Kidney and urinary tract disease

Clinical examination of the kidney and urinary tract

Many diseases of the kidney and urinary tract are clinically silent, at least in the early stages. Accordingly, it is common for these conditions to first be detected by routine blood tests or on dipstick testing of the urine. Several important abnormalities can also be picked up on physical examination, however, as summarised below.

This chapter describes the disorders of the kidneys and urinary tract that are commonly encountered in routine practice, as well as giving an overview of the highly specialised field of renal replacement therapy. Disorders of renal tubular function, which may cause alterations in electrolyte and acid–base balance, are described in Chapter 16.

Functional anatomy and physiology

The kidneys

The kidneys play a central role in excretion of many metabolic breakdown products, including ammonia, urea and creatinine from protein, and uric acid from nucleic acids, drugs and toxins. They also regulate fluid and electrolyte balance. This is achieved by making large volumes of an ultrafiltrate of plasma (120 mL/min, 170 L/day) at the glomerulus, and selectively reabsorbing components of this ultrafiltrate at points along the nephron. The rates of filtration and reabsorption are controlled by many hormonal and haemodynamic signals.

The kidneys also regulate acid–base homeostasis, calcium and phosphate homeostasis, vitamin D metabolism and production of red blood cells. They are important in regulating blood pressure. Renin is secreted from the juxtaglomerular apparatus in response to reduced afferent arteriolar pressure, stimulation of sympathetic nerves, and changes in sodium content of fluid in the distal convoluted tubule at the macula densa, and is the first step in the generation of angiotensin II and aldosterone release, which in turn regulate systemic vasoconstriction and extracellular volume.

Each kidney is approximately 11–14 cm in length in healthy adults; they are located retroperitoneally on either side of the aorta and inferior vena cava between the 12th thoracic and 3rd lumbar vertebra (Fig. 17.1A). The right kidney is usually a few centimetres lower because the liver lies above it. Both kidneys rise and descend several centimetres with respiration.

Fig. 17.1 Functional anatomy of the kidney.
A Anatomical relationships of the kidney. B A single nephron. For the functions of different segments, see Figures 16.2 and 16.3 (pp. 430 and 431). C Histology of a normal glomerulus. D Schematic cross-section of a glomerulus, showing five capillary loops, to illustrate structure and show cell types. E Electron micrograph of the filtration barrier. (GBM = glomerular basement membrane)

The kidneys have a rich blood supply and receive approximately 20–25% of cardiac output through the renal arteries, which arise from the abdominal aorta. The renal arteries undergo various subdivisions within the kidney, eventually forming interlobular arteries that run through the renal cortex. These eventually give rise to afferent glomerular arterioles that supply individual nephrons, which are the functional units of the kidney. The efferent arteriole, leading from the glomerulus, supplies the distal nephron and medulla in a ‘portal’ circulation (Fig. 17.1B).

The nephron

Healthy kidneys contain approximately 1 million individual nephrons. Each nephron consists of a glomerulus, which is responsible for ultrafiltration of blood, a proximal renal tubule, a loop of Henle, a distal renal tubule and a collecting duct, which together are responsible for selective reabsorption of water and electrolytes that have been filtered at the glomerulus (see Fig. 16.2, p. 430). Under normal circumstances, more than 99% of the 170 litres of glomerular filtrate that is produced each day is reabsorbed in the tubules. The remainder passes through the collecting ducts of multiple nephrons and drains into the renal pelvis and ureters.

The glomerulus

The glomerulus comprises a tightly packed loop of capillaries supplied by an afferent arteriole and drained by an efferent arteriole. It is surrounded by a cup-shaped extension of the proximal tubule termed Bowman’s capsule, which is comprised of epithelial cells. Blood that enters the glomerulus undergoes ultrafiltration across the glomerular basement membrane (GBM), which is formed by fusion of the basement membranes of tubular epithelial and vascular endothelial cells (Fig. 17.1C and D). The glomerular capillary endothelial cells contain pores (fenestrae), through which circulating molecules can pass to reach the underlying GBM. Glomerular epithelial cells (podocytes) have multiple long foot processes which interdigitate with those of the adjacent epithelial cells (Fig. 17.1E). As well as maintaining a selective barrier to filtration, podocytes are involved in regulating turnover of the GBM. Mesangial cells lie in the central region of the glomerulus. They have contractile properties similar to those of vascular smooth muscle cells but also have macrophage-like properties.

