1. Explain the definition of classification of Acute Renal Failure
   1. definition of Acute Renal Failure
      1. 'abrupt decline in renal function'
      2. sudden and usually reversible loss of renal function
      3. which develops over a period of days or weeks
      4. and is usually accompanied by a reduction in urine volume
   2. classification
      1. pre-renal
         1. reduced real or 'effective' blood volume
         2. structurally normal but functionally compromised
         3. inadequate perfusion
         4. 50-60%
      2. renal
         1. glomerulus
         2. tubules
         3. interstitium
         4. ie structurally abnormal
         5. intrinsic renal disease
         6. 20-35%
      3. post-renal
         1. obstruction - multiple levels (ureter, bladder etc)
         2. must be bilateral or single if there is only one functioning kidney
         3. urinary tract obstruction
         4. 15%
      4. RIFLE
         1. Risk
         2. Injury
         3. Failure
         4. Loss
         5. End Stage Renal Disease
2. Give examples of pre-renal, renal and post-renal ARF
   1. frequently multifactorial
   2. pre-renal
      1. inadequate cardiac function
         1. hypotension (reduced effective extracellular volume)
            1. septic/cardiogenic/anaphylactic shock
            2. liver failure
            3. heart failure
      2. circulatory volume depletion
         1. hypovolaemia
            1. bleeding
            2. 3rd space fluid losses (ie where fluid normally don't accumulate eg pleura)
            3. from pancreatitis
            4. or bowel obstruction
            5. overenthusiastic diuretic therapy
            6. dehydration
            7. secondary to renovascular disease (+/- ACEI)
            8. excessive loss of GI tract fluids
            9. diarrhoea
            10. vomiting
            11. excessive loss of fluid due to burn injury
      3. obstruction of arterial supply to kidneys /decreased renal perfusion
         1. renal artery stenosis
         2. vasoactive mediators
            1. endotoxins?
         3. drugs
            1. including radiocontrast agents
         4. hypercalcaemia
      4. elderly at high risk
         1. because of predisposition to hypovolemia
         2. and high prevalence of renal vascular disorders
   3. renal
      1. vascular insults
         1. large vessel
            1. renal artery occulsion
            2. bilateral renal artery stenosis
            3. in patients on ACEi
         2. intrarenal SMALL VESSEL occlusion
            1. haemolytic uraemic syndrome
            2. thrombotic thrombocytopaenic purpura
            3. scleroderma
            4. vasculitis
            5. atheroembolic disease with cholesterol emboli
      2. tubulointerstitium
         1. Acute tubular necrosis
            1. multifactorial
            2. GFR does NOT improve with restoration of renal blood flow in acute renal failure caused by ischaemic ATN, in contrast to pre-renal failure
            3. usually due to ischaemia
            4. hypotension
            5. from sepsis, bleeding
            6. dehydration
            7. burns
            8. inappropriate diuretics
            9. major surgery
            10. hypovolaemia
            11. or nephrotoxic agents
            12. NSAIDS
            13. aminoglycosides
            14. contrast agents
            15. urinary sepsis
            16. gentamycin
            17. cisplain
            18. amphotericin B
            19. or toxins from infection
            20. intratubular obstruction
            21. myoglobin
            22. rhabdomyolysis
            23. haemoglobin
            24. uric acid
            25. myeloma
         2. acute allergic interstitial nephritis
            1. drug related
            2. proton pump inhibitors
            3. NSAIDs
            4. diuretics
            5. allopurinol
         3. acute interstitial nephritis
            1. sarcoidosis
         4. myeloma kidney
            1. http://www.unckidneycenter.org/ kidneyhealthlibrary/myeloma.html
      3. glomerular
         1. rapidly progressive glomerulonephritis/ crescentic glomerulonephritis
            1. immunological aetiology
            2. characterised by glomerular crescents
            3. EXAMPLES
            4. Goodpasture's syndrome
            5. anti-GBM Ab
            6. Wegener's granulomatosis
            7. c-ANCA
            8. Microscopic polyarteritis
            9. p-ANCA
            10. Systemic Lupus Erythematosus
            11. anti-nuclear Ab
            12. anti-dsDNA Ab
         2. haemolytic uraemic syndrome
            1. e.coli 0157
            2. familial cases
            3. glomerular microvascular thrombosis
         3. thrombotic thrombocytopaenic purpura
   4. post-renal
      1. again, must be bilateral or equivalent
         1. in order to result in ARF
      2. prostate
         1. hypertrophy
         2. cancer
      3. bladder lesions
         1. tumour
      4. ureter
         1. <= calculi
            1. ureteral stones = kidney stones that have moved down ureter
         2. tumour
            1. transitional cell carcinoma
            2. = cancer that typically occurs in the urinary system
         3. extrinsic compression
            1. retroperitoneal fibrosis
            2. extra fibrous tissue forms around stomach and intestines
            3. the excess tissue can form a mass which can block the ureters
            4. tumour
            5. cervical cancer
3. Explain the metabolic disturbances caused by ARF if left untreated
   1. pre-renal
      1. when perfusion pressure falls, resistance vessels in kidneys dilate to facilitate flow.
