion
Toxins
Give 5 examples of toxins which may cause ATN
Hb/myoglobin
Aminoglycosides
Statins
Cisplatin
Ethylene glycol ("anti-freeze")Give 3 causes of interstitial nephritis
Drugs
Infection
Infiltration
Give 2 causes of glomerular damage
Inflammation (glomerulonephritis)
Thrombosis
Give 2 types of vascular disease which may cause intrinsic AKI
Inflammation (vasculitis)
Occlusion (thrombosis or embolism)
Is ATN reversible or irreversible?
Most often reversible
What occurs following initial hypoperfusion in ATN to worsen the disease process?
Reperfusion injury: restoration of blood flow to the damaged vascular network results in further inflammation
What are the 3 phases of ATN and what occurs in each?
Initiation: acute decrease in GFR to low or very low levels, increased sCr and urea
Maintenance: sustained reduction in GFR, continued increase in sCr and urea
Recovery: increased UO, gradual decrease in sCr and urea to pre-injury levels
How long does the recovery phase of ATN generally take? What is the risk here?
Up to 2-6 weeks
Risk of longterm chronic damage
What are the 5 main questions to ask when clinically evaluating AKI?
Is the impairment acute or chronic? Has obstruction been excluded? What is the pt's volume status? Is there evidence of other intrinsic renal disease apart from ATN? Has a major vascular occlusion occurred?
What clinical finding supports a diagnosis of AKI?
Oliguria
What 4 risk factors/clinical findings suggest CKD?
Pre-existing illness (e.g. DM, HTN, vascular disease)
Increased age
Previous sCr show gradual increase
Small, echogenic kidneys on US
What 3 clinical findings suggest obstruction causing AKI?
Complete anuria
Palpable bladder O/E
Bilateral hydronephrosis on renal US
What does volume depletion suggest about the cause of the pt’s AKI?
Implies a pre-renal cause (i.e. renal hypoperfusion)
What clinical measures can be used to assess a pt’s volume status?
JVP
Postural BP drop
Urinary concentration indices
Fluid challenge
What are 4 clinical features which might suggest a major vascular occlusion has occurred?
Hx of vascular disease
Renal asymmetry on US
Loin pain with macro haematuria
Complete anuria
Distinguish between pre-renal causes of AKI and ATN in terms of urine osmolarity, urine sodium, fraction excretion of sodium, fraction excretion of urea, urinary specific gravity, urine Cr/sCr ratio and urine sediment
Urine osmolarity: high vs low Urine sodium: low vs high Fraction excretion of sodium: low vs high Fraction excretion of urea: low vs high Specific gravity: >1020 vs
How is FENa+ calculated?
FENa+ = (urine Na+/plasma Na+) x (sCr/urine Cr) x 100
What are the 3 key area for investigation in the clinical assessment of AKI?
Volume status
Urine studies
Renal US
What clinical findings might suggest a diagnosis of thrombotic microangiopathy/HUS?
Thrombocytopaenia
Anaemia
What clinical findings might suggest a diagnosis of myeloma?
CRAB: hyperCalcaemia Renal failure Anaemia Bone lesions
List some clinical signs which may indicate rapidly progressive glomerulonephritis (RPGN)
Proteinuria Microscopic haematuria Fever, malaise Anaemia Nasopharyngeal disease (in Wegener's granulomatosis) Lung disease Arthralgias/arthropathy Rashes
Distinguish between proliferative and non-proliferative glomerular disease
Proliferative: haematuria, usually proteinuria (nephritic syndrome)
Non-proliferative: predominantly proteinuria, negligible haematuria (nephrotic syndrome)
Give 3 causes of proliferative glomerulonephritis
IgA nephropathy
Post-infectious GN
Vasculitides/RPGN
Give 3 causes of non-proliferative glomerulonephritis
Minimal change disease (MCD)
Focal segmental glomerulosclerosis (FSGS)
Membranous nephropathy
Give 6 examples of conditions which cause nephrotic sydrome
MCD FSGS Membranous nephropathy DM Endotheliosis Amyloidosis
Give 5 examples of conditions which cause nephritic syndrome
IgA nephropathy Post-infectious GN Vasculitides/RPGN Thin basement membrane Alport's syndrome
Give 2 examples of conditons causing endotheliosis
Pre-eclampsia
VEGF inhibitors
Give 5 examples of causes of vasculitides/RPGN
SLE
Anti-neutrophil cytoplasmic Ab (ANCA)-associated
Microscopic polyangitis (MPA)
Granulomatosis with polyangitis (Wegener’s granulomatosis, GPA)
Goodpastures disease (anti-GBM disease)
List 5 rarer causes of glomerular disease
Fabry disease c3 glomerulopathy (dense deposit disease) Fibrillary and immunotactoids Gns HIV nephropathies Warfarin-related nephropathy
What techniques are used to diagnose RPGN?
