Anatomy of Kidneys, Nephron and Urinary Drainage System

The functional anatomy of the renal system includes the two kidneys, ureters, bladder and urethra (see Figure 18.1). The ureters, bladder and urethra collect, drain and temporarily store the urine produced from each kidney.⁹ While important in providing the conduit for the final excretion of urine, the kidney is the primary organ of interest in the renal system, particularly in critical care practice, and hence will be described in more detail from the anatomical and physiological perspectives.

FIGURE 18.1 Kidney and urinary drainage system.¹⁰⁷

The kidneys are located in the retroperitoneal space on the posterior wall of the abdominal cavity, encased in a protective combination of the ribs, muscle, fat, tendon and the renal capsule. Each adult kidney weighs approximately 140 g. The kidneys may develop a different anatomical appearance, or vary in number and location from the classic description provided here. The functional unit of the kidney is the nephron, which consists of a filtrate-collecting device (the Bowman’s capsule), a convoluted tubule that varies in length and diameter, finally attaching to a common filtrate-collecting tubule and duct (see Figure 18.2). Within the Bowman’s capsule rests the glomerulus, a tuft of interlaced capillaries that arise from the afferent arteriole. The efferent arteriole then drains from the glomerulus via a closely entwined network called the peritubular capillaries, until these collect in the venous network of the kidney.

FIGURE 18.2 Nephron and glomerulus.¹⁰⁷

The glomeruli and nephrons lie in the cortical area of the kidney, while the collecting ducts gather together into the renal pyramids, which lie in the medulla of the kidney. The pyramids drain into the calyces of the kidney, which then drain into the renal pelvis where urine is gathered to drain into the ureter. The major blood vessels of the kidney, the renal artery and veins also enter the renal capsule through the pelvis of the kidney.⁹

Urine Production, Regulation of Gfr and Filtrate Reabsorption in the Nephron

Urine production consists of a three-stage process, which occurs in the nephron: glomerular filtration, tubular reabsorption and tubular secretion (see Figure 18.3). As previously noted, the production of urine is highly dependent on delivery of blood under pressure to the glomerulus. This results in the first step of the urine production process, glomerular filtration. The glomerular filtration rate (GFR) is about 125 mL/min under normal conditions. Changes in the diameter of the afferent and efferent arteriole help regulate glomerular blood flow, but this is unable to compensate for large variations of mean blood pressure; hence, filtration rates may rise or fall markedly over the course of a day.¹⁰

FIGURE 18.3 Urine formation: filtration, reabsorption and excretion.¹⁰⁸

As the filtrate transgresses the glomerulus it is collected into the Bowman’s capsule and delivered into the proximal convoluted tubule, loop of Henle and then the distal convoluted tubule, where a number of processes result in the reabsorption of about 99% of the glomerular filtrate. The remaining fluid within the tubule drains into the collecting tubule to form urine. This fluid has substantially different properties from the original glomerular filtrate, as fluid and many electrolytes and glucose are reabsorbed by the peritubular capillaries.¹⁰

Along with blood pressure, the sodium content of the extracellular fluid is critical in maintaining fluid balance, as it constitutes the major electrolyte and osmotic agent of the glomerular filtrate. It is imperative that sodium intake and loss is equally balanced, as excessive losses will result in associated fluid loss and excessive intake will result in fluid retention. If sodium balance is not maintained, other compensations such as a rise in blood pressure may result to restore fluid balance. As blood pressure rises, the excretion of sodium also increases by way of the production of additional glomerular filtrate. In this way, water and sodium balance are inextricably linked.¹⁰

Hormonal and Neural Regulation of Renal Function

Various feedback mechanisms exist that assist in precisely adjusting the final amount of fluid and electrolyte to be excreted from the kidney. These include the sympathetic nervous system response, angiotension II, aldosterone, antidiuretic hormone and atrial natriuretic peptide. All these mechanisms work in synchrony with blood pressure and sodium balance in ensuring a highly regulated circulating and extracellular fluid volume.¹⁰

Renin–Angiotensin–Aldosterone System (RAAS)

Renin is the chemical trigger to initiate a cascade system that results in two powerful hormones acting on the kidney to significantly influence sodium and water excretion (see Figure 18.4). Renin is produced and released from the juxtaglomerular apparatus, a collection of cells in the macula densa of the distal tubule, and the adjacent afferent arteriole next to the glomerulus, which monitors blood sodium concentration. When released, renin stimulates the activation of angiotensin I from angiotensinogen. Under the influence of coenzyme A, angiotensin I converts to angiotensin II, a potent vasoconstrictor and stimulus to reabsorb sodium and water. The vasoconstrictor effect raises blood pressure and flow to the glomerulus, inhibiting further renin release (a negative feedback mechanism) as perfusion pressure normalises. This allows the return of natriuresis (sodium excretion) and diuresis. This response is essential in assisting with retaining fluid in the event of a falling blood pressure, or boosting fluid excretion as blood pressure rises. It also responds effectively to a rise in sodium intake by reducing angiotensin II formation and allowing a larger natriuresis, resulting in maintenance of sodium balance, a key to tissue fluid distribution and balance.¹⁰

FIGURE 18.4 Renin–angiotensin–aldosterone system (RAAS).

Aldosterone is a mineralocorticoid excreted from the adrenal cortex in response to angiotensin II. Aldosterone increases the reabsorption of sodium, and hence water, in the cortical collecting tubules and increases the rate of potassium excretion. This has a dual effect of regulating sodium balance and extracellular fluid volume. As fluid volume accumulates, the rise in glomerular filtration rate self-limits the volume effect by increasing both diuresis and natriuresis.