         1. to compensate...
            1. vasodilator prostaglandins are important
            2. autoregulation, constriction of efferent arteriole through RAAS
      2. more severe/prolonged underperfusion
         1. lead to failure of compensatory mechanisms
         2. renal tubules become hyperfunctional
            1. ie Na/H2O reabsorption increased
            2. which produces concentrated, low volume of urine which is low in Na
   2. renal
      1. ATN
         1. tubular injury usually reversible
            1. process depends on recovery of injured cells, removal of necrotic cells and intratubular casts and regeneration of renal cells
            2. to restore normal continuity of tubular epithelium
         2. irreversible renal failure occurs...
            1. if ischemia is severe enough to cause cortical necrosis
         3. hyaline/granular casts
            1. =dead debris
   3. post-renal
      1. urinary obstruction
         1. stasis of urine
            1. infection
            2. stone formation
            3. development of backpressure
            4. interferes with renal blood flow
            5. destroys kidney tissue
            6. hydronephrosis
            7. =water in kidneys
            8. back-up of water from blockage further along the way
            9. dilated calyces
   4. General
      1. azotemia
         1. = accumulation of nitrogenous wastes (urea nitrogen, uric acid, creatinine) in blood
      2. when blood flow falls below ~20% of normal, ischaemic changes occur
         1. tubular epithelial cells most vulnerable
      3. sharp decrease in urine output
      4. disproportionate elevation of blood urea nitrogen (BUN) compared to creatinine
         1. 10:1 to 20:1
         2. because urea is reabsorbed back into blood
         3. whereas creatinine (big protein) stays in tubules
   5. CLINICAL COURSE
      1. 1. Onset/Initiating Phase
         1. lasts hours-days
         2. time from onset of precipitating event until tubular injury occurs
      2. 2. Maintenance Phase
         1. characterised by marked decrease in GFR
         2. cause sudden retention of endogenous metabolites
            1. eg urea
            2. potassium
            3. sulphate
            4. creatinine
         3. urine output lowest at this point (oliguria)
            1. if prolonged...
            2. hypertension develops
            3. uraemia develops
            4. neurologic manifestations
            5. neuromuscular seizures
            6. uraemic encephalopathy
            7. uraemic pericarditis
            8. with bleeding and cardiac tamponade
            9. somnolence
            10. extreme drowsiness
            11. coma
            12. death
            13. hyperkalaemia
            14. usually asymptomatic
            15. until serum levels of K rise above 6.0-6.5 mEq/L
            16. characteristic ECG changes
            17. muscle weakness
         4. fluid retention
            1. oedema
            2. water intoxication
            3. pulmonary congestion
      3. 3. Recover/Convalescent Phase
         1. repair of renal tissue takes place
         2. show gradual increase in urine output
            1. and fall in serum creatinine
            2. which means nephrons have recovered!
