SEMINAR

Seminar

Recurrent renal stone diseaseadvances in pathogenesis and

clinical management
Geoffrey Bihl, Anthony Meyers
Kidney stones are common in industrialised nations: up to 15% of white men and 6% of all women will develop one
stone, with recurrence in about half these people. Risk factors for formation of stones include urinary promoters
(calcium, urate, cystine, and sodium) and urinary inhibitors (magnesium, citrate, and nephrocalcin). Acute renal colic
can be precipitated by dehydration and reduced urine output, increased protein intake, heavy physical exercise, and
various medicines. Such colic manifests as severe loin pain and can be accompanied by frequent urination, dysuria,
oliguria, and haematuria. Documentation of stone characteristics is extremely important: type, size, location, and
underlying metabolic abnormalities. Such details can be obtained with a combination of biochemical investigations,
microscopic examination of urine under polarised light, and an intravenous pyelogram. Ultrasonography and plain
abdominal radiographs are also useful, especially for patients unable to tolerate an intravenous pyelogram. Acute
therapy includes complete pain relief, rehydration, and encouragement of diuresis. Long-term management
encompasses education of patients with regard to diet and fluid intake, control of calciuria, citrate replacement, and
treatment of any underlying urinary-tract infection or metabolic abnormality. Stones smaller than 5 mm normally pass
spontaneously, whereas larger stones, as big as 2 cm, are best treated with extracorporeal shock-wave lithotripsy. All
physicians should have a clear understanding of the pathogenesis and clinical management (acute treatment and
prevention of recurrence) of renal stone disease.
Renal stone disease is an ancient and common affliction,
whose clinical occurrence and presentation is described
in the Aphorisms of Hippocrates.1 Renal stones occur once
in a lifetime in 15% of white men and 6% of all women,
and recur in about half these people. Despite
urbanisation of black South Africans, renal stones have
been reported in less than 1% of this population.2,3 Up to
75% of stones are calcium oxalate, the others are
struvite (magnesium ammonium phosphate, 1020%),
uric acid (5%), 5% contain more than 50% brushite
(calcium monohydrogen phosphate) or hydroxyapatite,
and less than 1% are composed of cystine.4 Because the
treatment for every stone type is different, stone
composition should be analysed by polarisation
microscopy.5 Although much progress has been made in
understanding the pathophysiological mechanisms of
stone disease, allowing for more effective diagnosis and
treatment, stones still cause substantial morbidity from
pain, urinary-tract obstruction, and infection.

Pathogenesis
The mechanisms of crystallisation need to be
understood to outline the basis of stone formation. The
states of saturation of ions in a solution are governed by
their concentrations. For example, when concentrations
of calcium and oxalate reach saturation (the saturation
product), stone formation begins with association of
small amounts of crystalloid to form nuclei (nucleation).
These nuclei normally grow and aggregate on surfaces
Lancet 2001; 358: 65156
Addenbrookes Renal and Dialysis Centre, Addenbrookes Hospital,
Cambridge, UK (G Bihl FCP[SA]); and Stone Clinic, Johannesburg
Hospital, Johannesburg, South Africa (Prof A Meyers FCP[SA], G Bihl)
Correspondence to: Dr Geoffrey Bihl, Renal Unit, Department of
Internal Medicine, University of Stellenbosch, Tygerberg Hospital,
PO Box 19161, Tygerberg, Cape Town, South Africa
(e-mail: gbihl@maties.sun.ac.za)

