acute kidney injury (AKI) / acute renal failure (ARF)

see also:

• renal medicine (nephrology)
• chronic renal failure
• pathology tests - urea and creatinine
• urinalysis

• ARF is a common finding in the ED patient and one of the clinician's tasks is to decide on whether it is pre-renal, renal or post-renal.
• exclusion of urinary retention by checking with a bladder scanner is a simple first step
• patients in clinical the shocked hypotensive patient will obviously need this addressed ASAP.

• fractional excretion of sodium (Fe Na %):
  • = [(U_Na / P_Na) / (U_Cr / P_Cr)]x100
  • this reflects the fraction of filtered sodium that escapes reabsorption & is excreted in urine
  • note that urine & plasma levels of sodium & creatinine must be taken simultaneously

• renal failure index (RFI)

• urinary sodium indices
  • urinary sodium concentration provides information on the integrity of tubular reabsorptive function
  • normally urimary sodium concentration parallels sodium intake
  • low urinary sodium thus indicates not only intact tubular reabsoptive mechanism but also the presence of a stimulus to conserve sodium
  • urinary sodium concentration (and fractional excretion of sodium (FENa)) helps distinguish between the two most common causes of ARF: pre-renal azotaemia and ATN.
  • urinary indices are most helpful in oliguric patients. In euvolaemic individuals who are in sodium balance, & who have a normal sodium intake and normal renal function will have urinary sodium concentration < 20mEq/L & FENa < 1%
  • UNa < 20mEq/L, FENa < 1%
    • normal individuals
    • oliguric pts:
      • pre-renal azotaemia
      • acute glomerulonephritis (check urine microscopy for red cell casts)
      • acute obstruction
      • some cases of contrast-induced ATN
      • some cases of rhabdomyolysis-associated ATN
      • early sepsis
      • 10% of cases of oliguric ATN
  • UNa 20-40mEq/L:
    • non-discriminatory as may be either pre-renal, mild ATN or diuretic use, etc
  • UNa > 40mEq/L, FENa > 1%
    • 90% of cases of ATN
    • chronic obstruction
    • diuretic drugs
    • osmotic diuresis
    • underlying chronic renal failure

• usually have:
  • BUN:CRN ratio (in mM) > 100
  • FE Na < 1% & urinary sodium < 20 mEq/dL
• if it is severe & prolonged, may result in ATN
• NB. “renal dose” dopamine does not effect clinical outcomes in pts with ARF (Ann Int Med April 2005)

• GIT: vomiting, diarrhoea, NG drainage
• renal: diuresis
• blood loss
• insensible losses
• third space sequestration
• pancreatitis
• peritonitis
• trauma
• burns

• AMI, valvular disease, cardiomyopathy
• decreased effective arterial volume:
  • antihypertensive drugs
  • nitrates

• sepsis
• anaphylactic
• hypoalbuminaemia
  • nephrotic syndrome
  • liver disease

• ACE inhibitors
• NSAIDs (generally reversible):
  • inhibit the normal renal vasodilator PG's which are critical in maintaining glomerular perfusion in pts with diminished renal blood flow such as:
    • elevated renin/AGII levels as in CCF, CRF & cirrhosis
    • elderly, diuretic use, renovascular disease, diabetes

• most patients with Covid-19 AKI had at least mild chronic changes due to diabetic glomerulosclerosis or hypertensive nephroangiosclerosis ¹⁾
  • pathophysiology of COVID-19 kidney injury involves both direct effects of COVID-19 on the kidneys as well as mechanisms resulting from:
    • a) systemic consequences of the inflammatory response to the viral infection on hemodynamic stability (hypovolemia, sepsis);
    • b) effects of the virus on distant organs (organ crosstalk);
    • c) therapeutic interventions to manage critical COVID-19 disease (mechanical ventilation, nephrotoxins, inadequate correction of volume depletion)
  • Covid-19 vaccination has rarely been implicated as a cause of AKI but some have occurred including Acute Tubulointerstitial Nephritis after mRNA vaccines ²⁾

• large vessel:
  • renal artery thrombosis or stenosis:
    • Hx of AF/recent AMI; AAA; N/V/flank pain;­LDH; renal arteriogram;
  • renal vein thrombosis:
    • evidence of nephrotic synd. or PE; flank pain; haematuria; IVCgram;
  • atheroembolic disease:
    • usually age>50;recent aortic procedure;retinal plaques;s/c nodules;palpable purpura; livedo reticularis; vasculopathy; HT; eosinophilia; hypocomplementaemia; skin Bx; renal Bx
• small & medium vessel:
  • scleroderma
  • malignant HT:
    • severe HT with headaches, cardiac failure, retinopathy, CNS dysfn, papilloedema
    • RBC casts; LVH on ECG with resolution on control of BP
  • HUS, TTP:
    • compatible clinical Hx - diarrhoea; cyclosporin; anovulants;
    • fever, pallor, ecchymoses, neurological abnormalities
    • anaemia, thrombocytopenia, schistocytes, ­LDH, renal Bx
  • thrombotic microangiopathy (TMA)
    • COVID-19 coronavirus (2019-nCoV / SARS-CoV-2), quinine

