Clinical Acute Kidney Injury

Question 1

What is AKI?

Answer 1

-Sudden and often reversible deterioration of kidney function.
-Develops over days or weeks and is often accompanied by a reduction in urine volume.
-Like most forms of kidney disease, it is often silent and only detected by a rise in serum creatinine or a fall in urine output. AKI can be graded based on severity:

1. Increase in serum creatinine by ≥26.5micromol/L within 48 hours or
2. Increase in serum creatinine to ≥1.5 times baseline within the prior seven days, or
3. Urine volume <0.5ml/kg/hr for ≥ six hours (e.g. <30ml/hr in a 60kg person)

Stage 1: creatinine 1-1.9x baseline
Stage 2: 2-2.9x baseline
Stage 3: >3x baseline need for dialysis

*eGFR misleadingly high in AKI as creatinine level on which this is based is rapidly increasing so assess renal function as rate of change in creatinine

Question 2

How do we recognise AKI?

Answer 2

-Typically asymptomatic
-Increase in serum creatinine
=>26 umol/L in <48 hours
=>50% rise from baseline within last 7 days
-OR urine volume <0.5ml/kg/hr for 6 hours (oliguria)
=<30mls/hr in 60kg person

-eGFR not accurate in AKI- rate of decline!

Question 3

Patients at higher risk of AKI

Answer 3

-Elderly (65+)
-History of AKI
-Hypovolaemia, oliguria

-Existing co-morbidities
=CKD (<60)
=HF
=DM
=Liver failure
=HTN
=Vascular disease
=Urological disease/ obstructive
=Neurological or cognitive impairment or disability, which may mean limited access to fluids because of reliance on a carer
=Emergency surgery, ie, risk of sepsis or hypovolaemia
=Intraperitoneal surgery

-Medications
=Anti-HTN
=ACEi/ARB
=NSAIDs
=Diuretics
=Use of iodinated contrast agents within the past week
=Vancomycin and gentamycin/ aminoglycoside abx

Question 4

Examination of AKI (general)

Answer 4

-Pre-renal
=Vomiting/ diarrhoea/ diuretics
=Assess charts- obs, fluid balance
=Hypovolaemia: cold peripheries, weak pulse, increase HR, low BP, reduced skin turgor, dry mucous membranes
=reduced urine output
pulmonary and peripheral oedema
arrhythmias (secondary to changes in potassium and acid-base balance)
features of uraemia (for example, pericarditis or encephalopathy)

-Renal
=Systemic symptoms (fever, sweats, weight loss, arthralgia)
=Severe hypertension/ sepsis, drugs, purpuric rash, joint swelling

-Post-renal
=Lower urinary tract symptoms (common men >60yrs)
=History of urothelial cancer, enlarged bladder
=For both, hypervolaemia: cold peripheries, increase HR, high BP, high JVP, 3rd HS, bibasal creps, sacral, peripheral oedema
=if patients have no identifiable cause for the deterioration or are at risk of urinary tract obstruction they should have a renal ultrasound within 24 hours of assessment.

Question 5

Investigations in AKI

Answer 5

-Urinalysis – heavy proteinuria suggests glomerular disease. Haematuria may suggest glomerulonephritis if taken before catheterisation and in the absence of urine infection.

-FBC: Hb often normal, raised WCC (or CRP) in infection/inflammation, low platelets= marrow problem or HUS
-Calcium (hyper)
-Creatinine kinase (rhab)
-Plasma protein electrophoresis, Bence Jones protein (myeloma, pancytopenia)
-ANCA, Anti-GBM, ANA (glomerulonephritis/ vasculitis)
-Blood, urine cultures (sepsis)

-Normal kidney size on USS (chronic kidney disease often causes small, fibrosed kidneys)
-Normal haemoglobin (the half-life of a red blood cell is 120 days, so if failed kidneys stop producing EPO it would take several weeks to become anaemic in the absence of other causes)
-Normal PTH (hyperparathyroidism secondary to renal failure takes some time to develop)
-Chest X-ray – check for evidence of pulmonary oedema