Regulation of Acid–base and Electrolyte Balance

The kidney assists in the management of body pH by regulation of the excretion of H+ and HCO₃⁻ ions. While the renal response to alkalosis or acidosis is slow in comparison with plasma buffers and respiratory regulation (see Chapter 13), it does result in a net loss of H+ ions or recovery of HCO₃⁻ ions, which are the basis of human pH balance (see Figure 18.5). During acidosis the kidney raises H+ secretion by active transport to combine with ammonia (NH₃⁺) in the renal tubule to form ammonium (NH₄⁺), which is unable to be reabsorbed. Coincidentally, raised H+ excretion increases the reabsorption of sodium, which increases the alkalytic ion, bicarbonate (HCO₃⁻). Conversely, during alkalosis the reabsorption of hydrogen ions is increased. These changes in secretion of hydrogen ion concentration in the renal filtrate alter the pH of the urine down to a maximum level of 4. The buffering of H+ with ammonia reduces the acidifying effect of the hydrogen ions, particularly as some ammonium combines with chloride to form ammonium chloride.¹⁰

FIGURE 18.5 Hydrogen ion regulation in the kidney.

Prerenal Causes

Prerenal factors affecting blood supply to the kidneys, such as hypovolaemia, cardiac failure or hypotension/shock, can cause ARF. The mechanism and outcome are easily related. As blood flow to the kidneys is reduced, less glomerulofiltration occurs, urine production diminishes and wastes accumulate. This state can be reversed by restoration of blood volume or blood pressure. In the short term (1–2 hours), nephrons remain structurally normal and respond by limiting fluid lost by urine production while concentrating the excretion of waste products. The physiological process combines the neuroendocrine control of the hypothalamus and the sympathomimetic response, which then regulates both antidiuretic hormone secretion and the stimulation of the renin–angiotensin–aldosterone system (see Figure 18.4). This process is highly influenced by any preexisting illness or concurrent factors such as diabetes and systemic infection.¹²

Intrarenal (Intrinsic) Causes

Intrinsic damage to the nephron structure and function can be due to infective or inflammatory illness, toxic drugs, toxic wastes from systemic inflammation in sepsis, vascular obstructive thrombus or emboli. In differentiating this type of ARF, a process of elimination has been suggested where failure of kidney function persists after the restoration of adequate perfusion (blood flow), or where no loss of perfusion has occurred, and there is no obstruction to urine flow.¹⁵ Diagnosis is made by exclusion of other causes. The common causes of this type of ARF, glomerulonephritis, nephrotoxicity and chronic vascular insufficiency, are discussed below.

Postrenal Causes

Urinary tract obstruction is the primary postrenal cause of ARF, and is uncommon in the critical care setting as it is rarely associated with acute onset renal failure.¹³ Postrenal obstruction is more common in the community and is associated with urological disorders such as prostate gland enlargement in males, urinary tract tumours and renal calculi formation impairing urine outflow. It is essential that blockage of any urinary drainage device be excluded in the critically ill patient when undertaking an assessment of apparent oliguria.

Acute Tubular Necrosis and Acute Kidney Injury

Intrinsic ARF (described above) is often associated with typical microscopic changes on pathology examination of kidney tissue. This pathology is termed acute tubular necrosis (ATN), and possibly explains how and why, in the acute setting, kidneys can fail abruptly to minimal to no function (no urine output and therefore no waste clearance), and can then after a period of time, with artificial support, recover to normal function in many patients.²¹ This is an interesting area for current research into the mechanisms responsible for acute kidney failure that are yet to be fully understood.

Acute tubular necrosis describes damage to the tubular portion of the nephron and may range from subtle metabolic changes to total dissolution of cell structure, with tubular cells ‘defoliating’ or detaching from the tubule basement membrane.²² Most ARF is multifactorial in origin and may involve more than one causative mechanism and is not always an ischaemic or necrotic event.¹⁵ In critical illness, the most common combination causing ARF is the administration of nephrotoxic agents in association with prolonged hypoperfusion or ischaemia (oxygen deprivation).²² This type of tubular necrosis can be further mediated by infection, blood transfusion reactions, drugs, ingested toxins and poisons, or be a complication of heart failure or major cardiovascular surgery. The initial insult can also be compounded by metabolic disturbances and subsequent systemic infection.

ATN is the causative mechanism for up to 30% of acute kidney failure in the intensive care setting,²³ with the precise causative illness not easily identifiable in critically ill patients with multiple co-morbidities, for example diabetes, advanced age, investigations requiring radio-opaque dye administration, potent and nephrotoxic drug administration or major surgery with an inflammatory state due to an underlying infection. This is the context of critical illness and ARF where, despite modulation of the cause and support with artificial renal replacement therapies, mortality ranges from 28–90% depending on diagnostic criteria or definition.^3,24,25

This type of kidney damage is of particular importance, as ATN is abrupt in onset and causes a rapid cessation of normal nephron function, a picture typical of any critical illness and failure of other body organs. As this failure is commonly mediated by a loss in total or regional blood flow to the kidney,²⁶ it is more pronounced in the kidney medulla or outer regions sensitive to reduced blood flow. The cause of this loss in blood flow may be multifactorial but is commonly associated with shock and consequent low blood pressure (see Figure 18.6). Tubular cells suffer an ischaemic insult, causing a shedding of the cells from the nephron basement membrane. This shedding of cells has an initial loss of cell polarity, and then cell death, with a ‘patchy’ occurrence along the tubule basement membrane.²¹ In addition, some cells detach themselves before death in a response known as apoptosis (cell self-death)²¹ (see Chapter 21). The response is aimed at organ survival, with some individual cells ‘sacrificing’ themselves during a period of crisis. This protective response reduces oxygen demand by initiating cell death in some tubules, while others differentiate and/or proliferate for repair, and allows continuation of some normal function. If the causative process abates, remaining cells regenerate by differentiation and proliferation, tissue repair occurs with restoration of normal epithelium in some tubules and nephron function returns.

