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Treatment and Prevention of Perioperative Renal Dysfunction
KIDNEY
The normal GFR is around 125 ml/minute. Approximately 180 l of water is filtered in 24 hours, but about 1.5 l is lost in the urine. Autoregulation of renal blood flow results in a relatively stable glomerular hydrostatic pressure and therefore GFR. If arterial blood pressure falls below 60 mmHg (e.g. shock) glomerular filtration ceases and anuria occurs.
Treatment and Prevention of Perioperative Renal Dysfunction
Juxtaglomerular apparatus lies adjacent to the vascular pole of the glomerulus and secretes renin in response to the following: • reduced blood volume (low afferent arteriolar pressure) • sympathetic nerve stimulation (e.g. stress) • circulating catecholamines • low sodium concentration in distal tubule • renal ischaemia. Renin hydrolyses angiotensinogen to form angiotensin I. Angiotensin I is converted to angiotensin II by a converting enzyme which is found in the kidney and lung. Angiotensin II has the following effects: • stimulation of aldosterone release from the adrenal cortex • stimulation of sodium ions reabsorption in the proximal convoluted tubule • vasoconstriction of efferent arterioles to maintain GFR when blood pressure is low • stimulation of antidiuretic hormone (ADH) release • stimulation of thirst.
Andrew T Raftery
Basic renal physiology The kidneys contribute to biochemical homeostasis by: • eliminating waste products • regulating fluid and electrolyte balance • regulating acid–base balance. They also produce certain hormones, of which renin is the most important in the context of perioperative renal function. The basic unit of the kidney is the nephron, which is composed of a glomerulus and tubular system. The number of nephrons decreases with age. Blood is filtered at the glomerulus and enters Bowman’s capsule, from whence there is a system of tubules which modifies the filtered plasma. The tubular system comprises the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule and collecting ducts.
Tubular function The glomerular filtrate, which is isotonic with respect to plasma, is modified osmotically in the tubules so that water and electrolytes are conserved and waste products concentrated for elimination. Ninety-nine percent of the filtered volume (together with important constituents of the filtrate) are reabsorbed in the various tubules, which differ in their function.
Glomerular function The glomerular filtration rate (GFR) is dependent upon the glomerular capillary arterial pressure (60 mmHg) minus plasma colloid osmotic pressure (30 mmHg) plus the hydrostatic pressure in Bowman’s capsule (20 mmHg). That is, the filtration pressure is 60 − (30 + 20) = 10 mmHg. Arterioles before and after the capillary bed in Bowman’s capsule (afferent and efferent arterioles) are capable of adjusting glomerular pressure and therefore flow. Constriction of the afferent arterioles decreases capillary pressure and therefore filtration. Constriction of the efferent arteriole increases capillary pressure and increases filtration. GFR may be calculated by measuring the clearance of a substance from the blood into the urine. In clinical practice, GFR is usually measured as creatinine clearance, since creatinine is produced endogenously and does not need to be infused intravenously. GFR =
UV ml/minute P
where:
P = plasma concentration in mg/ml V = volume of urine in ml/minute U = urine concentration mg/ml
Proximal convoluted tubule: approximately 60–80% of filtered water and sodium is reabsorbed every 24 hours in the proximal tubules. In addition, the proximal tubular cells absorb potassium, phosphate and glucose, and secrete hydrogen ions and ammonia into the lumen. Loop of Henle is responsible for the creation of a high renal medullary osmotic pressure by a countercurrent multiplier system. There is active transfer of sodium from the tubular fluid into the interstitium by cells of the ascending limb creating a hypertonic environment in the interstitium of the medulla. By the time the filtrate enters the distal tubule in the cortex, it has lost a considerable amount of sodium and is hypo-osmotic with respect to cortical plasma. Distal convoluted tubule: sodium chloride is absorbed throughout the distal tubule. The distal part of the tubule is permeable to water, and 10–12 l of water per day is absorbed under the control of ADH. Potassium and hydrogen ions and ammonia are secreted into the distal tubule.
Andrew T Raftery is a Consultant in General Surgery and Renal Transplantation at the Northern General Hospital, Sheffield, UK. He qualified from Leeds University, UK, and trained in Leeds, Pontefract and Cambridge, UK. His research interests include peritoneal wound healing and adhesion formation, and cyclosporin nephrotoxicity. He is a member of the Court of Examiners of the Royal College of Surgeons, UK, and an examiner for the Intercollegiate Board in General Surgery.
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Collecting ducts pass through the renal cortex and medulla and drain urine into the renal pelvis. Sodium reabsorption continues in the collecting ducts. ADH primarily exerts its effects on the collecting ducts. In the absence of ADH secretion (as in diabetes
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insipidus), the permeability of the ductal epithelium to water is greatly reduced and patients may pass in excess of 20 l of urine in 24 hours with an osmolality of <50 mosmol/l. With maximal ADH levels, as little as 500 ml of urine is excreted in 24 hours, with an osmolality of about 1200 mosmol/l.
Oliguria is usually the first manifestation of renal dysfunction. Anuria is the complete absence of urine. Reduction in urine output despite adequate fluid replacement is normal in the early postoperative period after major surgery. Following surgery or trauma, certain physiological responses occur in the body. Catecholamines are released and stress stimulates the hypothalamo–pituitary–adrenal axis with an increase in secretion of cortisol and aldosterone. These hormones produce conservation of sodium and water by the kidney, resulting in a reduction of the urine volume and urine sodium concentration. ADH secretion from the posterior pituitary gland also leads to water retention. Causes of oliguria/anuria include: • blocked catheter • all causes of renal failure (see later) • all causes of shock. Acute renal failure is largely preventable by careful attention to the preoperative assessment of renal function, adequate fluid balance, prompt management of hypotension and sepsis, as well as avoidance and/or careful monitoring of nephrotoxic drugs. In patients who are considered high risk (e.g. pre-existing renal disease, obstructive jaundice, or those undergoing aortic surgery or cardiopulmonary bypass), consideration should be given to intraoperative renal dose dopamine to increase renal perfusion.
