Renal and urology system

Pain

Pain, which can occur throughout the urinary tract ( Table 17.1 ), tends to be caused by infection, tumour or obstruction. Unilateral loin pain can be caused by pyelonephritis, renal stones causing obstruction, urinary retention and bleeding cysts. Pyelonephritis can be of abrupt or insidious onset, associated with fever, vomiting, lower urinary tract symptoms and urinary abnormalities. Laboratory analyses frequently show elevated markers of inflammation. Occasionally, pain may reflect tracking of pus upwards to the diaphragm, causing diaphragmatic pain, or in the retroperitoneal space to the psoas muscle, leading to pain when the muscle is stretched.

Renal stones cause pain in the presence of infection if they cause obstruction to urine flow. In ureteric tract obstruction, classically unilateral pain radiates from loin to groin, and may radiate to the testes or labia. A history of similar symptoms or family history of renal stone disease can be useful.

Kidney tumours classically cause a triad of pain, episodic macroscopic haematuria and a palpable mass, although this is rarely seen in practice. Attention should be paid to other systemic symptoms that may alert to the presence of metastases, such as weight loss, respiratory symptoms from lung metastases and back pain from tumour in the spine.

Polycystic kidney disease causes a spectrum from no symptoms at all, to recurrent or persistent loin pain caused by cyst infection, haemorrhage or local obstruction.

Bladder outflow obstruction (BOO) causes severe suprapubic pain when acute, and is most frequently owing to prostatic obstruction. BOO can also be caused by bladder or pelvic masses and prolapse in women. Acute urinary retention, which can also cause suprapubic pain, can be caused by medications and infection, and in post-operative patients.

Suprapubic and perineal pain most commonly arises from lower urinary tract infection owing to cystitis or urethritis. Such pain is frequently accompanied by dysuria, frequency or strangury (painful micturition). It is nearly always associated with urinary abnormalities on urine stick testing (protein, blood and leukocytes). In men prostatitis should be suspected in cases of severe perineal or rectal discomfort. In young children with urinary tract infection and cystitis the symptoms may be less obvious; cystitis should be suspected in any child who cries on micturating.

Bladder tumours infrequently cause pain; they are more commonly associated with painless haematuria and lower urinary tract symptoms.

Haematuria

Haematuria can be caused by bleeding anywhere in the genito-urinary tract. If visible to the naked eye it is termed macroscopic or visible haematuria; if seen only detectable using urine dipstick tests or microscopy it is termed non-visible, microscopic or dipstick haematuria. It can be continuous or intermittent, and painless or associated with pain and/or fever. Table 17.2 summarizes the causes of haematuria. Blood arising from renal parenchymal disease (glomerular bleeding) is usually, but not always painless, continuous and microscopic, but it can be macroscopic.. Haematuria from renal tumours is more frequently intermittent, macroscopic and associated with pain. Bleeding from bladder tumours is often intermittent, with associated local symptoms suggesting cystitis.

Infections in the urinary tract may also result in haematuria; the presence of microscopic haematuria should always be followed by urine microscopy and culture as part of the diagnostic process. It is important to decide whether haematuria originates from the kidneys or elsewhere in the urinary tract. This decision affects the order in which investigations should be conducted. Over the age of 40, bleeding should generally be assumed to be non-glomerular in the first instance, unless there is other compelling evidence for a glomerular lesion. Under the age of 40, the presence of associated proteinuria is likely to signify parenchymal renal disease, such as a glomerulonephritis.

Transient painless haematuria in the absence of any other urine abnormalities in women is most likely owing to contamination from menstrual blood. Other causes include exercise, intercourse and viral illnesses. Systemic conditions and medications can also cause haematuria; inquiry into a history of bleeding elsewhere may alert to this.

Discoloured urine with positive urine on dipstick can be owing to other causes. Myoglobin (released from muscle owing, for example, to rhabdomyolysis or trauma) and the presence of free haem both result in positive urine dipstick for blood in the absence of true blood in the urine. Various drugs and certain foods can also result in discoloured urine.

Oliguria/anuria

Oliguria is defined as the passage of less than 500 ml of urine per day, whilst anuria is the complete absence of urine flow. Progressive oliguria can be physiological, owing to inadequate intake, fluid loss such as in burns or blood loss, with preserved glomerular filtration rate (GFR). Here kidney function is not impaired; it is retaining sodium and water, resulting in concentrated urine; restoring adequate renal perfusion will restore normal urine output. However, if inadequate intake or excess loss leads to a significant reduction in the extracellular fluid compartment, the resulting decrease in renal blood flow leads to oliguria and a reduction in GFR. Oliguria owing to reduced renal blood flow is termed pre-renal; it can also occur in the context of cardiogenic or septic shock. Intrinsic renal disease causes loss of glomerular filtration in the absence of reduced blood flow to the kidneys; note that not all causes of intrinsic renal disease cause oliguria. Mechanical obstruction to urine flow, such as caused by stones, tumours or prostatic hypertrophy, is termed post-renal oliguria. When the lesion is at the level of the bladder, it may result in complete anuria.

