Nephrolithiasis- pathogenesis,

approach, and management

Seminar 04/08/2014
 Introduction
• Kidney stones probably represent the oldest documented human
ailment.

• Stones are composed of crystals, often of several different types, in

a protein matrix. The majority (>80%) of crystals are composed of
calcium complexed with oxalate and or phosphate

• The human skeleton is composed primarily of apatite—

Ca10(PO4)6(OH)2—and is, by far, the largest repository of calcium
in the body.

• Growth and pregnancy necessitate substantial absorption of dietary

calcium. Once skeletal formation is complete, nonpregnant humans
must excrete any absorbed calcium in the urine; however, absorption
is not precisely regulated, and it increases with additional dietary
intake, regardless of need.
• The ions that are most often complexed with calcium in kidney
stones, oxalate and phosphate, are, respectively, an end product of
metabolism and another principal component of bone whose
absorption is also poorly regulated.
 Epidemiology
• Kidney stones are common in industrialized nations, with an annual
incidence of 0.5% to 1.9% and a lifetime incident rate of
approximately 13% in men and approximately 7% in women.

• In one study, the mean age at the time of stone diagnosis was 45
years in men and 41 years in women, and the overall incidence
ratio of stones in men to stones in women was 1.73 .
• The risk of developing urolithiasis in adults appears to be higher in
the western hemisphere (5–9% in Europe, 12% in Canada, and 13–
15% in the USA) than in the eastern hemisphere (1–5%), although
the highest risks have been reported in some Asian countries such
as Saudi Arabia (20.1%) with lifetime recurrence rates of upto 50%.

• The interval between recurrences is variable, with approximately

10% within one year, 35% in five years, and 50% by 10 years.
• 75% of stones are primarily calcium oxalate, but up to 50% of
these include calcium hydroxyl phosphate (brushite or calcium
hydroxyapatite) in trace or greater amounts; Calcium phosphate in
stones is usually hydroxyapatite [Ca5(PO4)3OH] or, less commonly,
brushite (CaHPO4H2O), although the incidence of brushite stones
is increasing.

• 10–20% are composed of magnesium ammonium phosphate

(struvite or triple phosphate);

• 5% are composed of urate; and

• 1-2% are composed of cystine.
• In addition to age and gender, race, geography, and body mass
index (BMI) are risk factors for kidney stones.

• A BMI higher than 30, in comparison with a BMI between 21 and

22.9, is also associated with an increased risk of stone formation, as
is a weight gain of 35 pounds (16 kg) after young adulthood and an
increased waist circumference.

• It is not clear what types of stones are most prevalent in obesity, but
evidence is suggestive of mostly uric acid stones.
• Nephrolithiasis has been associated with chronic kidney disease
(CKD) but is rarely the cause of end-stage kidney disease.

• Even mild CKD is associated with significant adverse cardiovascular

events.
 Genetic contribution to nephrolithiasis

• Specific monogenic causes of kidney stones such as distal renal

tubular acidosis (RTA), primary hyperoxaluria, and cystinuria.

• In studies of familial aggregation, researchers have tried to find

whether frequencies of nephrolithiasis among families of affected
patients are statistically different from those among families of
unaffected individuals.

• Familial Aggregation = In the first large-scale retrospective case-

control study, McGeown examined 174 patients with renal stones
and 174 age- and gender-matched controls and found kidney
stones among significantly higher numbers of parents and siblings
of the stone formers than among relatives of controls.
• Many studies have indicated that 20% to 40% of stone formers have
positive family histories of stones; large databases, such as the
Nurses Health Cohort and Health Professional Follow-up Study,
reveal a relative risk of approximately twofold to fourfold.

• Inheritance pattern= An early attempt to model the segregation of

nephrolithiasis by tracking four generations of renal stone formers
led investigators to conclude that an autosomal dominant trait was
responsible for the disorder.
• The most acceptable notion is that nephrolithiasis is a complex trait
with polygenic contribution (determined by many genes), loci
heterogeneity (stones formers with different genetic backgrounds
are affected by different genes), incomplete penetrance (positive
genotype but negative phenotype), and extensive phenocopy
(nongenetic causes of the same phenotype).