Preoperative assessment of renal function The patient may have a known history of renal disease or may have other co-morbid conditions associated with impaired renal function, such as: • hypertension • congestive cardiac failure • diabetes mellitus • obstructive jaundice • drugs (e.g. NSAIDs). Simple preoperative renal monitoring requires: • urea, electrolytes, creatinine • urinalysis. If any of the above indices are abnormal, then further investigations may be required, including: • urine microscopy and culture • urinary electrolytes • urine osmolality • creatinine clearance • 24-hour urinary protein • full blood count (anaemia, sepsis) • clotting screen (coagulopathy) • blood gases (hypoxia, acidosis) • chest radiograph (fluid overload) • ECG (hyperkalaemia). Depending on the results of the above investigations, other, more sophisticated investigations may be required: • chromium-51-labelled ethylenediaminetetra-acetic acid (51CrEDTA, measures GFR) • dimethylenetriamine penta-acetic acid (DTPA) or dimercaptosuccinic acid (DMSA) nuclear imaging • CT scan • MRI scan • renal biopsy. Every effort should be made to optimize renal function prior to elective surgery. A nephrologist should be involved at an early stage. In patients with impaired renal function, the following are necessary: • avoidance of dehydration • central venous pressure (CVP) monitoring • avoidance of nephrotoxic drugs • strict fluid balance assessment.
Management of oliguria: after exclusion of catheter blockage by flushing or replacement of the catheter, consideration must be given to whether there is evidence of urinary tract obstruction. A thorough examination to exclude post-renal causes should be made. The penis should be inspected to exclude meatal stenosis, stricture or stone. Rectal examination should be performed to assess for prostatic enlargement and rectal or pelvic masses. Vaginal examination should be performed to exclude pelvic malignancy. The bladder (acute or chronic retention), and the kidneys (hydronephrosis, pyonephrosis) should be palpated. If there has been recent pelvic surgery, possible ureteric damage should be suspected if the patient is anuric. If urinary tract obstruction is suspected, or no other cause can be found, ultrasound examination is indicated. The most common causes of post-renal failure are calculous disease and prostatic hypertrophy. A characteristic feature of early post-renal acute renal failure is a rapid rise in blood urea compared to creatinine, due to tubular reabsorption of urea. Treatment of post-renal obstruction requires urgent intervention and often dialysis may be avoided if intervention is rapid and successful. Renal tract obstruction should be managed jointly by nephrologists, urologists and interventional radiologists. If the cause of acute renal failure is prostatic obstruction, urethral catheterization or suprapubic cystostomy is appropriate. In other cases, antegrade or retrograde pyelography may be required to make the diagnosis. Relief of obstruction will depend upon the cause and site. If this is in the upper urinary tract, ureteric catheterization or percutaneous nephrostomy will relieve the obstruction prior to definitive surgery. If there is no evidence of obstruction, then one must exclude a pre-renal cause. The distinction between pre-renal failure and acute tubular necrosis (ATN, see below) due to haemodynamic instability may be difficult. Biochemical analysis of the urine
Intraoperative management of renal function ECG and urine output monitoring should be performed. Avoid intraoperative administration of nephrotoxic drugs. In patients undergoing major surgery with a need for massive blood transfusion (particularly those with renal dysfunction) care should be taken to avoid hyperkalaemia and hypocalcaemia. Intraoperative renal dose dopamine may be beneficial in increasing renal perfusion. Oliguria Oliguria is the passage of <20 ml/urine per hour (400 ml/day).
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may be helpful. In pre-renal failure, the urine electrolyte levels reflect the response of normal tubules to impaired renal perfusion. There is retention of sodium and water leading to low urinary sodium with high urinary urea and creatinine. The urine osmolality is high. Restoration of renal perfusion leads to a rapid improvement in renal function. With ATN, the urinary sodium is elevated and concentrations of urea and creatinine are low. The urine osmolality is also low. These changes reflect tubular dysfunction. Whatever the treatment of tubular dysfunction, renal function rarely improves rapidly. The changes in urinary biochemical indices in pre-renal failure and ATN are shown in Figure 1. If there is a pre-renal cause, the factors responsible for this should be corrected e.g. correct hypovolaemia, correct hypotension, correct cardiac failure. Monitoring should include: • accurate fluid balance chart (pulmonary oedema) • urea and electrolytes (hyperkalaemia) • arterial blood gases (metabolic acidosis). Having excluded catheter blockage (urinary retention) or renal tract obstruction, oliguria or anuria may be considered to be due to a pre-renal or renal cause. In the majority of cases this will be due to pre-renal causes and at this stage acute renal failure may be prevented by judicious management. The following sequence should be adopted: • Fluid challenge with a bolus of 250–500 ml of fluid. In the elderly or those with cardiac disease, CVP should be monitored. • If the above fails to produce a diuresis and the patient is adequately filled, frusemide (80–250 mg i.v.) should be administered. • If no response occurs, a CVP line should be inserted and adequate filling pressure established prior to administration of dopamine at a rate of 0.5–2.5 µg/kg/minute. Higher doses may cause arterial constriction. If these measures fail to produce a diuresis, then the patient is developing ATN, which should be managed jointly with a nephrologist.