Under normal circumstances, the glomerulus is impermeable to proteins the size of albumin (67 kDa) or larger, while proteins of 20 kDa or smaller are filtered freely. The ability of molecules between 20 and 67 kDa to pass through the GBM is variable and depends on the size (smaller molecules are filtered more easily) and charge (positively charged molecules are filtered more easily). Very little lipid is filtered by the glomerulus.

Filtration pressure at the glomerulus is normally maintained at a constant level, in the face of wide variations in systemic blood pressure and cardiac output, by alterations in muscle tone within the afferent and efferent arterioles. This is known as autoregulation. When there is a reduction in renal perfusion pressure, renin is released by specialised smooth muscle cells in the juxtaglomerular apparatus. Renin cleaves angiotensinogen to release angiotensin I, which is further cleaved by angiotensin-converting enzyme (ACE) to produce angiotensin II (Fig. 17.1D). This restores glomerular perfusion pressure in the short term by causing vasoconstriction of the efferent arterioles within the kidney and by inducing systemic vasoconstriction to increase blood pressure and thus renal perfusion pressure. In the longer term, angiotensin II increases plasma volume by stimulating aldosterone release, which enhances sodium reabsorption by the renal tubules (see Fig. 20.17, p. 771).

Renal tubules, loop of Henle and collecting ducts

The proximal renal tubule, loop of Henle, distal renal tubule and collecting ducts are responsible for reabsorption of water, electrolytes and other solutes, as well as regulating acid–base balance, as described in detail on page 430 and in Figure 16.3. They also play a key role in regulating calcium homeostasis by converting 25-hydroxyvitamin D to the active metabolite 1,25-dihydroxyvitamin D (p. 1126). Failure of this process contributes to the pathogenesis of hypocalcaemia and bone disease which occurs in chronic kidney disease (CKD, p. 483). Fibroblast-like cells that lie in the interstitium of the renal cortex are responsible for production of erythropoietin, which in turn is required for production of red blood cells. Erythropoietin synthesis is regulated by oxygen tension; anaemia and hypoxia increase production, whereas polycythaemia and hyperoxia inhibit it. Failure of erythropoietin production plays an important role in the pathogenesis of anaemia in CKD.

Ureters and bladder

The ureters drain urine from the renal pelvis (Fig. 17.1A) and deliver it to the bladder, a muscular organ that lies anteriorly in the lower part of the pelvis, just behind the pubic bone. The function of the bladder is to store and then release urine during micturition. The bladder is richly innervated. Sympathetic nerves arising from T10–L2 relay in the pelvic ganglia to cause relaxation of the detrusor muscle and contraction of the bladder neck (both via α-adrenoceptors), thereby preventing release of urine from the bladder. The distal sphincter mechanism is innervated by somatic motor fibres from sacral segments S2–4, which reach the sphincter either by the pelvic plexus or via the pudendal nerves. Afferent sensory impulses pass to the cerebral cortex, from where reflex-increased sphincter tone and suppression of detrusor contraction inhibit micturition until it is appropriate. Conversely, parasympathetic nerves arising from S2–4 stimulate detrusor contraction, promoting micturition.

The micturition cycle has a storage (filling) phase and a voiding (micturition) phase. During the filling phase, the high compliance of the detrusor muscle allows the bladder to fill steadily without a rise in intravesical pressure. As bladder volume increases, stretch receptors in its wall cause reflex bladder relaxation and increased sphincter tone. At approximately 75% bladder capacity, there is a desire to void. Voluntary control is now exerted over the desire to void, which disappears temporarily. Compliance of the detrusor allows further increase in capacity until the next desire to void. Just how often this desire needs to be inhibited depends on many factors, not the least of which is finding a suitable place in which to void.

The act of micturition is initiated first by voluntary and then by reflex relaxation of the pelvic floor and distal sphincter mechanism, followed by reflex detrusor contraction. These actions are coordinated by the pontine micturition centre. Intravesical pressure remains greater than urethral pressure until the bladder is empty.

The prostate gland

The prostate gland is situated at the base of the bladder, surrounding the proximal urethra. Exocrine glands within the prostate produce fluid, which comprises about 20% of the volume of ejaculated seminal fluid and is rich in zinc and proteolytic enzymes. The remainder of the ejaculate is formed in the seminal vesicles and bulbo-urethral glands, with spermatozoa arising from the testes.

