February 15,

ACUTE KIDNRY INJUREY

2017

Definition:
Sudden ,rapid and reversible reduction in renal functions developing over hours, days (rarely
weeks); resulting in decreased Cr clearance and elevation of serum urea and creatinine and
failure in maintaining fluid, electrolyte and acid base homeostasis. The Kidney Diseases
Improving Global Outcomes guidelines KDIGO suggest the following as criteria for the diagnosis
of AKI:
Rise in Cr more than 1.5x above the baseline
Rise in Cr more than 26 mol/l in 48 hours
Urine output less than 0.5 mL/Kg/h for more than 6 consecutive hours
AKI staging: KDIGO categorizes patients based on their serum Cr and urine output as biomarkers
of kidney functions.
KDIGO stage Serum Cr Urine output GFR (step up RIFLE (Risk/
criteria mentions it) Injury/Failure/Loss/END
STAGE RENAL DISEASE)
Stage 1 1.5-1.9 fold rise 0.5 ml/kg/h for 25% = risk
above the 6 -12 consecutive reduction in
baseline hours GFR
Stage 2 2-2.9 fold rise 0.5mL/Kg/h for 50% = Injury
above the 12 hrs reduction in
baseline GFR
Stage 3 3 fold rise or 0.3 ml/Kg/h for 75% = failure
absolute serum 24 hours or reduction in
Cr 345 mol/L absolute anuria GFR
with an acute for 12 hours
rise of
44mol/L or
Loss = persistent AKI or
complete loss of kidney
function requiring
dialysis for 4 weeks
End- stage renal disease:
complete loss of renal
function and need for
renal replacement
therapy for more than 3
months.
Risk factors for developing AKI:
1. Diabetes 2. Age 75 years 3. Chronic kidney disease 4. Chronic liver disease
5. Cardiac failure 6. Peripheral vascular disease 7. Drugs 8. Sepsis
9. Poor fluid intake/ increased losses 10. H/O urinary symptoms
General characteristics:
1. Weight gain and edema are the most common findings in AKI due to positive sodium and
water balance.
2. It is characterized by azotemia ( elevated BUN and Cr)
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2017

Other causes of high BUN: dietary protein intake / GI and soft tissue bleeding/ catabolic
drugs (steroids)
Other causes of high Cr: increased muscle breakdown / drugs. Remember that the baseline
proportionately varies with muscle mass.
Prognosis:
Depends on the severity and presence of other comorbidities.
More than 80% recover renal function completely
The older the patient and the more severe the insult, the lower the likelihood of
complete recovery.
The most common cause of death in these patients is infections (75% of all deaths)
followed by cardio-respiratory complications.
Diagnosis/ investigations:
Diagnosis of AKI is usually made by finding elevated BUN and Cr levels. Patients are usually
asymptomatic.
1. Blood tests:
1.Urinalysis Elevation in BUN and creatinine levels
Electrolytes (K, Ca++, PO4-3), albumin levels, CBC with differential
2. urine chemistry
2. Urinalysis:
Serum electrolytes (K,Na, Dipstick positive for protein + 3, +4 suggests intrinsic renal failure due to glomerular
BUN, Cr) CBC insult.
3. bladder Microscopic examination of urine sediment:
catheterization Hyaline casts are devoid of content, seen in pre-renal failure.
(diagnostic and
therapeutic ) RBC casts indicate glomerular disease Urine osmolality:

WBC casts indicate renal parenchymal inflammation -it is a measure of urine concentration.
4. renal US
Fatty casts indicate nephrotic syndrome. The higher the osmolality, the more
3. Urine chemistry: distinguishes different forms of AKI. concentrated the urine