Acute renal failure (ARF) ARF is defined as a rapid decline in renal function over hours or days which is of sufficient severity to disturb homeostasis. It may result from impaired renal perfusion (pre-renal), intrinsic renal disease (renal) or obstruction of the renal tract (post-renal). Causes of ARF are shown in Figure 2. The majority of causes of ARF are in the category of pre-renal failure or ATN. The term pre-renal is used when renal dysfunction is entirely attributable to hypoperfusion of the kidney and restoration of renal perfusion leads to resumption of renal function. The term ATN is used to define a sequence of events that comprises: • compromise of the circulation and/or effect of nephrotoxins • urinary abnormalities suggestive of tubular dysfunction • recovery of renal function within days or weeks. Pre-renal failure and ATN are invariably associated with shock. In the absence of shock it is unlikely that the cause of ARF is pre-renal or ATN due to haemodynamic compromise. In this context it is important to consider intrinsic renal or post-renal obstructive causes.
Causes of acute renal failure • Pre-renal Dehydration Haemorrhage Burns Acute pancreatitis Sepsis Congestive cardiac failure • Renal Renovascular disease embolus thrombosis Parenchymal renal disease renal ischaemia (acute tubular necrosis) nephrotoxins (e.g. gentamicin, radiographic) contrast medium glomerulonephritis interstitial nephritis impaired uric acid metabolism Myoglobinuria crush injury compartment syndrome Haemoglobinuria haemolysis
Distinction between physiological oliguria and acute renal failure Urine Specific gravity Osmolality mosm/kgH2O Sodium mmol/l Urine/serum creatinine Fractional sodium excretion* Renal failure index**
Physiological oliguria >1020 >500 <15 >40 <1 <1
Acute renal failure <1010 <350 >40 <20 >2 >2
• Post-renal Ureteric obstruction (e.g. calculous disease, especially with single kidney) Prostatic hypertrophy Urethral abnormalities Pelvic tumours Retroperitoneal fibrosis
* Fractional sodium excretion = Urine sodium × Plasma creatinine × 100 Plasma sodium x Urine creatinine ** Renal failure index =
Urine sodium × Plasma creatinine Urine creatinine
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Most aetiological factors leading to pre-renal failure are invariably associated with ADH secretion. ADH acts on the collecting ducts to increase tubular reabsorption of water but also of urea. This may explain why the plasma urea increases out of proportion to the creatinine in pre-renal failure. The clinical diagnosis of ARF is made when there is a progressive rise in serum urea and creatinine, which occurs only when more than 50% of glomerular function is lost. Other important changes of ARF include: • oliguria • salt and water retention (oedema) • hyperkalaemia • metabolic acidosis. Hyperkalaemia results, not only from reduced urinary excretion, but also from potassium released from cells associated with: • extensive tissue damage • increased catabolism (e.g. sepsis, burns) • rhabdomyolysis (e.g. crush injuries, compartment syndrome). In ARF, the plasma [Na+] is usually normal, since deficits of sodium are usually matched by those of water. Hence, extracellular volume may be reduced, but plasma sodium concentration remains the same. However, if water intake exceeds the rate of its excretion, then hyponatraemia may result. Classically, there are three phases of ARF, and these are discussed below.
tion may persist, with maximum concentrating capacity being permanently impaired in many patients.
Treatment of established ARF Initially, the precipitating cause should be treated. Renal support must then be instituted until renal function resumes. Fluid restriction is required. Fluid should be administered to cover insensible losses and other measured losses (e.g. nasogastric aspirate). Strict intake/output charts should be instituted and daily monitoring of urea and electrolytes and creatinine should be undertaken. The administration of nephrotoxic drugs should be avoided. The dosage of drugs that are excreted by the kidneys should be adjusted (e.g. cephalosporins). Attention should be given to nutritional requirements, which will usually be in the form of parenteral nutrition. Urgent attention should be given to rising [K+]. Temporary correction of hyperkalaemia ([K+] >6.5 mmol/l) with or without ECG changes (i.e. peaked T wave or wide QRS complex) should be achieved by one of the following: • 10–30 ml of calcium gluconate, 10% i.v. slowly • 15 units of soluble insulin, with 50 ml 50% glucose i.v. • 1.4% bicarbonate solution by i.v. infusion to correct acidosis. These measures are temporary and dialysis may be required. Absolute indications for renal replacement therapy include: • hyperkalaemia ([K+] >6.5 mmol/l) • severe metabolic acidosis ([HCO3-] <10 mmol/l) • fluid overload (pulmonary oedema) • severe uraemic complications (e.g. coma, fits, pericarditis). The techniques available for renal replacement therapy are described below.
Oliguric phase This usually occurs within 24 hours of the precipitating event. The average duration is 1–2 weeks but, if it lasts longer than 4 weeks, the diagnosis of ATN should be reviewed and other diagnoses (e.g. acute cortical necrosis) considered. The electrolyte and metabolic changes of the oliguric phase have been described above.
Haemodialysis rapidly clears urea and creatinine, corrects hyperkalaemia and acidosis and corrects fluid overload. It involves the movement of large volumes between body compartments and therefore carries risk in haemodynamically unstable patients. The majority of patients who develop postoperative ARF are likely to be nursed on ITU and be (or become) unstable. Therefore, the use of haemofiltration is more appropriate.