• The concordance rates were 32% among monozygotic twins and

17% among dizygotic twins.
 Why some people are more prone to develop kidney stones
Date:
April 18, 2012
Source:
Washington University in St. Louis

• A common genetic variation in a gene called claudin-14 recently

has been linked to a substantial increase in risk -- roughly 65
percent -- of getting kidney stones. In the new study, the
researchers have shown how alterations in the gene's activity
influence the development of stones.
 Mechanisms of crystal formation in
urine
In order for a stone to be formed,

• A solid phase needs to be first produced from microcrystals (the

nucleus), which are formed from salts (and other substances) that
are found dissolved in the urine (nucleosis of crystals).

• Afterwards, the crystals that constitute the core increase in size and
link up with each other (incorporation).
• In order to increase in size and the incorporation of crystals to take
place, hypersaturation, lack of inhibitors, organic substrate and
epitaxis, during which crystals of a substance are attached to the
surface of other crystals of different chemical structure (e.g. crystals
of oxalic calcium onto crystals of uric acid) are needed.

• The product of the free ionized calcium and oxalate concentrations

in such a solution is called the equilibrium solubility product. A
solubility product with lower free ion activity would cause the
crystals to dissolve; such a solution is called undersaturated.

• A solubility product with higher free ion activity would cause the
crystals to grow.
• A solution is considered saturated regarding a substance when it
contains in dissolution its highest possible concentration.

• If crystals pre-exist in the solution, they decrease in size and could

possibly dissolve (region of hyposaturation).
• If the density is increased, it will reach a point beyond which whatever
quantity of salt is added it is impossible to remain in dissolution and it
precipitates (‘solubility product’ or saturation level).

• A solution that causes growth of preformed crystals but not the

appearance of new solid phase is called metastable.

• If the activity product is raised sufficiently, however, new crystals

appear. This point is often called the formation product or the
upper limit of metastability (ULM).

• The region between the solubility product and the formation product
is called the transient or metastable region.
• When the density of the solvent exceeds the formation product (a
region of hypersaturation or an unstable region), precipitation of
crystals and the formation of a nucleus (homogeneous nucleosis)
takes place.

• In clinical practice, inspite of hypersaturation that can be the result

of either an increase in the excretion of solvents in the urine (e.g.
calcium, oxalates, cystine) or a reduction in the volume of the urine,
It is also influenced by the ionic activity of soluble salts, the pH,
as well as the existence of soluble complex salts.
• Thus, an acidic pH favours the precipitation of uric salts, whilst
the formation of inflammatory stones takes place in an alkaline
pH.
• Urine has the capacity to retain in dissolution ions that are found in
higher concentration than the level of saturation.

• This capacity is due to the formation of stable solvents of complex

salts that include charged anion-cation complexes, ions connected
with macromolecules (e.g. mucoproteins) and anion-cation
complexes connected with natural chemical substances, such as
citric and pyrophosphate salts.

• This can explain why the precipitation of salts and the nucleosis of
crystals in the transient region does not occur.

• It is also necessary for its concentration to be above the formation

product. Exceptions include uric acid, cystine and xanthine
stones where hypersaturation is sufficient for their formation.
• The activity product of a salt that is dissolved in ions C+ and A – is
calculated by the product K = [C +] · Fc · [A-] · fa
where [ ] represents the concentration of free ions and f the activity
constant.

• The relative saturation ratio (RSR) is the ratio of the activity product
divided by the solubility product. The solution is saturated when the
RSR is equal to 1, hypersaturated when the RSR is higher than 1
and hyposaturated when it is lower than 1.

• These may be estimated by the computer program Equil2.

• Prerequisits for the creation of a stone are hypersaturation, a

nucleus and time in order to be formed.
• The efficiency of heterogeneous nucleation depends on the
similarity between the spacing of charged sites on the preformed
surface and in lattice of the crystal that is to grow on that surface.
This kind of matching is referred to as epitaxis.

