Acute renal failure

RIFLE classification

Introduction

• Pre-renal
• Renal
• Post-renal
• Community-acquired
  • 70% pre-renal due to volume depletion vs. 20% intrinsic
  • 90% are reversible (mostly volume depletion)
• Hospital-acquired
  • 70% intrinsic, especially acute tubular necrosis, vs. 20% pre-renal
  • Often in ICU with other organ dysfunction
  • Much higher mortality, dialysis requirements, rates of progression to ESRF

Mortality

• Linear correlation of severity of ARF (as per RIFLE) and mortality
  • No renal injury 4.4%
  • Risk 15.1%
  • Injury 29.2%
  • Failure 41.1%
• ARF with sepsis increases mortality by 30% compared to ARF alone
• Mortality for patients presenting to ED with pre-renal ARF may be as low as 7%
• Patients >80yo with ARF have similar mortality rates to younger patients
• Mortality in paediatric ARF is 25%!!!

Pathophysiology

• Intrinsic
  • Can divide into tubular (ATN), glomerular, interstitial and small-vessel
  • Most common cause of intrinsic renal failure is ischaemic acute renal failure (aka ATN or AKI)
  • Occurs when renal perfusion is decreased enough to cause ischaemic injury to renal parenchyma
  • Patients with chronic hypertension can have alterations to autoregulation and suffer acute kidney injury at blood pressures that would be normal for most patients = normotensive ischaemic ARF
• Obstructive
  • Initially increased tubular pressure with reduced driving force for filtration
  • Pressure gradient soon equalisers and maintenance of depressed GFR requires vasoconstrictor release

Recovery

• Restoration of renal blood flow is the key to recovery
• Pre-renal: Volume restoration
• Post-renal: Rapid relief of urinary obstruction results in prompt decrease in vasoconstriction
• Intrinsic: Clearance of tubular toxins and initiation of therapy for glomerular diseases decreases vasoconstriction and helps restore renal blood flow
• Remaining functional nephrons increase their filtration and hypertrophy and GFR will recover proportionately to size of remnant nephron pool
• If nephron pool below critical number, continued hyperfiltration results in glomerulosclerosis and nephron loss ultimately leading to viscious cycle of damage and complete renal failure

Presentation

• Usually symptoms correlate with underlying cause rather than acute renal failure itself
• Pre-renal
  • Dehydration, excessive fluid losses, third-spacing

Presentation

• Intrinsic
  • Ischaemic AKI expected post-MI, severe sepsis or systemic hypotension
  • Crystal-induced nephropathy, nephrolithiasis and renal papillary necrosis present as flank pain and haematuria
  • Pigment-induced ARF should be suspected if possible rhabdo (e.g. myalgias, prolonged seizures, recent coma, recreational intoxication, excessive exercise) and with haemolysis
  • Acute GN – Darkening urine and oedema with constitutional symptoms (possibly preceded by pharyngitis (post-strep GN), cutaneous infection or viral infection [IgA nephropathy])
  • Interstitial nephritis – Fever (27%), arthralgia and rash (15%) common, eosinophilia (23%)
    • Triad of rash, fever, eosinophilia in 10% (CLASSIC)
    • Finding of eosinophilia in ARF with no clear cause should raise suspicion for AIN
    • Urine white cell casts suggest AIN
  • Acute renal artery occlusion marked by flank pain and haematuria
  • Pulmonary-renal syndrome – Cough, dyspnoea, haemoptysis (Goodpasture’s, Wegener’s)

Presentation

• Post-renal
  • Prostatic disease, IDC, alternating polyuria/oliguria, clots

Examination

• Vitals
  • Postural tachycardia >30 is suggestive of large volume loss but not sensitive for moderate losses
  • Must assess volume status
  • Fever suggests infectious or immunological cause
• Skin examination
  • Livedo reticularis, malar rash, digital ischaemia, palpable purpura, petechiae all suggest systemic vasculitis, atheroembolic disease or infective endocarditis
  • Maculopapular rash suggests allergic interstitial nephritis
  • Track marks suggest endocarditis
• Eyes
  • Keratitis, iritis, uveitis suggest autoimmune vasculitis
  • Jaundice suggests liver disease
  • Diabetic, hypertensive or atheroembolic retinopathy

Examination

• CVS
  • AF suggests embolic disease
  • Murmur suggests endocarditis or thrombus
  • S3 gallop, JVP distension, hepatojugular reflex all suggest heart failure
• Respiratory
  • Pulmonary exam may suggest CCF, Goodpasture’s, Wegener’s
• Abdomen
  • Examine for stones, flank tenderness, obstruction