Diuretic phase This phase is heralded by a progressive increase in urine volume. However, GFR takes time to return to normal and this is reflected by the fact that serum urea and creatinine fail to fall initially and, in patients with hypercatabolic states, may even continue to rise after the end of the oliguric phase. As GFR increases, the levels gradually return to normal, but this may take several weeks. During the diuretic phase, the kidneys do not have the capacity to handle sodium in the normal way, such that sodium excretion may be as much as 50–70 mmol/l. If the urine output is around 5 l/day, then about 300 mmol of sodium may be required to prevent negative balance. The diuretic phase may be excessive (e.g. in excess of 5 l/day) and dehydration must be avoided. However, such episodes are rare due to regular dialysis or haemofiltration during the oliguric phase. Therefore, fluid and electrolytes must be carefully monitored during this phase as persistent abnormalities in GFR may result in over-hydration, under-hydration, hypokalaemia, hyponatraemia or hypernatraemia.
Haemofiltration has certain advantages over haemodialysis, primarily that fluid removal can be achieved gradually over a period of time. It is highly efficient, gives good extracellular fluid volume control and can be used in the hypotensive patient. In patients with a robust circulation, intermittent haemodialysis can correct biochemical abnormalities, but is usually associated with a degree of hypovolaemia and hypokalaemia. It can also remove accumulated extracellular fluid in a short time. However, haemodialysis may lead to gross hypotension and cardiac arrhythmias due to rapid removal of volume. With continuous veno-venous haemofiltration almost any quantity of fluid can be removed over a 24-hour period, thus allowing for administration of other fluid, e.g. parenteral nutrition. The use of haemofiltration has coincided with a reduction in mortality from ARF. Haemodiafiltration is a combination of haemodialysis and haemofiltration. This can be achieved if the space surrounding the highly permeable membranes of the machine is perfused with a dialysate solution, so that diffusion down a concentra-
Recovery phase Improvement in renal function continues from 3–12 months after an episode of ATN. However, GFR returns to normal in only a minority of patients. There is also evidence that tubular dysfunc-
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tion gradient can occur across the membrane. Haemodiafiltration results in: • improved solute clearance • slower rates of ultrafiltration • easier management of fluid balance. These benefits make haemodiafiltration the renal support therapy of choice in the critically ill. The principles of haemofiltration and haemodiafiltration are shown in Figure 3.
the solubility of myoglobin and has been used as a manoeuvre aimed at reducing renal injury. In addition to tubular obstruction, myoglobin is directly toxic to tubular cells, leading to tubular necrosis throughout the nephron. This situation may be exacerbated by the additional effects of hypovolaemia following the initial injury and reduction in renal blood flow. The management of rhabdomyolysis includes early and aggressive fluid management to achieve a diuresis of 200–300 ml/hour. Guidelines suggest resuscitation with 6–12 l of fluid over a 24-hour period. This should be balanced against the risk of high volume resuscitation in the light of incipient renal failure and the potential that the patient may have an associated lung injury. In animal models, alkalization of the urine has been shown to reduce the fall in creatinine clearance associated with rhabdomyolysis. It has therefore been recommended that the urine pH should be maintained at >6 and the blood pH at <7, using up to 500 ml/hour of 1.24% bicarbonate. Urine output may need to be increased using frusemide to maintain fluid balance. The patient’s electrolytes should be monitored regularly. If renal failure develops despite these measures, hyperkalaemia may become a problem and be resistant to medical treatment. Early renal replacement therapy should be considered. u
Peritoneal dialysis: there are very few indications for the use of peritoneal dialysis in the setting of management of postoperative renal dysfunction. Its use has been largely superseded by haemofiltration. Previous or recent abdominal surgery makes peritoneal dialysis unsuitable. The only indication that remains is in a patient who has suffered ARF after non-abdominal surgery and where the administration of anticoagulant (necessary in haemodialysis, haemofiltration and haemodiafiltration) is deemed ‘unsafe’ (e.g. in a patient who has coexisting cerebral haemorrhage). Rhabdomyolysis Rhabdomyolysis occurs when there is striated muscle injury leading to breakdown of muscle tissue with the release of myocyte contents into the blood stream. This may be caused by major trauma, crush injuries, compartment syndrome, prolonged immobilization and burns. If the kidney receives a sufficient exposure to myoglobin, renal failure occurs. Diagnosis is suggested by a urine dipstick being positive for blood, but laboratory testing is required to confirm that it is due to myoglobin rather than haemoglobin. Other electrolyte disturbances include hyperkalaemia, hyperphosphataemia and hypocalcaemia. The serum creatinine: urea ratio may be disproportionately high, and creatinine kinase will be raised. The mechanism for renal damage involves tubular obstruction, tubular necrosis and reduced renal blood flow. The molecular weight of myoglobin ensures that it is easily filtered by the glomerulus, but then becomes deposited within the tubules, creating characteristic tubular casts that have been described as ‘brown sugar’ casts. Increasing the pH of urine increases
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FURTHER READING Ashford R, Evans N. Surgical Critical Care. London: Greenwich Medical Media, 2001. O’Callaghan C, Brenner B M, Eds. The Kidney at a Glance. London: Blackwell Science, 2000. Raftery A T. Fluid Balance. In: Principles of Surgical Practice. Kingsnorth A, Majid A, Eds. London: Greenwich Medical Media, 2001. CROSS REFERENCES Madden B P. Clinical assessment of renal function. Surgery 2000; 18(6): 135–8. Raftery A T. Renal failure: diagnosis management and dialysis. Surgery 1999: 17(9): 208–12.
