Acute Kidney injury

Question 1

What is AKI?

Answer 1

Clinical syndrome – abrupt decline in actual GFR (days to weeks), upset of ECF volume, electrolyte and acid/base homeostasis, accumulation of nitrogenous waste products.

Question 2

What is AKI clinically defined as?

Answer 2

Increase in serum creatinine by >/= 26.5 micro mol within 48 hours
Increase in serum creatinine by >/= 1.5 times baseline within 7 days
Urine volume < 0.5ml/kg/h for 6 hours (may not be used anymore)

Question 3

What are the stages of AKI

Answer 3

There are 3 stages each with worsening serum creatinine levels and urine output.

Question 4

What is the aetiology of AKI?

Answer 4

Incidence difficult to assess – variable criteria, In UK approximately 200p/mp/yr and ¼ of these need RRT (renal replacement therapy). 5% of hospitalised patients. 25-30% of patients admitted to intensive care unit. AKI is a medical emergency.

Question 5

What causes AKI?

Answer 5

• Pre-renal failure – blood supply compromised i.e. volume depletion, heart failure and cirrhosis etc.
• Intrinsic renal failure – renal artery/vein occlusion or renal parenchymal diseases – intrarenal vascular glomerulonephritis, ischaemic ATN (acute tubular necrosis), Toxic ATN, interstitial disease and intrarenal obstruction.
• Post renal failure (obstruction) – anything that compresses the urinary tract outside of the kidney

Question 6

What is the most common cause of AKI?

Answer 6

85% due to prerenal causes or ATN (acute tubular necrosis) in the UK. Worldwide can be due to infective causes such as haemorrhagic fevers, diarrhoea or obstetric.

Question 7

What is Pre renal AKI?

Answer 7

Acute GFR reduced due to decreased renal blood flow. No cell damage so kidneys work hard to restore blood flow. Avid reabsorption of salt and water (aldosterone and ADH release). Responds to fluid resuscitation i.e. IV fluids.

Question 8

How does autoregulation change with constant deviation from normal BP and what consequences does this have for Pre renal AKI?

Answer 8

Note kidney autoregulation takes place across a certain range of blood pressure. In hypertensive patients (the elderly) the kidneys adapt and have a new range of pressures they can autoregulate between. So if someone who is normally hypertensive resents with a BP of 110/70 then this could be a problem.

Question 9

Whats the difference between afferent and efferent arterioles/nerves

Answer 9

Afferent is away from the heart/stimulus (for nerves).

Question 10

When does autoregulation fail in normal patients?

Answer 10

When autoregulation responses are overwhelmed AKI occurs. Maximal dilation of arterioles at MAP of 80mmHg (higher if normally hypertensive) and below this GFR falls rapidly.

Question 11

What extrinsic modulators can exacerbate pre renal AKI?

Answer 11

Extrinsic modulators of renal haemodynamics include NSAIDs and ACE inhibitors or angiotensin receptor blockers. NSAIDs inhibits prostaglandins so the afferent arterioles cannot dilate as much whilst ACE inhibitors and ARBs block Ang II meaning you can’t constrict the efferent arteriole. Both of these drugs prevent your from responding to changes in GFR and so patients on them can rapidly progress into AKI

Question 12

How can we categorise different causes of pre renal failures?

Answer 12

Reduced effect extracellular fluid volume:
-Hypovolaemia
-Cardiac failure
Systemic vasodildation e.g. sepsis

Impaired renal autoregulation

• preglomerular vasoconstriction
• post glomerular vasodilation

Question 13

What is ATN?

Answer 13

Note you do not actually get tubular necrosis just cell damage that cannot be immediately reversed, these cells fall of the basement membrane, block tubes and stop working i.e. they cannot reabsorb salt and water efficiently or expel excess water and so aggressive fluid resuscitation risk fluid overload. This is particularly harmful in patients with heart failure.

Question 14

What causes ATN?

Answer 14

Can be caused by: ischaemia, nephrotoxins or sepsis.

Question 15

Why are tubular cells so sensitive to hypoxia?

Answer 15

The blood flow to the tubular parts of the nephron comes from the efferent arterioles of the corresponding glomerulus. As this blood moves, along it becomes increasingly deoxygenated. This means there is a gradient of PO2 of oxygen through the cortex into the medulla. At the cortex-medullary boundary, the cells are at the cusp of hypoxia.

Question 16

How is the urine biochemistry different between pre renal failure and ATN?

Answer 16

Pre-renal you will see an extremely concentrated urine as the kidney desperately try to carry on its job with a very small volume of urine and sodium levels will be normal. In ATN osmolality of urine will be low and urine sodium will be high as the cells begin to stop working.

Question 17

What is nephrotoxic ATN?

