Acute Kidney Injury

Question 1

Define “acute kidney injury”

Answer 1

A decline in kidney function during 48hrs as demonstrated by increase in serum Cr of more than 50%, or the development of oligouria

Question 2

Outline the KDIGO AKI stages of severity

Answer 2

Stage 1:
Serum creatinine 1.5-1.9 times baseline OR >_ 0.3 mg/dL (>_26.5 umol/L) increase in serum creatinine.
Urine output <0.5 mL/kg/h for 6-12 hours.

Stage 2:
Serum creatinine 2.0-2.9 times baseline.
Urine output <0.5 mL/kg/h for >_12 hours.

Stage 3:
Serum creatinine 3 times baseline OR serum creatinine increased to >_ 4 mg/dL (>353.6 umol/L) OR initiation of renal replacement therapy OR in patients <18 years, decreased eGFR to <35mL/min per 1.73m^2.
Urine output <0.3 mL/kg/h for > 24 hours OR anuria for >_ 12 hours.

Question 3

In-hospital mortality associated with AKI in critically ill patients is…

Answer 3

50%

Question 4

Long-term effects of AKI (stats)

Answer 4

Only 50% of survivors are alive at 10 years.
Of survivors, 15% have clinically apparent residual CKD.
In survivors,
– 60% increased risk of heart failure
– 40% increased risk of MI
– 20% increased risk of stroke

Question 5

Organs affected by AKI

Answer 5

Brain
Lungs
Liver
GIT
Bone marrow
Heart

(through IL-6)

Question 6

Relationship between AKI and CKD

Answer 6

AKI is a risk factor for CKD
(Repeated episodes of AKI and the
severity of the AKI will ↑ ↑ ↑ the risk of CKD)

Question 7

Conventional markers (urea + creat) indicate AKI too late. What other markers may be linked to damage caused by AKI?

Answer 7

NGAL, KIM-1, IL-18

Question 8

4 common misconceptions regarding renal function

Answer 8

1) ‘normal creatinine = normal renal function’
2) Rising creatinine = worsening renal function
3) Improving creatinine in patients on dialysis
4) Use of eGFR in patients with AKI/non steady-state

Question 9

NB risk factors for AKI (5)

Answer 9

Sepsis
Critical illness
Circulatory shock
Trauma
Nephrotoxic drugs

Question 10

Causes of pre-renal failure (3)

Answer 10

(not filtering enough blood to make urine)
1) Prerenal azotemia (hypovolaemia/cardiac failure/hepatorenal syndrome)
2) Renal artery (occlusion/vasculitis)
3) Renal vein (thrombosis)

Question 11

Causes of intra-renal failure (5)

Answer 11

(not able to make urine)
1) Small-vessel disease (thrombotic microangiopathy/atheroembolism/ vasculitis)
2) Glomerular disease (anti-GBM disease/lupus nephritis/post-infectious glomerulonephritis/infective endocarditis/membranoproliferative glomerulonephritis/cryoglobulinaemia/IgA nephropathy/Henoch-Schonlein purpura)
3) Acute tubular necrosis (ischaemia/nephrotoxins/ rhabdomyolysis/radiocontrast agents)
4) Acute interstitial nephritis (drugs/infection/systemic disease)
5) Intratubular obstruction (casts/drugs/crystalluria)

Question 12

Causes of post-renal failure (1)

Answer 12

(blockage, urine can’t come out)
Post-renal obstruction (bladder outlet obstruction, tumours, renal calculi, papillary necrosis, retroperitoneal fibrosis)

Question 13

Definition of pre-renal failure

Answer 13

There is a impaired perfusion of the
kidney with blood. This results from either Hypotension, Hypovolaemia, Impaired cardiac pump efficiency, Vascular disease limiting renal blood flow, Drugs (NSAID and ACEi)

Question 14

How do NSAIDs affect the glomerulus?

Answer 14

Cause vasodilation of of afferent arteriole (promotes blood flow into glomerulus)

Question 15

How do ACE inhibitors affect the glomerulus?

Answer 15

Cause vasoconstriction of the efferent arteriole (help maintain intra-glomerular pressure)

Question 16

Signs that indicate fluid status (6)

Answer 16

Thirst
Dry mucous membranes (Tongue)
No sweat
Decreased skin turgor
Sunken eyes
Decreased urine output

Question 17

Biochemical evaluation of pre-renal failure

Answer 17

Urea:creatinine ratio: 20:1
Urine specific gravity: >1.020
Urine Osmolality (mOsm/kg): >500
Urinary Na+ : <20
Fractional excretion of Na+ : low

Question 18

Biochemical evaluation of intra-renal failure

Answer 18

Urea:creatinine ratio: may return to normal but creatine continues to rise
Urine specific gravity: <1.010
Urine Osmolality (mOsm/kg): <350
Urinary Na+ : >40
Fractional excretion of Na+ : higher

Question 19

Why is urine osmolality high in pre-renal failure?

