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Renal failure

Up Renal failure Renal replacement therapy RTA


Hepatorenal syndrome
IAP measurement
Rhabdomyolysis
Sepsis & AKI

Renal failure - acute

Aetiology

Pathogenesis

Clinical presentation

Investigations

Prevention

Management

Renal replacement therapy

Intra-abdominal pressure

Hepatorenal syndrome

Rhabdomyolysis

Epidemiology

Difficult to determine incidence accurately due to varying definitions of acute renal failure

  • occurs in ~15-25% of ICU admissions
  • in ~10% of cases acute renal failure occurs in isolation (ie single organ failure)

Aetiology

Pre-renal

  • hypovolaemia
  • low cardiac output states
  • solute depletion
  • septic shock
  • liver dysfunction
  • drugs (eg cyclosporin, tacrolimus) may induce vasoconstriction of small renal vessels
  • combination of ACE inhibitors and diuretics can cause prerenal failure in patients with large or small vessel renal vascular disease

Renal

Tubular necrosis

  • Ischaemic
    Many factors can lead to renal ischaemia. These include:
    - intravascular volume depletion and hypotension
    – renal vascular disease (large/small vessel) 
    – decreased effective intravascular volume (CCF, cirrhosis, nephrosis, peritonitis)
    – drugs eg cyclosporin, tacrolimus, ACE inhibitors, NSAIDs, radiocontrast, amphotericin B
    – sepsis
    – hepatorenal syndrome
    Most cases are reversible if underlying cause is treated but irreversible renal failure may occur if ischaemia is severe.
  • Toxic
    aminoglycosides and radiocontrast most common
    – haem pigments
    – chemotherapy (eg cisplatin)
    – myeloma light chain proteins

Interstitial nephritis

Most commonly due to allergic reaction to a drug

Other causes include autoimmune disease (eg SLE), infiltrative disease (eg sarcoid), infections (eg Legionnaire’s, hantavirus)

Often reversible after treatment of underlying cause

Acute glomerulonephritis

  • especially acute post-streptococcal GN, SBE, shunt nephritis, RPGN, anti GBM GN

Acute pyelonephritis

Renal graft rejection

Post renal

  • obstructive nephropathy
  • raised intra-abdominal pressure. Pressure ³ 25 cm H2O considered significant although there is data suggesting that pressures as low as 12 cm H2O may reduce renal blood flow

Drugs frequently responsible for renal dysfunction:

  • radiocontrast agents
  • aminoglycosides
  • b lactams
  • acyclovir
  • amphotericin
  • pentamidine
  • heavy metals
  • sulphonamides
  • cisplatin
  • methotrexate
  • NSAIDs

Pathogenesis

Mechanisms responsible vary according to aetiology. In the case of "acute tubular necrosis" mechanisms include:
- medullary ischaemia (particularly of the thick ascending loop of Henle) with activation of tubuloglomerular feedback and subsequent decrease in GFR and urine output
- tubular obstruction due to casts of damaged tubular cells
- interstitial oedema due to back diffusion of ultrafiltrate from tubular lumen through damaged tubular cells
- severe, humorally mediated vasoconstriction due to systemic release of vasoactive substances in context of sepsis and organ injury

Inadequate renal blood flow common in critically ill patients. Frequently results in a reduction of GFR. Lower limit for autoregulation is approx. 80 mm Hg for RBF and 10-15 mm Hg higher for GFR. Below this level the pressure-flow relationship is linear and thus optimization of renal perfusion pressure is critical. Although there is a theoretical risk of renal vasoconstriction with the use of vasopressors both laboratory and clinical data suggest that such reactions rarely occur with IV infusions of these drugs and that RBF and renal function usually improve when renal perfusion pressure is augmented during shock.

Animal experiments suggest that even relatively minor insults which are insufficient to cause a clinically detectable change in renal function may abolish autoregulation. The result of this is that even a relatively small fall in renal perfusion pressure may then cause impaired renal function.

The outer medulla functions normally under hypoxic conditions as a result of limited regional oxygen supply (due to the countercurrent arrangement of the vasa recta in this region) and as a result of high oxygen consumption for urinary concentration. Oxygen extraction is approx. 90% for this region (cf approx 10% for the kidney as a whole). Any factors which decrease oxygen delivery or increase oxygen consumption may lead to medullary ischaemic damage. In experimental models more than one factor is required to produce ischaemic damage: an insult plus a factor which interferes with the compensatory mechanisms. Conditions which predispose to medullary hypoxic injury:

  • systemic causes for renal hypoperfusion
  • causes of medullary hypoperfusion
    - altered vascular architecture/external compression: chronic renal disease, atherosclerosis, obstruction, pyelonephritis
    - rheological alterations: endotoxaemia, severe dehydration, contrast, sickle cell anaemia, falciparum malaria
    - impaired nitrovasodilatation: aging, atherosclerosis, hypertension, contrast
    - impaired PG synthesis: NSAIDs
    - excessive local endothelin activity: cyclosporin, contrast, regional hypoxaemia
  • increased medullary oxygen demand
    - compensatory hypertrophy of remnant nephrons: any chronic renal disease
    - solute diuresis: uncontrolled DM, hypercalcaemia, mannitol, contrast, dopamine, polyene antibiotics
    - augmented GFR: pregnancy, early DM