FIGURE 18.6 Neuroendocrine response to shock, resulting in oliguria.

During this period cellular ‘debris’ collects in the tubule loops, causing obstruction of tubular flow, with backleak of filtrate occurring through the ‘patchy’ exposed tubular membrane surface. An inflammatory process is also stimulated due to release of cell adhesion factors and leucocyte activation,²⁷ which in turn causes further vasoconstriction and ischaemia²⁸ in the acute stage. The backleakage and static tubular fluid creates a concentrate that, by diffusion, raises blood levels of wastes such as urea, creatinine and other toxins. Along with this cessation of urine flow, toxicity occurs with high serum levels of wastes such as urea, creatinine, potassium and undefined toxins.²⁷ This is the clinical state of ARF associated with the pathology of ATN and now referred to as acute kidney injury (AKI) to better describe the total ‘picture’ of pre-illness status, immediate causative events and degree of injury determined by patient serum creatinine or urine output.^1,2

Some authors prefer the term ‘ATN’ to describe ARF,¹¹ using it as a surrogate for ARF in the acute setting, as it focuses on the pathophysiology of tubular damage, recognising this damage as a final outcome of all causative factors. However, more recently, with the development of a consensus definition for ARF describing stages of illness severity, the term acute kidney injury (AKI) is now used reflecting pathophysiology, the outcome of many causative factors, and the clinical context where small derangements may be evident with reversibility of dysfunction and recovery, through to irreversible damage with kidney failure.^1,2

The kidneys are vital human body organs essential to sustaining life. An important interrelationship of the kidneys and other body organs exists, with the brain, heart, liver and lungs dependent on receiving ‘clean’ blood to function. As toxins accumulate in ARF these organs become dysfunctional,^29,30 although many of these interrelationships (e.g. the liver) are poorly understood.³¹

Clinical Assessment

Clinical assessment of the patient with impending renal failure can involve myriad tests and investigations; however, the majority of these are not used to assess the critically ill patient. The clinical history is important in differentiating preexisting renal disease and cataloguing the numerous factors already discussed that can contribute to renal dysfunction. As the majority of renal failure patients in the ICU will succumb to the combination of prerenal renal failure and ATN, the key assessments used in monitoring renal function are urine output, serum creatinine and urea levels, combined with more general haemodynamic measures including HR, CVP, BP, PCWP. These measures are essential for the critically ill patient, and alterations provide the diagnostic key. They also link into the wider assessment of fluid and electrolyte balance, as described in Chapters 9 and 19.

Diagnosis

The management of ARF begins with making the diagnosis, based on the patient’s presenting signs and symptoms linked to a patient history. A long-term history of renal disease involving urinary tract infections, diabetes, cardiac failure and systemic inflammatory illnesses are all highly relevant.¹¹ Immediate history of presentation to a hospital involving surgery or any life-threatening illness with associated shock is also highly relevant in association with reduced urine output volumes over time.

Nurses in the critical care setting who measure urine output hourly, readily recognise a key sign of impending renal dysfunction. Oliguria in the absence of catheter obstruction should be responded to quickly, as this suggests inadequate kidney blood flow and to some extent is a delayed observation considering the continual moderation of kidney function producing urine output. Persisting oliguria or the onset of anuria with associated rises in blood creatinine defines renal failure. This sequence of events can be identified in a criteria pathway published following a consensus meeting of physicians. The ‘RIFLE’ criteria³² – risk, injury, failure, and outcome criteria of loss and end-stage disease – provides an increasingly widely-accepted approach to diagnosing and classifying ARF.

Consensus Definition: the Rifle Criteria

The RIFLE criteria are indicated in Figure 18.7, and use raising creatinine and lowering urine output as highly sensitive and specific indicators for a continuum of renal failure. This is a useful classification system to grade loss of kidney function, reflecting stages of injury to the kidney before failure occurs. Without this, the small but important losses of kidney function before the failure state are not adequately considered.¹ This approach provides a consensus definition for loss of kidney function that is useful for clinical practice and research into this area, with clinicians all talking the same ‘language’ when comparing patients and/or results from clinical trials. The shape of the diagram indicates that more people will develop symptoms of ARF linked to kidney ‘injury’ and be considered ‘at risk’ (high sensitivity) than those at the bottom of the definition, who are fewer in number but need to fulfil strict criteria (high specificity).

FIGURE 18.7 Criteria for diagnosis of acute renal failure: the risk, injury and failure criteria with outcomes of loss and end-stage renal disease (RIFLE).³²

To better understand the RIFLE criteria in a clinical care context, the following discussion is useful to consider in association with a review of Figure 18.7. In a hospital setting, those patients with a risk of renal injury would be identified by a low urine output of less than 0.5 mL/kg/h for 6 hours. In this situation their creatinine would be expected to rise, indicating a concurrent reduction in glomerular filtration rate. Reducing renal risk requires basic measures such as increasing their fluid intake and continuing to closely monitor urine output, whilst reviewing the patient’s medications, haemodynamic state and possible other causes of injury in order to prevent further deterioration.

In the event that urine output decreases further, or was worse than this when first identified, with less than 0.5 mL/kg/h or a creatinine increase of twice the normal, renal injury is likely, with these clinical changes proposed as being highly sensitive towards injury occurring. At this stage the above measures would be appropriate and requires further investigation into the cause. With close monitoring, support of haemodynamics and fluid administration, most patients should not progress further in the failure continuum.