in evalua ting eleva ted Cr,
fi rs t determine the Cr
baseline in the pa tient if
possible to determine
whether the pa tient has
AKI, CKD or chroni c renal
insuffi ciency/ failure wi th
superi mposed AKI ( a cute
on chronic renal failure)
Urine Na, Cr and osmolality. ( urine Na depends on dietary intake). - Dehydration in a healthy person
FENa+: collect urine and plasma electrolytes simultaneously
[ (UNa/ PNa)/ ( UCr/PCr) ]
Values below 1% suggest pre-renal AKI
Values above 2% to 3% suggests ATN
FENa is most useful if oliguria is present.
Renal failure index 5 (UNa/ ( UCr/PCr) ) *100
Values below 1% suggest pre-renal AKI
Values above 1% suggest ATN
results in incaresed urine
concentration(osmolality):
dehydration reduces intravascular
volume which triggers ADH release
which stimulates water reabsorption
and leads to more concentrated urine.
- in ATN, the tubular cells are damaged
and cant reabsorb water and sodium,
so the urine cant be concentrated
which leads to low urine osmolality.

4. Urine culture and sensitivity if infection is suspected

5. Renal US to evaluate for kidney size and exclude urinary tract obstruction evident by
bilateral hydronephrosis or hydro-ureter.
It is ordered for most patients with AKI unless the cause is
Obvious and not postrenal.
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ACUTE KIDNRY INJUREY
2017

In evaluating a 6. CT scan of abdomen and pelvis- usually done if renal US shows an abnormality such as
patient with AKI,
hydronephrosis.
first exclude pre-
renal and post- 7. Renal biopsy if GN or allergic interstitial nephritis is suspected.
renal causes and 8. Renal arteriography: to evaluate for renal artery occlusion; only performed if specific
then investigate
intrinsic renal
therapy will make a difference.
causes.
Urinanalysis Findings in Renal Failure
Cause Urine sediment Protein Blood
Pre-renal Benign sediment- few Negative Negative
hyaline casts
Intra-renal
ATN Muddy brown casts, renal Trace Negative
tubular cells/casts,
granular casts
Acute Dysmorphic RBCs, RBCs 4+ 3+
GN with casts, WBCs with
casts, fatty casts
Acute RBCs, WBCs, WBCs with 1+ 2+
interstitial casts, eosinophils
nephritis
Postrenal Benign, +/- RBCs, WBCs Negative Negative

Causes :
Pre- renal AKI/ pre-renal azotemia:
This is the most common cause if AKI; 40-70% of the cases
Patho-physiology:
Causes of pre-
It is caused by hypoperfusion of kidneys lowering the GFR which leads to decreased
renal AKI:
clearance of metabolites (BUN, Cr, uremic toxins). It is potentially reversible with
1.Volume restoration of renal blood flow. The renal parenchyma is undamaged, and therefore the
loss/sequestration tubular function (concentrating ability of the kidney) is preserved and kidneys respond
appropriately conserving as much sodium and water as possible. If hypoperfusion
2. Low CO persists, ischemia can result causing acute tubular necrosis and intrinsic AKI.
Cause:
Hypotension
1. Hypovolemia/ reduction in circulating blood volume:
Hemorrhage
Dehydration
GI loss ( diarrhea/ vomiting)
Renal loss: Excessive diuretic use/ diabetic ketoacidosis ?
Loss of plasma in burns and crushing injuries.
Skin loss: sweating
2. Hypotension: (systolic BP less than 90 mmHg)
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2017

Septicemia causing peripheral vasodilation

Excessive anti-hypertesnive medications
Bleeding/ dehydration
3. Disease of major renal blood vessels; renal arterial obstruction (thrombosis) causing
hypoperfused kidneys despite elevated BP ( other causes include aortic aneurysm
and thrombosis of the aorta)
4. Severe liver failure; hepato-renal syndrome
5. CHF and cardiogenic shock; reduction of CO

Precipitant factors in pre-renal AKI:

1. NSAIDS : constrict afferent arterioles
2. ACEi: cause efferent arteriole vasodilation
3. Cyclosporine

Clinical features:
Signs of volume depletion:
1. Dry mucous membranes
2. Hypotension
3. Tachycardia
4. Decreased tissue turgor
5. Oliguria/ anuria