Question 6

Management in established AKI

Answer 6

1. Control intake of fluid.
   =If patient is euvolaemic on fluid balance, simply replace predicted losses (+ 500mls ‘insensible’ loss).
   =If hypovolaemic: optimise systemic haemodynamic status with fluid challenge and inotropes if necessary.
   =If fluid-overloaded, prescribe diuretics (loop diuretics at high dose will often be required); if the response is unsatisfactory, dialysis may be required.
2. Treat primary cause where possible
   = If K + >6.5 mmol/L and ECG changes of hyperkalaemia are present administer calcium gluconate to stabilise myocardium, lower potassium by oral potassium exchange resin to prevent potassium absorption, or administering intravenous glucose/insulin or sodium bicarbonate to move potassium intracellularly. These are holding measures until a definitive method of removing potassium is achieved (restoration of renal function or dialysis)
   =Discontinue potentially nephrotoxic drugs and reduce doses of therapeutic drugs according to level of renal function
   =Ensure adequate nutritional support
   =Consider proton pump inhibitors to reduce the risk of upper gastrointestinal bleeding
   =Screen for intercurrent infections and treat promptly if present
3. Indications for dialysis or other renal replacement therapy:
   =Pulmonary oedema
   =Severe hyperkalaemia despite medical management
   =Symptomatic, or very poor biochemical results, and unlikely to recover renal function quickly
   =Pericarditis

Question 7

Management after AKI

Answer 7

-A polyuric phase is typical in the recovery phase of ATN in previously healthy kidneys, but not universal.
=It is partly due to excess electrolyte and fluid retained during AKI, but also because the tubules are recovering from injury and are less responsive to angiotensin/aldosterone/ADH – hence they do not appropriately retain salt and water and the patient may become volume deplete unless they have sufficient intake.
=A rough rule is to ensure total fluid (oral and iv fluids if necessary) is equal to the urinary volume from the previous day, but this may be reduced if the fluid balance assessment suggests that the patient is overloaded.

=Recovery of kidney function after AKI may be incomplete. Poor outcomes are more likely with increasing severity of the insult, prolonged duration of AKI, older patients and those with pre-existing kidney disease

Question 8

Fluid prescribing in AKI (general)

Answer 8

-Haemodynamically unstable: fluid resuscitate with up to 2L (plasmalyte)
-Dehydrated/ postural hypotension: more cautious fluid challenge
-Euvolaemic: monitor and replace UO
-Hypervolaemic: restrict fluids +/- IV diuretics or dialysis

Bladder outlet obstruction: insert urinary catheter

Question 9

Indications for dialysis AKI

Answer 9

-Pulmonary oedema unresponsive to diuretics
-Hyperkalaemia unresponsive to treatment
-Severe uraemia (cardiac rub, encephalopathy)
-Severe acidosis

Peritoneal dialysis is now rarely used in AKI. Haemodialysis may need to be given frequently (e.g. daily) in order to prevent large fluid swings and give enough biochemical clearance. Slow continuous treatments (haemodialysis or haemofiltration) are often used in an intensive care or high dependency setting

Question 10

Overview of pre-renal failure

Answer 10

Reduced renal blood flow/ reduced perfusion to kidney caused by hypotension/ effective circulating volume depletion due to:

1. Severe dehydration – poor oral intake, excessive GI, skin or urinary losses
2. Shock (haemorrhagic, septic, cardiogenic: cardiac failure, vascular occlusion)
3. Fluid in third space (low oncotic pressure in hypoalbuminaemia, nephrotic syndrome often oedematous despite intravascular depletion)

-If not treated promptly can progress to ATN (renal occlusion)