The next progression in clinical deterioration is oliguria, or urine output being less than 0.5 mL/kg/h for 24 hours or anuria for 12 hours. The creatinine increase is now proposed as being three times the normal level, and, with minimal to no urine output, renal ‘failure’ is proposed as a clinical diagnosis using this criterion. It is at this stage when renal replacement therapy would need to be considered and, if necessary, to transfer patients to ICU. A continuous therapy, or continuous renal replacement therapy (CRRT), is recommended. This term is more specific for the modes of treatment commonly applied in the ICU. Renal replacement therapy (RRT) refers to any treatment that replaces renal function and includes intermittent haemodialysis (IHD) and peritoneal dialysis. It is also important to understand that in the setting of an acute illness, many patients progress through these stages of renal dysfunction to the failure stage quickly and/or the problem is unidentified until the failure stage is met. The timing for taking a blood sample to measure creatinine or when a urine catheter is passed to measure urine output also influences this identification. The diagnosis may be made only at the failure stage, without any identifiable period of risk or injury as proposed by the RIFLE criteria. With a critical illness, serum values of creatinine, urea, pH and potassium are readily available in the ICU and are used for diagnosis in association with the RIFLE definition. Daily monitoring of these values as a minimum is necessary for diagnosis and monitoring during CRRT in the ICU. The normal laboratory values for these biochemical markers is essential knowledge for nurses to understand renal failure and management.

Treatment with CRRT may not be implemented until failure is evident, by anuria and uraemia, or until patients meet the RIFLE definition criteria. However, in some patients, CRRT may be commenced earlier, in anticipation of failure and as a strategy to prevent further kidney damage or complications of functional renal deterioration.

Clinical Management

In the critically ill patient, kidney function failure may be associated with an initial renal response to a fall in perfusion associated with systemic shock. As the majority of patients recover their renal function from ICU ARF,⁸ initial clinical management is aimed at reducing further renal damage. If kidney function becomes so compromised that blood pH, fluid and electrolyte balance cannot be sustained, then a replacement therapy will need to be introduced. This is continued until kidney function is marked by the return of urine production or patients are moved to a more chronic form of replacement therapy, such as intermittent haemodialysis.

Nutrition

When ARF is persistent, providing nutritional support is another important management strategy. A review of nutrition in ARF suggested that an intake of 30–35 kcal/kg/day and a protein intake of 1–2 g/kg/day is essential due to the combined increase in protein catabolism and caloric requirements of associated critical illness.³⁴ This nutrition is provided by the enteral or parenteral route and constitutes an increase in body fluids and nitrogen load. Ironically, this aspect of managing ARF in critical illness may also be an indication for starting RRT³⁵ (see Chapter 19 for further discussion on nutritional requirements in critical illness).

Renal Replacement Therapy

If conservative measures fail, then the ongoing management of the patient with ARF requires RRT. This enables control of blood biochemistry, prevents toxin accumulation, and allows removal of fluids so that adequate nutrition can be achieved. The criteria and indications for initiating RRT are listed in Box 18.1. One indication is sufficient to initiate RRT, while two or more make RRT urgent and mandatory. Combined derangements can create the necessity to commence therapy before individually-defined limits have been reached. Early initiation of treatment is widely advocated and may confer more rapid renal recovery.

History

Dialysis is a term describing RRT and refers to the purification of blood through a membrane by diffusion of waste substances.³⁶ Table 18.1 outlines the historical events in the development of dialysis. The Kolff rotating drum kidney, one of the earliest attempts at RRT (illustrated in Figure 18.8), used cellulose tubing rolled around a wooden skeleton built as a large, drum-styled cage. Cellulose acetate (material similar to ‘sticky tape’) tubing was strong, did not burst under pressure and could be sterilised.³⁷ The drum with the blood-filled cellulose tubing wound around it was immersed in a bath of weak salt solution, and as blood passed through, the rotating cellulose tubing allowed waste exchange to occur by diffusion. This method and the diagram included is useful information as it is essentially the key concepts for how dialysis is today with modern machines and dialysis membranes. A major impediment to the safe use of this system was, however, the large amount of patient blood required in the tubing and membrane.

TABLE 18.1 Historical events in the development of dialysis

FIGURE 18.8 Kolff dialyser.⁷¹

This large extracorporeal blood volume became a focus for further development of the therapy. The goal was to develop a membrane for solute exchange with a greater surface area than the cellulose membrane used by Kolff but needing less blood volume. This led to the development of the hollow-fibre filter membrane structure in the 1960s, the same design concept that is used today. Since then significant developments have occurred, with new fibres using the polymer polysulfone or other artificial synthetic chemical structures that better imitate the nephron glomerulus and the ability to transfer wastes and plasma water³⁸ for an effective ‘artificial kidney’.

This combination of extracorporeal circuit (EC), blood pump and filter membrane (or artificial kidney or dialyser), and the associated nursing management is now commonly known as haemodialysis. The major treatment components are essentially the same as those first developed in the 1960s, with the key component being the device membrane. Over the past 50 years, industrial and scientific developments such as plastics moulding and electronics have made current dialysis techniques safe, effective and a life-sustaining treatment for the millions of people who suffer acute and chronic kidney failure.^39,40

Development of Renal Replacement Therapy in Critical Care

Improvements in many fields of health care, including resuscitation and treatment for shock, and the growing number of patients undergoing and surviving extensive surgery and trauma, have led to developments and challenges in critical care practice. Many patients who would previously have died from an acute illness now survive, but develop ARF as a complication, or coexisting organ failure secondary to a primary problem with their heart or other major organ system. The pathogenesis and epidemiology of ARF have thus changed.