Causes of acute renal failure

Factors that increase susceptibility

• Failure to decrease arteriolar resistance
  • Old age, atherosclerosis, chronic HTN, CKD
  • Reduction in vasodilatory prostaglandins (NSAID’s, COX-2 inhibitors)
  • Afferent vasoconstriction (sepsis, hypercalcaemia, hepatorenal syndrome, contrast, tacrolimus/cyclosporine)
• Failure to increase efferent arteriolar resistance
  • ACEi, ARB
  • Much more common if volume deplete as reliant on post-glomerular vasoconstriction for maintenance of GFR
• Renal artery stenosis

Pre-renal differential

• Hypovolaemia
  • GI loss, diuretics, third-spacing, burns, post-obstructive diuresis, poor intake
• Hypotension (relative)
  • Sepsis, haemorrhage, reduced CO, antihypertensives, high-output failure
• Renal artery/small vessel
  • Embolism, thrombosis, sickle cell, dissection, NSAIDs/ACEi/ARB (microvasculature), cyclosporine/tacrolimus
  • Microvascular thrombosis: Pre-eclampsia, HUS, DIC, vasculitis, sickle call
  • Hypercalcaemia

Post-renal 

• Risk factors
  • Increasing age
  • Male
  • Malignancy
  • Nephrolithiasis
  • Retroperitoneal disease
  • GU surgery
  • IDC
• Significant permanent loss of renal function occurs within 10-14 days if complete obstruction exists
  • Risk significantly increased if complicated by UTI

Post-renal differential

• Trauma
• Blood clots
• Urethral phimosis/stricture
• Neurogenic bladder: Diabetes, spinal cord injury, MS, anticholinergics, alpha antagonists, opioids
• Calculus BOO
• Prostatism
• Cancer of prostate, bladder, cervix, colon
• Ureter: Stone, papillary necrosis (DM, sickle cell, pyelo), tumors of any abdominal structure, retroperitoneal fibrosis (idiopathic, TB, sarcoidosis, propranolol)
• Aortic aneurysm, pregnant uterus, IBD, accident surgical ligation

Intrinsic renal failure

• In community-acquired: Drugs and infection
• In hospital-acquired: Toxins and ischaemic insults
• DDx
  • Tubular disease
    • Ischaemic ATN
    • Nephrotoxins: Aminoglycosides, radiocontrast, cisplatin, rhabdo
    • Obstruction: Uric acid, calcium oxalate, myeloma light chains, amyloid, acyclovir, indinavir

Intrinsic renal failure

• DDx continued…
  • Interstitial disease
    • Acute interstitial nephritis: NSAID’s, penicillin, diuretics, phenytoin, allopurinol, rifampicin, bactrim, cipro, PPI’s
      • May be an association between PPI and recurrent AIN with subsequent CKD
      • Drugs are the cause of 70-75% of cases (30-50% antibiotics)
    • Infection: Bilateral pyelo, Legionella, Leptospirosis, Streptococcal infection (4-10%)
    • Infiltrative: Sarcoidosis, lymphoma
    • Autoimmune: SLE 

Intrinsic renal failure

• DDx continued…
  • Glomerular disease
    • Rapidly progressive GN: Goodpasture’s, Wegener’s, HSP, SLE, membranoproliferative
    • Post-infectious GN: Post-strep, IgA nephropathy (post-viral)
  • Small-vessel disease
    • Microvascular thrombosis: Vasculitis, pre-eclampsia, HUS, DIC, TTP
    • Malignant hypertension
    • Scleroderma
    • Renal vein thrombosis

Intrinsic renal failure

• Crystal-induced nephropathy
  • Precipitation of crystals in tubules leading to mechanical and inflammatory injury
  • Most often seen with elevated uric acid levels due to tumor lysis syndrome

Intrinsic renal failure

• Radiocontrast-induced nephropathy
  • Increasing creatinine over 3-5 days, followed by complete resolution
  • Risk factors include CKD, diabetes (insulin-dependent), metformin, older age, hypovolaemia, hypoalbuminaemia
  • Significant concern if GFR <60
  • Gadolinium should not be given if eGFR <30 due to risk of nephrogenic systemic fibrosis
  • Identify at risk patients, avoid other nephrotoxins, provide adequate hydration and use low or iso-osmolar radiocontrast dyes
  • No conclusive evidence for N-acetylcysteine, sodium bicarbonate
  • Some evidence that effect of contrast has been overstated (find reference)

Intrinsic renal failure

• ACEi
  • Dilate postglomerular capillaries to increase renal blood flow and decrease the glomerular filtration fraction
  • Leads to 10-20% rise in creatinine normally but rarely can be more severe
  • Consider bilateral renal artery stenosis, volume depletion or concomitant use of other nephrotoxic agents
• NSAID’s
  • Decrease synthesis of vasodilatory prostaglandins, resulting in reduced GFR and renal blood flow
  • Risk factors include older age, CKD, CCF, diabetes, volume depletion and use of diuretics/ACEi
• Aminoglycosides
  • Trough concentration is most predictive of renal injury (hence once daily dosing)