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The normal GFR is around 125 ml/minute. Approximately 180 l of water is filtered in 24 hours, but about 1.5 l is lost in the urine. Autoregulation of renal blood flow results in a relatively stable glomerular hydrostatic pressure and therefore GFR. If arterial blood pressure falls below 60 mmHg (e.g. shock) glomerular filtration ceases and anuria occurs.
Treatment and Prevention of Perioperative Renal Dysfunction
Juxtaglomerular apparatus lies adjacent to the vascular pole of the glomerulus and secretes renin in response to the following: • reduced blood volume (low afferent arteriolar pressure) • sympathetic nerve stimulation (e.g. stress) • circulating catecholamines • low sodium concentration in distal tubule • renal ischaemia. Renin hydrolyses angiotensinogen to form angiotensin I. Angiotensin I is converted to angiotensin II by a converting enzyme which is found in the kidney and lung. Angiotensin II has the following effects: • stimulation of aldosterone release from the adrenal cortex • stimulation of sodium ions reabsorption in the proximal convoluted tubule • vasoconstriction of efferent arterioles to maintain GFR when blood pressure is low • stimulation of antidiuretic hormone (ADH) release • stimulation of thirst.
Andrew T Raftery
Basic renal physiology The kidneys contribute to biochemical homeostasis by: • eliminating waste products • regulating fluid and electrolyte balance • regulating acid–base balance. They also produce certain hormones, of which renin is the most important in the context of perioperative renal function. The basic unit of the kidney is the nephron, which is composed of a glomerulus and tubular system. The number of nephrons decreases with age. Blood is filtered at the glomerulus and enters Bowman’s capsule, from whence there is a system of tubules which modifies the filtered plasma. The tubular system comprises the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule and collecting ducts.
Tubular function The glomerular filtrate, which is isotonic with respect to plasma, is modified osmotically in the tubules so that water and electrolytes are conserved and waste products concentrated for elimination. Ninety-nine percent of the filtered volume (together with important constituents of the filtrate) are reabsorbed in the various tubules, which differ in their function.
Glomerular function The glomerular filtration rate (GFR) is dependent upon the glomerular capillary arterial pressure (60 mmHg) minus plasma colloid osmotic pressure (30 mmHg) plus the hydrostatic pressure in Bowman’s capsule (20 mmHg). That is, the filtration pressure is 60 − (30 + 20) = 10 mmHg. Arterioles before and after the capillary bed in Bowman’s capsule (afferent and efferent arterioles) are capable of adjusting glomerular pressure and therefore flow. Constriction of the afferent arterioles decreases capillary pressure and therefore filtration. Constriction of the efferent arteriole increases capillary pressure and increases filtration. GFR may be calculated by measuring the clearance of a substance from the blood into the urine. In clinical practice, GFR is usually measured as creatinine clearance, since creatinine is produced endogenously and does not need to be infused intravenously. GFR =
UV ml/minute P
where:
P = plasma concentration in mg/ml V = volume of urine in ml/minute U = urine concentration mg/ml
Proximal convoluted tubule: approximately 60–80% of filtered water and sodium is reabsorbed every 24 hours in the proximal tubules. In addition, the proximal tubular cells absorb potassium, phosphate and glucose, and secrete hydrogen ions and ammonia into the lumen. Loop of Henle is responsible for the creation of a high renal medullary osmotic pressure by a countercurrent multiplier system. There is active transfer of sodium from the tubular fluid into the interstitium by cells of the ascending limb creating a hypertonic environment in the interstitium of the medulla. By the time the filtrate enters the distal tubule in the cortex, it has lost a considerable amount of sodium and is hypo-osmotic with respect to cortical plasma. Distal convoluted tubule: sodium chloride is absorbed throughout the distal tubule. The distal part of the tubule is permeable to water, and 10–12 l of water per day is absorbed under the control of ADH. Potassium and hydrogen ions and ammonia are secreted into the distal tubule.
Andrew T Raftery is a Consultant in General Surgery and Renal Transplantation at the Northern General Hospital, Sheffield, UK. He qualified from Leeds University, UK, and trained in Leeds, Pontefract and Cambridge, UK. His research interests include peritoneal wound healing and adhesion formation, and cyclosporin nephrotoxicity. He is a member of the Court of Examiners of the Royal College of Surgeons, UK, and an examiner for the Intercollegiate Board in General Surgery.
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Collecting ducts pass through the renal cortex and medulla and drain urine into the renal pelvis. Sodium reabsorption continues in the collecting ducts. ADH primarily exerts its effects on the collecting ducts. In the absence of ADH secretion (as in diabetes
100
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insipidus), the permeability of the ductal epithelium to water is greatly reduced and patients may pass in excess of 20 l of urine in 24 hours with an osmolality of <50 mosmol/l. With maximal ADH levels, as little as 500 ml of urine is excreted in 24 hours, with an osmolality of about 1200 mosmol/l.
Oliguria is usually the first manifestation of renal dysfunction. Anuria is the complete absence of urine. Reduction in urine output despite adequate fluid replacement is normal in the early postoperative period after major surgery. Following surgery or trauma, certain physiological responses occur in the body. Catecholamines are released and stress stimulates the hypothalamo–pituitary–adrenal axis with an increase in secretion of cortisol and aldosterone. These hormones produce conservation of sodium and water by the kidney, resulting in a reduction of the urine volume and urine sodium concentration. ADH secretion from the posterior pituitary gland also leads to water retention. Causes of oliguria/anuria include: • blocked catheter • all causes of renal failure (see later) • all causes of shock. Acute renal failure is largely preventable by careful attention to the preoperative assessment of renal function, adequate fluid balance, prompt management of hypotension and sepsis, as well as avoidance and/or careful monitoring of nephrotoxic drugs. In patients who are considered high risk (e.g. pre-existing renal disease, obstructive jaundice, or those undergoing aortic surgery or cardiopulmonary bypass), consideration should be given to intraoperative renal dose dopamine to increase renal perfusion.