Smooth muscle fibres within the prostate, which are under sympathetic control, play a role in controlling urine flow through the bulbar urethra, and also contract at orgasm to move seminal fluid through ejaculatory ducts into the bulbar urethra (emission). Contraction of the bulbocavernosus muscle (via a spinal muscle reflex) then ejaculates the semen out of the urethra.

The penis

Blood flow into the corpus cavernosum of the penis is controlled by sympathetic nerves from the thoracolumbar plexus, which maintain smooth muscle contraction. In response to afferent input from the glans penis and from higher centres, pelvic splanchnic parasympathetic nerves actively relax the cavernosal smooth muscle via neurotransmitters such as nitric oxide, acetylcholine, vasoactive intestinal polypeptide (VIP) and prostacyclin, with consequent dilatation of the lacunar space. At the same time, draining venules are compressed, trapping blood in the lacunar space with consequent elevation of pressure and erection (tumescence) of the penis.

Investigation of renal and urinary tract disease

Glomerular filtration rate

The glomerular filtration rate (GFR) is the rate at which fluid passes into nephrons after filtration and is a measure of renal function. It is proportionate to body size and the reference range is usually expressed after correction for body surface area as 120 ± 25 mL/min/1.73 m². The GFR may be measured directly by injecting and measuring the clearance of compounds such as inulin or radiolabelled ethylenediamine-tetracetic acid, which are completely filtered at the glomerulus and are not secreted or reabsorbed by the renal tubules (Box 17.1). However, this is not performed routinely and is usually reserved for special circumstances, such as the assessment of renal function in potential live kidney donors. Instead, GFR is usually indirectly assessed in clinical practice by measuring serum levels of endogenously produced compounds that are excreted by the kidney. The most widely used is serum creatinine, which is produced by muscle at a constant rate, is almost completely filtered at the glomerulus, and is not reabsorbed. Although creatinine is secreted to a small degree by the proximal tubule, this is only usually significant in terms of GFR estimation in severe renal impairment, where it accounts for a larger proportion of the creatinine excreted. Accordingly, provided muscle mass remains constant, changes in serum creatinine concentrations closely reflect changes in GFR, although the reference range for creatinine is wide due to the fact that muscle mass varies widely between different individuals (Fig. 17.2). Several methods have been developed with which to estimate GFR from serum creatinine measurements (see Box. 17.1) but the most widely used is the MDRD equation, which is now the accepted standard for assessing estimated GFR (eGFR). Although the eGFR has several limitations (Box 17.2), its routine reporting by laboratories has increased recognition of moderate kidney damage and encouraged early deployment of protective therapies (Box 17.3).

17.1

How to estimate glomerular filtration rate (GFR)

Measuring GFR

• Direct measurement using labelled EDTA or inulin

• Creatinine clearance (CrCl)

Minor tubular secretion of creatinine causes CrCl to exaggerate GFR when renal function is poor, and can be affected by drugs (e.g. trimethoprim, cimetidine)

Needs 24-hr urine collection (inconvenient and often unreliable)

CrCl (mL/min)=urine creatinine concentration (μmol / L)×volume (mL)plasma creatinine concentration (μmol/L)×time (min)

Estimating GFR with equations

• Cockcroft and Gault equation

Reasonably accurate at normal to moderately impaired renal function

Estimates CrCl, not GFR

Requires patient weight

CrCl=(140 − age in yrs)×lean body weight (kg)× (1.22 males or 1.04 females)serum creatinine (μmol/L)

• The Modification of Diet in Renal Disease (MDRD) study equation (see www.renal.org/eGFR)

Performs better than Cockcroft and Gault at low GFR

Requires knowledge of age and sex only

Can be reported automatically by laboratories

For limitations, see Box 17.2

eGFR=186*×(creatinine in μmol/L/88.4)−1.154×(age in yrs)−0.203 × (0.742 if female)×(1.21 if black)

• No equations perform well in unusual circumstances, such as extremes of body (and muscle) mass or in acutely unwell patients (see Box 17.2)

*A correction factor, either a value recommended by the laboratory/assay manufacturer or a default value of 186; see www.renal.org/ckd. To convert creatinine in mg/dL to µmol/L, multiply by 88.4.