• Monosodium urate and uric acid are excellent heterogeneous nuclei

for calcium oxalate, therefore, uric acid or urate could, by
crystallizing, lower the ULM (upper limit of metastability ) for
calcium oxalate. Heterogeneous nucleation may be the mechanism
linking hyperuricosuria to calcium oxalate stones.

• Epitaxial overgrowth of calcium oxalate on a surface of uric acid has

been experimentally documented.
• Calcium phosphate (Randall) plaques found in the renal papilla
may act as nucleating sites for calcium oxalate stones.

• The Randall plaque is formed in the interstitium of the papilla but

can erode through the papillary epithelium to be exposed to the
urine.

• The plaque provides a preferred nucleating site, lowering the free

energy needed for crystallization of calcium oxalate. At the same
time, the plaque provides an anchoring site that allows the new
crystals to be retained in the kidney and provides sufficient time for
them to grow to a clinically significant size.
 Cell-Crystal Interactions

• Finlayson and Reid proposed that crystals cannot grow or

aggregate fast enough to anchor in the urinary tract during the
normal transit time through the nephron.

• Therefore, to grow large enough to be of clinical significance,

crystals must anchor to the renal tubule epithelium or urothelium:
This is the fixed particle theory.

• Although Randall plaques may offer an anchoring or nucleating site,

it is also clear that not all stone formers have Randall plaques.
• In vitro studies have shown adherence of calcium oxalate crystals to
collecting duct epithelial cells in rats, and adherence and
subsequent endocytosis of calcium oxalate crystals by kidney
epithelial cells in monkeys.

• The adherence and uptake of crystals appear to be crystal-specific:

greater for calcium oxalate than calcium phosphate
 Inhibitors of Stone Formation
There are at least four types of inhibitors in urine:

• multivalent metallic cations, such as magnesium;

• small organic anions, such as citrate;
• small inorganic anions, such as pyrophosphate; and
• macromolecules, such as osteopontin and Tamm-Horsfall protein.

Li and associates126 found that magnesium inhibited both nucleation

and growth of calcium oxalate crystals.
• Citrate inhibits the nucleation, growth, and aggregation of calcium
oxalate crystals.

• During metabolic acidosis, proximal citrate reabsorption increases,

reducing the amount of citrate excreted in the urine. A reduction of
urinary citrate, caused by an increase in the acid load generated
from ingested dietary protein, can promote formation of both calcium
oxalate and uric acid stones.

• Pyrophosphate has been shown to retard the growth of calcium

phosphate and calcium oxalate crystals. Schwille and colleagues
found a reduced ratio of pyrophosphate to creatinine in half of stone
formers, which suggested that a lack of pyrophosphate may
predispose to nephrolithiasis.
•
Macromolecules - are potent inhibitions of calcium oxalate
crystallization. These inhibitory molecules are generally highly
anionic and contain large amounts of acidic amino acid.

• Osteopontin - is normally expressed in cells of the thick ascending

limb of Henle’s loop and the distal convoluted tubules and is
secreted into the tubules Osteopontin inhibits nucleation, growth,
and aggregation of calcium oxalate stones in vitro

• Tamm-Horsfall protein synthesized in the thick ascending limb of

Henle’s loop inhibits calcium oxalate crystal aggregation but does
not alter growth or nucleation
Other macromolecules

• Urinary prothrombin fragment 1

• Bikunin
• Nephrocalcin - is a 14-kDa glycoprotein that was the first urinary
protein found to have crystal inhibitory properties.
• Urinary trefoil factor 1 (TFF1)
• Calgranulin
 Signs and symptoms

• The classic presentation for a patient with acute renal colic is the
sudden onset of severe pain originating in the flank and radiating
inferiorly and anteriorly; at least 50% of patients will also have
nausea and vomiting.

