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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2826_Библиотеки_им_академика_М_И_Перельмана.pdf
Investigation of Renal Disease 353
White cells
Ten or more white cells per cubic millimetre in fresh, unspun, mid-stream
urine is abnormal, and indicates an inflammatory reaction within the urinary
tract, usually a UTI. Sterile pyuria (i.e. pus cells without bacterial infection)
occurs in a partially treated UTI, urinary tract tuberculosis, calculi, bladder
tumour, papillary necrosis and tubulointerstitial nephritis.
Red cells
One or more red cells per cubic millimetre is abnormal and must be investigated (see Haematuria).
Casts
Mucoprotein precipitated in the renal tubules results in the formation of
hyaline casts. On their own these are a normal finding but the incorporation
of red cells results in red cell casts, a finding pathognomonic of glomerulonephritis. White cell casts may be seen in acute pyelonephritis. Granular
casts result from the disintegration of cellular debris and indicate glomerular
or tubular disease.
Bacteria
A UTI is diagnosed when greater than 105 or 103 pathogenic organisms per
mL of urine is detected in a fresh mid-stream specimen in a symptomatic
woman or man, respectively. In a woman, the diagnosis is also made with
102 coliform organisms per mL in the presence of pyuria (>10 white cells/
mm3). Any growth of pathogenic organisms in urine by suprapubic aspiration
is diagnostic of a UTI.
Imaging techniques
Plain X-ray is useful to identify renal calcification or radiodense calculi in
the kidney, renal pelvis, line of the ureters or bladder.
Ultrasonography of the kidneys is the method of choice for assessing
renal size, checking for pelvicalyceal dilatation (indicative of chronic renal
obstruction), characterizing renal masses, diagnosing polycystic kidney
disease, and detecting intrarenal and/or perinephric fluid (e.g. pus, blood). It
has the advantage over X-ray techniques of avoiding ionizing radiation and
the use of an intravascular contrast medium. Doppler ultrasonography is
used to demonstrate renal artery perfusion and detect renal vein thrombosis.
Bladder wall thickening can be detected in a distended bladder and an
assessment of bladder emptying made by scanning after voiding.
CT is used as a first-line investigation in cases of suspected ureteric
colic (e.g. CT of kidneys, ureters and bladder [CT KUB]). CT imaging is also
used to characterize renal masses that are indeterminate at ultrasonography,
to stage renal, bladder and prostate tumours, and to detect ‘lucent’ calculi;
354 Renal disease
low-density calculi which are lucent on plain films (e.g. uric acid stones),
are well seen on CT. It is also used to look for retroperitoneal disease such
as tumours and fibrosis, and CT angiography is used to visualize the renal
arteries and veins.
Magnetic resonance imaging (MRI) is used to characterize renal
masses as an alternative to CT, to stage renal, prostate and bladder cancer
and also to image the renal arteries by magnetic resonance (MR) angiography
with gadolinium as contrast medium. In experienced hands, its sensitivity and
specificity approaches renal angiography.
Excretion urography (also known as intravenous urography [IVU] or
intravenous pyelography [IVP]) is rarely used now and has largely been
replaced by ultrasonography and CT scanning.
Renal arteriography (angiography) is used in the diagnosis of renal
artery disease, but MR and spiral CT angiography are being used increasingly.
The technique requires cannulation of the femoral artery and injection of
a contrast medium. Complications include cholesterol embolizations and
contrast-induced kidney damage.
Anterograde pyelography involves percutaneous puncture of a
pelvicalyceal system with a needle and the injection of contrast medium to
outline the pelvicalyceal system and ureter to the level of obstruction. Drains
can be sited, and stents placed during the procedure.
Retrograde pyelography under screening control allows a contrast
study of the ureter from the bladder. It is invasive, commonly requires a
general anaesthetic and may result in the introduction of infection.
Renal scintigraphy involves the intravenous injection of a
radiopharmaceutical (e.g. diethylenetriaminepentaacetic acid [DPTA] labelled
with technetium-99m) which is extracted from the bloodstream by the kidneys
and subsequent imaging on a gamma camera with computer acquisition.