Laboratory findings:
1. Oliguria: always found in pre-renal AKI to preserve volume
2. Increased serum BUN: Cr ratio 20:1 because kidneys can reabsorb urea.
3. Decreased serum Na+ 20 mEq/L with fractional excretion of Na+ FENa+ 1%
because Na+ is avidly reabsorbed
4. Increased urine osmolality 500 mOsm/Kg H2O; because the kidneys are able
to reabsorb water.
5. Increased urine-plasma Cr ratio 40:1 because much of the filtrate is
reabsorbed BUT NOT the creatinine.
6. Bland/ scant urine sediment
Management:
1. General management:
Assess the volume status:
Volume depleted: low urine output/ non-visible JVP/ poor tissue
turgor/ low BP
Fluid overloaded: high BP/high JVP/lung crepitations/ peripheral
edema/ gallop rhythm on auscultation
Correct fluid imbalance:
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IV fluid for volume depleted patients.

Aim for euvolemia (balance between correcting volume deficit and
avoiding volume overload)
Titrate input hourly by matching previous hours output +
25 ml/h for insensible losses ( not practical outside
ICU/HDU)
Match input to loss (urine, vomit, diarrhea, drains) over 24
hours+ 500 mL for insensible losses (more if T is high).
Avoid K containg fluid unless hypokalemic
Caution in cardiac patients; dont overload them
Diuretics for volume overloaded patients especially if they are oliguric
or anuric. Furesemide 180 mg IV then fluid intake = output + 500 ml as
above once fluid balance is corrected
Avoid/ stop medications that reduce the renal blood flow (NSAIDS) or that are
nephrotoxic.
For high risk patients (diarrhea, vomiting, 3rd space losses e.g pancreatitis, poor
intake, sepsis, or other causes of hypotension):
Medications to Avoid/withhold:
1. Diuretcis
2. ACEi
3. Antihypertensive if BP is low (beta blockers shouldnt be stopped
acutely; consider lowering the dose)
4. Metformin if Cr is 150 mmol/L due to risk of lactic acidosis
5. NSAIDS
6. Nephrotoxic antibiotics (e.g. gentamicin, nitrofurantoin)
Medications to be used with caution:
1. Opiates can accumulate in renal failure; so start with lower dose
and buid up to patients pain threshold and keep naloxone handy.
Contrast: acutely unwell patients often have multiple contrast CT scans
and procedures which is an important cause of AKI. Radiographic
contrast media can cause ATN rapidly by causing spasm of the afferent
arteriole.
Prevention: Ensure well hydration: 1 L of 0.9% saline over 12 hours pre
and post procedure.
Adjust dosage of medications for level of renal function.
Monitoring: consider transferring the patient to ICU or high dependency unit
HDU.
Check pulse, BP, JVP, urine output hourly (insert a urinary catheter).
Consider inserting CVP line if on HDU/ICU
Daily U&E
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ACUTE KIDNRY INJUREY
2017

Daily fluid balance chart and daily weight measurement (most accurate
estimate) and intake output records.
Watch for infection
Watch Hb and Hct for anemia.
Correct electrolyte disturbances if present.
Optimize cardiac output. BP should be approximately 120 to 140/80 to 90
mmHg
Order dialysis for patients with the following:
Indications of dialysis in AKI:
1. Severe hyperkalemia 7 mmol/L
2. Severe or worsening metabolic acidosis; pH 7.2
3. Fluid overload not controlled by conservative measures causing pulmonary
edema
4. Symptomatic uremia; uremic encephalopathy (seizures), uremic
pericarditis .
5. Blood urea above 200 mg/dL?
6. Creatinine above 10 mg/dL?

Nutrition: is vital in unwell patients. Aim for normal calorie intake (higher in
high catabolic states as in burns and sepsis). If oral intake is poor, consider
nasogastric nutrition ; parenteral if NGT is impossible.
2. Management of pre- renal AKI:
Treat the underlying disorder
Give NS for to maintain euvolemia and restore BP- dont give to patients with
edema or ascitis. Stop antihyperetsnive medications.
Eliminate any offending agent (ACEI/NSAIDS)
If the patient is unstable, Swan- Ganz monitoring for accurate assessment of
intravascular volume.
Antibiotics for sepsis.
Consider transfer to ICU for inotropic support if signs of shock.