• Stones obstructing ureteropelvic junction: Mild to severe deep flank

pain without radiation to the groin; irritative voiding symptoms (eg,
frequency, dysuria); suprapubic pain, urinary frequency/urgency,
dysuria, stranguria, bowel symptoms
• Stones within ureter: Abrupt, severe, colicky pain in the flank and
ipsilateral lower abdomen; radiation to testicles or vulvar area;
intense nausea with or without vomiting

• Upper ureteral stones: Radiate to flank or lumbar areas

• Midureteral calculi: Radiate anteriorly and caudally

• Distal ureteral stones: Radiate into groin or testicle (men) or labia

majora (women)

• Stones passed into bladder: Mostly asymptomatic; rarely, positional

urinary retention
 Major causes of renal stone
For calcium stones (75-85%)

• urinary risk factors include hypercalciuria, hyperoxaluria,

hypocitraturia, and

• dietary risk factors such as a low calcium intake, high oxalate intake,
high animal protein intake, high sodium intake, or low fluid intake.

• Increased intake of Vitamin C has been associated with a higher risk

of stones in men
 Approach to nephrolithisis
A well-conducted history provides

• Age
• Inherited causes

• Underlying structural abnormalities.

• Dehydration - oliguria, excessive sweating, and diarrhea

• Nutritional history of estimated dietary contents of calcium, oxalate,

sodium, acid (protein), potassium-rich citrus fruits, and purine

• Gastrointestinal diseases - chronic diarrhea states, ileal resection,

jejunoileal bypass, or weight reduction surgery
• immobilization, metastatic diseases, multiple myeloma, and primary
hyperparathyroidism;

• Recurrent UTI with urease-positive organisms

• Gout, diabetes, obesity, and the metabolic syndrome are risk factors
for kidney stone formation, particularly uric acid stones

• Drug history
Laboratory

• urinalysis, Urine crystals examination

• specific gravity and osmolality

• low urinary pH (<5.5) raises is suspect for uric acid stones. A

moderately high pH (6.5 to 7.2) may reflect complete or incomplete
distal RTA. An extremely high pH (>7.4) is usually indicative of the
splitting of urea into ammonium and bicarbonate.

• Plasma calcium, phosphorus, and uric acid.

• Parathyroid hormone (PTH), 25-hydroxycholecalciferol, and 1,25-
dihydroxycholecalciferol [1,25(OH)2D3]
• Calcium oxalate crystals - uniform small double pyramids that often
appear as crosses in a square.

• Calcium phosphate crystals - narrow rectangular needles, often

clumped in a flower-like configuration.

• Uric acid crystals - form only in an acidic urine, which favors the
conversion of relatively insoluble urate salts into insoluble uric acid.

• Calcium magnesium ammonium pyrophosphate (so-called triple

phosphate) crystals - form domed rectangles that take on the
appearance of coffin lids.
Next step is the outpatient 24-hour urine analysis on a random diet

• measurements of Ca, P, oxalate, uric acid, sodium, potassium,

pH, bicarbonate, sulfate, ammonium, titratable acid, citrate, and
creatinine, and the relative supersaturation ratios of calcium
oxalate, calcium phosphate, monosodium urate, and concentration
of undissociated uric acid should be calculated.

• Computer-based programs have the advantage of accounting for all

parameters involved and generating one number that indicates the
relative supersaturation - Equil2 , Joint Expert Speciation System
( JESS) program.
Stone Analysis

• All attempts should be made to encourage the patient and the

primary care physician to capture the stone and submit it for
analysis.

• Composition of stones should always be determined by x-ray

crystallography or infrared spectroscopy. Both tests are
relatively inexpensive and can lead to important diagnoses,
especially cystinuria or crystallization of drugs.

• cystine stones are diagnostic for congenital cystinuria; a struvite or

carbonate stone is indicative of urinary tract infection with urease-
positive organisms; triamterene and indinavir stones are
pathognomonic for the precipitation of these drugs.
• For patients with hypercalciuria and calcium stones, measurement
of BMD may be useful

• Stone composition is always important, but young age, decreased

glomerular filtration rate, proteinuria, and extremes of oxaluria
are among the variables that should lead to more complete
evaluation.