Historically, ARF was treated in the ICU with the use of peritoneal dialysis (PD), which did not require specialist nurses or physicians.⁴⁵ This simple technique removes wastes by infusing a dialysis fluid into the abdomen, allowing diffusion and osmosis to occur between the peritoneum and fluid before draining out again in repeated cycles.⁴⁶ This was performed by the ICU nurse and prescribed by ICU physicians, but was inadequate in its clearance of waste and fluid volume, and was associated with infection, limiting respiratory function and exacerbated glucose intolerance.^14,47

In 1977 Peter Kramer, a German ICU physician, frustrated with the limitations of PD and the delays in gaining a dialysis nurse and machine to attend the ICU, developed a new dialytic technique by inserting a catheter into the femoral artery and allowing blood to flow to a membrane and back to the femoral vein. As the blood passed through the membrane, plasma water was filtered out.⁴⁸ The technique was called continuous arteriovenous haemofiltration (CAVH). It was later renamed slow continuous ultrafiltration (SCUF), as it enabled the removal of plasma water in addition to dissolved wastes (convective clearance of solutes) at a flow rate of 200–600 mL/h by passive drainage from the membrane as blood flowed through it. Kramer reported ‘considerable therapeutic potential’ after treating 12 patients in the ICU, although suggesting that this level of ultrafiltration and waste clearance was inadequate for optimal support of ARF in many critically ill patients.⁶ This marked the beginning of continuous RRT in the ICU as an intervention prescribed and managed by ICU nurses and doctors for patients with ARF. A schematic diagram of Kramer’s original technique is illustrated in Figure 18.9.

FIGURE 18.9 CAVH used in the ICU in the late 1970s. Patient arterial blood pressure provides flow to the membrane, and blood returns via a large vein. Plasma water removal occurs via filtration and is pressure-dependent.⁴⁸

The increase in demand for chronic renal failure dialysis made it problematic to provide any service to patients in the ICU with ARF by dialysis nurses. Dialysis for patients in the ICU was often delayed or unavailable while using the same human and material resources from a dialysis unit.⁴⁹ It was thus inevitable that in the ARF context ICU nurses would adopt the role of the dialysis nurse, in addition to their established role in ICU of caring for critically ill patients using mechanical ventilation and haemodynamic interventions. Physician-prescribing rights also favoured this role for nursing in Australia and New Zealand, as the ICU physician can prescribe renal dialysis without the referral of the patient to a nephrologist that is required in other countries.^8,49,50 In the Australian context, this resulted in the provision of renal support for critically ill patients by ICU nurses alone, or in a shared role with renal dialysis nurses.⁵⁰

Different approaches or models of care are created by many factors, including the presence of a dialysis service in a hospital, the number of patients requiring treatment in an ICU per annum, physician rights of prescribing as specified by health insurance scheme structures, and the number, professional competence and flexibility of the nursing workforce available for an ICU or dialysis service in a given hospital.^44,50,51

Haemodialysis, Haemofiltration and Haemodiafiltration

There are numerous approaches to the delivery of RRT. Haemodialysis, haemofiltration and haemodiafiltration are three common techniques used to achieve artificial kidney support in ARF. The basic blood path or circuit for these therapies is indicated in Figure 18.10 and is useful to review as a basis for understanding each of the three circuits for each therapy and where the RRT fluids are then applied to this circuit differentiating them as alternative techniques.

The extracorporeal component is a common factor in all these different circuit designs. The difference between treatments is how the solutes (urea, creatinine and other waste products) and solvent (blood plasma water) are removed from the blood as it passes through the filter membrane (artificial kidney), and the intermittent versus continuous prescription of the therapy. This is determined by the way in which the dialysis fluids are mixed with or exposed to the blood, the rate and direction of blood and fluid flows, and how fluid loss or a negative fluid balance is achieved. The three physical mechanisms of fluid and solute management are convection, diffusion, and ultrafiltration. Table 18.2 lists the commonly-used abbreviations to describe the timing of treatment, blood access for the therapy and mode of solute removal.

TABLE 18.2 Abbreviations describing modes of renal replacement therapy

Convection

Convection is the process whereby dissolved solutes are removed with blood plasma water as it is filtered through the dialysis membrane. The word is derived from the Latin convehere, meaning ‘to remove or to carry along with’.⁶⁵ This process is very similar to that occurring in the native kidney glomerulus, as plasma water is filtered across the nephron tubule via the Bowman’s capsule. In RRT, the plasma water with the dissolved wastes is discarded; the plasma water deficit is then replaced with manufactured artificial plasma water in equal or slightly lower amounts to achieve a desired fluid balance. This blood washing (purification) process is commonly known as haemofiltration. When applied on a continuous basis in the ICU, haemofiltration can adequately replace essential renal functions, and is particularly effective in managing fluid balance.^66–70 Figure 18.11 illustrates the circuit and set-up for continuous veno-venous hemofiltration.

FIGURE 18.11 Continuous veno-venous haemofiltration (CVVH) circuit.