Intrinsic renal failure

• Other drugs
  • Amphotericin
  • Beta-lactams (interstitial nephropathy)
  • Sulphonamides
  • Acyclovir
  • Methotrexate
  • Cisplatin
  • Cyclosporin A
  • Tacrolimus

Papillary necrosis

• Associated with DM, analgesics, pyelonephritis and urinary obstruction
• Analgesic nephropathy
  • Characterised by papillary necrosis and chronic interstitial nephritis
  • Typically combination agents that contain codeine or caffeine
  • Phenacetin was particularly associated with this
  • Usually no symptoms
  • Flank pain or haematuria can occur in the setting of papillary necrosis
  • USS and CT show small kidneys, renal papillary calcifications and an indented/irregular kidney contour

Hepatorenal syndrome

• Acute renal failure in setting of severe liver dysfunction without other cause
• Progressive oliguria with very low urine sodium <10mmol/L
• Other causes of acute renal failure are much more common in this setting including sepsis, paracentesis-induced hypovolaemia, raised intra-abdominal pressure, diuretic-induced hypovolaemia, lactulose-induced hypovolaemia, alcoholic cardiomyopathy
• Avoidance of hypovolaemia with albumin use during paracentesis decreases the incidence of renal failure

Rhabdomyolysis induced ARF

• 5-10% of acute renal failure presenting to ICU is due to rhabdo
• Need prompt and aggressive fluid resuscitation
• Eliminate causative agents
• Correct compartment syndromes
• Alkalinise urine pH >6.5
• Maintain polyuria (>300mL/hr)
• Mannitol is controversial

Labs

• Patient with low baseline Creatinine can lose up to 50% of functioning nephrons before creatinine is “elevated”
• Those with lower muscle mass have lower GFR’s for any creatinine level
• GN causes increased tubular secretion of creatinine and falsely decrease serum creatinine (thus falsely elevating GFR)
• Trimethoprim, cimetidine and salicylates decrease tubular secretion of creatinine and falsely increase serum creatinine (thus falsely depressing GFR)
• In patients with no glomerular filtration, creatinine rises 90-270micromol/L/day
  • If faster than this, suggests rhabdo
  • If slower than this, suggests residual nephron function

Labs

• Urea:creatinine ratio
  • Both passively filtered at glomerulus 
  • Creatinine remains in tubule
  • Urea is passively reabsorbed with sodium
  • In setting of active sodium reabsorption (hypovolaemia), urea clearance is as low as 30% of GFR with resultant Urea:creatinine ratio >100 (mmol/L:mmol/L)
    • Remember creatinine provided in micromol/L so need to divide by 1000
  • Caveats:
    • Urea may be elevated by GI haemorrhage, protein loading or trauma
    • Urea may be low in malnutrition and hepatic synthetic dysfunction

Labs

• Urine microscopy
  • Red cell casts and dysmorphic cells occur in glomerulonephritis due to increased tonicity of the renal medulla
  • In ATN tubular epithelial cells break down allowing protein and epithelial cells to enter urine

Labs

• Urine microscopy
  • Casts
    • Hyaline casts: Common in prerenal failure but can be normal
    • Pigmented granular casts: Ischaemic or ATN
    • Brown granular casts: Pigment nephropathy
  • Hb on dipstick with no red cells on microscopy = myoglobinuria

Labs

• Fractional excretion of sodium
  • Measured percent of filtered sodium excreted in urine to differentiate pre-renal from ATN
  • If pre-renal, get low FENa <1% as kidneys attempt to reabsorb Na
  • If ATN, get failure of tubular function and subsequent failure to reabsorb Na with FENa >2%
  • If 1-2%, could be either
  • = (UNa x Serum Creatinine) / (Serum Na x Urine Creatinine) x 100

Imaging

• Rule out lower tract obstruction with bedside USS
• Upper tract obstruction 
  • USS
    • Preferred with 90% sensitivity and specificity for hydronephrosis due to mechanical obstruction
    • Hyperechogenicity indicates diffuse parenchymal disease
    • Colour flow Doppler allows assessment of renal blood flow
    • Caveats
      • May have functional hydronephrosis in chronic reflux nephropathy
      • May not show hydronephrosis even with complete obstruction in the setting of retroperitoneal fibrosis
      • Intermittent or partial obstruction may not result in hydronephrosis
  • Non-contrast CT KUB
    • Sensitivity equivalent to USS but will localise obstructing pathology

Diagnostic sequence

• ABC
• Volume status
• VBG/ECG for hyperkalaemia
• CXR for volume/effusions/pneumonia
• Find and treat underlying cause
  • Exclude urinary obstruction early
• Find and treat complications
• Labs as above
• Postvoid residual >125mL suggests bladder outlet obstruction and need to leave IDC in until cause and solution found