Polyuria

Polyuria implies no more than a high urinary flow rate. It is caused by excessive intake, an osmotic diuresis, or renal tubular dysfunction ( Table 17.3 ). Recovery from acute kidney injury, particularly following obstruction, can be accompanied by polyuria; the concentrating ability of the renal tubules recovers later than glomerular function. The description of polyuria should always be accompanied by a query about nocturia and polydipsia. The latter, in particular, is a presentation of diabetes. Medications, such as diuretics, can result in polyuria, whilst long-term lithium use is a common cause of nephrogenic diabetes insipidus. A broader past medical history and systems inquiry assists in differentiating among causes.

Frequency of micturition

Increased frequency of micturition results from polyuria, a reduction in functional bladder capacity, or bladder/urethral irritation ( Table 17.4 ). The most common cause is polyuria and excessive fluid intake, but it is also a feature of urinary tract infection (UTI). Incomplete bladder outlet obstruction, particularly when it is chronic, can result in frequency without accompanying polyuria. Some patients with neurological disease, in particular multiple sclerosis, have frequency of micturition. The detrusor muscle of the bladder contracts at an inappropriately low bladder volume, resulting in a low functional bladder capacity.

Nocturia

The term nocturia implies the need to empty the bladder during the hours of sleep. In the presence of a normal urinary tract and normal renal function, there is diurnal variation in the urinary flow rate: at night time there is a reduction in urine flow, and micturition is unnecessary. Polyuria can result in nocturia, along with a reduction in functional bladder capacity, which can happen with age. Polydipsia at night and the use of diuretics later in the day are also a cause. In chronic kidney disease, even in the early stages, the concentrating ability of the kidneys is reduced, and nocturia can be an early symptom of renal impairment. Sickle cell disease results in similar loss of concentrating ability.

Dysuria

Dysuria is discomfort arising from the urinary tract in which there is pain immediately before, during or after micturition. The urine is often described as ‘burning’ or ‘scalding’, and there is usually associated frequency and decreased functional bladder capacity. Infection or inflammation in the bladder or urethra are the most common causes. Malignancy in the lower urinary tract can also cause dysuria. An extreme form of dysuria, strangury, implies an unpleasant and painful desire to void when the bladder is empty or near empty.

Urgency of micturition, incontinence and enuresis

Urgency is the loss of the normal ability to postpone micturition beyond the time when the desire to pass urine is initially perceived. Incontinence is the involuntary passage of urine. Urgency may lead to urge incontinence. Stress incontinence is leakage of urine associated with straining or coughing, often owing to weakened pelvic floor muscles after vaginal childbirth. Enuresis is defined as involuntary micturition after the age at which bladder control begins, and usually refers to nocturnal enuresis. It can be primary, when in the vast majority of cases is a developmental delay, or secondary (nocturnal enuresis after a period of dryness). Occasionally, it can be a presentation of urinary tract infection or type 1 diabetes mellitus.

Slow stream, hesitancy and terminal dribbling

The triad of slow stream, hesitancy and terminal dribbling is most frequently seen in older men with prostatic hypertrophy. Here, the bladder outlet is partially obstructed by the enlarging prostate gland, and the maximum achievable urinary flow rate is reduced. There is often difficulty in initiating micturition (hesitancy) and in completing micturition (terminal dribbling). The symptoms are nearly always associated with frequency of micturition and nocturia. There is progressive bladder enlargement, with eventual overflow incontinence and continuous or intermittent dribbling of urine.

Urethral discharge

Urethral discharge is usually noticed only by men and always requires further investigation. There may be associated symptoms of urethral irritation and the underlying pathology is likely to be urethritis, which is often infective and sexually transmitted (see Chapter 18 ).

Past medical history

A history of urinary problems as a child may be suggestive of structural abnormalities such as posterior urethral valves. Previous urinary symptoms, specifically a history of UTI or recurrent dysuria, stones and prostate problems, should also be sought. Episodic macroscopic haematuria during upper respiratory tract infection is a classic presentation of IgA nephropathy. Haemoptysis is a feature of rare, but important, pulmonary renal syndromes, such as antineutrophil cytoplasmic autoantibody-associated vasculitis and antiglomerular basement membrane disease. Upper respiratory tract symptoms, such as epistaxis, may also be present. Systemic illnesses, in particular hypertension, diabetes and cardiovascular disease (ischaemic heart disease, stroke and peripheral vascular disease), are a risk factor for chronic kidney disease, which, particularly in the early stages, can present with few or no symptoms, and only be identified on screening.

