RENAL AND UROLOGY I

Management ofstone diseaseBeverley Wilkinson

James Hall

Causes of urolithiasis

Renal and ureteric calculiC Idiopathic

C Dietary factors (e.g. low intake of fluid, high intake of purine)

C Gouty diathesis

C Metabolic anomalies (e.g. hyperparathyroidism)

C Heredity (e.g. cystinuria, xanthinuria)

C Urinary stasis: congenital (e.g. obstruction of the pelvi-ureteric

AbstractUrolithiasis is common, affecting 10% of Caucasian men. Factors affecting

stone formation can be intrinsic to the individual and are influenced by

environmental factors.

Patients presenting with loin/groin pain to the surgical team are

common and ureteric colic should be considered in this group. The rele-

vant investigations with regards to blood, urine and imaging tests to

diagnose stone disease are discussed. In addition, the absolute indica-

tions for urgent intervention are reviewed.

Treatment for ureteric stones and renal calculi includes a wide arma-

mentarium of endourological techniques including extracorporeal shock

wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy, if

conservative therapy fails.

Therapy is guided by anatomical factors, stone factors, previous treat-

ment failures as well as the patient’s wishes.

Indications, contraindications and complications of the common proce-

dures are discussed.

Keywords Bladder stone; kidney stone; ureteric stone

Introduction

Urolithiasis is a disorder characterized by the presence of calculi at

any point along the urinary tract. The disease affects 1e5% of the

population in industrialized countries, with men three times more

likely to be affected than women. It has a peak incidence between

20 and 50 years of age. The lifetime risk of developing a calculus in

a Caucasian man is nearly 10% with a recurrence risk of 50% at 10

years. Table 1 outlines the possible causes of urolithiasis.

Clinical features

junction, horseshoe kidney) or stricture

C

Pain

Chronic infection (urease-producing organisms (e.g. Proteus)

may lead to magnesium ammonium phosphate staghorn calculi

in the renal pelvis)

C Foreign bodies (ureteric stents, suture material)

C Diseased tissue (e.g. tuberculosis)

C Prolonged immobility (e.g. spinal injury, spina bifida)

Vesical calculi

C Voiding dysfunction (e.g. urethral stricture, benign prostatic

Pain is the most common presenting symptom of ureteric calculi

and is caused by obstruction and distension of the upper urinary

tract. Obstruction can occur anywhere but the three most

common sites are the pelvi-ureteric and vesicoureteric junctions,

where there is anatomical narrowing and at the pelvic brim

where the ureter crosses the iliac vessels.

Typical renal colic is characterized by an acute onset of severe

loin pain that radiates to the ipsilateral groin and scrotum in men

Beverley Wilkinson MD FRCS (Urol) is a Specialist Registrar on the North

Trent Training Programme, UK. Conflicts of interest: none declared.

James Hall FRCS (Urol) is a Consultant Urological Surgeon at the Royal

Hallamshire Hospital, Sheffield, UK. Conflicts of interest: none declared.

SURGERY 28:7 338

or labia majora in women. The patient will move about in an

attempt to relieve the pain, and unlike patients with peritonitis

will not gain relief by keeping still. Nausea and vomiting are also

commonly associated with an acute episode of ureteric colic.

Lower urinary tract symptoms

Lower urinary tract symptoms such as dysuria, suprapubic

discomfort, urgency and strangury (an unsuccessful desire to

void) are associated with bladder stones, or ureteric calculi that

are sitting at the vesicouretric junction.

Haematuria

Haematuria is present in 85% of patients with ureteric calculi and

is usually microscopic, that is detected on dipstick testing, occa-

sionally frank blood may be observed. Absence of haematuria,

though unusual, does not rule out the presence of urinary calculi.

Infection

Infection with urease-producing organisms, for example Proteus,

causes alkalinization of the urine which is a fundamental step in

the formation of magnesium ammonium phosphate stones

(struvite). Typically large staghorn calculi develop. Calcium

phosphate and matrix calculi are also associated with infection.

Recurrent urinary tract infection can be the presenting complaint

in patients with stone disease.