Isotope studies are helpful for dynamic or static studies of perfusion or
excretion. It is used to detect anatomical or functional abnormalities of the
kidneys or urinary tract. Dynamic renal scintigraphy is used to assess renal
blood flow in suspected renal artery stenosis, renal function in obstruction
and in detection of vesicoureteric reflux. Static renal scintigraphy enables
assessment of the size and position of the kidneys, differential function of
each kidney and parenchymal defects (scars, ischaemic areas, tumours).
Transcutaneous renal biopsy
This is carried out under ultrasound control in specialized centres and
requires interpretation by an experienced pathologist. Microscopy is helpful
in the investigation of the nephritic and nephrotic syndromes, AKI and CKD,
haematuria after negative urological investigations and renal graft dysfunction. Complications include haematuria, flank pain, infection and perirenal
haematoma formation.
Glomerular Diseases 355
(A)
(B)
Efferent
cell
GLOMERULAR DISEASES
Normal glomerular structure
There are about one million renal glomeruli in each kidney, and each consists
of a capillary plexus invaginating the blind end of the proximal renal tubule
(Fig. 9.4). The glomerular capillaries are lined by a fenestrated endothelium,
arteriole
Glomerular
capillary loops
Glomerular
filtrate flow
Fenestra
PLASMA
Blood
flow
Brush
border
Proximal
tubule
Afferent
arteriole
Mesangial
matrix
Bowman’s
space
Urinary
epithelial
cell
FILTRATE
Slit pore
Capillary
endothelial
Basement
membrane
Epithelial cell
Fig. 9.4 (A) Diagrammatic representation of the normal glomerulus.
(B)Components of the glomerular membrane. (Adapted from Read et al. (1993).
Essential medicine. Edinburgh: Churchill Livingstone; Guyton (1987). Human
physiology and mechanisms of disease (4th ed.). London: WB Saunders.)
356 Renal disease
which rests on the glomerular basement membrane (GBM). External to the
GBM are the visceral epithelial cells (podocytes) which only make contact
with the GBM by finger-like projections, called foot processes, which are
separated from one another by ‘filtration pores’. This unique structure of the
glomerular membrane accounts for its tremendous permeability, allowing
125–200 mL of glomerular filtrate to be formed every minute (the GFR). The
composition of the glomerular filtrate is similar to plasma but contains only
small amounts of protein (all of low molecular weight), most of which is reabsorbed in the proximal tubule. Tubular reabsorption and secretion normally
substantially alter the water and electrolyte composition of the glomerular
filtrate until it reaches the renal pelvis as urine.
Pathogenesis and terms in glomerular disease
The nomenclature for glomerular disease can be confusing because descriptive terms (as seen on histology) overlap with clinical syndromes and more
recent molecular insights into the pathogenesis of disease. If there is predominant inflammation on histology, glomerular disease may be described
as a glomerulonephritis. If inflammation is absent, glomerulopathy is more
correct. There remains much overlap between the two, and the terms are
often (wrongly) used interchangeably. The kidneys are symmetrically involved
and the renal lesion may be primary or part of a generalized disease, e.g.
systemic lupus erythematosus (SLE). Glomerular disease is usually described
according to the findings on renal biopsy, and commonly used important
terms include:
• Focal: some, but not all, glomeruli show the lesion
• Diffuse (global): most of the glomeruli (>75%) contain the lesion
• Segmental: only a part of the glomerulus is affected (most focal lesions
are also segmental, e.g. focal segmental glomerulosclerosis)
• Global: all of the glomerulus is symmetrically involved
• Proliferative: an increase in cell numbers due to hyperplasia of one or
more of the resident glomerular cells with or without inflammation
• Membrane alterations: capillary wall thickening due to deposition of
immune deposits or alterations in basement membrane
• Crescent formation: epithelial cell proliferation with mononuclear cell
infiltration in the Bowman’s space.