Medication history

Many drugs can cause renal injury, or be nephrotoxic in the context of kidney disease. Table 17.5 summarizes some of the more common drugs of which to be aware.

Social history

Smoking increases the risk of cardiovascular disease and chronic kidney disease (CKD), and also the risk of many cancers, including urothelial cancer. Also enquire about risk factors for HIV and hepatitis B and C. Drug use, including ketamine, cocaine and cannabis, is important. Ketamine can cause ‘ketamine bladder’, a syndrome characterized by pain, microscopic haematuria and reduced functional bladder capacity, whilst cocaine is associated with several patterns of renal injury. Occupation has been implicated in urothelial cancer (painters, dry cleaners, diesel fumes, metal-workers).

Family history

A family history of diabetes, hypertension, cardiovascular disease and CKD, including dialysis and transplantation, is important for assessing the risk of advanced kidney disease and identifying potential causes of CKD. Inherited kidney disease is relatively rare, the most common being autosomal-dominant polycystic kidney disease (ADPKD). Certain other rare genetic disorders may also have renal involvement, for example cysts and tumours in the kidney in von Hippel-Lindau syndrome.

Systems enquiry

Systems enquiry may point to a cause of kidney disease, or the consequences of CKD. Table 17.6 summarizes systemic conditions associated with CKD and associated signs on clinical examination.

Acute kidney injury

Acute kidney injury (AKI) is the onset of declining renal function occurring over a period of hours or days, usually but not always accompanied by oliguria. There is a rapid decline in the GFR, leading to electrolyte dysregulation, and nitrogen retention. The outlook depends on the cause, which can be divided into pre-renal, intrinsic and post-renal ( Table 17.8 ). The most common cause of intrinsic AKI is acute tubular necrosis (ATN)—loss of renal tubular epithelial cells, usually as a result of pre-renal ischaemia or nephrotoxins. A variety of classification systems for AKI use measurement of serum creatinine and urine output to stratify it into mild, moderate or severe. These are used as a guide to predict risk of mortality and outcome in hospitalized patients. It may reverse spontaneously (repair of ischaemic injury in tubular necrosis) or as a result of therapy (removal of stone or other cause of obstruction). Severe AKI can manifest with uraemic symptoms (see below). These are pre-terminal, but reversible with dialysis to remove the excess uraemic toxins. Failure to recover GFR partially or fully can result in progression to CKD.

Chronic kidney disease

Chronic kidney disease is defined by a persistent (>3 months) disorder of kidney function or structure. It can be caused by chronic renal ischaemia from renal parenchymal disease, failure of acute kidney injury to recover or unrelieved urinary obstruction. The most widely used classification for CKD divides it into stages based on GFR measurement and the presence or absence of albuminuria ( Fig. 17.1 ), which, whilst imperfect, enables stratification of risk of progression to end stage kidney disease (ESKD).

If renal impairment is severe, there may be clinical manifestations of uraemia. These are usually evident when the GFR has fallen to <20 ml/min (CKD 4 or 5), and are most severe once GFR is <10 ml/min. Lethargy, poor concentration, irritability and failure of higher mental functions and ability to handle tasks are all commonly reported, as are nausea, anorexia and vomiting. In advanced renal insufficiency, there may be confusion, fits and stupor. The presence of these symptoms indicates the need for dialysis to remove uraemic toxins, or transplantation to restore GFR. Even in the absence of uraemic symptoms, renal replacement therapy (dialysis or transplantation) may be indicated once GFR falls to <15ml/min.

The nephritic syndrome

The nephritic syndrome is historically described as the constellation of oliguria, microscopic haematuria and hypertension, and is usually accompanied by mild proteinuria and impaired renal function. It usually has a fairly brisk onset (days, weeks or months). It is caused by injury to the glomerulus, which can be insidious or acute. Many of the causes of acute nephritis are associated with functional abnormalities of the immune system that may be detected by laboratory tests and which may also manifest with disease in other organs, for example the skin, joints or eyes, as in SLE, Henoch-Schönlein purpura ( Fig. 17.2 ) and systemic vasculitis, post-infectious glomerulonephritis (GN), anti-GBM disease and membranoproliferative glomerulonephritis (MPGN).