THE LANCET Vol 358 August 25, 2001

such as collecting ducts and renal papillary epithelium.6

Renal epithelial cells specifically bind and internalise
calcium oxalate monohydrate crystals. Events that occur
after crystal binding could be important in pathogenesis
of stonesie, cellular responses might be essential for
initiation of stone formation.7,8
Fortunately, stone formation is inhibited in urine of
mammals by substances that prevent crystallisation, and
will only take place once the formation product (the
metastable limit) has been exceeded. Therefore,
crystallisation in undiluted human urine will begin only
in a supersaturated solution of calcium and oxalate.
Estimates of urine saturation with stone-forming salts
such as calcium, phosphate, urate, and oxalate are
important in calculation of overall propensity to crystal
formation. Urinary saturation with calcium oxalate is
common in the general population so the role of other
factors in stone formation must be crucial.
However, before discussion of inhibitory and
promoting substances, other important factors need to
be stressed. First, uric acid can precipitate in
persistently acid urine, even in the absence of
hyperuricaemia or hyperuricosuria. Second, uric acid
can cause formation of calcium oxalate stones without
being incorporated into the crystals. This catalyst-like
ability is known as salting out, and is enhanced in acid
urine.9 Finally, urinary pH has an essential role in many
other inhibitor or promoter reactions. Lithogenic risk
factors include stone promoters and inhibitors (panel 1).
Effects of inhibitors on stone formation have been most
studied in calcium oxalate stones. Most inhibitors are
anionic and seem to exert their effects by binding to the
calcium oxalate surface, although the specific structural
mechanisms of this process are not known.10
The many proteins found in stones could cause, be
the result of, or have no role in their formation.
Nephrocalcin is an acidic protein of renal tubular origin,
and in some people who form stones this protein lacks
the aminoacid, -carboxyglutamic acid, which reduces
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Panel 1: Urinary stone promoters and

inhibitors6,10
Promoters

Calcium
Sodium
Oxalate
Urate
Cystine
Low urine pH
Tamm-Horsfall protein
Low urine flow
Bacterial products

Inhibitors
Inorganic
Magnesium
Pyrophosphate
Citrate
Organic
Nephrocalcin
Tamm-Horsfall protein
Urinary prothrombin fragment 1
Protease inhibitor: inter--inhibitor
Glycosaminoglycans
High urine flow

its ability to inhibit nucleation. Additionally,

nephrocalcin inhibits calcium oxalate aggregation,
which some believe is a crucial step in initiation of stone
formation.11 Nephrocalcin might also affect calcium
phosphate crystallisation. Tamm-Horsfall protein
(THP) is the most abundant protein in human urine,
and is synthesised and secreted by epithelial cells of the
thick ascending limb of the loop of Henle and early
distal convoluted tubule. THP remains at crystal
surfaces, and thus mainly affects aggregation of
preformed crystals. Controversy still exists about
whether this protein is a promoter or inhibitor of
crystallisation.12,13 Glauser and colleagues14 measured
THP in 24 h urine samples from people who formed
stones and from healthy individuals. They showed that a
rise in THP excretion correlated with increasing urinary
calcium and oxalate excretion in healthy people but not
in those who formed stones. This result could indicate
that THP has an inhibitory role that prevents
lithogenesis.
Of considerable interest is the role of proteins that are
incorporated in substantial amounts in renal stones, and
their effects on stone formation. One such protein,
crystal matrix protein or prothrombin fragment 1, is a
peptide generated from sequential cleavage of
prothrombin by factor Xa and thrombin. This peptide is
present in epithelial cells of the thick ascending limb of
the loop of Henle and the distal convoluted tubule in
greater quantities in people who form stones than in
healthy individuals.15 The peptide inhibits calcium
oxalate crystal aggregation and growth in rats,16 and
might be excreted by the kidney to protect against stone
formation, but further research is required to show that
this process occurs in people.
The peptide chain of inter--inhibitor has been
isolated from urine, and has been reported to inhibit
calcium oxalate crystallisation.17 Although research on
this protein continues, Dean and colleagues18 concluded
that inter--inhibitor does not have a substantial
inhibitory role in crystallisation, which emphasises the
point that some proteins associated with stones could

652

have no active involvement in their formation. Lastly,

glycosaminoglycans, or urinary polyanions, are potent
inhibitors of growth of calcium oxalate in urine, and
block adhesion of uric acid crystals.19,20