Classification and presentation of glomerulopathies
The presence of some form of glomerular disease, as opposed to tubulointerstitial or vascular disease, is usually suspected from the history and from
one or more of the following urinary findings:
• Haematuria (particularly if the red cells are abnormally shaped or
distorted, i.e. dysmorphic)
• Red cell casts
Nephrotic Syndrome 357
• Proteinuria, which may be in the nephrotic range (>3.5 g/day).
Glomerulopathies are classified and discussed as they relate to four
major glomerular syndromes:
• Nephrotic syndrome: massive proteinuria (>3.5 g/day),
hypoalbuminaemia, oedema, lipiduria and hyperlipidaemia
• Acute glomerulonephritis (acute nephritic syndrome): abrupt onset of
haematuria with casts or dysmorphic red cells, non-nephrotic range
proteinuria, oedema, hypertension and transient renal impairment
• Rapidly progressive glomerulonephritis: features of acute nephritis,
focal necrosis with or without crescents and rapidly progressive renal
failure over weeks
• Asymptomatic haematuria, proteinuria (or both): these are usually
incidental findings on urinary dipstick testing and may be an early
indicator of renal disease. The causes and further investigation
are discussed in the sections Haematuria (p. 351) and Proteinuria
(p.350).
NEPHROTIC SYNDROME
Nephrotic syndrome describes a condition in which there is significant
increased filtration of macromolecules across the glomerular capillary wall
due to structural and functional abnormalities of the glomerular podocytes.
• Hypoalbuminaemia (serum albumin <30 g/L) develops as a consequence
of heavy proteinuria (>3.5 g/24 hours in adults) and increased renal
catabolism of filtered protein.
• Peripheral oedema is primarily due to sodium retention in the renal
collecting tubules, together with an increase in capillary permeability.
A reduction in effective circulating volume also leads to oedema through
similar mechanisms that occur in cardiac failure and cirrhosis (p. 161).
• Hypercholesterolaemia and hypertriglyceridaemia are common in
nephrotic syndrome due to increased synthesis and impaired catabolism.
Aetiology
Nephrotic syndrome with ‘bland’ urine sediments
The glomerulopathies associated with the nephrotic syndrome are demonstrated in Table 9.2. Membranous nephropathy and focal segmental
glomerulosclerosis are the most common causes in adults and minimalchange nephropathy in children.
Membranous nephropathy is usually idiopathic but may occur
in association with drugs (e.g. penicillamine, gold, non-steroidal antiinflammatory drugs [NSAIDs]), autoimmune disease (e.g. SLE, thyroiditis),
neoplasia (carcinoma of lung, colon, stomach, breast and lymphoma),
infections (e.g. hepatitis B and C, schistosomiasis and Plasmodium malariae)
and other causes (sarcoidosis, sickle cell disease). There is deposition of
358 Renal disease
Table 9.2 Glomerulopathies associated with the nephrotic
syndrome
Nephrotic syndrome with ‘bland’ urine sediments
Primary glomerular disease:
Minimal-change glomerular disease
Membranous nephropathy
Focal segmental glomerulosclerosis
Congenital nephrotic syndrome
Secondary glomerular disease:
Amyloidosis
Diabetic nephropathy
Nephrotic syndrome with ‘active’ urine sediments (mixed nephrotic/
nephritic)
Primary glomerular disease:
Mesangiocapillary glomerulonephritis
Mesangial proliferative glomerulonephritis
Secondary glomerular disease:
Systemic lupus erythematosus
Cryoglobulinaemic disease
Henoch–Schönlein syndrome
Idiopathic fibrillary glomerulopathy
Immunotactoid glomerulopathy
Fibronectin glomerulopathy
IgG and complement C3 along the outer aspect of the glomerular basement
membrane. Expansion of the basement membrane appears with time as the
deposits are surrounded by basement membrane and eventually undergo
resorption. Focal segmental glomerulosclerosis is of unknown aetiology and
is a particular common cause of nephrotic syndrome in black adults. A similar
histological type occurs in human immunodeficiency virus (HIV) infection.
Minimal-change nephropathy occurs most commonly in boys under
5 years of age. It accounts for 90% of cases of nephrotic syndrome in
children and 20%–25% in adults. The pathogenesis is unknown; immune
complexes are absent on immunofluorescence but the increase in glomerular
permeability is thought to be immunologically mediated. The glomeruli
appear normal on light microscopy while on electron microscopy fusion of
the foot processes of epithelial cells (podocytes) is evident.
