Acute Kidney Injury

 

• Background

  Criteria

  Any 1 of:

  • Creatinine ↑≥26 μmol/L in 48 hours.
  • Creatinine x1.5 from baseline in 1 week.
  • Urine output (UO) <0.5 ml/kg/hr for 6 hours or 8 hours in kids.
  • GFR ↓25% in children over 7 days.

  KDIGO stages:

  1. Creatinine x1.5 or UO <0.5 ml/kg/hr for 6 hours.
  2. Creatinine x2 or UO <0.5 ml/kg/hr for 12 hours.
  3. Creatinine x3 or UO <0.3 ml/kg/hr for 24 hours or creatinine ≥4 mg/dL or dialysed.

  Prevalence in inpatients

  • 1% at admission.
  • 5% during stay.
  • 15% of ITU patients.

  Pathophysiology and causes

  In order of frequency, AKI is prerenal, postrenal, or intrarenal.

  Prerenal AKI

  Pathophysiology:

  • Renal hypoperfusion → ↓GFR as an appropriate response to retain Na+/H2O. There is no renal cell injury, and restoration of perfusion restores function.
  • Aka prerenal azotaemia, azotaemia meaning an accumulation of uraemic waste.
  • Prolonged hypoperfusion can lead to acute tubular necrosis, thus ischaemic AKI is a spectrum from pre-renal to intrinsic AKI, differentiated by presence of renal cell injury.

  Causes:

  • Diarrhoea and vomiting, shock (e.g. sepsis, haemorrhage).
  • ↓Cardiac output: heart failure.
  • Hepatorenal syndrome.
  • Drugs: NSAIDs constrict afferent arterioles, ACEi and ARBs dilate efferent arterioles (more than afferent). Diuretics cause hypovolaemia.

  Intrinsic AKI

  Tubulo-interstitial disease:

  • Acute tubular necrosis (ATN). Commonest intrinsic cause, and usually ischaemic.
  • Acute interstitial nephritis (AIN).

  Glomerulonephritis, including rapidly progressive glomerulonephritis (RPGN).

  Vascular disease causing afferent vasoconstriction:

  • Renal artery stenosis.
  • Malignant hypertension.
  • Vasculitis. May also cause glomerulonephritis.
  • Microangiopathy: HUS, TTP, DIC, pre-eclampsia.

  Postrental AKI

  Pathophysiology:

  • Obstruction which may be intra-renal – tubules including collecting duct – or extra-renal – renal calyces to urethral meatus.

  Causes:

  • Common: stones, catheter, strictures, prostatism, UTI.
  • See urinary obstruction and urinary retention.

• Signs and symptoms

  General:

  • Oliguria
  • Fluid overload: pulmonary oedema (± orthopnea and paroxysmal nocturnal dyspnoea), peripheral oedema.
  • Uraemic symptoms: fatigue, nausea and vomiting, confusion.

  Specific:

  • Prerenal AKI: postural hypotension, diarrhoea and vomiting, ↑HR.
  • Intrinsic AKI: symptoms of systemic disease.

  Polyuric (aka diuretic) phase:

  • As kidney heals from AKI, tubules regenerate but water concentration is last function to return.
  • There may also be ↑osmotic load from renal toxin accumulation.
  • Leads to massive polyuria.
  • Treat with IV fluids to replace loss.

• Risk factors

  • Organ failure: chronic kidney disease, liver disease (hepatorenal syndrome), heart failure.
  • Age
  • Hypovolaemia and shock.
  • Nephrotoxic drugs. There are many, but common, important causes are FANG: Furosemide, ACEi and ARBs, NSAIDs, Gentamicin.
  • Diabetes
  • Urinary obstruction.

• Investigations

  General approach

  Investigating ↑creatinine or oliguria:

  1. Establish as AKI not CKD.
  2. Consider prerenal or postrenal causes, which are much commoner.
  3. Consider intrinsic cause, and if so, which.

