Hepato-renal syndrome (HRS) occurs in patients with advanced cirrhotic liver disease, obstructive jaundice or acute liver failure and is a diagnosis that involves the exclusion of other causes of AKI. The pathophysiology of HRS is complex and incompletely understood. With progressive liver disease there is a rise in cardiac output and a fall in systemic vascular resist- ance (SVR). The decrease in SVR results from the splanchnic vasodilation that occurs in asso- ciation with liver disease and has been proposed to be secondary to an increased secretion of a number of mediating factors, including glucagon, prostacyclin, nitric oxide and bacterial translocation. The reduced SVR in turn results in renal vasoconstriction and decreased renal blood flow (RBF) secondary to increased secretion of catecholamines, angiotensin, endothelin and antidiuretic hormone (ADH). Decreased RBF results in decreased renal perfusion and pre- renal AKI.
The onset of HRS is generally insidious but can be precipitated in a patient with advanced liver disease and ascites by a number of different insults, including gastrointestinal haemor- rhage, sepsis, excessive diuresis and nephrotoxins. A low urinary sodium (< 10 mmol/L) is characteristic but not diagnostic of HRS. Management includes central venous monitoring and optimisation of the patient’s volume status using colloid (20% salt-poor human albumin solution) while closely monitoring the urine output. Sepsis must be treated and intra-abdomi- nal hypertension from tense ascites relieved if present. Large volume paracentesis has been demonstrated to result in a reduction in intravascular volume and renal dysfunction. The cur- rent recommendation based on the International Ascites Club guidelines is to infuse 6–8 g of albumin per 1 L of ascites fluid removed for paracentesis volumes greater than 5–6 L. There are some reports of success using terlipressin and human albumin solution to improve renal perfu- sion or the use of transjugular intrahepatic portosystemic shunt (TIPS) in patients with chronic liver disease. Patients with HRS secondary to liver cirrhosis have a mortality greater than 95 per cent. Renal replacement therapy is considered only if the patient is judged to have recoverable liver function or is a candidate for liver transplantation.
Rhabdomyolysis (crush syndrome)
Rhabdomyolysis results from skeletal muscle injury and cell lysis with the release of myoglobin and other muscle breakdown products (K+, PO43–, urate). Myoglobin is freely filtered by the
Specific syndromes of acute kidney injury 83
Consider non-contrast investigation
(MRA, Doppler, CO2)
Adequate hydration is essential to reduce risk
*eGFR
mL/min/1.73 m2
eGFR
60
Assess fluid status
• oral fluids • 1 L pre- and post-procedure
All patients:
• assess volume status • minimise contrast volume • iso-osmolar contrast (iodixanol)
Admit pre-procedure:
• renal consultation • assess volume status
• IV sodium chloride 0.9% (**5% dextrose if liver disease) 1 mL/kg/h (caution if CCF) 12 h pre- and post-procedure • iso-osmolar contrast (iodixanol) • minimise contrast volume • serial serum Cr before discharge
In-patients:
• IV sodium chloride 0.9% • 1 mL/kg/h, 12 h pre- and post- procedure
• serial serum Cr before discharge
Out-patients:
• IV sodium chloride 0.9% started on admission, 1 mL/kg/h, 4–12 h post- procedure Diabetes mellitus, multiple myeloma, CCF, **liver disease eGFR 30–59 eGFR 30 or renal transplant or acute kidney injury Withhold for 24 h:
• ACE-I (unless CCF) • Loop diuretics (unless CCF) • NSAIDs/metformin (avoid in CKD) • Metformin (stop at the time of, or
before, the procedure and restart after 48 h if Cr stable)
No Yes
Avoid further contrast exposure for 72 h if possible
Figure 6.2 ● Contrast nephropathy protection guidelines.
ACE-I, angiotensin-converting enzyme inhibitor; CCF, congestive cardiac failure; CKD, chronic kidney disease; Cr, creatinine; eGFR, estimated glomerular filtration rate; MRA, magnetic resonance angiography; NSAID, non-steroidal anti- inflammatory drug.