Question 11

Pre-renal focussed history

Answer 11

-Poor oral fluid intake
-Vomiting/ diarrhoea
-Fever
-Diuretics (new start or changes in dose)
-Blood loss
-Cardiac history
-Negative fluid balance
-Fall in body weight
-Postural dizziness
-Thirst
-Reduced UO
-Rash, joint, weight loss
-Recent change in medication

Question 12

Pre-renal examination

Answer 12

-Cold, clammy peripheries/ warm potentially in sepsis (peripheral vasodilatation may be triggered by bacterial toxins and immune mediators)
-Delayed CRT
-Reduced skin turgor
-Weak, thready pulse
-Tachycardia
-Low BP (relative to normal, postural hypotension if >20/10 mmHg fall)
-JVP not visible lying down (if raised despite low BP consider cardiogenic shock)
-Dry mucous membranes
-Sunken orbits

Question 13

Pre-renal investigations

Answer 13

-High urine concentration (high specific gravity of urinalysis- 1.03)
-Urinary sodium <20 mmolL (unless on diuretics)
-High urea: creatinine ratio

Question 14

Pre-renal vs ATN

Answer 14

-Pre-renal (kidneys hold onto sodium to preserve volume)
=Urine sodium <20 mmolL (>40 ATN)
=Urine osmolality >500 (<350 ATN)
=Fractional sodium excretion <1% (>1% ATN)
=Good response to fluid challenge (poor ATN)
=Serum urea: creatinine ratio raised (Normal ATN)
=Fractional urea excretion <35%
=Urine: plasma osmolality >1.5 (<1.1 ATN)
=Urine: plasma urea >10:1 (<8:!)
=Normal bland sediment in urine (brown granular casts ATN)

Question 15

Pre-renal management

Answer 15

-If volume deplete and JVP not elevated (cardiogenic failure) then give IV fluids
-Rate of delivery depends on severity of haemodynamic disturbance- fluid resuscitate if hypotensive/ tachycardic
-In resus use high salt fluids; plasmalyte preferred to due to risk of hyperchloraemic acidosis with 0.9% sodium chloride
-Regular fluid balance assessment required- once euvolaemic, switch to a maintenance regime replacing UO

-In dehydration due to fluid intake high losses, fluid replacement may be sufficient
-Haemorrhage: identify and achieve homeostasis
-Sepsis: cultures, abx, inotropes
-Cardiac: ECG, ECHO, troponins
-Stop offending drugs- anti-hypertensives, diuretics SGLT2i, NSAIDs

PROGRESSION TO ATN

Question 16

Management in transient or non severe hypotension (pre-renal)

Answer 16

-Readily reversible by fluid resuscitation and treatment of the underlying cause.
-In pre-renal AKI, the tubules remain intact and will appropriately avidly retain salt and water to defend blood volume, hence it is characterised by low urinary sodium (typically <20mmol/L, due to activation of the renin-angiotensin-aldosterone system), and high urinary osmolality/specific gravity (due to secretion of ADH).

Question 17

Management in very severe/ prolonged hypotension (pre-renal)

Answer 17

-Acute tubular necrosis (ATN) may develop due to ischaemic injury, hence the need to treat low blood pressure promptly.
-Once the tubules are necrotic they no longer function appropriately to conserve salt and water and hence urinary sodium may be elevated (>40mmol/L) and the urine may be inappropriately dilute. Importantly, once ATN develops, fluid resuscitation alone is unlikely to improve kidney function as the kidneys will not recover until the tubules regenerate and this can take several days or weeks.
=Hence it is important to resuscitate aggressively and early, but once blood the clinical examination indicate the patient is euvolaemic, reduce fluid administration to match the urine output.

=Mortality of over 50% for ATN occurring in hospital is usual, not just because of renal failure directly, but also because of its association with failure of other organs and with severe sepsis.