Post-obstruction diuresis

• Seen following prolonged obstruction, usually with ARF
• Admission recommended if diuresis >250mL/hr for >2 hours with otherwise uncomplicated urethral obstruction
• Can be fatal

Medical Therapy

• Manage hyperkalaemia aggressively
• Frusemide
  • If hypervolaemic and NOT anuric UpToDate advises 80mg IV trial
• Sodium bicarbonate
  • Jaber et al. 2018 showed potential benefit on mortality and time on vasopressors and need for haemodialysis in a predominantly septic group with AKI
  • Target pH 7.25-7.30 and normal serum bicarbonate
  • Risks of hypocalcaemia, hypokalaemia, hypervolaemia and CO2 accumulation if not able to hyperventilate
  • 100mmol over an hour is a reasonable start
  • If patient is anuric, remember 1000mOsm/L means will rapidly draw free water into vascular compartment and potentially worsen APO

Indications for emergency dialysis

• Oliguria (UO <200mL/12hrs)
• Anuria (0-50mL/12hrs)
• Refractory hyperkalaemia >6.5 or rapidly rising
• Refractory metabolic acidosis pH 7.1
• Refractory fluid overload with hypoxia
• Uraemic encephalopathy/pericarditis/myopathy/neuropathy
• Serum Na <115 or > 165
• Life-threatening dialysable intoxication e.g. lithium, aspirin, methanol, ethylene glycol or theophylline
• Temperature >40
• Controversial excessive urea/creatinine levels
  • Urea >35
  • Creatinine >400

Renal replacement therapy

• Water removal
  • Ultrafiltration by driving pressure achieved by generating a transmembrane pressure which is greater than oncotic pressure (HF or IHD) or increasing the osmolarity of the dialysate (PD)
• Solute removal
  • Electrochemical gradient across membrane using a flow-past system with toxin-free dialysate (diffusion) (as in IHD and PD)
  • Creating a transmembrane pressure-driven ‘solvent drag’, where solute moves with solvent (convection) across a porous membrane, is then discarded and replaced with toxin-free fluid (HF)

Continuous renal replacement therapy (CRRT)

• Continuous venovenous haemodialysis/haemodiafiltration
  • Dialysate is delivered countercurrent to blood flow to achieve either pure diffusive clearance or mixed diffusive/convective clearance
  • Dosing
    • Expressed as effective effluent per kg per hour
    • Typically 25mL/kg/hr
  • Anticoagulation
    • Low-dose heparin (<500IU/hr) is sufficient in most patients to achieve adequate filter life (24 hours) and has almost no effect on patient coagulation profiles
    • Regional heparin/protamine anticoagulation is an option if frequent filter clotting occurs and further anticoagulation of the patient is considered dangerous
    • Heparinoids may be required if HITTS is suspected

CRRT

• Filter clotting
  • Often due to inadequate flow, inadequate access, kinking rather than inadequate anticoagulation
  • Simply increasing anticoagulation is a mistake
  • 13.5Fr at femoral position have the least risk of inadequate flow (<200mL/min)

Intermittent HD

• Countercurrent dialysate flow is still used
• Higher dialysate flows (300-400mL/min) and runs for only 3-4 hours every 2^nd day
• Rapid volume removal can cause hypotension
• Solute removal is episodic
• Shifts in brain water content can raise ICP

Haemoperfusion

• Charcoal cartridge used instead of dialysis membrane
  • Remove molecules fo 300-500Da MW
• Ion exchange resin (Amberlite) can also be used
• Can cause rapid shift in intravascular volume due to large volume for priming of cartridge (260mL)
• Glucose absorption is significant
• Thrombocytopaenia is common
• May be useful in life-threatening theophylline toxicity

Plasmapheresis/plasma exchange

• Plasmafilter (allows passage of molecules up to 500kDa and filtrate (plasma) is discarded
• Post-filter replacement of 50/50 FFP/albumin for example
• Effective for TTP, GBS, cryoglobulinaemia, myaesthenia gravis, Goodpasture’s due to antibody removal

SLEDD (slow low-efficiency daily dialysis)

• 12 hour treatments
• No anticoagulation required
• No mortality difference vs. CRRT
• Can use SLEDD-F (SLED-diafiltration) to remove middle molecules in SIRS
• Cheaper than CRRT
• Unknown effects on drug clearance
• Risk of hypophosphataemia and hypothermia

What sort?

• Fear of early dialysis stems from risk of cardiovacular instability seen with intermittent HD
• Continuous RRT and slow low-efficiency daily dialysis (SLEDD) minimise these effects
• Targets
  • Urea 15-25 with protein intake around 1.5g/kg/day
  • Easily achieved with 35-45L/day urea clearance rate with CVVHDF

Last Updated on November 11, 2020 by Andrew Crofton