Different stone types

Calcium stones
Most stones contain calcium combined with oxalate,
phosphate, or occasionally uric acid. All calcium stones
are radio-opaque, and calcium oxalate and calcium
phosphate stones are black, grey, or white and
small (1 cm in diameter), dense, and sharply
circumscribed on radiographs. Different conditions
contribute to calcium stones. Hypercalciuria (defined as
01 mmol/kg bodyweight of patient per day, calculated
for ideal bodyweight) can be idiopathic or result from
any disorder that induces even mild hypercalcaemia.
Such disorders include:
(1) primary hyperparathyroidism, which results from an
adenoma in 85% of cases, and is associated with mild to
moderate hypercalcaemia. People who form stones and
have hypercalcaemia are almost certain to have this
parathyroid problem. Hypercalciuria is a result of excess
parathyroid hormone, which causes overproduction of
1,25dihydroxyvitamin D in the kidney; both factors
promote bone resorption, increasing the filtered load of
calcium and hence calciuria.
(2) Other disorders that induce hypercalcaemia can also
result in hypercalciuria: malignancies, granulomatous
diseases, sarcoidosis, thyrotoxicosis, and immobilisation.
(3) Idiopathic hypercalciuria is a familial disorder
affecting both sexes equally, in which urinary calcium
concentration is raised despite normal concentrations of
blood calcium. The primary mechanisms for such
hypercalciuria can occur individually or in combination21
and include high intestinal calcium absorption (the
commonest mechanism), with a normal or slightly raised
serum calcium, suppressed parathyroid hormone, and
increased renal filtered load; increased bone resorption;
defective renal-tubular calcium reabsorption, with an
inappropriately high phosphate excretion for any given
calcium concentration, which might induce increased
activation of 1,25dihydroxyvitamin D; and raised
phospholipid-arachidonic acid concentration in serum
and erythrocytes, with raised urinary prostaglandin E2
concentrations.22
(4) Mutations in the CLCN5 chloride channel in
Japanese patients resulted in low-molecular-weight
proteinuria, hypercalciuria, and calcium stone
formation.23
(5) Other causes of hypercalciuria are inherited
syndromes of familial benign and autosomal dominant
hypercalciuric hypocalcaemia. These disorders are the
result of a mutation in the calcium receptor gene. The
calcium receptor facilitates regulation of parathyroid
hormone
secretion
and
renal-tubular
calcium
reabsorption in response to changes in extracellular
calcium concentrations.24
Another condition associated with renal stone
formation is hyperoxaluria. Oxalate is an end-product of
metabolism, is largely derived from endogenous sources,
and is excreted unchanged in urine. Foods rich in
oxalaterhubarb, standard teas, nuts, beans, spinach,
coffee, and chocolatescan increase concentrations in
urine to 670 mol/day (normal value 440 mol/day).
However, concentrations of more than 890 mol/day
indicate enteric oxaluria (associated with malabsorptive
small-bowel diseases), mild metabolic hyperoxaluria, or
primary hyperoxaluria.

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SEMINAR

Mild metabolic hyperoxaluria does not seem to

represent a substantial fraction of hyperoxalurias,
although in one study from South Africa, 20% of
patients with recurrent renal stones had this disorder.3
Cytosolic enzyme perturbations are thought to result in
mild hyperoxaluria and recurrent calcium oxalate
stones, but the exact pathogenic mechanisms have not
been identified. Pyridoxine, which is a cofactor in
shunting glyoxalate to glycine and pyruvate (ie, away
from oxalate), has been successfully used to treat these
patients.
Primary hyperoxaluria type 1 disease is caused by lack
of the liver enzyme alanine:glyoxylate aminotransferase,
and type 2 disease by lack of D-glycerate
dehydrogenase.25 The defective genes that cause these
diseases and their abnormal liver enzyme products cause
excessive oxalate metabolism, which results in systemic
calcium-oxalate deposition from a young age.
Finally, hypocitraturia is also associated with renal
lithogenesis. Citrate forms a highly soluble complex with
calcium, and thus acts as an inorganic inhibitor of stone
formation and interferes with surface-controlled
crystallisation. Hypocitraturia could result from causes of
intracellular acidosis such as renal failure, potassium
deficiency, distal renal tubular acidosis, chronic
diarrhoeal states, and drugs such as acetazolamide. Many
patients with stones have unexplained low urinary citrate,
dysfunction of the renal sodium-citrate cotransporter has
been proposed as a possible mechanism.26
Uric acid stones
Uric acid stones are smooth, round, yellow-orange and
nearly radiographically transparentunless mixed with
calcium crystals or struvite. They are typically seen as
filling defects on intravenous pyelograms, and computed
tomography scanning can distinguish them from kidney
tissue or blood clots. Diets high in purines, especially
those containing organ meats and fish, result in
hyperuricosuria, and, in combination with low urine
volume and low urinary pH (as a result of impaired renal
ammonia production), can exacerbate uric-acid stone
formation. Uric acid salts out calcium oxalate, and can
precipitate out in acid urine even in the absence of raised
serum or urinary uric-acid concentrations. Furthermore,
hyperuricaemic disorders including gout (about 20% of
patients with gout are hyperuricosuric), myeloproliferative
disorders, tumour lysis syndrome, and inborn errors of
metabolism (such as Lesch-Nyhan syndrome and glucose6phosphatase deficiency) result in an increased filtered
load of uric acid and thus, hyperuricosuria.27
As with all stones, certain drugs may enhance stone
formation, and in the case of uric acid stones,
hyperuricosuric agents include low dose salicylates,
probenecid, and thiazides.
Struvite or triple phosphate stones
Radiographs show struvite stones as large, gnarled, and
laminated. They are associated with substantial
morbidity including bleeding, obstruction, and urinarytract infection. Signs of struvite stones include urinary
pH greater than 7, staghorn calculi, and urease that
grows bacteria on culture (proteus, klebsiella,
pseudomonas). Stones develop if urine is alkaline, has a
raised concentration of ammonium, contains trivalent
phosphate, and contains urease produced by bacteria.
Cystine stones
Cystine stones should be suspected in patients with a
history of childhood stones or a strong family history.