Infection in an obstructed system (pyonephrosis) secondary to

a ureteric stone is a urological emergency which should be

treated aggressively. The clinical presentation can vary from

asymptomatic bacteruria to fulminant sepsis. The condition can

cause permanent loss of renal function and death if unrecognized

and untreated.

hyperplasia, stenosis of the bladder neck)

C Foreign bodies (long-term urethral/suprapubic catheterization,

ureteric stents)

C Reconstructed bladder (enterocystoplasty/bladder substitution)

C Detrusor failure

Table 1

� 2010 Published by Elsevier Ltd.

RENAL AND UROLOGY I

Physical examination

Physical examination often reveals no abnormality except for

some tenderness on the affected side. Marked tenderness in the

loin is indicative of more severe infection, that is pyonephrosis.

In this scenario signs of sepsis, pyrexia, tachycardia, hypoten-

sion, may be noted. The differential diagnosis in ureteric colic is

considered in Table 2.

Laboratory investigations

Blood tests

Blood tests including a full blood count may reveal a markedly

raised leucocyte count due to infection or sepsis. Typically a mild

leucocytosis is seen as part of an acute phase response in patients

with ureteric stones. Urea and electrolytes are mandatory to

assess renal function.

Where a renal/ureteric stone is diagnosed metabolic causes

for stone formation should be sought. These include measure-

ment of serum calcium, phosphate and uric acid and levels of

parathyroid hormone if the serum calcium is raised.

Dipstick urinalysis

Dipstick urinalysis will be positive for blood in 85% of cases and

may also demonstrate leucocytes and nitrites if there is infection

present. pH may be indicative of the type of stone, acidic urine

suggests uric acid stones whilst alkaline urine is suggestive of

infection. A mid-stream urine (MSU) sample should be sent to

identify infection and urea-splitting organisms. A spot test can be

performed to identify patients with cystinuria.

Stone analysis

Stone analysis should be performed if available, as this may direct

treatment in patients who suffer from recurrent stone disease.

The chemical composition of urinary tract calculi include:

� calcium oxalate 60%

� calcium phosphate 20%

Differential diagnosis of urolithiasis

Non-urological

C Appendicitis

C Diverticulitis

C Ectopic pregnancy

C Salpingitis

C Torsion of an ovarian cyst

C Ruptured abdominal aortic aneurysm

C Biliary colic

UrologicalC Tumour

C Pyleonephritis

C Retroperitoneal fibrosis

C Stricture

C Obstruction of the pelvi-ureteric junction

C Papillary necrosis

C Renal infarction

C Testicular torsion

Table 2

SURGERY 28:7 339

� uric acid 10%

� cystine 3%

� struvite 7%.

Imaging

Non-contrast computed tomography (CT) of the kidneys,

ureters and bladder (NCCT-KUB)

Imaging for the diagnosis of ureteric colic has significantly

advanced over the last 5 years with a non-contrast CT of the

kidneys, ureters and bladder (NCCT-KUB) recommended as the

first-line investigation by the Royal College of Radiologists. Using

modern multi-slice scanners, the investigation is rapid and has

a sensitivity of 99%, (it does not detect indinavir stones). It carries

none of the risks associated with contrast media and does not

require normal renal function. In addition, in the absence of

ureteric calculi approximately 30% of CT-KUB investigations will

reveal an alternative diagnosis, for example appendicitis, diver-

ticulitis, adnexal masses, that would not have been apparent on an

intravenous urogram. However, NCCT-KUB involves 1.5 times

more radiation than a standard intravenous urogram (IVU).

Typical signs of ureteric calculi on NCCT-KUB include, fat

stranding around the kidney suggesting obstruction, proximal

hydronephrosis and hydroureter which can be traced to a stone

(Figure 1). Three-dimensional formatting can be invaluable in

complex patients with a large stone burden to plan treatment and

access to the kidney.

A plain radiograph of the kidneys, ureters and bladder

(KUBXR) must be obtained in combination with the NCCT-KUB

scan. If the stone is visible, further plain radiographs of the

kidneys, ureter and bladder can be used for follow-up; if the stone

is not visible, repeat CT scans may be needed. Only 60% of stones

are radio-opaque on plain films with uric acid being radiolucent.

Intravenous urogram

IVU has been superseded by NCCT-KUB in most units, but is occa-

sionally still used. An IVU consists of a preliminary control KUBXR

followed by an intravenous bolus injection of iodinated contrast

medium. Serial radiographs are taken at intervals of 5 minutes,

15 minutes and then culminating in a post-micturition film.