         3. diuresis (urine production) often occurs before renal function is normal
            1. BUN and serum creatinine, potassium, phosphate levels may remain elevated/ rise even if urine output is increased
         4. in some cases, mild-moderate kidney damage persists
4. Explain the indications for commencing renal replacement therapy in patients with ARF
   1. Diagnosis
      1. clinical history
         1. past renal history
            1. infections
            2. family history
            3. prostatism
            4. decreased force of urination
            5. dysuria
            6. from enlarged prostate
            7. anuria
         2. drugs or contrast exposure
         3. hypertension/diabetes
         4. systemic symptoms
            1. rash
            2. joint symptoms
            3. haemoptysis
            4. for autoimmune disease with underlying rapidly progressive glomerulonephritis
      2. clinical examination
         1. fluid status
            1. bp - postural drop
            2. JVP
            3. sacral/peripheral oedema
            4. lung crepitations
            5. body weight for acute changes
         2. other
            1. rash
            2. drug reaction
            3. bruit over arteries
            4. fundoscopy
            5. palpable kidneys
            6. adult polycystic disease or hydronephrosis
            7. palpable bladder
            8. obstructive uropathy
      3. investigations
         1. urine tests
            1. urine myoglobin
            2. rhabdomyolosis
            3. dipstick
            4. proteinuria
            5. haematuria
            6. = glomerular inflammation
            7. biochemistry
            8. to differentiate pre-renal uraemia from established ATN
            9. pre-renal uraemia suggested by
            10. urine Na < 10 mmol/L
            11. urine osmolality >500 mosmol/kG
            12. ratio of urine to plasma osmolality > 1.5
            13. Specific gravity > 1.018
            14. i.e. an appropriately concentrated urine
            15. ATN suggested by
            16. urine Na > 40
            17. osmolality < 300
            18. ratio of urine to plasma osmolality < 1.1
            19. Specific gravity < 1.015
            20. i.e. isotonic urine that has not been altered much during passage through the nephron
            21. Bence Jones protein
            22. for light chains indicated in myeloma
         2. blood tests
            1. full blood count and blood film
            2. clotting screen
            3. biochemistry
            4. Ca or phosphate
            5. liver function test
            6. albumin
            7. creatine kinase
            8. very high in rhabdomyolosis since it's released from injured muscle
            9. blood culture
            10. for infection
            11. virology and serology
            12. Hep B
            13. Anti-Streptolysin O
            14. for streptococci infections
         3. immunological tests
            1. immunoglobulins and serum electrophoresis
            2. for myeloma
            3. complement levels
            4. SLE
            5. autoantibodies
            6. ANA
            7. SLE
            8. ANCA
            9. vasculitis
            10. anti-GBM Ab
            11. Goodpasture's syndrome
         4. other tests
            1. ULTRASOUND CRITICAL
            2. renal biposy
            3. in those with normal sized kidneys, no obstruction, ARF if it could be ATN
            4. angiography
            5. +/- intervention in renovascular disease
            6. chest X-ray
            7. cardiac size, pulmonary oedema, haemorrhage
            8. ECG
            9. hyperkalaemia
   2. Indications for dialysis/continuous renal replacement therapy
      1. when nitrogenous wastes and water/electrolyte balance cannot be kept under control by other means
      2. severe uraemia
         1. very high urea/creatinine
         2. with NO PROSPECT OF IMMEDIATE IMPROVEMENT
      3. hyperkalaemia unresponsive to medical treatment >6.5
      4. fluid overload
         1. esp pulmonary oedema
         2. resistant to treatment with diuretics/fluid restriction
      5. severe acidosis
         1. ADMINISTRATION OF NaHCO3 CAN EXACERBATE Na/water OVERLOAD
5. Explain the principles underlying the treatment of acute renal failure
   1. optimise fluid balance and circulation
   2. institute specific treatment for underlying cause
      1. examples
         1. obstruction
            1. drain renal tract
         2. Sepsis
            1. culture then give effective antibiotics
         3. RPGN
            1. Wegener's granulomatosis
            2. immunosuppression
            3. steroids
            4. cyclophosphamide
            5. Goodpasture's syndrome
            6. plasma exchange (to remove circulating autoantibodies and immunosuppression
         4. compartment syndrome
            1. fasciotomy
            2. to release muscle compression and limit further muscle damage
   3. stop exacerbating factors
      1. examples
         1. nephrotoxic drugs
   4. appropriate prescribing
   5. supportive treatment
      1. dialysis
         1. intermittent haemodialysis
            1. vascular access related complications
            2. pneumothorax
            3. infection
            4. bleeding
            5. dialysis membrane- 'biocompatible' synthetic membranes now used
            6. anticoagulation
            7. hypotension may be troublesome
            8. sepsis
            9. ischaemic heart disease
            10. diabetes
         2. continuous haemodialysis
            1. useful in ITU setting
            2. for haemodynamically unstable, hypercatabolic patients with large fluid fluxes
            3. CVVH
            4. CVVHD
         3. peritoneal dialysis
      2. nutrition
         1. low K+ diet for those with hyperkalaemia