THE LANCET Vol 358 August 25, 2001

Panel 2: Drugs associated with renal stone

formation
Drugs that promote calcium stone formation:

Loop diuretics
Antacids (calcium and non-calcium)
Acetazolamide
Glucocorticoids
Theophylline
Vitamins D and C

Drugs that promote uric acid stone formation:

Thiazides
Salicylates
Probenecid
Allopurinol
Drugs that precipitate into stones:
Triamterine
Aciclovir
Indinavir
(Adapted with permission from Monk).27

They are greenish-yellow, flecked with shiny crystallites,

and are moderately radio-opaque with a rounded
appearance. Calcium stones are denser than vertebral
bodies, whereas cystine stones are less dense. People
who are homozygous for cystinuria (an autosomal
recessive disorder) excrete more than 600 mg per day of
insoluble cystine. More than half the stones in cystinuria
are of mixed composition, and many patients have
associated physiological problems such as hypercalciuria
(19% of patients), hyperuricosuria (22%), and
hypocitraturia (44%).28

Clinical presentation of acute stone episode

When a urinary stone moves into the renal collecting
system, the resulting increase in intraluminal pressure
stretches nerve endings in the mucosa, and produces a
severe and often colicky pain. This pain radiates
downward on the anterior from the flank toward the
groin, and is often accompanied by frequent urination,
dysuria, oliguria, haematuria, acute nausea, and
hypotension. In the acute setting, stones can obstruct
the urinary tract producing serious symptoms, or
obstruction can be a relatively slow and painless process
resulting from slow stone growth and presenting with
advanced renal parenchymal damage. Precipitants of
acute stone episodes include dehydration and reduced
urine output, increased protein intake, heavy physical
exercise, and various drugs (panel 2).

Investigations
Acute setting
Documentation of stone characteristics is extremely
important (type, size, and location). Although there is a
risk of allergy and contrast nephropathy, intravenous
pyelography remains the gold standard for such
identification. Ultrasonography can indicate whether a
stone is in the kidney or ureter, the degree of any
obstruction, and quality of renal parenchyma. Plain
abdominal radiography is useful for stones above the
pelvic brim, and, with ultrasonography, is the
investigation of choice in patients unable to tolerate an
intravenous pyelogram (for reasons such as allergy to
iodine or renal insufficiency).
Medical management of a stone depends on the type
of stone, and includes correction of dietary aberrations,
metabolic defects, or both. Panel 3 shows recommended
investigations.

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Panel 3: Investigations for a renal stone

Blood

Full blood count

Urea and electrolytes
Calcium
Phosphate
Bicarbonate or carbon dioxide
Uric acid
Parathyroid hormone
Alkaline phosphatase
Cholesterol

Urine
Spot pH (include an acid load test if pH >54)
Specific gravity
Culture
24-h analysis of urinary: volume, calcium, sodium, urate,
creatinine, phosphate, citrate, and oxalate
Polarisation microscopy (after fracture of calculi)
Urinary calcium: creatinine ratios
Infrared spectrometry

Classification of hypercalciurias is of limited use in

management patients with calcium stones, and the
calcium-loading test has become obsolete.29
Chronic setting
All kidney stones should be investigated30 and
assessment needs to include a thorough medical history,
drugs taken, family history, lifestyle and diet, fluid
intake, and a clinical examination. Investigations
outlined in panel 3 should be done. Saturation with
stone-forming salts can be calculated from these
measurements with commercially available computer
software. More than one 24 h urine sample might be
needed, especially to be able to define a stone as
idiopathic if all results are negative. Optimum values of
24 h urine sample constituents are shown in panel 4.