Morphology
Special stains (e.g. silver for GBM)
Immunohistochemistry/immunofluorescence
Sometimes requires EM
What is the drawback of using EM for diagnosis of RPGN?
Time delay
What background morbidities increase risk of AKI?
Age CKD HF Liver disease DM Vascular disease Background nephrotoxic medications
Give 4 examples of acute insults which may precipitate AKI
Sepsis and hypoperfusion
Toxicity
Obstruction
Parenchymal kidney disease
What is the most important preventative action against AKI?
Optimising ECV to prevent volume depletion
What are the 4 key steps for prevention of AKI?
Monitoring
Maintaining circulation
Minimising kidney insults (e.g. infection, drugs)
Managing the acute illness (e.g. sepsis, HF, liver failure)
What 7 investigations should be ordered where AKI is suspected?
Urine dipstick (+ RBC morphology if +ive for blood)
Urine PCR
Renal US
LFTs
CRP
CK
Platelet count (+/- blood film, haptoglobin, etc)
Define oliguric RF functionally and in terms of UO
UO < than that required to maintain solute balance (can’t excrete all solute taken in)
UO <400 mL/24 hr
Define anuric RF in terms of UO
<100 mL/24 hr
What 3 conditions may cause anuric RF?
Complete obstruction Major vascular catastrophy Severe ATN (more commonly)
What 2 conditions is oliguria more common with?
Obstruction
Pre-renal azotemia
What class of conditions typically cause non-oliguric RF? Give 3 examples
Intrinsic renal causes (e.g. nephrotoxic ATN, acute GN, AIN)
Does oliguric or non-oliguric RF have a higher mortality?
Oliguric (80% vs 25%)
List 4 important aspects of supportive AKI care
Discontinue offending agents and any nephrotoxins (e.g. NSAIDs, antihypertensives if low BP)
Review drug doses and adjust accordingly
Assess volume status to prevent overload
Nephrology input to gauge need for dialysis
Are loop diuretics indicated in AKI?
Controversial - main indication for use is volume overload
What are the 6 acute metabolic complications of AKI?
Volume overload Hyperkalaemia Metabolic acidosis Hypocalcaemia Infections Nutrition
How is volume overload as a result of AKI treated?
Salt and water restriction
Diuretics
Dialysis for refractory cases
How is hyperkalaemia as a result of AKI treated?
Restrict K+ intake IV glucose and insulin Kayexalate Calcium gluconate Acute dialysis
How is metabolic acidosis as a result of AKI treated?
HCO3- (if <7.2)
Dialysis
How is hypocalcaemia as a result of AKI treated?
Calcium carbonate
Calcium gluconate
What are the principles underlying peritoneal dialysis?
Visceral peritoneum acts as semi-permeable membrane
Solutes leave the blood via diffusion
Fluids move from blood to dialysate via osmotic and hydrostatic pressures
What is the osmotically active agent in peritoneal dialysis?
Glucose
How does haemodialysis work?
Blood circulates at high volume through dialyser composed of many capillary width tubes of semi-permeable membrane
Solutes move via osmosis
Fluids move via ultrafiltration (pressure gradient)
How are solutes moved in haemofiltration?
Via convection (swept through membrane by moving stream of ultrafiltrate; “solvent drag”)
List 8 causes of hyperkalaemia
Metabolic acidosis Insulin deficiency (i.e. DKA, HHS) Release from pathological cells Non-selective B-blockers Reduced RAAS release or effect Reduced renal blood flow Abnormal tubular function (AKD, CKD) Increased intake
How should mild hyperkalaemia be treated?
Identify and correct underlying cause
How should moderate hyperkalaemia be treated?
As for mild
Also identify ECG changes
How should severe hyperkalaemia be treated?
Stabilise myocardium
Insulin + dextrose
Correct acidosis if volume deplete
Define mild, moderate and severe hyperkalaemia
Mild: 5.5-5.9 mM
Moderate: 6.0-6.9 mM
Severe: >7.0 mM, or >6.5 mM and rapidly increasing or evidence of ECG changes
List 5 causes of hypokalaemia
Diarrhoea Diuretics Polyuria Hyperaldosteronism Shift into cells
What are 3 conditions which may cause K+ to shift into cells, producing a hypokalaemia?
Alkalosis
B-agonists
Insulin