Nephrotic syndrome associated with renal amyloid (p. 675) and diabetes
mellitus (p. 644) is not immune mediated. Other renal diseases, e.g.polycystic
Nephrotic Syndrome 359
kidneys and reflux nephropathy, may cause proteinuria, but are rarely severe
enough to cause the nephrotic syndrome.
Nephrotic syndrome with ‘active’ urine sediments (mixed nephrotic/nephritic)
Mesangiocapillary (membranoproliferative glomerulonephritis) occurs with
chronic infection (abscesses, infective endocarditis, infected ventriculoperitoneal shunt), cryoglobulinaemia secondary to hepatitis C infection or
may be idiopathic. A different type occurs with partial lipodystrophy (loss of
subcutaneous fat on the face and upper trunk). Most patients develop renal
failure over several years. Mesangial proliferative glomerulonephritis presents with heavy proteinuria with minimal changes on light microscopy. There
are deposits in the glomerular mesangium of IgM and complement (IgM
nephropathy) or C1q (C1q nephropathy). Some patients respond to steroids
but others progress to renal failure.
Clinical features
The principal clinical feature patients report is oedema of the ankles, genitals
and abdominal wall. The face (periorbital oedema) and arms may be involved
in severe cases.
Differential diagnoses
Nephrotic syndrome must be differentiated from other causes of oedema and
hypoalbuminaemia. In congestive cardiac failure there is oedema and raised
JVP. In nephrotic syndrome the JVP is normal or low unless there is concomitant
renal failure and oliguria. Hypoalbuminaemia and oedema occur in cirrhosis, but
there are usually signs of chronic liver disease on examination (p. 171).
Investigations
Investigations are indicated to make the diagnosis, monitor progress and
determine the underlying aetiology (Table 9.3).
Management
General oedema
General oedema is treated with dietary salt restriction and a thiazide
diuretic, e.g. bendroflumethiazide, followed by furosemide and amiloride for
unresponsive patients. Intravenous diuretics and occasionally intravenous
salt-poor albumin are required to initiate a diuresis, which, once established,
can usually be maintained with oral diuretics alone. Proteinuria is reduced by
administration of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor antagonists; patients should be advised to eat a normal
rather than high protein diet, which increases proteinuria. Prolonged bed
rest should be avoided and long-term prophylactic anticoagulation should
be administered in view of the thrombotic tendency (see Complications).
360 Renal disease
Table 9.3 Investigations indicated in glomerular disease
Investigations Significance
Baseline measurements
Estimated glomerular filtration
rate
Urinary protein
Serum urea and electrolytes
Serum albumin
Diagnostically useful tests
Urine microscopy Red cell casts indicate
Culture (swab from throat or
infected skin)
Serum antistreptolysin-O titre
Blood glucose Diagnosis of diabetes mellitus
Serum tests:
Antinuclear and anti-DNA
antibodies
ANCA
Anti-GBM antibody
Hepatitis B surface antigen
Hepatitis C antibody
HIV antibody
Cryoglobulins
Chest X-ray Cavities in Wegener’s granulomatosis,
Ultrasound of kidneys Renal size, to look for renal vein
Renal biopsy Diagnosis of any glomerulopathy
ANCA, antineutrophil cytoplasmic antibody; GBM, glomerular basement membrane; HIV,
human immunodeficiency virus; SLE, systemic lupus erythematosus.
To determine current status, monitor
progress and response to treatment
glomerulonephritis
Diagnosis of recent streptococcal
infection
Present in significant titre in SLE
Positive in vasculitis
Present in anti-GBM glomerulonephritis
Hepatitis B infection
Hepatitis C infection
HIV infection
Increased in cryoglobulinaemia
malignancy
thrombosis
Infections are treated aggressively and patients should be offered influenza
and pneumococcal vaccination (p. 502).