Management of acute stones

Pain relief
Renal colic is one of the most intense forms of pain and
requires prompt symptomatic treatment. Non-steroidal
anti-inflammatory drugs given orally or intravenously
have good analgesic properties,31 although they also have
serious gastrointestinal and renal side-effects. Renal
side-effects are especially important in dehydrated
patients and those at risk of allergy to these drugs.

Panel 4: Optimum values of 24 h urine sample

constituents
Volume
pH
Calcium

Oxalate
Uric acid
Citrate
Sodium
Phosphate

>225 L
>55 and <70 (a spot urine
specimen will suffice)
<01 mmol/kg, or <75 mmol in
men, <63 mmol in women
180350 mol
1544 mmol
2451 mmol
<200 mmol
<352 mmol

To ensure adequacy of collection, urine creatinine should be:

71159 mmol in men
52141 mmol in women
(Adapted with permission from Monk).27

654

Cyclo-oxygenase-II inhibitors have been developed to

reduce gastrointestinal effects, but they also inhibit renal
vasoactive substances and are contraindicated in
patients with renal insufficiency.32
Paracetamol given every 4 h is well tolerated, but
pain relief is often inadequate with this agent
alone. Narcotic analgesics including morphine
(given intramuscularly or intravenously) and pethidine
offer excellent pain relief and are the drugs of choice for
acute renal colic. However, they are sedative and have
the risk of dependence if used for a long time. Their
emetogenic side-effects can be counteracted with
antihistamines such as hydroxyzine, which has additive
analgesic properties in combination with narcotic
agents. Codeine is physiologically related to morphine,
and, when combined with paracetamol or aspirin, is
effective for moderate pain. Dextropropoxyphene
combined with paracetamol has been used in the acute
setting, and offers fair pain relief if other opiates are
contraindicated.
Fluids
An increase in diuresis will help patients to pass stones,
and stone and urinary supersaturation can be reduced
by judicious fluid management. Patients should drink
23 L of water daily, or be given water by intravenous
infusion if nauseous. However, an increase in diuresis
can worsen pain, hydronephrosis, and ureteral function,
in which case ureteral stenting might be necessary.
General therapies
A regular catharsis should be encouraged, and although
uncommon in the acute setting, urinary-tract infection
should be investigated and treated if found. Education
of patients about maintenance of adequate hydration,
and avoidance of precipitating drugs and foods should
begin as soon as possible after an acute event.

Management of chronic stones

General measures
Non-pharmacological interventions reduce 5 year rate of
stone recurrence by up to 60%33 in people who adhere to
a sensible diet. Patients should be encouraged to
increase their basic intake of water to at least 2 L daily,
and especially so during heavy exercise, pyrexial
episodes, and when travelling long distances. Maximum
urine output should be encouraged in patients with
renal insufficiency, with careful monitoring of volume
status and weight gain.
A non-animal low protein diet (0810 g/kg per day)
prevents the mild acidosis induced by animal protein
breakdown, and improves calcium homoeostasis. Severe
protein restriction results in malnutrition and muscle
breakdown and should be discouraged.34 Measurement
of urea and, if possible, inorganic sulphate excretion are
easy ways to assess total and animal protein intakes.
Calcium binds oxalate in the gut, thus people who form
stones and are on a high calcium diet paradoxically have
a lower occurence of stone formation than those not on
such a diet. Dietary calcium should be limited to about
1 g/day in patients who remain hypercalciuric despite
pharmacological treatment. An increased tubular
sodium load results in reduced tubular reabsorption of
calcium, therefore a low sodium diet (23 g/day) is
recommended for hypercalciuric patients.
Specific therapies
These therapies are designed for
metabolically active stone disease.