Answer 17

Nephrotoxins damage the epithelial cells lining the tubules and cause cell death and shedding into the lumen. Nephrotoxins can be endogenous or exogenous (drugs). ATN is much more common with reduced perfusion and a nephrotoxin. Generally, it is safe to treat all drugs as a nephrotoxin until proven otherwise.

Question 18

What exogenous and endogenous nephrotoxins are there?

Answer 18

Endogenous Nephrotoxins: Myoglobin (rhabdomyolysis, injury and overdosing/elderly falling), urate and bilirubin.

Exogenous Nephrotoxins: Endotoxins, X-ray contract, drugs and other poisons such as weed killers and antifreeze.

Question 19

How does glomerular and arteriolar disease cause intrinsic renal failure?

Answer 19

Examples are IgA nephropathy and vasculitis, other causes include haemolytic uraemic syndromes, malignant hypertension or pre-eclampsia, all of these lead to endothelial damage, platelet thrombi, partial obstruction of small arteries and destruction of RBCs by microangiopathic haemolytic anaemia (RBC can’t fit down capillaries and arterioles causing them to lyse).

Question 20

What is acute tubulo-interstital nephritis?

Answer 20

This is can be caused by infection such as acute pyelonephritis or it can be toxin induced (most commonly – antibiotics, NSAID’s and proton pump inhibitors). Glomerulus looks normal but the interstitium has a massive inflammatory invasion causing the tubules to becomes really spread out.

Question 21

How common is post renal failure?

Answer 21

This accounts for 5-10% of acute kidney injury cases and is most common in the elderly.

Question 22

How does post renal failure occur?

Answer 22

To causes AKI obstruction must block both kidneys or a single functioning kidney. Obstruction with continuous urine production causes a rise in intraluminal pressure, dilation of renal pelvis (hydronephrosis) and decrease in renal function. This obstruction can be in 3 places:

1. Within the lumen – stones, blood clot and tumours
2. Within the wall – congenital megaureter and strictures post TB
3. Pressure from outside – enlarged prostate, tumour, aortic aneurysm, ligation of ureter

Question 23

What is important to consider the the management of AKI?

Answer 23

Main priority is the kidneys control of blood volume and BP. Other functions of the kidney which we must consider is pH. Electrolytes, Osmolarity, excretion, metabolism and endocrine (1-alpha calcidol, renin and erythropoietin). The endocrine functions are much more important in CKD, less so in AKI.

Question 24

What are the ECG changes that occur with increasing hyperkalaemia?

Answer 24

Hyperkaliaemic ECG changes in order of appearance: Tall T waves, Small or absent P waves, increased P-R internal, wide QRS complex, sine wave patter and then asystole.

Question 25

What’s the first thing we must assess and deal with?

Answer 25

Must first assess fluid volume – are they volume depleted (cool peripheries, increased pulse, Low BP/postural hypotension, Low JVP, reduced skin turgor) or are they volume overload (gallop rhythm, raised JVP, pulmonary oedema or peripheral oedema).

Question 26

What are the 4 most common causes of AKI in order?

Answer 26

STOP – Sepsis, Toxins, Obstruction and Parenchymal. Reason for AKI in order of most common to least common.

Question 27

What does oliguria mean and what should you do if completely anuric?

Answer 27

Note if completely anuric check for obstruction especially in catheters. Oliguria = low urine volume

Question 28

What investigations should be done?

Answer 28

Urinalysis – dipstick for detection of blood, protein, leukocytes, if large amounts of either of these then intrinsic renal disease is likely. Note blood always present with catheters. Culture urine if dipstick is positive.

Imaging – ultrasound scan to check for obstructive if you are yet to find out the cause. CXR to check for fluid overload +/- infection. Kidney biopsy only obtained when pre and post renal AKI is ruled out and a confidence diagnosis of ATN can’t be made.

Question 29

How do we manage established AKI?

Answer 29

• Volume overload - restrict dietary Na and restrict water
• Hyperkalaemia - calcium gluconate, restrict dietary K, stop K sparing diuretics, ACEi and ARB, exchange resin, dextrose and insulin, sodium bicarbonate (only if bicarbonate is low) B2 agonists.
• Acidosis - sodium bicarbonate

Question 30

When should dialysis be started?

Answer 30

High K+ or acidotic that can’t be treated medically, if fluid overload, uraemic (pericarditis, reduced consciousness and intractable Nausea and vomiting) and if there is presence of dialyzable nephrotoxin such as aspirin overdose.

Question 31

What is the recovery rate and mortality of AKI?

Answer 31

Recovery within 2-3 weeks if uncomplicated. Mortality 30-80%, hospital acquired 30-50% and ITU – 70-80%.

After Aki you are at increased risk of death for a year after and increased risk of developing long term CKD.