Preoperative assessment of renal function The patient may have a known history of renal disease or may have other co-morbid conditions associated with impaired renal function, such as: • hypertension • congestive cardiac failure • diabetes mellitus • obstructive jaundice • drugs (e.g. NSAIDs). Simple preoperative renal monitoring requires: • urea, electrolytes, creatinine • urinalysis. If any of the above indices are abnormal, then further investigations may be required, including: • urine microscopy and culture • urinary electrolytes • urine osmolality • creatinine clearance • 24-hour urinary protein • full blood count (anaemia, sepsis) • clotting screen (coagulopathy) • blood gases (hypoxia, acidosis) • chest radiograph (fluid overload) • ECG (hyperkalaemia). Depending on the results of the above investigations, other, more sophisticated investigations may be required: • chromium-51-labelled ethylenediaminetetra-acetic acid (51CrEDTA, measures GFR) • dimethylenetriamine penta-acetic acid (DTPA) or dimercaptosuccinic acid (DMSA) nuclear imaging • CT scan • MRI scan • renal biopsy. Every effort should be made to optimize renal function prior to elective surgery. A nephrologist should be involved at an early stage. In patients with impaired renal function, the following are necessary: • avoidance of dehydration • central venous pressure (CVP) monitoring • avoidance of nephrotoxic drugs • strict fluid balance assessment.
Management of oliguria: after exclusion of catheter blockage by flushing or replacement of the catheter, consideration must be given to whether there is evidence of urinary tract obstruction. A thorough examination to exclude post-renal causes should be made. The penis should be inspected to exclude meatal stenosis, stricture or stone. Rectal examination should be performed to assess for prostatic enlargement and rectal or pelvic masses. Vaginal examination should be performed to exclude pelvic malignancy. The bladder (acute or chronic retention), and the kidneys (hydronephrosis, pyonephrosis) should be palpated. If there has been recent pelvic surgery, possible ureteric damage should be suspected if the patient is anuric. If urinary tract obstruction is suspected, or no other cause can be found, ultrasound examination is indicated. The most common causes of post-renal failure are calculous disease and prostatic hypertrophy. A characteristic feature of early post-renal acute renal failure is a rapid rise in blood urea compared to creatinine, due to tubular reabsorption of urea. Treatment of post-renal obstruction requires urgent intervention and often dialysis may be avoided if intervention is rapid and successful. Renal tract obstruction should be managed jointly by nephrologists, urologists and interventional radiologists. If the cause of acute renal failure is prostatic obstruction, urethral catheterization or suprapubic cystostomy is appropriate. In other cases, antegrade or retrograde pyelography may be required to make the diagnosis. Relief of obstruction will depend upon the cause and site. If this is in the upper urinary tract, ureteric catheterization or percutaneous nephrostomy will relieve the obstruction prior to definitive surgery. If there is no evidence of obstruction, then one must exclude a pre-renal cause. The distinction between pre-renal failure and acute tubular necrosis (ATN, see below) due to haemodynamic instability may be difficult. Biochemical analysis of the urine
Intraoperative management of renal function ECG and urine output monitoring should be performed. Avoid intraoperative administration of nephrotoxic drugs. In patients undergoing major surgery with a need for massive blood transfusion (particularly those with renal dysfunction) care should be taken to avoid hyperkalaemia and hypocalcaemia. Intraoperative renal dose dopamine may be beneficial in increasing renal perfusion. Oliguria Oliguria is the passage of <20 ml/urine per hour (400 ml/day).
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may be helpful. In pre-renal failure, the urine electrolyte levels reflect the response of normal tubules to impaired renal perfusion. There is retention of sodium and water leading to low urinary sodium with high urinary urea and creatinine. The urine osmolality is high. Restoration of renal perfusion leads to a rapid improvement in renal function. With ATN, the urinary sodium is elevated and concentrations of urea and creatinine are low. The urine osmolality is also low. These changes reflect tubular dysfunction. Whatever the treatment of tubular dysfunction, renal function rarely improves rapidly. The changes in urinary biochemical indices in pre-renal failure and ATN are shown in Figure 1. If there is a pre-renal cause, the factors responsible for this should be corrected e.g. correct hypovolaemia, correct hypotension, correct cardiac failure. Monitoring should include: • accurate fluid balance chart (pulmonary oedema) • urea and electrolytes (hyperkalaemia) • arterial blood gases (metabolic acidosis). Having excluded catheter blockage (urinary retention) or renal tract obstruction, oliguria or anuria may be considered to be due to a pre-renal or renal cause. In the majority of cases this will be due to pre-renal causes and at this stage acute renal failure may be prevented by judicious management. The following sequence should be adopted: • Fluid challenge with a bolus of 250–500 ml of fluid. In the elderly or those with cardiac disease, CVP should be monitored. • If the above fails to produce a diuresis and the patient is adequately filled, frusemide (80–250 mg i.v.) should be administered. • If no response occurs, a CVP line should be inserted and adequate filling pressure established prior to administration of dopamine at a rate of 0.5–2.5 µg/kg/minute. Higher doses may cause arterial constriction. If these measures fail to produce a diuresis, then the patient is developing ATN, which should be managed jointly with a nephrologist.