  Tests

  Urinalysis

  Dipstick:

  • Blood (haematuria) and protein (albuminuria): glomerulonephritis, stones, UTI, tumour, trauma. Microscopic in AIN.
  • WBCs (pyuria): UTI, AIN.

  Microscopy:

  • RPGN: red cell casts.
  • AIN: eosinophils and eosinophil casts. Neutrophils may also be seen.
  • ATN: granular or tubular epithelial cell casts.

  Further tests:

  • Urinary Na+: <1% (or <20 mmol/L) if prerenal, as kidneys retain Na+ to maintain volume.
  • Myoglobinuria: rhabdomyolysis.
  • Culture if there are signs of infection.
  • Immunoelectrophoresis in suspected myeloma.

  Bloods

  Basic bloods:

  • FBC: ↓Hb (CKD), ↑WBC (infection, eosinophilia in AIN), ↓PLT (HUS, TTP).
  • U+E: urea, creatinine, ↑K+. Also check HCO3- and Ca2+.
  • LFT: hepatorenal syndrome.
  • Coag: DIC in sepsis, altered clotting in CKD.
  • CK: rhabdomyolysis.
  • CRP: infection.
  • ABG: metabolic acidosis.

  Further bloods:

  • Immune markers: ANCA, anti-GBM, ANA, anti-dsDNA, RF, antistreptolysin O, complement, cryoglobulins.
  • Serum electrophoresis and immunoglobulins in suspected myeloma.
  • Culture in sepsis.

  Imaging

  Kidney:

  • US for suspected obstruction or if no cause found. Hydronephrosis (dilated calyces) if postrenal. Otherwise normal size in AKI, but small in CKD.
  • Further options: abdo XR, abdo CT.

  Others:

  • ECG: ↑K+.
  • CXR: pulmonary oedema, systemic disease.

  Biopsy

  Indications:

  • Any suspicion of RPGN.
  • Prolonged ATN (not recovered <3 weeks).
  • No cause found for AKI.

  Distinguishing from CKD

  • Look at previous bloods.
  • Monitor GFR over 24-48 hours, with rise suggesting AKI.
  • US: normal size in AKI, small in CKD.
  • Shorter symptom duration in AKI.
  • Nocturia in CKD.
  • Hb and Ca2+ usually normal in AKI, unlike CKD, but not that helpful as can become abnormal within 2 days.
  • Remember that it could be acute on chronic failure.

• Management

  Treat underlying cause:

  • Prerenal: fluids. Antibiotics if sepsis.
  • Intrinsic: stop causative drug, immunosuppress if RPGN.
  • Postrenal: catheterize.

  Fluid balance:

  • Monitor fluid balance to prevent hypovolaemia or overload.
  • Role of furosemide is uncertain. Some advocate it for fluid overload, but NICE doesn't and there is no good trial evidence.

  Referral if cause unclear or not responding to treatment:

  • Nephrology if intrinsic, especially in suspected glomerulonephritis.
  • Urology if postrenal. May use nephrostomy or stenting.

  For severe cases, see renal replacement therapy (RRT) in AKI.

  Prevention in high risk patients:

  • Pause ACEi and avoid NSAIDs in diabetes or CKD patients around time of surgery.
  • For acutely ill patients getting iodinated contrast, give IV fluids.

• Complications and prognosis

  Complications:

  • Metabolic acidosis.
  • ↑K+
  • Pulmonary oedema.

  Poor prognostic factors:

  • >50 years old.
  • AKI that develops in hospital.
  • Rising urea.
  • Oliguria >2 weeks.
  • Other organ failure.

• Tubulo-interstitial kidney disease

  Acute tubular necrosis (ATN)

  • Due to ischaemia, drug toxicity, or heme pigment (which my be exacerbated by crystal obstruction).
  • Causes, MIRACLE: Myoglobin (from rhabdomyolysis), Ischaemia, Radiocontrast, Aminoglycosides, Cisplatin, Lithium, Excess urate (gout).
  • Urine dipstick often normal.

