Renal - AKI

Question 1

what is AKI?

Answer 1

Acute decrease in GFR (hrs-days) due to abrupt loss of kidney function. Results in:

• disruption in ECF volume, electrolyte and acid-base homeostasis
• accumulation of nitrogenous waste products (urea and creatinine)

Question 2

what is the most common cause of AKI?

Answer 2

90% develop in community due a pre-renal state, typically hypotension associated with sepsis and/or fluid depletion (e.g. diarrhoea, vomiting).

Question 3

describe the causes of pre-renal AKI

Answer 3

Involve decreased renal perfusion.

1. True hypovolaemia
   - volume depletion, e.g. haemorrhage, severe vomiting/diarrhoea, burns, inappropriate diuresis
2. Relative hypovolaemia
   - septic, anaphylactic or neurogenic shock (systemic vasodilation… hypotension)
   - oedematous states: HF (causing decreased CO), cirrhosis, nephrotic syndrome
   - renal hypoperfusion: drugs (NSAIDs, ACEi), renal artery stenosis or occlusion, hepatorenal syndrome

Question 4

how do NSAIDs and ACEi affect renal perfusion?

Answer 4

Override intrinsic autoregulatory mechanisms:

• NSAIDs: prevent vasodilatory effects of prostaglandins on afferent arteriole
• ACEi/ARBs: prevent vasoconstrictive effect of AngII on efferent arteriole

Question 5

describe the causes of post-renal AKI

Answer 5

Significant urinary obstruction causes increased intraluminal pressure… urine backup into kidneys… hydronephrosis. If affects both kidneys (or single functioning kidney), causes decreased GFR.

Causes of obstruction include:

1. within lumen (kidney, ureter, bladder, urethra): calculi, blood clots, tumours
2. within wall (usually causes CKD rather than AKI): congenital megaureter, post-TB stricture
3. pressure from outside: BPH, abdo. tumour

Question 6

name the 3 types of causes of intrarenal AKI

Answer 6

1. Acute tubular necrosis (ATN) = damage to renal tubule epithelium
2. Acute interstitial nephritis = damage to interstitum
3. Glomerular disease

Question 7

describe the causes of ATN

Answer 7

a) pre-renal AKI: decreased perfusion to kidney results in epithelial cell ischaemia… depletion of cellular ATP, cell damage and loss of function
b) nephrotoxins: myoglobin (in rhabdomyolysis), uric acid (e.g. released in tumour lysis syndrome), bilirubin, endotoxins, radiocontrast dye, aminoglycoside antibiotics (e.g. gentamicin)
c) sepsis

Question 8

describe the causes of acute interstitial nephritis

Answer 8

a) toxin-induced, e.g. NSAIDs, penicillins, diuretics: infiltration of immune cells… inflammation (type I or IV hypersensitivity)… renal papillary necrosis
b) can also be caused by infection or autoimmune disease

Question 9

explain how types of glomerular disease can result in AKI

Answer 9

1. glomerulonephritis (e.g. causes of nephritic syndrome): Ag-Ab complexes deposited in glomerulus… activation of complement system… inflammation and podocyte damage
2. thrombotic microangiopathy (haemolytic-uraemic syndrome, malignant HTN, scleroderma, pre-eclampsia): endothelial cell damage results in platelet thrombi formation and RBC destruction (microangiopathic haemolytic anaemia)… glomerular damage

Question 10

what parts of the nephron are especially prone to ischaemic injury?

Answer 10

Terminal PCT and TAL:

i. located in renal medulla - relatively low O2 saturation at baseline due to geometry of vasa recta
ii. highly metabolically active - substantial amounts of reabsorption and secretion occur

Question 11

describe the clinical consequences of AKI

Answer 11

Occur as a result of decreased GFR:

1. decreased urine production (oliguria) and thus build-up of metabolites such as creatinine and BUN (azotaemia)
2. acid-base disturbance: metabolic acidosis due to decreased excretion of metabolic acids and decreased HCO3- reabsorption and regeneration in PCT
3. electrolyte disturbances: hypernatraemia due to reduced Na+ excretion, hyperkalaemia due to decreased K+ excretion (risk of arrhythmias) and hyperphosphataemia due to insufficient excretion of plasma phosphate +/- phosphate release from damaged cells

Question 12

what is uraemia?

Answer 12

Endpoint of loss of kidney function as a result of decreased GFR. Includes consequences of AKI plus:

1. secondary HTN (increased ECF volume)
2. secondary hyperparathyroidism
3. normocytic anaemia (decreased EPO synthesis)
4. acute pericarditis (unclear pathogenesis)

Question 13

describe the common symptoms of AKI

Answer 13

1. oliguria or anuria
2. nausea and vomiting
3. confusion

Question 14

describe the common signs of AKI

Answer 14

1. dehydration
2. HTN (unless hypotension/pre-renal AKI is cause)
3. fluid overload with raised JVP, pulmonary oedema and peripheral oedema
4. pericardial rub

Question 15

what would blood Uand Es show in AKI

Answer 15

raised urea, creatinine, Na+, K+ and Pi

Question 16

how would you distinguish between pre-renal AKI and ATN

Answer 16

Urine biochemistry:
1. in pre-renal AKI, kidney is functional so high osmolality (>500 mOsm/kg) and specific gravity (>1.018) as trying to excrete waste products in as little solute as possible (as state of hypovolaemia). Low urinary Na+ (<10 mmol/L) as trying to retain water.

2. in ATN, damaged kidney cells unable to concentrate urine, causing low osmolality (<250 mOsm/kg) and specific gravity (<1.012), and unable to reabsorb Na+, so high urinary Na+ (>20 mmol/L).

Question 17

how would you manage a pt with AKI

Answer 17

1. Treat underlying cause:
   
   • pre-renal: fluid resuscitation or treatment of organ failure to restore renal perfusion
   • renal: restrict dietary Na+ and water (<1L/day) if volume overload, may require immunosuppression
   • post-renal: urological intervention
2. Supportive management, e.g. stop nephrotoxic drugs where possible
3. Monitoring:
   
   • measure UO
   • monitor creatinine, Na+, K+, Ca+, Pi and glucose (insulin therapy may be required in critically ill pts to avoid hyperglycaemia, and has effect of driving K+ into cells)

Question 18

in which cases is RRT considered?

Answer 18

If any of the following not responding to medical management:

• hyperkalaemia (>6.5 mmol/L)
• pulmonary oedema
• severe metabolic acidosis (pH <7.2) due to kidney failure
• progressive renal failure (creatinine >300 umol/L and/or rise in creatinine >100 umol/L/day)
• uraemic complications (pericarditis or uraemic encephalopathy)
• CKD stage 4 or 5
• renal transplant
• pt suspected of intrinsic renal disease (vasculitis, primary glomerulonephritis, interstitial nephritis)