Question 18

Intrinsic renal disease causes

Answer 18

-Renovascular disease
=Large (must be bilateral to cause AKI/ unilateral in single functioning kidney) and small vessel occlusion: main renal artery thrombosis/ embolus/ cholesterol emboli
=Microangiopathic haemolytic anaemia/ haemolytic uraemic syndrome
=Malignant hypertension
==Associated with high BP, no response to fluid resus, minimal/no blood or protein, typically present with volume expansion, oliguria/ anuria, mild if any loin pain

-Glomerular disease
=Typically present with volume expansion
=Nephrotic (proteinuria): Minimal change nephropathy, amyloid, anti-GBM, diabetic, rapidly progressive glomerulonephritis
=Nephritic (haematuria): post-streptococcal glomerulonephritis, small vessel vasculitis, Anti-GBM disease, SLE, IgA nephropathy, infectious endocarditis (blood and protein)
==Typically present with volume expansion

-Tubulointerstitial disease
=Volume expansion not prominent (nocturia)
=ATN (most common ICU)
=tubules may be damaged/blocked by toxins such as hypercalcaemia, myoglobin (rhabdomyolysis), light chains (myeloma), crystals (oxalate crystals in ethylene glycol poisoning) or drugs (aminoglycosides, cisplatin). Here the urinalysis typically shows no or minimal blood and protein
=Contrast nephropathy-Interstitial nephritis

-AIN
=idiosyncratic allergic response, typically to drugs such as antibiotics (penicillins, cephalosporins), NSAIDS or proton pump inhibitors. Here the urinalysis typically shows no or minimal blood and protein, but may be positive for leucocytes.

Question 19

Mechanisms activated in hypovolaemia and management

Answer 19

SNS
=Tachy, vasoconstriction
-Renin-angiotensin axis
=Vasoconstriction
=Aldosterone stimulates salt and water retention

MAINTAIN BP AND PERFUSION OF VITAL ORGANS

-500mL 0.9% sodium chloride or plasmalyte over 15 minutes, repeat if no repsonse, do not give more than 2000mL as resus

Question 20

Post renal causes of AKI

Answer 20

Obstruction to flow in the renal tract may cause renal failure, but it needs to affect both kidneys (unless you have a single functioning kidney)

-The presence of complete anuria suggests a mechanical problem, such as obstruction or arterial thrombosis. However, obstruction can paradoxically present with polyuria when the back pressure causes tubular injury and a concentrating defect, while the obstruction is intermittent allowing some urine to pass.

-At level of bladder outlet
=BPH
=Bladder/ cervical tumor (can invade lower ureters)
=External compression: retroperitoneal fibrosis or aortic lymphadenopathy
=Ureteric stricture
=Meatal stenosis/ phimosis
=Blocked catheter

-Less commonly in ureter
=Peri-ureteric obstruction
=Stones (bilateral urinary calculi)/ clot
=Cancer
=Retroperitoneal fibrosis

Question 21

Post renal failure history

Answer 21

-Male >60yrs
-Lower urinary tract symptoms – hesitancy, frequency, nocturia, poor flow, etc
-Macroscopic haematuria (if not catheterised): malignancy
-Complete anuria: obstruction
-Loin pain after high fluid intake
-History of urothelial/cervical cancer
-History of single functioning kidney

Question 22

Post renal failure clinical examination

Answer 22

Patients should be examined clinically to look for evidence of a distended bladder
=Palpate and percuss

Question 23

Post renal failure investigations

Answer 23

-Renal tract USS
=Dilated calyces
- Evidence of obstruction above the level of the bladder. Post-renal AKI is usually accompanied by hydronephrosis.

Question 24

Post-renal failure management

Answer 24

-Bladder outlet obstruction - catheterisation
-Ureteric obstruction - nephrostomy
-Renal stones: ureteric stent

-Beware post-obstructive diuresis due to:
=Retained salt and water during obstruction
=Tubular injury – nephrogenic diabetes insipidus
=If euvolaemic – monitor and replace urine output
=If hypervolaemic – allow controlled negative balance 1-1.5L/day

In post-renal AKI, the obstruction should be relieved as soon as possible. This may involve urinary catheterisation for bladder outflow obstruction, or relief of ureteric obstruction with ureteric stents or percutaneous nephrostomies.