Clinical presentation

  • oliguric or polyuric. Latter associated with a better prognosis but there is no evidence that conversion of former to latter results in an improvement in outcome
  • once renal failure becomes established and supportive care is initiated duration of oliguria and inadequate excretory function is variable. Depends on resolution of intial injury, its severity, and premorbid condition of kidneys. Generally a period of 2 weeks is required before sufficient renal function returns (range: few days-many weeks)
  • initially urine output returns but excretory function is limited, With time latter also increases
  • ± polyuria in recovery phase. Care should be taken to avoid hypovolaemia which will cause further injury
  • current evidence suggests that continuous renal replacement therapy or intermittent HD with biocompatible membranes may be associated with faster recovery than conventional intermittent HD

Investigations

Urinary profile (value controversial)

 

Pre-renal

ATN

Sediment

Normal

Tubular cells, cell & granular casts

Sodium*

Low; <20 mmol/l

High; >40 mmol/l

U:P urea

High >20

Low <10

U:P creatinine

High >40

Low <10

U:P osmolality

High >2.1

Low <1.2

Osmolality*

High (>serum + 100)

Low (<serum + 100)

  • NB *= not applicable unless the patient is clinically dehydrated. None of the above biochemical tests are valid if the patient has already received diuretics

In absence of red cells heme-positive urine on dipstick testing suggests presence of myoglobin or haemoglobin (ie rhabdomyolysis or intravascular haemolysis)

Do not allow complete separation of pre-renal failure and ATN. For example, early in the course of certain conditions which lead to tubular damage (eg myoglobinuria, exposure to radiocontrast, sepsis or obstruction) urinary sodium may be low

Urine microscopy and culture

  • important in all patients with acute renal failure regardless of likely aetiology
  • urinary sepsis must always be excluded
  • examine sediment for WBCs, WBC and RBC casts and fragmented RBCs. Pigmented granular casts typically found in ischaemic or toxin induced renal failure, white cell cases suggest interstitial nephritis and red cell casts glomerulonephritis.
  • urinary eosinophilia suggests allergic interstitial nephropathy but is also associated with atheroembolism and pyelonephritis

Ultrasound

  • to exclude obstruction
  • bilateral small kidneys suggest chronic renal disease
  • enlargement of kidneys often occurs transiently following ATN and in acute GN

± IVP

  • nephrogram persisting for hours/days suggests ATN rather than pre-renal renal failure

Renal biopsy

Indications:

  • features suggesting pathology other than ATN
  • prolonged recovery

Prevention

  • Measures to enhance GFR in the context of acute renal failure should be carefully evaluated as they could further compromise medullary oxygen balance if associated with increased tubular work.
  • Frusemide theoretically could improve medullary oxygen balance by inhibition of regional oxygen requirements although it reduces medullary blood flow. In experimental models of contrast nephropathy frusemide in combination with hydration attenuated tubular damage. However, in clinical practice it may adversely affect renal function because of both volume depletion and systemic and medullary vasoconstriction. Systemic vasoconstriction may be particularly prominent with bolus injection and continuous infusion may be preferable if frusemide is used.
  • Mannitol is potentially deleterious to medullary oxygenation, its protective effect on the kidney has not been established and it may not be any more effective than volume expansion with saline.
  • Although dopamine has the potential to specifically increase RBF and GFR current data do not conclusively show any benefit and no prospective, randomized clinical study has demonstrated a specific advantage. Increased urine output following the administration of dopamine may simply reflect its diuretic action or its haemodynamic effects. Also although dopamine has differential dose related effects it may not be possible to predict the effect from the infusion rate. In a study in critically ill adults plasma levels of dopamine were found to bear no relationship to infusion rate. With regard to medullary oxygenation dopamine’s potential beneficial action is a possible improvement in renal microcirculation but against this must be balanced its effect on medullary oxygen demand. Clinical and laboratory studies suggest that regional hypoxaemia is not improved and intrarenal damage may actually increase in some circumstances.
  • Dobutamine (2.5 m g/kg/min) has been shown to increase creatinine clearance with a small increase in urine volume in a small study of critically ill patients thought to be at increased risk of developing renal failure. The rise in creatinine clearance was associated with a rise in cardiac output. In the same patients dopamine increased urine output without increasing creatinine clearance (ie its effect on the kidney was limited to diuresis)

Management

Renal replacement therapy

  • current trend is towards early and aggressive therapy rather than waiting for complications such as hyperkalaemia, acidosis, pulmonary oedema and uraemia to develop

Nutrition

  • administration of a low protein diet to delay inevitable renal replacement therapy or to lengthen the interval between sessions is physiologically unsound
  • nutritional requirements are no different from critically ill patients who do not have renal failure

Infection

  • increased risk of infection: uraemia associated with impaired immune function and invasive lines predispose to infection
  • remove urinary catheter if oliguria or anuria are present

Intra-abdominal pressure

  • Raised intra-abdominal pressure reduces renal perfusion pressure by increasing downstream pressure
  • Also reduces splanchnic blood flow
  • 25 cmH2O is usual threshold for relief of raised IAP but there is evidence that IAP as low as 12 mmHg may have deleterious effects on renal function
  • can be measured via urinary catheter

© Charles Gomersall November 1999

 

©Charles Gomersall, April, 2014 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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