Intrinsic AKI:
10-30% of cases of AKI
Pathophysiology: kidney tissue is damaged impairing the glomerular filtration and
tubular function. The kidneys are unable to concentrate urine effectively.
Causes:
1. Glomerular:
Primary GN
Secondary GN; diabetic, amyloidosis, systemic vasculitis (SLE, polyarteritis,
Wegner granulomatosis)
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2. Tubular: acute tubular necrosis

It is the most common cause of AKI and is characterized by acute tubular cell damage.
Tubular cells have the capacity to regenerate and return to normal of the patient is
kept alive during the regeneration phase.
Types of AKI:
1. Ischemic due prolonged hypoperfusion ( same causes of pre renal AKI;
hemorrhage, sepsis, DIC, CHF)
2. Nephrotoxic: direct injury to renal parenchyma and tubular cell death
Endogenous toxins:
Rhabdomyolysis: uric acid,
hemoglobinuria ( from hemolysis)
-Skeletal muscle breakdown caused by trauma,
crush injuries, prolonged immobility, seizures, snake myoglobinuria (from muscle damage, rhabdomyolysis, sternous
bites. exercise ) ,
-Release of muscle fiber contents (myoglobin) into calcium,
bloodstream. Myoglobin is toxic to kidneys and can Kappa and gamma light chains produced in multiple myeloma
lead to AKI.

-presents with markedly elevated creatinine Exogenous toxins: drugs:

phosphokinase CPK, hyperkalemia, hypocalcemia,
antibiotoics ( e.g. amnioglycoside, vancomycin),
hyperuricemia.
heavy metals (mercury),
-treat with IV fluids, mannitol (osmotic diuretic) and radiocontrast dye ,
bicarbonate ( drives K+ back into the cells)
chemical such as carbon tetrachloride
Chemotherapeutic drugs (cisplatin)
NSAIDS (esp. in the setting of CHF)
3. Vascular causes ( diseases of renal arterioles)
Vasculitis (PAN)
TTP/ HUS
Renal artery occlusion ( athetoma)
4. Acute interstitial nephritis ( see later)
The clinical course of ATN: about 10-25 days:
1. Pre-oliguric phase (0 -2 days):
It is the period of time from the insult until the beginning of the oliguria.
It can be rapidly reversed with early restoration of circulation.
2. Oliguric phase:
Average length is 10-14 days.
Characterized by oliguria (urine output less than 400 mL in 24 hours . anuria ( urine
output less than 50 mL is rare. There is azotemia and uremia.
The longer the patient remains in this phase, the poorer the prognosis due to
development of complications ( fluid overload, electrolyte imbalance, and metabolic
waste products retention).
3. Diuretic phase:
Average length is 10 days.
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2017