Diffusion

Diffusion refers to the physical movement of solutes across a semipermeable membrane from an area of high concentration to that of a relatively low concentration;⁶⁶ that is, solutes move across a concentration gradient.⁷¹ A higher concentration gradient results in a greater rate of diffusive clearance. As blood passes through the dialysis membrane, dialysate fluid, reflecting normal blood chemistry, is exposed to the blood on the opposing side of the membrane fibre. Diffusive clearance is continuous as solute exchange occurs by diffusion with the dialysate fluid and the blood continually moving in and out of the membrane. As ‘dirty’ or waste-laden blood enters the membrane and ‘clean’, fresh dialysate is in continuous supply, this process performs an effective waste-removal process. The two mediums are usually established in a countercurrent or opposing flow to each other, making diffusion another process, mimicking the normal nephron function of the kidneys.⁷¹

Diffusive clearance technique can be performed with increasing intensity and effect by making the blood and dialysate flow faster, with technical problems associated with delivering the high fluid and blood flow being the main limiting factor increasing clearance. The two flows need to be maintained in relation to each other; for the diffusive clearance to be efficient the dialysate flow must always equal or exceed the blood flow. A common setting for an intermittent dialysis treatment would be a blood flow and dialysate fluid flow of 300 mL/min each. A faster blood flow is not useful unless dialysate flow is also increased, as more waste solutes will not be cleared if the dialysate fluid and blood are in diffusive equilibrium. The technique of solute removal using diffusion alone is termed dialysis; when used with blood, the process is termed haemodialysis (HD). When applied on an intermittent basis, as is normal for patients receiving RRT for chronic renal failure, it is called intermittent haemodialysis (IHD).⁷² Figure 18.12 illustrates the circuit set-up for IHD.

FIGURE 18.12 Intermittent haemodialysis circuit. RO = reverse osmosis ‘treated water’

Ultrafiltration

Ultrafiltration is the process that allows plasma water to leave the blood, achieving body fluid or water loss. Dialysis nurses measure a fluid loss by weighing the patient before and after a treatment. This process is primarily used to achieve fluid balance, an important function of the kidneys.^33,66 The only difference between this process and the convective clearance of solutes is that this fluid is not replaced, and it is therefore not considered an adequate solute management method. Ultrafiltration cannot be undertaken in large amounts without fluid replacement, as it would cause hypovolaemia. It is therefore implemented during a dialysis period by removing small amounts each hour (e.g. 250 mL/h for 4 hours) of the intermittent treatment cycle.

There are different therapeutic effects from each form of RRT and different operational prescriptions of blood and fluid flow. Combinations of convection and diffusion can be used, known as haemodiafiltration (CVVHDf).⁶⁶ An increase in the diffusive component (i.e. raising the dialysate flow rate in CVVHDf) will increase the removal of small-molecular-weight substances such as potassium and assist with hydrogen ion exchange via buffer solution. This can also be achieved via increasing filtration fluid flow (convective clearance), which will also add an increase in clearance of larger molecules, for example those associated with severe infection and systemic inflammation or sepsis. Figure 18.13 illustrates the circuit and set-up for CVVHDf.

FIGURE 18.13 Continuous veno-venous haemodiafiltration (CVVHDf) circuit.

Membranes

The filter or haemofilter (blood filter) is the primary functional component of the RRT system, responsible for separating plasma water from the blood and/or allowing the exchange of solutes across the membrane by diffusion. The filter is made of a plastic casing, containing a synthetic polymer inner structure arranged in longitudinal fibres. A schematic diagram of a haemofilter is shown in Figure 18.14. The fibres are hollow and have pores along their length with a size of 15,000–30,000 daltons. This allows plasma water to pass through, carrying dissolved wastes out of the blood (most of which have a molecular weight <20,000 daltons), while larger plasma proteins and blood cells (at least 60–70,000 daltons) are retained.⁶⁵ Plasma water separated from the blood in this way is carried away from the filter by a side exit port and a pump, where it is measured and directed into a collection bottle or bag as waste; this convective clearance of solutes is similar to urine produced by the normal kidneys. The plasma water loss is replaced in equal volume with a commercially-manufactured plasma water substitute, either after the ‘filtered’ blood exits the haemofilter (postdilution) or prior to the blood entering the haemofilter (predilution) or both at the same time. The plasma water replacement contains no metabolic wastes and achieves blood purification as it is continuously replaced.^67–7073

FIGURE 18.14 Haemofilter (dialysis membrane). Cross-sectional view indicating longitudinal synthetic fibres conveying blood into and out of the plastic casing outer structure. Plasma water is removed via the side ultrafiltrate port during CVVH applying convective clearance. In CVVHDf, the blood is exposed to fluid via the membrane fibres so that diffusive clearance can occur.

Filter membrane polymers are of different materials: AN69 (acrylonitrile/sodium methallyl sulfonate), PAN (polyacrylonitrile) or PA (polyamide), and polysulfone;⁷⁴ however, all demonstrate similar artificial kidney effects and are generally applied according to the physician’s preference.⁴² The most important characteristics of filters used in continuous modes of therapy are: (a) a high plasma water clearance rate at low blood flow rates and circuit pressures; and (b) high permeability to middle-sized molecular weight substances (500–15,000 daltons, e.g. inflammatory cytokines), which are often encountered in critical illness.

Vascular Access

As previously noted, in order to establish CRRT it is necessary to create a blood flow outside the body using the EC. Blood is most commonly accessed from the venous circulation of the critical care patient via a catheter placed in a central vein (e.g. femoral). Blood is both withdrawn from the vein and returned to the same vein – that is, veno-venous (VV) access by means of a double (dual)-lumen catheter.⁷⁰ When the same procedure is carried out by accessing the blood from the patient’s systemic circulation via an artery and returning it to a vein, the term arteriovenous (AV) is used.^75,76 In this system there is no mechanical blood pump required, as the patient’s arterial blood pressure provides a flow of blood in the EC. Veno-venous haemofiltration (CVVH) has the advantages of requiring only a single venipuncture, a reliable blood flow delivered from a blood pump, and alternative venous access sites if site infection or access is difficult.⁷⁷ While it is easy to establish flow within AV-driven circuits and no complex system of blood pumps and pressure sensors is necessary, this method is susceptible to flow problems associated with low patient arterial blood pressure and high venous pressures, a common occurrence in critically ill patients.

