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’.