MANAGEMENT OF ACUTE KIDNEY INJURY IN SURGICAL PATIENTS 84
kidneys and is directly toxic to the tubular epithelial cells, particularly in the setting of hypo- volaemia and acidosis. There are a number of causes, including trauma, burns, compartment syndrome and drugs (e.g. ecstasy, statins). Investigations supporting a diagnosis of rhabdomyo - lysis include increased CK, increased aspartate aminotransferase (AST) and urinary myoglo- bin. Additional electrolyte abnormalities include increased K+, increased PO43–, increased
Diagnosis of rhabdomyolysis • clinical presentation •↑CK
• urinary myoglobin
Assessment of volume status • CVP, BP, urine output urine pH No No No No Yes Yes Yes Euvolaemia IV 0.9% sodium chloride 10–15 mL/kg/h Aim for urine output
100 mL/h Hypervolaemic
Monitor clinical status closely
Monitor clinical status and U&Es
closely
Consider IV 50 mL 20% mannitol Avoid if hypervolaemic or in
established AKI
Monitor clinical status and U&Es
closely
May require RRT Urine output
100 mL/h
Urine output
100 mL/h chloride to volume-↑IV 0.9% sodium replete patient IV 0.9% sodium chloride to achieve urine output 100 mL/h Euvolaemic
Yes Consider adding
IV 1.26% sodium bicarbonate to fluid replacement regimen
Stop IV sodium bicarbonate if patient commences RRT or develops hypernatraemia or an alkalosis Avoid if • hypocalcaemia • oliguric • volume overloaded Urine pH 6.5 Yes Hypovolaemic
Figure 6.3 ● Prevention of rhabdomyolysis-induced acute kidney injury.
AKI, acute kidney injury; BP, blood pressure; CK, creatine kinase; CVP, central venous pressure; IV, intravenous; RRT, renal replacement therapy; U&Es, urea and electrolytes.
Specific syndromes of acute kidney injury 85 urate and decreased Ca2+(binds to damaged muscle). Effective management requires correc- tion of hypovolaemia in order to maintain renal perfusion pressure and dilute myoglobin and other toxins as outlined in Figure 6.3. Fluid resuscitation with 0.9% sodium chloride is pre- ferred at a rate of 10–15 mL/kg/h. The effective circulating volume must be restored to main- tain the urine flow rate of 100–150 mL/min. Although there is limited clinical evidence, it has been common practice to alkalinise the urine in order to prevent tubular precipitation of myo- globin. This can be achieved by the addition of sodium bicarbonate 1.26% to this regimen to maintain urinary pH above 6.5. Care must be taken to avoid causing hypernatraemia or pre- cipitating a metabolic alkalosis and hypokalaemia.
Mannitol has traditionally been used to prevent AKI secondary to rhabdomyolysis because of its free-radical-scavenging activity and ability to promote renal vasodilation and osmotic diuresis. There is no evidence, however, that mannitol is superior to aggressive fluid resuscita- tion in preventing AKI in the setting of rhabdomyolysis. Mannitol can be harmful due to the risk of rapid intravascular volume expansion leading to pulmonary oedema and resulting in hyperoncotic kidney injury. Its use should therefore be restricted to the high dependency unit/intensive care unit environment and then only after careful evaluation of the patient’s volume status. Hypocalcaemia should not be treated per se unless the patient is symptomatic or if intravenous calcium is required to treat hyperkalaemia, due to the risk of metastatic calcifi- cation and further tissue necrosis. Rebound hypercalcaemia can occur later following release of calcium from damaged muscle.
Obstruction
Urinary tract obstruction is identified in the majority of cases by ultrasound; however, the renal tract may fail to dilate in patients with obstruction secondary to retroperitoneal fibrosis or malignancy encasing the pelvis or ureter. Failure to identify obstruction may also occur when the patient is both obstructed and hypovolaemic. If obstruction is strongly suspected, then a computed tomography (CT) scan or cystoscopy with retrograde pyelography should be consid- ered. Prompt relief of the obstruction must be achieved, as delay increases the risk of long-term kidney damage. Obstruction of a pyelonephrosis can result in rapid destruction of renal tissue.