Begins when urine output is 500 ml. urine output increases to about 3-5 liters
daily (may cause dehydration).
Explanation of the high urine output:
Damaged tubular epithelium is replaced by an epithelium that has not yet
developed concentrating capacity. Delayed recovery of epithelial cells
relative to GFR.
Excretion of retained salt, water and other solutes that were retained in the
oliguric phase.
Osmotic diuresis: due to retained solutes during the oliguric phase
4. Recovery phase: takes about 4-6 months
Recovery of tubular functions, from the time of stabilization of serum laboratory
values until the patient attains normal renal function.
Clinical features: depend on the cause. Edema is usually present.
Laboratory findings:
1. Decreased BUN: Cr ratio 20:1; typically closer to 10:1. Both BUN
Pre-renal Intri nsic renal
AKI AKI and Cr are elevated but less urea is reabsorbed than in pre-renal
Urinanal ysis Hyaline Abnormal failure.
cas ts
2. Increased urine Na+ 40mEq/L with FENa+ 2-3%; because Na is
BUN/Cr ra tio 20: 1 20:1
FEN+ 1% 1% poorly reabsorbed.
Urine 500 250-350mOs m 3. Decreased urine osmolality 350 mOsm/kg H2O due to impaired
os molality mOs m
water reabsorption.
Urine sodium 20 mEq/L 40 mEq/L
4. Decreased urine- plasma Cr ratio 20:1, because the filtrate cant
be reabsorbed. Dopamine infusion in ATN: can be combined with frusemide
Management:
At low doses, it causes renal vasodilation, sodium diuresis, and
Management: increased cardiac output (+ve inotrope)
Management of oliguric phase:
In large doses, it causes vasoconstriction.
1. Maintenance of fluid balance ( see earlier)
2. Maintenance of electrolyte balance: sodium and potassium restriction (kidneys cant excrete
them). Hyperkalemia should be corrected with dialysis.
3. Control of uremia by dietary restriction of protein with adequate calories from carbohydrate
and fats.
4. Control acidosis with dialysis. Sodium bicarbonate may cause fluid overload.
5. Diazepam for sedation and prevention of fits
6. Metochlopramide for N/V 10 mg IM.
7. Packed cell volume for anemia
8. Rantidine (inj. Zantac 50 mg twice daily) to prevent stress ulcers.

Management of diuretic phase:

It remains for 3-4 days. This phase requires sufficient fluid and electrolyte replacement.
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ACUTE KIDNRY INJUREY
2017

post-renal AKI: Pre- renal failure versus ATN

Pre-renal ATN
The least common cause of AKI (5-15%)
AKI
3 basic tes ts for post- Pathophysiology: obstruction of any segment of
The urinary tract ( with intact kidneys) causes Urine 500 350
renal AKI:
Increased tubular pressure ( urine produced but osmolarity mOsm mOsm
-Physi cal exa mina tion- Cant be excreted) which leads to decreased GFR. Urine Na+ 20 40
palpa te the bladder Blood supply and renal parenchyma are intact. Both FENa+ 1% 1%
Kidneys must be obstructed for Cr to rise. Urine sediment scant Full
-US: look for obs truction,
Renal function is restored if obstruction is brownish
hydronephrosis
Relieved before the kidneys are damaged. pigment,
-Ca theter look for large If untreated, it can lead to ATN. granular
volume of urine casts, with
Causes: epithelial
casts.
1. Urethral obstruction secondary to enlarged prostate (BBH) is the most
Renal vs pos trenal AKI:
common cause.
2. Obstruction of solitary kidneys.
-urine anal ysis showing RBC cas ts/ 3. Nephrolithiasis
hypotension/ sepsis/ use of 4. Obstructing neoplasm (bladder, cervix, prostate
nephrotoxi c drugs a re sugges ti ve of 5. Retroperitoneal fibrosis
intrinsi c AKI. 6. Uretral obstruction is uncommon because obstruction must be bilateral
to cause renal failure.
-H/O renal s tones sugges t obs tructi ve
Clinical features: H/o previous urinary symptoms ( loin pain, hematuria/
nephropathy.
renal colic/ nocturia/ difficulty in micturition). Anemia is common.
Anuria mus t alwa ys be considered due Diagnosis: antegrade or retrograde pyelography may reveal the obstruction.
to obstruction until proven otherwise. Management: relieve the obstruction

Complications of AKI:
1. Fluid overload; ECF volume expansion and resulting pulmonary edema.
2. Metabolic complications:
Hyperkalemia: occurs due to impaired renal excretion of potassium and movement
The most common of potassium from ICF to ECF due to tissue destruction and acidosis.
mortal complications ECG changes in hypokalemia occur in order /sequence as follows: tall tented T waves;
in early AKI are small/flat or absent p wave; increased PR interval; widened QRS complex; ( sine wave
hyperkalemic cardiac pattern; asystole according to oxford?) and ventricular fibrillation.
Metabolic acidosis with increased anion gap due to decreased excretion of
arrest and pulmonary
hydrogen ions.
edema. Hyponatremia due to dilutional effect of excessive intravascular fluid. It can occur in
volume depleted patient consuming excessive hypotonic solutions ( note that
hypernatremia may also be seen in hypovolemic states)
Hyperphosphatemia
Hypocalcemia
Hyperuricemia and uremic syndrome:
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ACUTE KIDNRY INJUREY
2017