17.2 Limitations of eGFR

• It is only an estimate, least reliable at extremes of body composition (malnourished, amputees) and in hospital inpatients (as it was derived from outpatients)

• Confidence intervals are wide (90% of patients will have eGFR within 30% of their measured GFR, and 98% within 50%)

• Values are consistent in individuals, so changes mean more than absolute values

• Creatinine level must be stable over days; eGFR is not valid in assessing acute kidney injury

• It tends to underestimate normal or near-normal function, so slightly low values should not be over-interpreted. Many laboratories report only up to > 60 mL/min/1.73 m² for this reason

• In the elderly, who constitute the majority of those with low eGFR, there is controversy about categorising people as having chronic kidney disease (CKD; Box 17.3) on the basis of eGFR alone, particularly at stage 3A, since there is little evidence of adverse outcomes when eGFR is > 50 unless there is also proteinuria

• eGFR is not valid in under-18s or during pregnancy

• The equation was originally validated in US patients and eGFR for any given creatinine was 21% higher in blacks. Performance in other racial groups is under investigation

17.3 Stages of chronic kidney disease (CKD)

Stage¹	Definition²	Description	Prevalence³	Clinical presentation⁴
1	Kidney damage with normal or high GFR (> 90)	Mild CKD	6.5%	Asymptomatic
2	Kidney damage and GFR 60–89			Asymptomatic
3A⁵	GFR 45–59	Moderate CKD	4.5%	Usually asymptomatic
3B⁵	GFR 30–44			Anaemia in some patients at 3B Most are non-progressive or progress very slowly
4	GFR 15–29	Severe CKD	0.4%	First symptoms often at GFR < 20 Electrolyte problems likely as GFR falls
5	GFR < 15 or on dialysis	Kidney failure		Significant symptoms and complications usually present Dialysis initiation varies but usually at GFR < 10

¹ Stages of CKD 1–5 were originally defined by the US National Kidney Foundation Kidney Disease Quality Outcomes Initiative 2002.

² Kidney damage means pathological abnormalities or markers of damage, including abnormalities in urine tests or imaging studies. Two GFR values 3 mths apart are required to assign a stage. All GFR values are mL/min/1.73 m².

³ From the NHANES III study of > 15 000 US adults (Am J Kid Dis 2003; 41:1–12).

⁴ For further information, see page 483.

⁵ 3A/3B split recommended for UK in 2007/8, plus a suffix P, indicating presence of proteinuria (albumin:creatinine ratio (ACR) > 30 or protein:creatinine ratio (PCR) > 50 mg/mmol), e.g. 3 Ap, in view of the prognostic importance of proteinuria.

A potentially more accurate assessment of GFR can be obtained by collection of a 24-hour urine sample and relating serum creatinine levels to urinary creatinine excretion (see Box 17.1).

Urinalysis

Screening for the presence of blood, protein, glucose, ketones, nitrates and leucocytes and to assess pH and osmolality of urine can be achieved by dipstick testing (p. 474). Urine microscopy (p. 463) or flow cytometry can detect erythrocytes, which are indicative of bleeding from the urogenital tract (anywhere from kidney to tip of penis); dysmorphic erythrocytes, which suggest the presence of nephritis; red cell casts, indicative of glomerular disease; and crystals, which may be observed in patients with renal stone disease. It should be noted that calcium oxalate and urate crystals can sometimes be found in normal urine that has been left to stand, due to crystal formation ex vivo. The presence of leucocytes and bacteria in urine is indicative of renal tract infection. White cell casts are strongly suggestive of pyelonephritis. Urine pH can provide diagnostic information in the assessment of renal tubular acidosis (p. 446). Urine collection over a 24-hour period can be performed to measure excretion of solutes, such as calcium, oxalate and urate, in patients with recurrent renal stone disease (p. 507). Proteinuria can also be measured on 24-hour collections but is usually now quantified by protein/creatinine ratio on spot urine samples.

Other dynamic tests of tubular function, including concentrating ability (p. 794), ability to excrete a water load (p. 438) and ability to excrete acid (p. 426), and calculation of fractional calcium, phosphate or sodium excretion, are valuable in some circumstances. The fractional excretion of these ions can be calculated by the general formula: (urine concentration of analyte × serum creatinine) / (serum concentration of analyte × urinary creatinine). For example, familial benign hypercalcaemia is characterised by a very low fractional excretion of calcium (p. 770), and hypophosphataemic rickets (p. 1128) by an increased fractional excretion of phosphate. Calculation of fractional excretion of sodium (FENa) can help differentiate volume depletion, when the tubules are avidly conserving sodium (FENa typically < 1.0), from acute tubular necrosis, when the tubules are damaged and are less able to conserve sodium (FENa typically > 1.0).