The dual-lumen catheter used for veno-venous access has an internal diameter of 1.5–3 mm and the ends of the catheter are sufficiently separated from each other in the patient’s vein to prevent filtered blood from mixing with unfiltered blood when used in the recommended sequence.⁷⁷ This ensures that filtered blood does not simply pass back through the artificial kidney, where there would be minimal waste clearance compared with ‘fresh’ unfiltered blood; this design is illustrated in Figure 18.15a. The catheter must be small enough to place into a vein but large enough to provide blood flow of at least 200 mL/min for an adult CRRT circuit. Catheters are made with different arrangement of the lumens revealing variation in their cross section profile (see Figure 18.15b) There is no evidence to suggest which profile is better, but the larger the internal diameter, the less likely flow will be obstructed during patient care with CRRT. After a catheter is threaded into a vein, the blood flow may be adequate, but later during patient care it may obstruct due to different nursing interventions and patient movement, which may alter blood flows within the low pressure venous system.⁷⁰

FIGURE 18.15 (A) Vascular access catheters for CRRT. Dual-lumen, Bard^® Niagara™ and Gambro Dolphin Protect™ catheters; (B) Concept diagram of catheter lumen profiles used for dual lumen CRRT catheters.

Insertion sites may be affected by nursing care interventions. Placement of the catheter is usually in the subclavian or femoral vein, and occasionally in the internal jugular vein.⁷⁸ Anecdotally, the subclavian position is more easily managed for dressing and securing, continuous observation and patient comfort, but is more problematic in terms of flow reliability. Intrathoracic pressure changes associated with physiotherapy or spontaneous patient coughing and breathing, coupled with the upright position of patients, may hinder blood flow from the subclavian-sited access catheter. While these issues are not encountered with a femoral-placed catheter, flow problems can arise due to side lying and flexion at the groin or hip.⁴²

The flow performance of any vascular-access catheter can be affected by the patient’s position in bed, spontaneous movement and repositioning activities as part of routine nursing care in the critically ill for pressure-area prevention. Catheter lumen outlet or inlet obstruction can be due to contact with the vessel wall, or to a sharp bend occurring due to the patient’s movement. These factors contribute to compromising blood flow in the EC,^42,77 and have been identified by ultrasound Doppler flow probe attached to the circuit tubing.⁷⁹

Blood Pump

In veno-venous modes, a pump component is essential as part of the patient’s blood volume flows externally to the body via the EC. Blood flow is maintained by a ‘roller pump’ (see Figure 18.16), that propels the blood along the tubing in a peristaltic fashion (milking along by compression of the tubing), compressing the blood-filled tubing but having no contact with the blood itself. This roller rotates at a rate providing a flow of fresh unfiltered blood to the haemofilter, enabling it to clear metabolic waste products.

FIGURE 18.16 Roller pump for RRT.

The roller pump has a central anticlockwise rotating shaft driving two roller wheels inside a rigid housing. Blood-filled tubing sits stationary inside the housing and is compressed by the outer surface of the roller wheels during 180 degrees (half) of their rotation through the pump housing. This means that one of the two wheels is almost continuously compressing the tubing, moving blood forward out of the roller housing. The compression is not absolutely continuous, as there is a short time (<0.5 sec) where there is no compression to allow the tubing to refill with fresh blood. The compressed tubing reexpands behind the rotating roller and fills with fresh blood from the EC.

Venous Return Line Bubble Trap Chamber

The purpose of this chamber is to prevent any gas bubbles in the EC from entering the patient’s circulation by allowing them to rise to the top of a small, vertically positioned collection reservoir (see Figure 18.17). Venous pressure is commonly measured via a tubing connection into the top of the venous chamber, and additional IV fluids can be administered into this chamber via a secondary tube connection. The level of the blood in the chamber must be below the top, to prevent spillage into the pressure monitoring line. It is advised that the blood level be adjusted to near full but allow for visual inspection of incoming blood flow and to ensure that any air bubbles are trapped here.⁶⁹ As this creates a gas–blood interface within the venous chamber there is a potential source of venous chamber clotting and hence circuit failure.^42,69,80 Addition of replacement fluids into this chamber when using post-dilution fluid administration can cause a plasma fluid layer to develop above the blood level and may reduce clotting by stopping blood foaming on its surface and eliminates air or gas contact with the blood.⁸¹

FIGURE 18.17 Schematic of typical venous bubble trap design.

Anticoagulation

There are several different drugs utilised to prevent blood clotting in the EC; heparin, prostacyclin and sodium citrate have been used separately or in various combinations (see Table 18.3).^82–84 As blood comes into contact with the plastic tubing and the polymer fibres of the filter, various clotting systems are activated. This is a normal action of blood when exposed to non-biological surfaces. The aim of anti-clotting drugs is to delay clot formation while the blood is outside the body, particularly when within the densely-packed fibres of the filter. As calcium, blood platelet cells or thrombin are vital in clot formation,⁸⁰ these drugs are targeted to one of these elements. This targeting must not be too pronounced, as the patient may begin to bleed when the blood returns from the EC to the body.⁸⁰

TABLE 18.3 Commonly used anti-clotting agents for CRRT

Heparin is the most commonly-used agent for the prevention of clotting, as it is inexpensive, widely available and easily reversed by another drug, protamine.⁸² Heparin is commonly administered into the EC before the blood enters the filter, although the optimal place to administer any anticoagulant drug during CRRT is not agreed upon.^85,86 A bolus is often given prior to circuit connection, either in the circuit prime or via the venous access catheter. A maintenance dose (5–15 units/kg/h) is then adjusted against the relevant laboratory tests and a visual inspection for clotting in the EC is undertaken, particularly noting the venous bubble trap.