It is manifested as anorexia, nausea, vomiting, ileus, pericarditis, pericardial

effusion, lethargy, confusion, stupor, coma, agitation, psychosis and seizures.
It is caused by urea and other toxic metabolites.
3. Infections:
Common and serous complication of AKI (50-60% of cases) due to impaired
immunity from uremia.
Examples include pneumonia, UTI, wound infection, and sepsis.
4. Hematologic complications:
Bleeding disorders due to platelet dysfunction and clotting factors abnormalities. GI
bleeding.
Anemia due to hemodilution, inhibition of erythropoiesis, hemolysis bleeding,
frequent phlebotomy.
5. Cardiac arrhythmias
6. Malnutrition due to increased breakdown and reduced synthesis of muscle protein, anorexia
and increased hepatic gluconeogenesis.

Management of complications:
Management of fluid overload:
It is managed by salt and water restriction and diuretics (furosemide). If these fail,
dialysis is done.
Management of pulmonary edema:
1. Sit the patient up and give high flow oxygen
2. Venous vasodilator (e.g. diamorphine 2.5 mg IV) (+anti-emetic e.g. cyclizine 50 mg
IV)
3. Furosemide 80-250 mg IV either as IVI over 1 h or boluses titrated to response (large
doses are needed in renal failure).
4. If no response, urgent hemodialysis or hemofiltration is needed
Consider continuous positive airway pressure ventilation CPAP
IV nitrates also have a role
Management of hyperkalemia:
Immediate treatment:
1. 10 ml of 10% calcium gluconate IV via a big vein over 2 minutes; repeated as needed
until ECG improves. This is only cardio-protective; it doesnt change potassium
levels.
2. Glucose and IV insulin: 50 ml 50% dextrose water + 10 units of insulin over 10
minutes. Insulin stimulates intracellular uptake of K lowering serum K by 1-2 mmol/L
over 60 minutes. The effect lasts for several hours.
3. Salbutamol (beta 2 agonist) nebulizer work in the same way as insulin/glucose but
high doses are required (10-20 mg) and tachycardia limit use.
4. If venous bicarbonate is low ie the patient is acidotic, give IV sodium bicarbonate 50
mL of 8.4% of sodium bicarbonate NaHCO3 as an infusion or bolus into a bog vein.
Sodium bicarbonate can drive K into cells though the effect is unpredictable.

All of these measures are temporary and buy time to definitely lower K levels via
either renal clearance (e.g. relieving obstruction with catheter or correcting pre -
renal failure with fluids) or hemodialysis /filtration if the patient is oliguric.
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Management of infections with antibiotics

Management of uremic syndrome: emergency dialysis
Management of hematologic disorders: transfusion, estrogen, crypreciptate, dialysis
Management of hyperphsphatemia: aluminium containing antacids.
Management of malnutrition:
1. Provide adequate calories to prevent catabolism.
2. Most of the calories are provided in the form of carbohydrate.
3. Protein should be given in small quantity 0.6-0.8 g/day
Management of metabolic acidosis:
1. Dietary protein restriction.
2. Sodium bicarbonate to maintain serum bicarbonate above 20 mEq/L
3. Dialysis
Hypocalcemia doesnt require specific treatment.

See graph step up on page 273 ] pre renal vs intra renal

Severity of renal failure
Underlying health of
patient
Clinical circumstance
Prognostic factors in AKI
Magnitude of increase in Cr
Presence of oliguria
FENa+
Requirement for dialysis
Duration of severe renal failure
Marked abnormalities on urinalysis
Age
Presence, severity and reversibility of underlying
disease
Cause of renal failure
Severity and reversibility of acute process
Number and type of other failed organ system
Development of sepsis and other complications