Blood tests

Haematology

A normochromic normocytic anaemia is common in CKD and is due in part to deficiency of erythropoietin and bone marrow suppression secondary to toxins retained in CKD. Other causes of anaemia include iron deficiency from urinary tract bleeding, and haemolytic anaemia secondary to disorders such as haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Other abnormalities may be observed that reflect underlying disease processes, such as neutrophilia and raised erythrocyte sedimentation rate (ESR) in vasculitis or sepsis; lymphopenia and raised ESR in systemic lupus erythematosus (SLE); and fragmented red cells in HUS and TTP.

Biochemistry

Abnormalities of routine biochemistry are common in renal disease. Serum levels of creatinine may be raised, reflecting reduced GFR (see above), although serum creatinine values can remain within the reference range in patients with reduced muscle mass, even when the GFR has fallen by more than 50%. Serum levels of urea are often increased in kidney disease but this analyte has limited value as a measure of GFR since levels increase with protein intake, following gastrointestinal haemorrhage and in catabolic states. Conversely, urea levels may be reduced in patients with liver failure or anorexia and in malnourished patients, independently of changes in renal function. Serum calcium tends to be reduced and phosphate increased in CKD, in association with high parathyroid hormone (PTH) levels caused by reduced production of 1,25(OH)₂D by the kidney (secondary hyperparathyroidism). In some patients, this may be accompanied by raised serum alkaline phosphatase levels, which are indicative of renal osteodystrophy. Other biochemical abnormalities may be observed that reflect underlying disease processes, such as raised glucose and HbA_1c levels in diabetes mellitus (p. 807) and raised levels of C-reactive protein (CRP) in sepsis and vasculitis.

Immunology

Antinuclear antibodies, antibodies to extractable nuclear antigens and anti-double-stranded DNA antibodies may be detected in patients with renal disease secondary to SLE (p. 1109). Antineutrophil cytoplasmic antibodies (ANCA) may be detected in patients with glomerulonephritis secondary to systemic vasculitis (p. 1115), as may antibodies to GBM in patients with Goodpasture’s syndrome (p. 497) and low levels of complement in SLE, systemic vasculitis and HUS.

Imaging

Ultrasound

Renal ultrasound is a valuable non-invasive technique that is indicated to assess renal size and to investigate patients who are suspected of having obstruction of the urinary tract (Fig. 17.3) or renal tumours, cysts or stones. It is often the only method required for renal imaging and has the advantage of showing other abdominal, pelvic and retroperitoneal pathology. Ultrasound can also be used to provide images of the prostate gland and bladder, and to estimate the completeness of emptying in patients with suspected bladder outflow obstruction. Ultrasonography may show increased density of the renal cortex with loss of distinction between cortex and medulla, which is characteristic of CKD. Doppler imaging can be used to study blood flow in extrarenal and larger intrarenal vessels and can assess the resistivity index, which is the ratio of peak systolic and diastolic velocity. This is influenced by the resistance to flow through small intrarenal arteries and may be elevated in various diseases, including acute glomerulonephritis and rejection of a renal transplant. High peak velocities can also occur in severe renal artery stenosis. However, renal ultrasound is operator-dependent, the stored images convey only a fraction of the dynamic information gained during the investigation, and the results are often less clear in obese patients.

Computed tomography

Computed tomography urography (CTU) is used to evaluate cysts and mass lesions in the kidney or filling defects within the collecting systems. It usually entails an initial scan without contrast medium, and subsequent scans following injection of contrast to obtain a nephrogram image and images during the excretory phases. This technique gives more information than intravenous urography (IVU) but entails a substantially larger radiation dose. Contrast enhancement is particularly useful for characterising mass lesions within the kidney and differentiating benign from malignant lesions (see Fig. 17.32A, p. 516). Computed tomography without contrast (CT) gives clear definition of retroperitoneal anatomy regardless of obesity and is superior to ultrasound in this respect. Non-contrast CT of kidneys, ureters and bladder (CTKUB) is the method of choice for demonstrating stones within the kidney or ureter.