Answer 19

Concentrated urine because you are reabsorbing water

Question 20

Why is urinary Na+ low in pre-renal failure?

Answer 20

Wherever sodium goes,
water goes. Urea gets reabsorbed
with sodium as well… so low sodium in urine pulling water and urea back into blood

Question 21

Why can the tubules not do their job in Intra-renal failure?

Answer 21

Hypoperfusion/blood loss causing hypoxia/ATP loss/metabolic changes –> epithelial cells die –> slough off into tubular lumen where the casts create an obstruction to urine

Question 22

Pathogenesis of Rhabdomyolysis

Answer 22

Muscle injury –> myoglobin breaks down.
Sequestration of fluid as it is pulled into injured muscle (activates RAAS and CNS) .
Dying muscle releases K+ , uric acid and PO4- (all elevated in blood).
Calcium moves into muscle causing hypocalcaemia.
Generation of oxygen free radicals.
Renal vasoconstriction due to increased ET, TXA2, TNF-alpha, F2IP, and decreased NO.
Filtered myoglobin causes damage to tubules – leaves behind pigmented granular myoglobin casts (obstruction distally if injury is proximal).

Question 23

What colour is urine in rhabdomyolysis, and why is this not caused by RBCs?

Answer 23

Coke-coloured/reddish-brown.
The colour is caused by myoglobinuria (Dipstix will show haematuria, but this is because of haemoglobin in the urine, not RBCs)

Question 24

Things to rule out in post-renal failure (4)

Answer 24

Enlarged prostate
Cervical CA
Percuss bladder – also blocked catheter
Ultrasound to rule out hydronephrosis (only 85% sensitive!)

Question 25

Most patients with renal obstruction are…

Answer 25

Not oliguric, and may be anuric depending on position of obstruction

Question 26

Generic management
of AKI

Answer 26

Prevention is the biggest cure! (Optimise Fluids or lack thereof, Monitor urine output, Pre-hydrate patients at risk of contrast nephropathy)
Maintain fluid/electrolyte/pH/solute balance within safe limits (K+ NB to manage!!!)
Correct acidosis
Find baseline creatinine and review for chronicity
Treat underlying cause of AKI

Question 27

How to restore effective circulation (4)

Answer 27

IV fluids and/or blood products (prefer crystalloids; beware of fluid overload)
Vasopressors
Consider reversible causes of pump failure
Check renal arteries and veins for obstruction

Question 28

List nephrotoxic drugs (7)

Answer 28

– Contrast
– Aminoglycosides
– Tenofovir
– Acyclovir
– Amphotericin B
– NSAIDS
– ACE inhibitors/angiotensin receptor blockers

Question 29

Principles of drug prescription in renal failure

Answer 29

1) Avoid nephrotoxic drugs
2) Adjust drugs doses (especially antibiotics)
3) Gentamycin and cyclosporin need therapeutic monitoring
Treat underlying conditions ASAP (e.g. sepsis)
4) IV contrasted is decided upon by the treating dr (pre-hydration NB, preferably use low/iso-osmolar contrast solutions) – Modern IV contrast not a threat if use is indicated

Question 30

Indications for dialysis

Answer 30

A: Resistant acidosis
E: K+ - > 6.5 mmol, resistant to treatment, symptomatic on ECG, rapidly rising, oliguria
I: Excessive input leading to fluid overload
O: Volume overload and oliguria (furosemide 240 mg)
U: Uraemia or rapidly rising urea and creatinine (Symptoms and signs include CNS depression / Encephalopathy, Pericarditis)

Need for concurrent toxin removal:
(e.g. Dialysable toxins: ethylene glycol, barbiturates, salicylates,
lithium, theophylline )

Question 31

According to the 2010: UK National Confidential Enquiry into Patient
Outcome and Death (NCEPOD), how many patients who died due to AKI received good care?

Answer 31

50%

Question 32

NCEPOD recommendations to prevent death due to AKI (5)

Answer 32

1) All emergency admissions should have risk assessment for AKI.
2) Everyone should have electrolytes checked.
3) All admissions should receive consultant review within 12 hrs.
4) Undergrad medical training should include recognition of acutely ill patient and prevention, diagnosis and management of AKI.
5) Postgrad training in all specialities should include training in detection, prevention and management of AKI.