• systemic diseases:
  • COVID-19 coronavirus (2019-nCoV / SARS-CoV-2) - micro-clots
    • collapsing glomerulopathy mostly observed in black patients, and was associated with high-risk APOL1 genotypes
    • focal segmental glomerulosclerosis - mainly non-ICU patients
  • SLE, infective endocarditis, systemic vasculitis (PAN, Wegener's), HSP, cryoglobulinaemia
  • Goodpasture's syndrome
• primary renal disease:
  • post-strept. & other post-infectious GN
  • rapidly progressive GN

• infections:
  • acute bilateral pyelonephritis
  • critical severity Covid-19 infection
• allergic interstitial nephritis:
  • recent ingestion of drug - b lactams, NSAIDs, diuretics, proton pump inhibitors, sulphonamides, allopurinol, rifampicin
  • LOW, malaise, fever, rash or arthralgias
  • classic triad uncommon: fever, rash and eosinophilia
  • WBC casts (often eosinophils); RBCs; proteinuria (occas. nephrotic)
  • eosinophilia; skin Bx of rash (leukocytoclastic vasculitis); 
  • renal Bx - mononuclear infiltrates of lymphocytes, plasma cells & eosinophils +/- histiocytes
• drugs/toxins (many):
  • heavy metals, ethylene glycol, etc
• multiple myeloma:
  • bone pain; dipstick neg. proteinuria; circ. or urinary paraprotein;
• acute tubular necrosis (ATN)
  • ischaemia:
    • shock
    • sepsis
    • all causes of severe pre-renal azotaemia
  • nephrotoxins:
    • antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), radiographic contrast agents
    • the fungal mycotoxin, Ochratoxin A (OTA), a secondary metabolite produced by several fungal species, in particular from Aspergillus ochraceus and Penicillium verrucosum which may contaminate foods such as cereals
  • pigments:
    • myoglobinuria:
      • rhabdomyolysis (this may also occur in patients with mild Covid-19 kidney damage), vigorous exercise, status epilepticus, myonecrosis, heat illness and heat stroke
      • myopathy
      • urine supernatant tests +ve for heme;
    • haemoglobinuria:
      • haemolytic anaemias
      • urine supernatant pink & tests +ve for heme;
      • pink plasma +ve for Hb
  • crystals:
    • uric acid:
      • tumour lysis (chemotherapy); urate crystals on micro.;
    • oxalate:
      • ethylene glycol ingestion; oxalate crystals on micro; tox. screen; acidosis; osmolal gap;

• in the absence of infection, full renal recovery from post-renal ARF is said to be possible even after 1-2 weeks full obstruction, although serum CRN may not return to baseline for several weeks
• as the onset of irreversible loss of renal function with obstruction appears to be gradual, a few days delay in diagnosis generally is considered acceptable, although common sense dictates that obstructions should be detected and relieved as expeditiously as possible.

• kidney stone
• sloughed papilla (esp. if sudden deterioration of renal fn in diabetes, analgesic nephropathy or HbS)
• malignancy
• retroperitoneal fibrosis
• crystal precipitation - uric acid (eg. with tumour lysis), oxalic acid, sulphonamide
• methotrexate, aciclovir and related antivirals (famciclovir, valaciclovir) or Bence Jones protein precipitation
• surgical misadventure

• acute urinary retention
• chronic urinary retention
• kidney stone
• blood clot
• prostatic hypertrophy
• bladder carcinoma
• neurogenic bladder

• phimosis
• stricture

• pulmonary oedema
• arrhythmia due to hyperkalaemia
• hypertension
• pericardial effusion
• AMI
• PE

• decreased serum levels of:
  • sodium physiology
  • calcium
• increased serum levels of:
  • potassium physiology
  • acids
  • phophate
  • magnesium
  • uric acid

• asterixis
• NM irritability
• mental state changes
• somnolence
• coma
• seizures

• nausea, vomiting
• gastritis
• peptic ulcers
• GIT bleeding
• malnutrition

• anaemia
• haemorrhagic diathesis

• pneumonia
• septicaemia
• urinary tract infections (UTIs) / cystitis
• wound infection