Computed tomography and angiography

This technique (CT-angiography) involves performing computed tomography, following an intravenous injection of contrast medium, to obtain images of the renal vasculature. It produces high-quality images of the main renal vessels and is of value in patients who have suffered renal trauma and those with haemorrhage from the renal tract, and in the investigation of renal artery stenosis. Other vascular structures, such as angiomyolipomas and aneurysms, can also be detected. Drawbacks include the fact that relatively large doses of contrast medium are required, which can cause renal dysfunction, and that the radiation dose is significant (Box 17.4).

17.4 Renal complications of radiological investigations

Contrast nephrotoxicity

• Acute deterioration in renal function, sometimes life-threatening, commencing < 48 hrs after administration of IV radiographic contrast media

Risk factors

• Pre-existing renal impairment

• Use of high-osmolality, ionic contrast media and repetitive dosing in short time periods

• Diabetes mellitus

• Myeloma

Prevention

• Provide hydration with free oral fluids plus IV isotonic saline 500 mL, then 250 mL/hr during procedure

• Avoid nephrotoxic drugs; withhold non-steroidal anti-inflammatory drugs (NSAIDs). Omit metformin for 48 hrs after the procedure, in case renal impairment occurs

• N-acetylcysteine may provide some protection but data are conflicting

• If the risks are high, consider alternative methods of imaging

Cholesterol atheroembolism

• Typically follows days to weeks after intra-arterial investigations or interventions (p. 496)

Nephrogenic sclerosing fibrosis after MRI contrast agents

• Chronic progressive sclerosis of skin, deeper tissues and other organs, associated with gadolinium-based contrast agents

• Only reported in patients with renal impairment, typically on dialysis or with GFR < 15 mL/min/1.73 m², but caution is advised in patients with GFR < 30 mL/min/1.73 m²

Magnetic resonance imaging

Magnetic resonance imaging (MRI) offers excellent resolution and gives good distinction between different tissue types (see Fig. 17.26, p. 506). It is very useful for local staging of prostate, bladder and penile cancers. Magnetic resonance angiography (MRA) provides an alternative to CT-angiography for imaging renal vessels but involves administration of gadolinium-based contrast media, which may carry risks for patients with impaired renal function (see Box 17.4). Whilst MRA gives good images of the main renal vessels, stenosis of small branch arteries may be missed.

Renal arteriography

Renal arteriography involves taking X-rays following an injection of contrast medium directly into the renal artery. The main indication is to investigate renal artery stenosis (p. 494) or haemorrhage. Renal angiography can often be combined with therapeutic balloon dilatation or stenting of the renal artery and can be used to occlude bleeding vessels and arteriovenous fistulae by the insertion of thin platinum wires (coils). These curl up within the vessel and promote thrombosis, thereby securing haemostasis.

Intravenous urography

Intravenous urography (IVU) involves taking serial plain X-rays immediately before and after an intravenous injection of contrast medium. It has largely been replaced by ultrasound, CTKUB and CTU for most renal imaging purposes but remains a useful method of viewing the renal papillae, stones and urothelial malignancies (Fig. 17.4). The initial X-rays may show the renal outlines (if perinephric fat and bowel gas shadows allow), as well as radio-opaque calculi and calcification within the renal tract. Early films taken 1 minute after injection can be used to assess renal perfusion, whereas films at later time points provide images of the collecting system, ureters and bladder. The disadvantages of this technique are the need for an injection, dependence on adequate renal function, and exposure to irradiation and contrast medium (see Box 17.4).

Fig. 17.4 Intravenous urography (IVU).
A Normal nephrogram phase at 1 minute. B Normal collecting system at 5 minutes. C Bilateral reflux nephropathy (and chronic pyelonephritis), showing clubbing of the calyces that is particularly marked in the upper right pole.

Pyelography

Pyelography involves direct injection of contrast medium into the collecting system from above or below. It offers the best views of the collecting system and upper tract, and is sometimes used to identify the cause of urinary tract obstruction (p. 472). Antegrade pyelography requires the insertion of a fine needle into the pelvicalyceal system under ultrasound or radiographic control. This approach is much more difficult and hazardous in a non-obstructed kidney. In the presence of obstruction, percutaneous nephrostomy drainage can be established, and often stents can be passed through any obstruction. Retrograde pyelography can be performed by inserting catheters into the ureteric orifices at cystoscopy (Fig. 17.5).