  Acute interstitial nephritis (AIN)

  • 90% are hypersensitivity reactions triggered by drugs.
  • Most commonly NSAIDs and β-lactams. Also: thiazides, furosemide, rifampicin, PPIs, and allopurinol. Note that thiazides and furosemide, like all diuretics, are more likely to cause prerenal AKI due to volume depletion.
  • In a minority (around 30%), there is an allergic type presentation: rash, fever, arthralgia, eosinophilia.
  • Can also be caused by Infection: legionella, leptospira, Group A Strep, CMV.
  • Urine dipstick shows leukocytes and may show mild blood and protein. Microscopy shows eosinophils and eosinophil casts.

• Rapidly progressive glomerulonephritis (RPGN)

  Definition

  • Rapid decline in kidney function – sometimes defined as GFR ↓50% within 3 months – and progression to end-stage kidney disease.
  • Aka crescentic glomerulonephritis (GN).

  Causes

  Mnemonic for causes is PIG. Note that most of these conditions usually cause a milder, less acute renal disease.

  Pauci-immune vasculitis (50%):

  • Type 3 RPGN.
  • Small vessel vasculitis causing aneurysms, stenosis, or occlusion.
  • Constitutional symptoms plus organ-specific signs e.g. vasculitic rash, pulmonary haemorrhage.
  • Usually granulomatosis with polyangiitis (c-ANCA) or microscopic polyangiitis (p-ANCA).

  Immune complex disease (40%):

  • Type 2 RPGN, type 3 hypersensitivity.
  • Lupus nephritis, usually in patient with known SLE.
  • Post-infectious GN, usually post-streptococcal GN.
  • IgA nephropathy.

  Anti-Glomerular basement membrane disease (10%):

  • Type 1 RPGN, type 2 hypersensitivity.
  • Antibody against type 4 collagen of glomerular and alveolar basement membrane.
  • Known as Goodpasture's syndrome if both RPGN and pulmonary haemorrhage is present.
  • Biopsy shows linear IgG deposition.

  Presentation

  • Renal features: oliguria, haematuria, proteinuria (sometimes nephrotic), oedema.
  • Systemic: vomiting, fatigue, fever.

  Management

  Immunosuppression:

  • Methylprednisolone IV plus cyclophosphamide IV.
  • Rapid treatment can salvage damaged nephrons.

  Prognosis

  90% of RPGN progresses to end-stage kidney disease.

• Renal replacement therapy (RRT) in AKI

  Indications

  Ahh FUK:

  • Severe metabolic Acidosis: pH <7.1.
  • Refractory Fluid overload or pulmonary oedema.
  • Symptomatic Uraemia: pericarditis, encephalopathy.
  • Refractory ↑K+ >6.5 or ECG signs.

  Modalities

  • Intermittent haemodialysis (IHD) or continuous renal replacement therapy (CRRT). CRRT uses haemofiltration (HF), haemodialysis (HD), or combined haemodiafiltration (HDF).
  • It can be arteriovenous (blood out of artery → into machine → back into vein), or venovenous (vein → machine → vein). Venovenous is generally preferred as is safer.
  • Clinical trials don't clearly demonstrate superiority of any particular modality, so choice of therapy often depends on local availability and experience.

  Haemofiltration: definition and mechanism

  • Uses hydrostatic pressure gradient to move plasma across a semi-permeable membrane. The use of a pressure gradient, as opposed to a concentration gradient, is what distinguishes it from dialysis.
  • Solutes are carried along with the fluid ('convection' or 'solvent drag'), and are removed proportional to their concentration in the blood.
  • The porosity of the membrane can determine which solutes are removed. Relative to HD, HF more efficiently removes middle and larger molecular weight substances.
  • Around 25% of the plasma is removed as it passes through the machine (the 'filtration fraction'), though this can be altered by adjusting the pressure gradient.
  • Plasma that is removed needs to be replaced by an appropriately balanced fluid solution, which can be adjusted to achieve desired plasma solute concentrations.