Diagnostic accuracy of an intravenous urogram approaches

90% and it gives good anatomical information of the pelvicaly-

ceal system and ureters. Some functional information can also be

obtained because excretion of the contrast requires a functional

renal unit. Obstruction is shown by a dense nephrogram and

a lack of contrast entering the collecting system. Delayed films

may be required to identify the point of obstruction. Disadvan-

tages of the IVU are that the quality of the images will be reduced

in patients with poor renal function, there is a risk of contrast

allergy, anaphylaxis and nephrotoxicity.

Intravenous contrast should be avoided in patients taking

metformin who are at risk of developing lactic acidosis.

Ultrasound

Ultrasound scanning (USS) can be used with a KUBXR as an

alternative to NCCT-KUB but at best diagnostic accuracy is only

75%. It is the first-line investigation in pregnancy. It is not

affected by the stone composition and will clarify if opacities

seen on a KUB are within the kidney. Its accuracy is operator

dependent, and it is poor at detecting stones in the ureter.

� 2010 Published by Elsevier Ltd.

Non-contrast computed tomography of the kidneys, ureters and bladder that demonstrates: a hydronephrosis of right kidney and b dilated ureter

traced to upper ureteric calculus.

Figure 1

RENAL AND UROLOGY I

Isotope renography

Isotope renography uses intravenous technetium-99 labelled

pharmaceuticals to assess different parameters of renal function.

A dynamic scan will give information with regards to function

and obstruction and for this mercaptoacetyltriglycine (MAG3) is

commonly used. A static scan uses dimercaptosuccinic acid

(DMSA) as the pharmaceutical. This gives an assessment of

‘functioning nephrons’ and values of relative (split) renal func-

tion. This is invaluable in treatment planning particularly in

those with staghorn calculi where if the relative function is less

than 15%, nephrectomy may be more appropriate for the patient.

Magnetic resonance urography

Magnetic resonance urography is rarely indicated, but is useful

in pregnancy, when ionizing radiation should be avoided. It has

an accuracy of 95% at diagnosing ureteric obstruction, but does

not visualize stones well. However it is costly, time consuming

and is not used as a routine. It should be avoided in the first

trimester.

Management of ureteric calculi

Conservative

Ureteric calculi presenting as an emergency should be given

analgesia, for example diclofenac or pethidine, and antiemetics as

required. A conservative approach can be adopted for most

ureteric stones. As a general rule the smaller and more distal the

stone the more likely it is to pass spontaneously. Stones measuring

4 mm or less will pass in about 80% of patients. However, this falls

to only 10% for stones measuring 6 mm or larger. For small stones

visible on KUB X-ray the patient can be reviewed in the outpatient

clinic in 2e4 weeks after discharge. Serial KUB X-rays will confirm

movement or passage of the stone.

Medical expulsive therapy (MET) is the use of oral medication to

try and increase the stone expulsion rate. This has been developed

from several physiological and pathophysiological observations.

SURGERY 28:7 340

The ureter is lined by smooth muscle cells that relax when there is

a decrease in calcium ion concentrations. Furthermore, smooth

muscle cells are densely populated by alpha-1-adrenoreceptors.

Blocking of these prevents ureteric spasm but allows normal

peristaltic waves. Many trials have been performed using calcium

channel blockers, alpha blockers and anti-inflammatory drugs.

Meta-analyses of pooled data analysing the use of alpha blockers

have suggested an increase of 28% in the stone expulsion rate. This

is an off licence use of the drug, and must be explained to the

patient when prescribed. The only randomized controlled study on

this does not demonstrate an increase in expulsion rate although

the use of analgesics and the time to expulsion decreased in the

treatment group. This treatment has gained popularity despite

a lack of randomized controlled trials on the topic.

Dissolution therapy can be employed with the best results

obtained in patients with uric acid stones. A combination of high

intake of fluid, urinary deacidification with high doses of potas-

sium citrate, and administration of allopurinol can lead to

dissolution of these stones.

Some stones will inevitably require intervention, which may

be absolute or relative.

Indications for Intervention: absolute indications are usually

manifested by a deterioration of the patient’s clinical condition,

that is pyonephrosis and urosepsis or worsening renal function.