Radionuclide studies

These are functional studies requiring the injection of gamma ray-emitting radiopharmaceuticals that are taken up and excreted by the kidney, a process that can be monitored by an external gamma camera.

Dynamic radionucleotide studies are performed with mercaptoacetyltriglycine labelled with technetium (^99mTc-MAG3), which is filtered by the glomerulus and excreted into the urine. Imaging following ^99mTc-MAG3 injection can provide valuable information about the perfusion of each kidney but is not a reliable method for identifying renal artery stenosis. In patients with significant obstruction of the outflow tract, ^99mTc-MAG3 persists in the renal pelvis and a loop diuretic fails to accelerate its disappearance. This can be useful in determining the functional significance of a ‘baggy’ or equivocally obstructed collecting system without undertaking pyelography.

Formal measurements of GFR can be made by radionuclide studies following the injection of diethylenetriamine pentacetic acid (^99mTc-DPTA).

Static radionucleotide studies are performed with dimercaptosuccinic acid labelled with technetium (^99mTc-DMSA), which is taken up by proximal tubular cells. Following intravenous injection, images of the renal cortex are obtained that show the shape, size and relative function of each kidney (Fig. 17.6). This is a sensitive method for demonstrating cortical scarring in reflux nephropathy and a way of assessing the individual function of each kidney.

Fig. 17.6 DMSA isotope renogram.
A posterior view is shown of a normal left kidney and a small right kidney (with evidence of cortical scarring at upper and lower poles) that contributes only 39% of total renal function.

Radionuclide bone scanning following the injection of methylene diphosphonate (^99mTc-MDP) is indicated to assess the presence and extent of bone metastases in men with advanced prostate cancer (p. 517).

Renal biopsy

Renal biopsy is used to establish the nature and extent of renal disease in order to judge the prognosis and need for treatment (Box 17.5). The procedure is performed transcutaneously with ultrasound or contrast radiography guidance to ensure accurate needle placement into a renal pole. Light microscopy, electron microscopy and immunohistological assessment of the specimen may all be required.

17.5 Renal biopsy

Indications

• Acute kidney injury that is not adequately explained

• CKD with normal-sized kidneys

• Nephrotic syndrome or glomerular proteinuria in adults

• Nephrotic syndrome in children that has atypical features or is not responding to treatment

• Isolated haematuria or proteinuria with renal characteristics or associated abnormalities

Contraindications

• Disordered coagulation or thrombocytopenia. Aspirin and other antiplatelet agents increase bleeding risk

• Uncontrolled hypertension

• Kidneys < 60% predicted size

• Solitary kidney * (except transplants)

Complications

• Pain, usually mild

• Bleeding into urine, usually minor but may produce clot colic and obstruction

• Bleeding around the kidney, occasionally massive and requiring angiography with intervention, or surgery

• Arteriovenous fistula, rarely significant clinically

^*Relative contraindication.

Presenting problems in renal and urinary tract disease

The presence of bladder enlargement in a middle-aged or elderly man suggests benign or malignant enlargement of the prostate gland as a potential cause of oliguria or anuria (pp. 515 and 517). It is important to note that about 50% of cases of acute urinary retention are seen after general anaesthesia, particularly in patients with pre-existing prostatic enlargement. Partial obstruction can be associated with a normal or even high urine volume due to chronic tubular injury, which causes loss of tubular concentrating ability. This chronic tubular injury can also produce a type 1 renal tubular acidosis (p. 446). Over time, even partial obstruction can cause tubular atrophy and irreversible renal failure.

All patients with oliguria or anuria should have routine biochemistry and haematology checked. Catheterisation should be performed so that urine volumes can be accurately monitored and the urine analysed for evidence of proteinuria and red cell casts, which may be found in patients with glomerulonephritis and systemic diseases such as vasculitis or SLE. Isolated haematuria may be indicative of an obstructive uropathy secondary to urinary calculi (p. 507) or tumours affecting the renal tract. If oliguria persists without any other clear explanation, ultrasound examination should be undertaken promptly to look for evidence of obstruction. Rarely, however, the urinary tract may not be particularly dilated in patients with acute kidney injury due to obstruction because of lack of urine production.

Management of oliguria and anuria should be directed at the underlying cause. While relief of obstruction is usually accompanied by a rapid return of renal function, tubular function may be impaired, resulting in polyuria and failure to conserve electrolytes.