Acute renal failure (ARF) ARF is defined as a rapid decline in renal function over hours or days which is of sufficient severity to disturb homeostasis. It may result from impaired renal perfusion (pre-renal), intrinsic renal disease (renal) or obstruction of the renal tract (post-renal). Causes of ARF are shown in Figure 2. The majority of causes of ARF are in the category of pre-renal failure or ATN. The term pre-renal is used when renal dysfunction is entirely attributable to hypoperfusion of the kidney and restoration of renal perfusion leads to resumption of renal function. The term ATN is used to define a sequence of events that comprises: • compromise of the circulation and/or effect of nephrotoxins • urinary abnormalities suggestive of tubular dysfunction • recovery of renal function within days or weeks. Pre-renal failure and ATN are invariably associated with shock. In the absence of shock it is unlikely that the cause of ARF is pre-renal or ATN due to haemodynamic compromise. In this context it is important to consider intrinsic renal or post-renal obstructive causes.
Causes of acute renal failure • Pre-renal Dehydration Haemorrhage Burns Acute pancreatitis Sepsis Congestive cardiac failure • Renal Renovascular disease embolus thrombosis Parenchymal renal disease renal ischaemia (acute tubular necrosis) nephrotoxins (e.g. gentamicin, radiographic) contrast medium glomerulonephritis interstitial nephritis impaired uric acid metabolism Myoglobinuria crush injury compartment syndrome Haemoglobinuria haemolysis
Distinction between physiological oliguria and acute renal failure Urine Specific gravity Osmolality mosm/kgH2O Sodium mmol/l Urine/serum creatinine Fractional sodium excretion* Renal failure index**
Physiological oliguria >1020 >500 <15 >40 <1 <1
Acute renal failure <1010 <350 >40 <20 >2 >2
• Post-renal Ureteric obstruction (e.g. calculous disease, especially with single kidney) Prostatic hypertrophy Urethral abnormalities Pelvic tumours Retroperitoneal fibrosis
* Fractional sodium excretion = Urine sodium × Plasma creatinine × 100 Plasma sodium x Urine creatinine ** Renal failure index =
Urine sodium × Plasma creatinine Urine creatinine
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Most aetiological factors leading to pre-renal failure are invariably associated with ADH secretion. ADH acts on the collecting ducts to increase tubular reabsorption of water but also of urea. This may explain why the plasma urea increases out of proportion to the creatinine in pre-renal failure. The clinical diagnosis of ARF is made when there is a progressive rise in serum urea and creatinine, which occurs only when more than 50% of glomerular function is lost. Other important changes of ARF include: • oliguria • salt and water retention (oedema) • hyperkalaemia • metabolic acidosis. Hyperkalaemia results, not only from reduced urinary excretion, but also from potassium released from cells associated with: • extensive tissue damage • increased catabolism (e.g. sepsis, burns) • rhabdomyolysis (e.g. crush injuries, compartment syndrome). In ARF, the plasma [Na+] is usually normal, since deficits of sodium are usually matched by those of water. Hence, extracellular volume may be reduced, but plasma sodium concentration remains the same. However, if water intake exceeds the rate of its excretion, then hyponatraemia may result. Classically, there are three phases of ARF, and these are discussed below.
tion may persist, with maximum concentrating capacity being permanently impaired in many patients.
Treatment of established ARF Initially, the precipitating cause should be treated. Renal support must then be instituted until renal function resumes. Fluid restriction is required. Fluid should be administered to cover insensible losses and other measured losses (e.g. nasogastric aspirate). Strict intake/output charts should be instituted and daily monitoring of urea and electrolytes and creatinine should be undertaken. The administration of nephrotoxic drugs should be avoided. The dosage of drugs that are excreted by the kidneys should be adjusted (e.g. cephalosporins). Attention should be given to nutritional requirements, which will usually be in the form of parenteral nutrition. Urgent attention should be given to rising [K+]. Temporary correction of hyperkalaemia ([K+] >6.5 mmol/l) with or without ECG changes (i.e. peaked T wave or wide QRS complex) should be achieved by one of the following: • 10–30 ml of calcium gluconate, 10% i.v. slowly • 15 units of soluble insulin, with 50 ml 50% glucose i.v. • 1.4% bicarbonate solution by i.v. infusion to correct acidosis. These measures are temporary and dialysis may be required. Absolute indications for renal replacement therapy include: • hyperkalaemia ([K+] >6.5 mmol/l) • severe metabolic acidosis ([HCO3-] <10 mmol/l) • fluid overload (pulmonary oedema) • severe uraemic complications (e.g. coma, fits, pericarditis). The techniques available for renal replacement therapy are described below.
Oliguric phase This usually occurs within 24 hours of the precipitating event. The average duration is 1–2 weeks but, if it lasts longer than 4 weeks, the diagnosis of ATN should be reviewed and other diagnoses (e.g. acute cortical necrosis) considered. The electrolyte and metabolic changes of the oliguric phase have been described above.
Haemodialysis rapidly clears urea and creatinine, corrects hyperkalaemia and acidosis and corrects fluid overload. It involves the movement of large volumes between body compartments and therefore carries risk in haemodynamically unstable patients. The majority of patients who develop postoperative ARF are likely to be nursed on ITU and be (or become) unstable. Therefore, the use of haemofiltration is more appropriate.