In pyonephrosis, placement of a percutaneous nephrostomy

drain is the first-line treatment which is performed under USS

guidance. In the authors’ experience, this is safer and more

reliable than any form of retrograde intervention (stent place-

ment or ureteroscopy) (Figure 2). This approach also facilitates

future antegrade studies, allows antegrade stent placement and

can provide access for percutaneous stone surgery. Occasionally,

decompression will allow spontaneous passage of the stone.

Relative indications for intervention include intractable pain,

large stone, failure of progression, patient request and occupa-

tion (for example airline pilots).

� 2010 Published by Elsevier Ltd.

a Pelvic stone on kidneys, ureters and bladder X-ray and b needle puncture of the collecting system, with injection of contrast to confirm position

in pelvis prior to nephrostomy insertion.

Figure 2

RENAL AND UROLOGY I

For those patients that fail a conservative trial of passage of

ureteric calculi, the two main options for treatment are extra-

corporeal shock wave lithotripsy (ESWL) or ureteroscopy with

stone fragmentation. Percutaneous nephrolithotomy is occa-

sionally used in larger (>1 cm) upper ureteric or pelvi-ureteric

junction (PUJ) stones. These will each be considered in turn.

Extracorporeal shock wave lithotripsy (ESWL) is a commonly

used and routinely available technique for the treatment of ureteral

and renal calculi. It is usually performed as an outpatient proce-

dure and is well-tolerated requiring intramuscular analgesia. It has

comparable results to ureteroscopy particularly for proximal

stones, but multiple treatments may be required and the patient

may continue to experience symptoms during this time. If ESWL is

unsuccessful after two treatments then an alternative should be

sought.

The absolute contraindications to ESWL are:

� uncorrected coagulopathy

� urosepsis

� pregnancy

� renal artery aneurysm or aortic aneurysm.

ESWLattempts to break up the stone byusing an externally applied,

focused, high-intensity acoustic pulse. Three components to the

machine are as follows: (i) an energy source to create the shock

wave; (ii) a coupling mechanism(usually a water-filled membrane)

to transfer the energy from outside to inside the body; (iii) a guid-

ance system, usually fluoroscopy but USS can be used.

The three types of energy sources are:

Electrohydraulic e an underwater spark discharge generates

a hydrodynamic pressure wave, which is released at the focal

point of a parabolic reflector

Electromagnetic e a charge difference between two plates

will cause motion and generation of a shock wave which can

be focused by an acoustic lens.

SURGERY 28:7 341

Piezoelectric e an array of piezocrystals arranged in a semi-

circular fashion, focused at the centre of its sphere generates

peak pressures sufficient for stone fragmentation.

The successive shock wave pressure pulses result in direct

shearing forces, as well as cavitation bubbles surrounding the

stone, which fragment the stones into smaller pieces that then

can easily pass through the ureters.

After treatment most patients will have some pain that can be

controlled at home on oral analgesia, and haematuria is common.

The occasional complications after ESWL are:

� infection

� renal haemorrhage/haematoma

� adjacent organ injury

� steinstrasse (‘stone street’), a column of obstructing stone

fragments in the ureter

� possible hypertension and renal dysfunction (delayed effect).

Ureteroscopy is the examination of the ureter using a specially

designed ureteroscope. The two types of ureteroscopes in

common use are the semi-rigid and flexible ureteroscope

(Figure 3). With a single treatment the stone clearance rates are

better for ureteroscopy than for ESWL.

Indications for ureteroscopy are:

� the calculi cannot be visualized for ESWL

� calculi resistant to ESWL (for example cystine).

Semi-rigid scopes are constructed of metal and have high-density

fibreoptic bundles for both light and image transmission.

Although it is possible to advance a semi-rigid ureteroscope into

the renal pelvis, this instrument is primarily used for accessing

and fragmenting stones within the ureter.

Flexible ureteroscopes again use fibreoptic bundles but of

much smaller diameter, which increases the manoeuvrability and

permits access to all parts of the renal collecting system (including

the pelvis and the calyces). All types of ureteroscope have

� 2010 Published by Elsevier Ltd.

Figure 3 Equipment used to treat stone disease.

RENAL AND UROLOGY I

a working channel through which instruments (for example

guidewires, fragmentation devices, stone retrieval instruments)

can be passed. In order to fragment and extract calculi using

an ureteroscope, the following endoscopic lithotrites are available.