Specific treatment
Treatment of the underlying disease or cessation of the offending drug is
usually associated with improvement in secondary glomerulopathy. Only
Nephrotic Syndrome 361
selected patients with moderate or severe progressive idiopathic membranous nephropathy should receive specific treatment as there is a high
rate of spontaneous improvement. Treatment is with cyclophosphamide
or chlorambucil with prednisolone. Rituximab (p. 250) is used in resistant
disease. Minimal-change nephropathy is almost always steroid responsive in
children, although less commonly in adults. High-dose prednisolone therapy
is given for 4–6 weeks and then tapered slowly. Further courses are given if
the patient has a relapse. In patients with frequent relapses and in steroidunresponsive patients, immunosuppressive therapy with cyclophosphamide
or ciclosporin may be used.
Complications
• Venous thrombosis. Loss of clotting factors in the urine predisposes
to thrombus formation in both peripheral and renal veins. The latter
presents with renal pain, haematuria and deterioration in renal function
and is diagnosed by ultrasonography.
• Sepsis. Loss of immunoglobulin in the urine increases susceptibility to
infection, which is a common cause of death in these patients.
• AKI. This is rarely the result of progression of the underlying renal
disease and more often a consequence of hypovolaemia (particularly
after diuretic therapy) or renal vein thrombosis.
Acute glomerulonephritis (acute nephritic syndrome)
Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease (Table 9.4). The typical case of
post-streptococcal glomerulonephritis develops in a child 1–3 weeks after
a streptococcal infection (pharyngitis or cellulitis) with a Lancefield group
A β-haemolytic streptococcus. The bacterial antigen becomes trapped in
the glomerulus, leading to an acute diffuse proliferative glomerulonephritis.
Clinical features
The syndrome comprises:
• Haematuria (visible or non-visible) – red cell casts are typically seen in
urine microscopy
• Proteinuria (usually <2 g in 24 hours)
• Hypertension and oedema (periorbital, leg or sacral) caused by salt and
water retention
• Oliguria
• Uraemia.
Investigations
The history and examination will help to assess the severity of the illness and
to determine any associated underlying conditions. Investigations performed
in the nephritic syndrome are listed in Table 9.3. If the clinical diagnosis of
362 Renal disease
Table 9.4 Diseases commonly associated with the acute
nephritic syndrome
Post-streptococcal glomerulonephritis
Non-streptococcal post-infectious glomerulonephritis, e.g. Staphylococcus,
mumps, Legionella, hepatitis B and C, schistosomiasis, malaria
Infective endocarditis
Shunt nephritis
Visceral abscess
Systemic lupus erythematosus
Henoch–Schönlein syndrome
Cryoglobulinaemia
a nephritic illness is clear-cut, e.g. in post-streptococcal glomerulonephritis,
renal biopsy is usually unnecessary.
Management
Post-streptococcal glomerulonephritis usually has a good prognosis and supportive measures are often sufficient until spontaneous recovery takes place.
Hypertension is treated with salt restriction, loop diuretics and vasodilators.
Fluid balance is monitored by daily weighing and daily recording of fluid input
and output. In oliguric patients with evidence of fluid overload (e.g. oedema,
pulmonary congestion and severe hypertension), fluid restriction is necessary. Life-threatening complications such as hypertensive encephalopathy,
pulmonary oedema and severe uraemia will require further specific management. In glomerulonephritis complicating SLE or the systemic vasculitides
(see below), immunosuppression with prednisolone, cyclophosphamide,
azathioprine or rituximab improves renal function.
Rapidly progressive glomerulonephritis
There are three main causes: on a background of acute nephritic syndrome
(see above), anti-glomerular basement membrane disease (which with lung
involvement is called Goodpasture’s syndrome, p. 539) and antineutrophilic
cytoplasmic antibody (ANCA)-associated vasculitis. Investigations are listed in
Table 9.3 and the management is based on general treatment of AKI (p. 375)
and specific treatment directed against the causes.
URINARY TRACT INFECTION
UTI is common, particularly in women, with about half of all women experiencing a UTI in their lifetime. Most UTIs occur in isolation and are uncommon
in men and children unless there is an abnormality of the urinary tract.