patients with
After general

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SEMINAR

measures have been instituted, further treatment is

based on stone composition and abnormalities noted
from the 24 h urine sample analyses.
Calcium stoneshypercalciuria
Thiazide diuretics such as hydrochlorothiazide (at doses
of 2550 mg/day) increase distal tubular reabsorption
and reduce intestinal calcium reabsorption. Indapamide
(2550 mg/day) has been shown to be best for
treatment of recurrent stones associated with idiopathic
hypercalciuria. This agent has fewer untoward
metabolic effects than other thiazides if used in high
doses.35 Addition of potassium citrate maintains
potassium concentration at the ideal of 3540 mmol/L
and this, together with citrate, improves citrate
excretion in the tubules thereby reducing crystal
agglomeration.36 Persistent hypercalciuria can respond
to potassium-sparing diuretics, calcium restriction
(8001000 mg/day), and reassessment of compliance.
Phosphate rarely needs to be replaced even in patients
with phosphate-losing tubular defect. In patients with
intractable
stone
recurrence
and
idiopathic
hypercalciuria, Coe and colleagues37 recommend a
calcium-binding resin (sodium cellulose phosphate)
with a thiazide diuretic, although no controlled clinical
studies in support of such treatment have been done.
Use of ethyl icosapentate (a polyunsaturated fatty acid)
has yielded disappointing results with regard to urinary
calcium and oxalate excretion, although calciuria was
reduced in some patients and further research is
advocated.38
Calcium stoneshyperoxaluria
First principles of treatment include increased fluid
intake and urinary alkalinisation, treatment of the
underlying cause of disease, dietary restriction of foods
high in oxalate, and an increase in dietary calcium.
Calcium carbonate (500650 mg tablets, two or three to
be taken with every meal) binds dietary oxalate, and
potassium citrate (450 mg capsules taken two to three
times per day) in combination with magnesium
gluconate (0510 g/day) is a useful adjunct.39 Mild
metabolic hyperoxaluria can be treated with pyridoxine,
but not very successfully. Primary hyperoxaluria can be
cured only by liver transplantation, although pyridoxine
supplementation may reduce endogenous oxalate
production.
Calcium stoneshypocitraturia
Because citrate forms a soluble complex with calcium,
citrate is an effective treatment for most calcium stones,
irrespective
of
their
cause.
Urinary
citrate
concentrations
should
be
maintained
above
2451 mmol/day, and an initial dose of 450 mg of
potassium citrate two to three times daily might have to
be increased to achieve this level. Potassium citrate must
be used rather than sodium bicarbonate, because
sodium bicabonate increases delivery of sodium to the
renal tubules, which results in an increase in urinary
calcium.

Calcium stoneshyperuricosuria
Recommended therapies are increased fluid intake,
treatment of the underlying cause of disease, and a low
purine diet with the addition of allopurinol if other
measures fail.
Uric acid stones
Recommended therapies include adequate fluid intake,
a low purine diet, and urinary alkalinisation (pH 65)
with potassium citrate. Such measures should pre-empt
use of allopurinol and acetazolamide for urinary uric
acid secretion and alkaline pH maintenance.
Acetazolamide should not be used in the long term.
Struvite stones
Because urease-producing bacteria are often embedded
in these stones, antibiotics can be ineffective in
eradication of the offending pathogen. Early urological
intervention is warranted in patients with these stones,
as is use of culture-specific antibiotics around the time
of operation. Furthermore, once the patient is stone
free, Wong and colleagues41 recommend continuation of
antibiotics until cultures remain negative for at least
3 months. As an adjunct, oral phosphate binders reduce
phosphate content of these stones.
Cystine stones
Treatment for these stones is aimed at improvement of
solubility of cystine in urine, by increase of fluid intake
to more than 4 L/day and alkalisation of urinary pH to
more than 74 with potassium citrate. Treatment also
includes restriction of dietary sodium, and occasionally,
d-penicillamine can be used as a chelating agent
although occasionally side-effects (agranulocytosis and
thrombocytopenia) limit its clinical use.42 Because
cystine stones do not disperse well with extracorporeal
shock-wave lithotripsy, formal urological procedures
might be necessary to remove these stones.
Urological intervention43
Advances in urological techniques have drastically
altered management of patients with symptomatic
stones that require treatment. Most symptomatic upper
urinary-tract stones are small, occur in normal kidneys,
and pass spontaneously if less than 5 mm in diameter.
Up to 85% of stones smaller than 2 cm in diameter that
need to be removed are best treated with extracorporeal
shock-wave lithotripsy. An endoluminal approach with
ureteroscopy or percutaneous nephrolithotomy is best
suited for large or complex stones, stones associated
with urinary tract abnormalities, those in the lower
ureter, or ones that do not fragment after extracorporeal
shock-wave lithotripsy. Fortunately, formal surgical
lithotomy has been relegated to anecdotal status.
We thank Maria Martins for her assistance, advice, and encouragement
with the preparation of this manuscript.

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with type 1 renal tubular acidosis (distal), raised urinary
pH promotes calcium phosphate precipitation, and high
doses of potassium might be necessary to prevent stone
formation.

THE LANCET Vol 358 August 25, 2001

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