Ballistic lithotripsy: examples include the lithoclast, which uses

a direct-contact, solid, rigid probe to fragment calculi using

mechanics similar to those of a pneumatic jackhammer. The

lithoclast has a wide margin of safety.

Laser lithotripsy: a progression of laser modalities led to the

development of the holmium/YAG laser, which is a thermal laser

using light at a wavelength of 2140 nm. It acts to vaporize calculi,

producing fine dust and small particulate debris that can, in part,

be irrigated from the urinary tract during treatment. It is well

absorbed by water and urine with a penetration depth of 0.4 mm;

it therefore has minimal effect on local tissues and is very safe.

Electrohydraulic lithotripsy (EHL) was the first modality of

intracorporeal lithotripsy. An electric discharge vaporizes the

surrounding fluid, creating a cavitation bubble that impacts on

the stone. Tissue damage with this technique is common and it is

now rarely used in the ureter.

Ultrasonic lithotripsy: this utilizes the piezoelectric principle to

generate vibrational energy to create a drilling effect at the tip of the

probe. Modern ureteroscopes are too small to accommodate these

probes. This method is used in percutaneous nephrolithotomy.

Ballistic and laser lithotripsy are currently the most common

techniques used with the semi-rigid ureteroscopes. The most

effective lithotriptor for use through a small-diameter flexible

ureteroscope is the holmium/YAG laser (200 mm).

Stents after ureteroscopy

A double J stent is occasionally inserted after ureteroscopy, they

will not aid stone passage and are indicated if:

� there has been ureteric injury, or if a stricture has been

encountered and dilated

� there are residual stones that may obstruct the ureter

� there are solitary kidneys.

Percutaneous nephrolithotomy

Percutaneous nephrolithotomy (PCNL) can be used as an ante-

grade approach to large upper ureteric calculi or in patients

where access from the ureters is not possible, for example in

patients that have a loop diversion following cystectomy. This

procedure is discussed in detail in the next section.

SURGERY 28:7 342

Laparoscopic ureterolithotomy

Laparoscopic ureterolithotomy can be utilized in patients with

a large stone burden in the proximal ureter, that may require

multiple treatments to be rendered stone-free. Ureterolithomy

provides an option for stones to be removed in a single procedure

and, with the increasing experience with laparoscopy in urology,

this can be performed with low morbidity. Open surgery for

stones is rarely performed in the UK.

Renal calculi e treatment

Renal calculi

Renal calculi may present with symptoms or commonly are found

incidentally as patients are investigated for other disorders.

Presenting symptoms include:

� pain

� haematuria (microscopic, occasionally macroscopic)

� recurrent urinary tract infections

� rarely, struivite stones present with infective complications

for example pyonephrosis, perinephric abscess, xanthogra-

nulomatous pyelonephritis (XPN).

Conservative management

This should be employed in asymptomatic patients with:

� renal calculi <5 mm in diameter

� medullary sponge kidney

� stones in calyceal cysts.

Surveillance with KUB radiographs is required to monitor

progress.

ESWL

This is the recommended treatment for non-complex renal

calculi. However, stone clearance after ESWL is dramatically

reduced when the stone size exceeds 2 cm. Similarly, retreatment

and complication rates increase with larger calculi.

Certain anatomical and stone considerations can be poor

prognostic factors for successful ESWL. It is not recommended

for patients with a stone burden >2 cm, staghorn calculi, stones

associated with abnormal renal anatomy (for example pelvi-

ureteric junction (PUJ) obstruction, horseshoe kidney, calyceal

diverticulum) and cystine stones.

PCNL

PCNL is a very successful single-staged procedure for patients with

larger stones. For stones >2 cm and staghorn calculi it is the rec-

ommended treatment of choice (Figure 4). Access to an appropriate

calyx is obtained via a needle puncture under radiological guidance

that permits endoscopic access directly into the renal collecting

system and upper ureter. A guidewire is inserted to the collecting

system, over which the tract is dilated (to 30 Fr) with a pressurized

balloon or a series of graduated dilators. Once dilated, the tract is

maintained by an Amplatz sheath�, through which a nephroscope

is introduced. Fragmentation of the stone can be accomplished

using the lithotripsy techniques described above.

Following the procedure, a nephrostomy tube drain is often

left in situ and a ureteric stent may also be placed.