• Measures for detection of genetic nephrolithiasis - cystinuria,

primary hyperoxaluria, Dent disease, claudin mutations, and
adenine phosphoribosyltransferase deficiency.
• For patients in whom kidney stones are suspected of having
monogenic causes, more complicated tests are performed, usually
in an academic setting; these tests include genotyping and specific
metabolic tests such as ammonium chloride loading and urine-blood
carbon dioxide tension during bicarbonaturia (in RTA),
aminoaciduria (in Dent’s disease), and parathyroid suppression by
calcium infusion (resulting from an activating mutation of CaSR).
Imaging

• X- Ray- accuracy of interpretation of plain radiographs is less than

satisfactory.

• Ultrasonography is less useful because visualization in the kidney is

often suboptimal, and it is almost useless for discerning ureteral
stones, although it is excellent in detecting obstruction caused by
kidney stones, safe in children, pregnant women.

• Intravenous pyelography (IVP) has served well and been the

standard procedure for decades;

• unenhanced computer tomography (CT) is currently the diagnostic

procedure of choice.
• All kidney stones regardless of composition, with the exception of
indinavir stones, can be visualized by noncontrast CT, which can
reveal very small stones (as small as 1 mm) with sensitivity higher
than 94% and specificity higher than 92%.
• the “fast and load” calcium test, which can help distinguish
absorptive from renal hypercalciuria.

• This test entails a measurement of 2-hour fasting urinary calcium

level in the morning, along with a serum sample for calcium,
creatinine, and PTH, followed by a 1-g oral calcium load.

• Four hours later, urine is collected, and calcium and creatinine

levels are measured. The fasting sample enables calculation of
fractional excretion of calcium in the absence of calcium in the gut
and unveils urinary calcium leak. The post-load urinary calcium-
creatinine ratio allows clinicians to evaluate the intestinal
contribution. A normal value is less than 0.2 mg calcium/ mg
creatinine. This test, although informative, is frequently difficult to
perform in a practice setting.
 General Therapy
• Patients with a strong familial history of nephrolithiasis who have yet
to pass a stone are often given general advice on fluid and dietary
modification aimed at lowering urinary supersaturation with the goal
of preventing future stone formation- stone clinic effect.

• These nonpharmacologic measures include an increase in fluid

intake, which concomitantly increases urine volume; restriction of
dietary sodium, which leads to a reduction of urine calcium
excretion; restriction of animal protein, which also leads to a
reduction of urine calcium excretion and an increase in excretion of
the calcification inhibitor citrate; and ingestion of an age- and
gender- appropriate amount of dietary calcium.
Fluid Intake

• An increase in fluid intake that results in a urine volume of more

than 2 to 2.5 L daily is of proven efficacy in reducing the incidence of
stone formation.

• Patients should be encouraged to drink enough fluid in the evening

to provoke nocturia and then drink further fluid before returning to
bed.
Salt Intake

• Increasing renal sodium excretion leads to a direct increase in renal

calcium excretion

• Restriction of dietary sodium with the consequent decrease in urinary

sodium will lead to a reduction of urine calcium excretion and urine
supersaturation.

• A high sodium intake is associated with an increase in nephrolithiasis,

and reduction of intake lessens recurrent stone formation, especially in
combination with a diet that includes adequate amounts of calcium
and moderate amounts of protein.

• Patients with hypercalciuria are generally advised to limit their daily

sodium intake to 2000 mg (≈87 mmol) or lower.
Protein Intake

• The ingestion of animal protein increases renal stone formation by a

number of mechanisms.

• Metabolism of sulfur-containing amino acids increases excretion of

sulfate ions, which may render urinary calcium ions less soluble.

• The metabolism of a number of amino acids results in the

generation of hydrogen ions, which leads to calcium release from
bone as a result of buffering of the additional acid and an increase in
the filtered load of calcium
• Furthermore, metabolic acidosis or acid loading leads to an increase
in proximal tubule citrate reabsorption and a decrease in renal
citrate excretion. Thus, a diet rich in animal protein results in
increased urine calcium excretion in which the calcium is less
soluble because of the excess sulfate and reduced citrate.