Citrate is another popular anticoagulant for CRRT as an alternative to heparin. Citrate buffers pH and chelates calcium inducing anticoagulation of blood by reducing serum ionised calcium level. For anticoagulation, the dose and dose rate of citrate is commonly set to achieve a reduction in the CRRT circuit blood ionised calcium level to <0.3 mmol/L.^87–89 As ionised calcium is essential for the progression of the coagulation cascade to form a stable clot, an anticoagulant effect is achieved when the calcium is bound or chelated.⁸⁸ A continuous infusion of citrate is administered into the CRRT circuit, as patient blood enters the circuit similar to heparin administration. A new approach in Australia includes citrate as an additive to commercially-prepared CRRT replacement fluids.⁹⁰ When circuit blood returns to the patient circulation, it mixes with systemic blood and the calcium concentration is restored to normal; free citrate not binding to calcium is metabolised by the liver to provide carbon dioxide and bicarbonate as a necessary buffer.^87–89 However, citrate-bound calcium is lost in the waste fluid removed and requires replacement by a separate calcium infusion to maintain serum calcium levels to normal; at 1.0–1.3 mmol/L.⁸⁷ With this method, the circuit is anticoagulated, but the patient is not (also called a ‘regional’ method of anticoagulation) as the patient blood calcium level is restored to normal making this approach safer compared to heparin use and can be applied in auto-anticoagulated patients where premature circuit clotting continues to occur.⁹¹ Due to the complex nature of the citrate-based anticoagulation approach a number of different protocols have been proposed to aid in management.⁹² Not all methods will be applied in the one ICU, and local expertise development of one method and an alternative is common. Recent reviews provide a good synopsis of each method.⁹³

Normal clotting time, a laboratory test designed to measure the time taken for blood to clot under laboratory conditions, is used as a reference to determine a suitable therapeutic range of the anti-clotting drug during CRRT. Different tests are applicable to different medications and their site of action in the clotting cascade. When using any anti-clotting agent, a balance is required between the benefits of increased coagulation suppression and the higher risk of patient systemic bleeding. In each patient this risk may vary, depending on illness, accompanying liver failure and administration of concurrent anti-clotting agents such as activated protein C.

Fluids and Fluid Balance

A key component of any CRRT is the administration of a replacement solution for the fluid removed during haemofiltration (see Table 18.4). This same physiologically balanced solution is also used as a dialysis fluid if a dialytic mode is included. The solution may have a low potassium level, so this electrolyte can be removed rapidly if hyperkalaemia is part of the original indication for CRRT. Potassium must therefore be added later to the solution to ensure that hypokalaemia does not occur. In Australia and New Zealand these fluids are commercially prepared, with the only major choice being between the type of acid buffer: lactate or bicarbonate. Some small studies have compared the use of lactate and bicarbonate fluid buffer because of a concern that the lactate solution reduced heart performance by causing cardiovascular depression and made accurate determination of patient lactic acid accumulation difficult to interpret.^94–97 In most settings the use of lactate-buffered fluids in patients with cardiac and liver failure is avoided, as lactate accumulation (levels above 5 mmol/L) in these patients indicates inadequate metabolism of lactate to bicarbonate by the liver, with increased acidaemia.¹³ While bicarbonate solutions may appear to have an advantage over lactate-based solutions in critically ill patients, they are more expensive causing some physicians to only prescribe them when lactate accumulation is anticipated or after it occurs.

TABLE 18.4 Typical replacement/dialysate fluid constituents for CRRT

The higher cost, problems with reconstituting bicarbonate solution bags and manual handling of large (5 L) fluid bags has increased interest in ‘online’ fluid production from tapwater at the bedside. This approach can be cheaper, requires no bag changing or reconstituting by nurses,⁹⁸ but involves installation of a complex and expensive reverse osmosis machine, the cost of which would be offset if large volumes of fluid were then consumed from this online manufacture. This approach may alter fluid selection and use in the future, and is an essential feature of chronic dialysis and use of ICU daily dialysis (EDDf) modes of therapy.^59–61

Fluid balance maintenance is a key nursing responsibility in managing CRRT. Most machines now available to provide CRRT incorporate a mode selection program, including an automatic fluid balance system. This ensures delivery of a fluid prescription based on the input provided by the programming nurse. As many litres of fluid may be exchanged in an hour (25–35 mL/kg), the default setting is usually a net machine balance, where all fluids administered as either dialysate or replacement are recovered or balanced. The machine cannot, however, include fluids administered or expelled directly from the patient, so a fluid maintenance schedule must be established. This schedule is also based on input and output being equal. For example, if more fluid is being infused into the patient than being lost, as would be expected in ARF, then additional fluid would need to be recovered via the CRRT circuit: that is, less replacement fluid administered or more waste created. Consider the calculation steps in the example in Table 18.5.

TABLE 18.5 Example of CVVH fluid maintenance schedule to calculate replacement solution dose/hour

Irrespective of the accuracy of fluid replacement assessment prior to therapy, individual patient assessment for fluid status must occur at least twice a day. Subtle temperature changes in the patient, fluid boluses, diarrhoea and variable absorption of feed may all contribute fluid losses not included in routine fluid maintenance. As treatment progresses over time, this may exacerbate a general loss of body fluid and dehydrate the patient. Regular weighing of patients may assist in assessing this situation. Electrolyte disturbances may also occur despite use of balanced replacement solutions. Particular attention should focus on regular assessment of fluid and electrolytes, especially potassium, sodium, phosphate and magnesium levels (see Chapter 19).