Complications of PCNL are:

� infection

� haemorrhage, occasionally severe requiring embolization

� pleural/lung damage (higher risk in upper-pole punctures)

� 2010 Published by Elsevier Ltd.

a Staghorn calculus on kidneys, ureters and bladder X-ray. b Large perirenal haematoma following percutaneous nephrolithotomy (PCNL).

c Selective renal embolization for bleeding post-PCNL. Coil seen in vessels.

Figure 4

RENAL AND UROLOGY I

� residual stone fragments

� renal parenchymal damage

� damage to other organs (for example colon).

Laparoscopic surgery

Laparoscopic surgery may be employed for stone removal at the

time of definitive surgery for pyeloplasty, but it is rarely used alone.

In a poorly functioning kidney containing stones, that is less

than 15% split function on a DMSA renogram, nephrectomy is

advised. This can be performed laparoscopically, but such cases

are often difficult due to scarring around the kidney.

Bladder calculi

Bladder calculi are usually a manifestation of an underlying

pathological condition, including voiding dysfunction or

a foreign body within the bladder. Most vesical calculi are seen in

men, although, in the ‘developing’ world, they are frequently

found in prepubescent boys.

A solitary bladder calculus is more commonly seen (75%)

rather than multiple stones (Figure 5). Physical examination may

reveal benign prostatic enlargement and a palpable bladder may

be evident in patients with bladder outflow obstruction. A KUB

radiograph usually confirms the diagnosis, although cystoscopy

or NCCT-KUB is a more definitive test.

Management

Figure 5 Kidneys, ureters and bladder X-ray demonstrating bladder

stones.

The most important principle in treating vesical calculi is

prevention and eradication of the underlying cause (for example

transurethral resection of the prostate (TURP) for benign pros-

tatic hyperplasia (BPH)).

Endoscopic cystolitholapaxy allows most vesical calculi to be

fragmented and subsequently irrigated/washed out through the

cystoscope. Mechanical lithotrites should be used with caution to

prevent bladder injury when the jaws are closed. These instru-

ments are used with a partially full bladder and with direct

endoscopic visualization to ensure minimal complications.

SURGERY 28:7 343

Various types of endoscopic lithotrites (for example EHL,

ballistic, holmium/YAG laser) can be employed to fragment

vesical calculi that are too large to crush with the manual

mechanical devices.

� 2010 Published by Elsevier Ltd.

RENAL AND UROLOGY I

Open suprapubic cystolithotomy is reserved for endoscopic

failures and large stones at presentation with a narrow urethra,

particularly in children.

Complications of urinary calculi

Infection

All urinary calculi may be associated with infection secondary to

obstruction and stasis.

Ipsilateral renal function deterioration

This is associated with an obstructing ureteral or renal calculus

and may occur within days. Swift renal destruction occurs with

pyonephrosis.

Tissue damage

This can lead to fibrosis and ureteric strictures.

Xanthogranulomatous pyelonephritis

This is characterized by diffuse renal parenchymal destruction.

Obstructive uropathy secondary to renal calculi is usually

involved and it is frequently misdiagnosed as a renal tumour.

Squamous cell carcinoma

This can occur in patients with a history of staghorn calculi or

bladder stones related to chronic inflammation.

SURGERY 28:7 344

Prevention of recurrence

Approximately 50% of patients experience recurrent urinary

calculi within 5 years without prophylactic intervention. Risk

factors as described previously should be identified and modi-

fied. Patients should be instructed to increase fluid intake in

order to maintain a urine output of >2 litres/day. This is prob-

ably the single most important factor in preventing recurrence. In

addition, dietary oxalate and sodium intake should be limited to

decrease the urinary excretion of oxalate and calcium. Animal

protein (meat or fish) can increase urinary excretion of calcium,

and uric acid and should be limited. Sensible advice to give to

patients in clinic is to recommend that they:

� drink enough to void pale unconcentrated urine, that is more

on a hot day

� do not add salt to food

� eat no more than a piece of meat or fish the size of the palm of

your hand in one day.

Uric acid stones can be prevented by reducing intake of animal

protein, and deacidification of the urine using potassium citrate

is useful. Allupurinol is given and titrated according to the uric

acid level.

Cysteine stone formers are a special group who require

aggressive hydration, >4 litres/day, urinary alkalinization with

potassium citrate and the use of drugs such as D-penicillamine

which make the cysteine more soluble. A

� 2010 Published by Elsevier Ltd.