• Excess dietary protein is a risk factor not only for calcium-containing

kidney stones but also for uric acid stones.

• Stone formers are generally counseled to consume a diet moderate

in total protein (0.8 to 1.0 g/kg daily), especially proteins
derived from animal sources.
Calcium Intake

• An age-appropriate amount of calcium (for both men and women,

1000 mg of elemental calcium from ages 19 to 50 and then 1200 mg
of calcium there after) without supplements appears most prudent.

• A lower calcium diet not only increases stone formation but

increases the risk for bone demineralization, and a higher calcium
diet also increases nephrolithiasis without substantially improving
bone mineral density.
RECURRENT STONE FORMATION —

• patients with active stone disease should undergo evaluation for,

and appropriate treatment of, metabolic abnormalities that
predispose to stone formation, such as hypercalciuria,
hyperuricosuria, or hypocitraturia.
 Calcium stone
1. Idiopathic hypercalciuria - 50-55% - ? Hereditary-
Normocalcemia, unexplained hypercalciuria
T/T- Low-sodium, low-protein diet; thiazide diuretics

2. Hyperuricosuria - 20%- Diet - Urine uric acid >750 mg per 24 h

(women), >800 mg per 24 h (men) - Allopurinol or low-purine diet

3. Primary hyperparathyroidism - 3-5 % - M:F= 3:10 Neoplasia-

Hypercalcemia with nonsuppressed parathyroid hormone- Surgery

4. Distal renal tubular acidosis - Rare- Hereditary or acquired-

Hyperchloremic acidosis, minimum urine pH >5.5 - Alkali
replacement
5. Dietary hyperoxaluria 10–30% - High-oxalate diet or low-calcium diet
- Urine oxalate >40 mg per 24 h - Low-oxalate, normal-calcium diet

6. Enteric hyperoxaluria 1–2%- Bowel surgery- Urine oxalate >75 mg

per 24 h - Low-oxalate diet and oral calcium pills.

7. Primary hyperoxaluria Rare – Hereditary- Urine oxalate and glycolic

or l-glyceric acid increased - Fluids, pyridoxine, citrate and neutral
phosphate

8. Hypocitraturia 20–40 - ? Hereditary, diet - Urine citrate <320 mg per

24 h - Alkali supplements

9. Idiopathic stone disease 20% - Unknown - None of the above

present - Oral phosphate, fluids.
Uric acid stones 5–10 %

1. Metabolic syndrome 30% - Diet- Glucose intolerance, obesity,

hyperlipidemia - Alkali and allopurinol if daily urine uric acid >1000
mg.
2. Gout 30% - M:F 3:1 to 4:1 –Hereditary- Clinical diagnosis - Alkali
and allopurinol
3. Idiopathic 30% - ? Hereditary - Uric acid stones, no gout - Alkali
and allopurinol if daily urine uric acid >1000 mg
4. Dehydration
5. Lesch-Nyhan syndrome -Rare - Males only – Hereditary -
Reduced hypoxanthine-guanine phosphoribosyl transferase level –
Allopurinol.

Hyperuricosuria can be a cause of uric acid nephrolithiasis, and it is

also a well-documented risk factor for calcium oxalate stones.
• Cystine stones - 1%- Hereditary - Stone type; elevated cystine
excretion - Massive fluids, alkali, D-penicillamine if needed

• Struvite stones - 5% - Infection - Stone type - Antimicrobial agents

and judicious surgery.
 Options in the management of renal
and ureteral stones in adults
• The enthusiasm for PNL, ureteroscopy, and SWL must not
overshadow the importance of medical therapy to prevent new
stone formation. A treatable metabolic etiology of stone formation
can be detected in more than 95 percent of patients evaluated for
stone disease.

• High fluid intake for all forms of stone disease, a thiazide diuretic for
hypercalciuria, allopurinol or potassium citrate for hyperuricosuria,
potassium citrate for hypocitraturia, and potassium citrate for uric
acid stone formation due to persistently acid urine.