Hydronephrosis:
-Insert urinary catheter (decompression of renal tract)
-Start alpha-blocker (Tamsulosin), TWOC
-May need transurethral prostatic resection (TURP) surgery if renal function does not recover

Question 25

Approach to patient with oliguria

Answer 25

1. Is the AKI real – check the U+E result is genuine or in those with anuria flush an indwelling catheter to check that it isn’t blocked
2. Could it be pre-renal failure?
   =Assess circulatory state – capillary refill, blood pressure (versus patient’s normal, erect and supine BP may be informative to identify early volume depletion), JVP, mucous membranes
   =Check fluid balance– input and output over last 48h or longer. Any extra losses – vomiting, diarrhoea, fever, drains, third spacing due to sepsis, abdominal surgery
   =Check meds: new start/increase dose in diuretics, on ACE/ARB or NSAID that may exacerbate AKI?
   =If suspicion of pre-renal, then fluid resuscitate and re-assess frequently. If no haemodynamic improvement once >2L challenge, seek advice of senior colleague
3. Could it be post-renal failure?
   =Is the bladder palpable?
   =Is person at high risk: male >60yrs, history of bladder/cervical cancer, visible haematuria, loin pain
   =Do a bladder scan or order ultrasound scan of renal tracts
4. Could there by an intrinsic renal problem?
   =If there is no evidence of pre-renal and post renal problems, think renal causes:

Toxic ATN: drugs (e.g. aminoglycosides, cisplatin), myoglobin (check for dark urine if muscle pain), hypercalcaemia, myeloma casts (especially if anaemia/pancytopenia )

Tubulointerstitial nephritis: often due to drugs – penicillins, cephalosporins, NSAIDs, proton pump inhibitors, etc – check if eosinophil count raised, leucocytes on urinalysis in the absence of infection (but little blood/protein)

Glomerulonephritis – typically blood and protein on urinalysis. Consider post-infectious glomerulonephritis (check ASOT, complement), vasculitis (check CRP, ANCA if systemic symptoms), anti-GBM disease (especially if haemoptysis), IgA/Henoch Schloein Purpura (often with skin rash), occasionally lupus nephritis (check ANA/dsDNA)

-Regardless of cause, optimise circulation (fluid replacement; ?inotropic agents), but carefully – over-hydrated patients with established AKI have significantly worse outcomes. Hence, resuscitate early, but perform regular fluid balance assessment and once euvolaemic simply replace urine output.

Question 26

Acute kidney injury in old age

Answer 26

-Physiological change : nephrons decline in number with age and average GFR falls progressively, so many older patients will have established CKD and less functional reserve. Small acute declines in renal function may therefore have a significant impact.
-Creatinine : as muscle mass falls with age, less creatinine is produced each day. Serum creatinine can therefore underestimate the severity of renal failure.
-Renal tubular function : declines with age, leading to loss of urinary concentrating ability.
-Drugs : increased drug prescription in older people (diuretics, ACE inhibitors and NSAIDs) may contribute to the risk of AKI.
-Causes : infection, renal vascular disease, prostatic obstruction, myeloma and severe cardiac dysfunction are common.
-Mortality : rises with age, primarily because of comorbid conditions.

Question 27

Referral criteria for nephrologist

Answer 27

-Renal transplant
-ITU patient with unknown cause of AKI
-Vasculitis/ glomerulonephritis/ tubulointerstitial nephritis/ myeloma
-AKI with no known cause
-Inadequate response to treatment
-Complications of AKI
-Stage 3 AKI
-CKD stage 4 or 5
-Qualify for renal replacement hyperkalaemia / metabolic acidosis/ complications of uraemia/ fluid overload (pulmonary oedema)