Diuretic phase This phase is heralded by a progressive increase in urine volume. However, GFR takes time to return to normal and this is reflected by the fact that serum urea and creatinine fail to fall initially and, in patients with hypercatabolic states, may even continue to rise after the end of the oliguric phase. As GFR increases, the levels gradually return to normal, but this may take several weeks. During the diuretic phase, the kidneys do not have the capacity to handle sodium in the normal way, such that sodium excretion may be as much as 50–70 mmol/l. If the urine output is around 5 l/day, then about 300 mmol of sodium may be required to prevent negative balance. The diuretic phase may be excessive (e.g. in excess of 5 l/day) and dehydration must be avoided. However, such episodes are rare due to regular dialysis or haemofiltration during the oliguric phase. Therefore, fluid and electrolytes must be carefully monitored during this phase as persistent abnormalities in GFR may result in over-hydration, under-hydration, hypokalaemia, hyponatraemia or hypernatraemia.
Haemofiltration has certain advantages over haemodialysis, primarily that fluid removal can be achieved gradually over a period of time. It is highly efficient, gives good extracellular fluid volume control and can be used in the hypotensive patient. In patients with a robust circulation, intermittent haemodialysis can correct biochemical abnormalities, but is usually associated with a degree of hypovolaemia and hypokalaemia. It can also remove accumulated extracellular fluid in a short time. However, haemodialysis may lead to gross hypotension and cardiac arrhythmias due to rapid removal of volume. With continuous veno-venous haemofiltration almost any quantity of fluid can be removed over a 24-hour period, thus allowing for administration of other fluid, e.g. parenteral nutrition. The use of haemofiltration has coincided with a reduction in mortality from ARF. Haemodiafiltration is a combination of haemodialysis and haemofiltration. This can be achieved if the space surrounding the highly permeable membranes of the machine is perfused with a dialysate solution, so that diffusion down a concentra-
Recovery phase Improvement in renal function continues from 3–12 months after an episode of ATN. However, GFR returns to normal in only a minority of patients. There is also evidence that tubular dysfunc-
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tion gradient can occur across the membrane. Haemodiafiltration results in: • improved solute clearance • slower rates of ultrafiltration • easier management of fluid balance. These benefits make haemodiafiltration the renal support therapy of choice in the critically ill. The principles of haemofiltration and haemodiafiltration are shown in Figure 3.
the solubility of myoglobin and has been used as a manoeuvre aimed at reducing renal injury. In addition to tubular obstruction, myoglobin is directly toxic to tubular cells, leading to tubular necrosis throughout the nephron. This situation may be exacerbated by the additional effects of hypovolaemia following the initial injury and reduction in renal blood flow. The management of rhabdomyolysis includes early and aggressive fluid management to achieve a diuresis of 200–300 ml/hour. Guidelines suggest resuscitation with 6–12 l of fluid over a 24-hour period. This should be balanced against the risk of high volume resuscitation in the light of incipient renal failure and the potential that the patient may have an associated lung injury. In animal models, alkalization of the urine has been shown to reduce the fall in creatinine clearance associated with rhabdomyolysis. It has therefore been recommended that the urine pH should be maintained at >6 and the blood pH at <7, using up to 500 ml/hour of 1.24% bicarbonate. Urine output may need to be increased using frusemide to maintain fluid balance. The patient’s electrolytes should be monitored regularly. If renal failure develops despite these measures, hyperkalaemia may become a problem and be resistant to medical treatment. Early renal replacement therapy should be considered. u
Peritoneal dialysis: there are very few indications for the use of peritoneal dialysis in the setting of management of postoperative renal dysfunction. Its use has been largely superseded by haemofiltration. Previous or recent abdominal surgery makes peritoneal dialysis unsuitable. The only indication that remains is in a patient who has suffered ARF after non-abdominal surgery and where the administration of anticoagulant (necessary in haemodialysis, haemofiltration and haemodiafiltration) is deemed ‘unsafe’ (e.g. in a patient who has coexisting cerebral haemorrhage). Rhabdomyolysis Rhabdomyolysis occurs when there is striated muscle injury leading to breakdown of muscle tissue with the release of myocyte contents into the blood stream. This may be caused by major trauma, crush injuries, compartment syndrome, prolonged immobilization and burns. If the kidney receives a sufficient exposure to myoglobin, renal failure occurs. Diagnosis is suggested by a urine dipstick being positive for blood, but laboratory testing is required to confirm that it is due to myoglobin rather than haemoglobin. Other electrolyte disturbances include hyperkalaemia, hyperphosphataemia and hypocalcaemia. The serum creatinine: urea ratio may be disproportionately high, and creatinine kinase will be raised. The mechanism for renal damage involves tubular obstruction, tubular necrosis and reduced renal blood flow. The molecular weight of myoglobin ensures that it is easily filtered by the glomerulus, but then becomes deposited within the tubules, creating characteristic tubular casts that have been described as ‘brown sugar’ casts. Increasing the pH of urine increases
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FURTHER READING Ashford R, Evans N. Surgical Critical Care. London: Greenwich Medical Media, 2001. O’Callaghan C, Brenner B M, Eds. The Kidney at a Glance. London: Blackwell Science, 2000. Raftery A T. Fluid Balance. In: Principles of Surgical Practice. Kingsnorth A, Majid A, Eds. London: Greenwich Medical Media, 2001. CROSS REFERENCES Madden B P. Clinical assessment of renal function. Surgery 2000; 18(6): 135–8. Raftery A T. Renal failure: diagnosis management and dialysis. Surgery 1999: 17(9): 208–12.
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