• With medical treatment, investigator have found remission of stone

disease in more than 75% and a reduced rate of stone passage in
more than 94% of patients.
• Approximately 10 to 20 percent of all kidney stones require
surgical removal, which is determined based upon the presence of
symptoms and the size and location of the stones.

• Stone removal is also indicated for pain or obstruction or for an

infected struvite stone. On the other hand, no specific surgical
therapy is required for asymptomatic stones, particularly those that
are less than 5 mm in diameter.

• Three minimally invasive surgical techniques that significantly

reduce the morbidity of stone removal are currently available:

1. Percutaneous nephrolithotomy (PNL)

2. Rigid and flexible ureteroscopy (URS)
3. Shock wave lithotripsy (SWL)
Percutaneous nephrolithotomy, which requires general anesthesia
and hospitalization, is currently reserved for patients with the
following clinical characteristics

• Large (>2 cm in diameter) or complex calculi (filling the majority of

the intrarenal collecting system, such as staghorn calculi)
• Cystine stones (relatively resistant to shock wave lithotripsy)
• Anatomic abnormalities, including horseshoe kidneys or
ureteropelvic junction obstruction
• Stones within calyceal diverticula
Occasionally, a nephrostomy tube may be placed as a temporizing
measure, usually for patients who present with an obstructing stone
and sepsis. Proper drainage of the infected urine is essential. Once
the infection has cleared, the stone may be removed by one of the
methods previously listed.
 Management of ureteral calculi
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• The likelihood of spontaneous passage of a ureteral stone is related

to both stone size and location.

• Most stones ≤4 mm in diameter pass spontaneously. Stone

diameter ≥5 mm is associated with a progressive decrease in the
spontaneous passage rate, which is unlikely with stones ≥10 mm in
diameter.

• Proximal ureteral stones are also less likely to pass spontaneously.

• Emergency therapy — In septic patients with obstructing stones,

urgent decompression of the collecting system with either
percutaneous drainage or ureteral stenting is indicated in
combination with appropriate antimicrobial therapy- Definitive
treatment of the stone should be delayed until sepsis is resolved.
• Additional indications for urgent decompression include bilateral
obstruction with acute kidney injury and unilateral obstruction with
acute kidney injury in a solitary kidney.

• Medical therapy — In a patient who has a newly diagnosed ureteral

stone <10 mm and whose symptoms are controlled, observation
with periodic evaluation is an option for initial treatment. Such
patients may be offered an appropriate medical therapy to facilitate
stone passage during the observation period.
• Surgical therapy — In patients in whom emergency therapy is not
indicated, stone removal may be performed in the presence of
persistent obstruction, failure of stone progression, or in the
presence of increasing or unremitting colic.

• The ureteral stone that must be removed requires the use of a

modality such as lithotripsy or endoscopic removal.
PROXIMAL URETERAL CALCULI

Various first and second generation lithotriptors, which utilize

fluoroscopic and ultrasound imaging systems
• Flexible ureteroscopy
• Percutaneous antegrade techniques
• Retroperitoneal laparoscopy

For small proximal ureteral calculi (less than 10 mm), shock wave
lithotripsy and ureteroscopy are both considered first line therapy.
However, with proximal ureteral stones that are larger than 10 mm,
flexible ureteroscopy combined with holmium laser lithotripsy and
intraoperative fragment retrieval offers optimal results
MID-URETERAL CALCULI —

The highest stone-free rates and lowest number of required re-

treatments are associated with ureteroscopy with holmium laser
lithotripsy. Thus, flexible ureteroscopy is generally preferred over in
situ SWL.

DISTAL URETERAL STONES

• Some investigators believe the treatment of distal ureteral stones

may best be managed initially with endoscopic techniques, and this
is supported by meta-analyses of randomized trials. However, SWL
is utilized by some clinicians. Failure of both treatment options may
require antegrade percutaneous management or (in extremely rare
cases) open or laparoscopic ureterolithotomy.