Literature Review on Nephrolithiasis (Kidney Stones

A LITRATURE REVIEW
ON
NEPHROLITHIASIS
(KIDNEY STONE)
BY :- INDRA KUMAR DHOOT
MAIP (RUHS, JAIPUR)

NEPHROLITHIASIS
MAHARISHI ARVIND INSTITUTE OF PHARMACY, JAIPUR Page 2
1.1 THE URINARY SYSTEM AND NEPHROLITHIASIS :
The purpose of the urinary system is to filter blood and eliminate wastes
from the bloodstream in the form of urine. The urinary system, also known as the
renal system (relating to, involving, or located in the region of the kidneys), is in
charge of eliminating these wastes from the body.1
The renal system is also responsible for regulating blood volume and
pressure, controlling levels of electrolytes and metabolites, and regulating blood
pH. The urinary system, or urinary tract, includes two kidneys, two ureters, a
bladder, and a urethra.1
The kidneys are two bean-shaped organs, each about the size of a fist and
located just below the rib cage on either side of the spine. The kidneys process
about 200 quarts of blood each day to produce about 1 to 2 quarts of urine. The
urine flows from the kidneys through the ureters to the bladder, where it is stored
until released through urination. During urination, urine flows out of the body
through a tube at the bottom of the bladder called the urethra. Male and female
urinary systems are very similar.1
Fig. 1.1 :- Urinary System22 Fig. 1.2 :- Stone in Kidney1

NEPHROLITHIASIS
1.2 RATIONALE:
Nephrolithiasis is a very common disease, with an increasing incidence
and prevalence, and a significant economic impact associated with its treatment.
The surgical management of kidney stone disease has changed dramatically over
the past 25 years, as a result of revolutionary technologic and treatment advances.
In particular, ureteroscopy (URS) has been significantly impacted, by these
advances. In light of these technologic improvements, the literature suggests that
over time URS become more efficacious, associated with less complications and a
more accessible and commonly used modality than before.2
However, the studies demonstrating increased utilization of URS have
been predominantly based on physician surveys and or retrospective series from
single centres. More importantly, although numerous studies and even a meta-
analysis have shown a high success rate and low complication rate with modern
URS, these studies have largely been completed at high volume centres with
technical expertise. At present, large population based evaluations have not been
conducted to accurately assess:2
 The trends over time in the utilization of different treatment modalities in
management of kidney stone disease.2
 The subsequent effect of these trends and technologic advances on patient
morbidity in the “real world”, including the need for repeat or auxiliary
treatment.2
 Our aim was to examine surgical treatment trends over time for
nephrolithiasis, in the province of Ontario. Administrative databases,

NEPHROLITHIASIS
within the context of the universal Health are system in Ontario, provided
an excellent opportunity to study this at a population level.2
1.3 KIDNEY STONES :
Kidney stones are a crystal aggregation formed in the kidneys from dietary
minerals in the urine. The physical process of stone formation is a complex
cascade of events. It begins with urine that becomes supersaturated with stone
forming salts (e.g., calcium, oxalate, uric acid, magnesium, phosphate) resulting
in their precipitation out of solution to form crystals. Once formed, crystals may
flow out with the urine or be retained in the kidney at anchoring sites that result in
growth and aggregation, ultimately leading to stone formation.3

NEPHROLITHIASIS
2.1 KIDNEY STONES MORPHOLOGY:
There are several types of kidney stones based on the type of crystals,
which they are composed of Calcium stones are the most common type of kidney
stones and constitute approximately 80-90% of all renal stones.4
Calcium stones are generally a mixture of calcium phosphate and calcium
oxalate precipitate. Depending on the main constituent (>50%) of the stone, we
call them either calcium oxalate or calcium phosphate stone.4
In the majority of calcium kidney stones, calcium oxalate is the main
constituent and calcium phosphate precipitate is present in amounts ranging from
1% to 10%. Calcium phosphate stone are less common and only about 15% of
kidney stones fall in this category.4
2.2 TYPE OF KIDNEY STONE:
Figure-2.1 :- Proportion of kidney stones by types5

NEPHROLITHIASIS
There are four major types of kidney stones that can form in the urinary
system. Uric acid stones form when urine is persistently acidic. Struvite stones
result from kidney infections, while cystine stones are caused by a genetic
disorder that results in the amino acid, cystine, to leak through the kidneys and
into the urine.5
Calcium stones are the most common type and are caused by a
combination of high calcium content in the urine, as well as high pH. About 80
percent of all kidney stones are formed from calcium-based compounds, most
commonly calcium oxalate.
Classification6
 Overall, calcium-based stones are the most common and appear
predominantly as calcium oxalate or calcium phosphate salts. These stones
are radiopaque. Calcium phosphate stones can appear as elongated, blunt
crystals and form in alkaline urine. Calcium oxalate stones can be found in
acidic urine and can be dumbbell-shaped or appear as paired pyramids
(giving them an envelope appearance when viewed on end).6
 Uric acid stones can be idiopathic or develop as part of hyperuricosuric
states such as gout and myloproliferative disorders. These stones are
radiolucents and found in acidic urine. Uric acid exhibits a variety of
shapes, with needles and rhomboid forms being the most common.6
 Struvite stones contain magnesium, ammonium and phosphate. They
develop in alkaline urine associated with urea-splitting organisms (e.g.,
Proteus, Klebsiella). They are radiopaque and van extend to fill the renal
pelvis, taking on an staghorn configuration. On microscopy, struvite
crystals have a characteristic coffin-lid shape.6

NEPHROLITHIASIS
 Cystine stones are uncommon and can form as the result of an autosomal
recessive disorder. These stones have an intermediate radiolucency and
appear as hexagonal crystals in the urine.6
2.3 MANIFESTATION OF STONES:
As stones grow on the surfaces of the renal papillae or within the
collecting system, they do not necessarily produce symptoms. Asymptomatic
stones may be discovered during the course of radiographic studies undertaken for
unrelated reasons. Stones are a common cause of isolated hematuria. Stones
become symptomatic when they enter the ureter or occlude the ureteropelvic
junction, causing pain and obstruction.7
Stone Passage
A stone can traverse the ureter without symptoms, but passage usually
produces pain and bleeding. The pain begins gradually, usually in the flank, but
increases over the next 20–60 min to become so severe that narcotics may be
needed for its control.7
The pain may remain in the flank or spread downward and anteriorly
toward the ipsilateral loin, testis, or vulva. A stone in the portion of the ureter
within the bladder wall causes frequency, urgency, and dysuria that may be
confused with urinary tract infection. The vast majority of ureteral stones <0.5 cm
in diameter pass spontaneously.7
Helical computed tomography (CT) scanning without radiocontrast
enhancement is now the standard radiologic procedure for diagnosis of
nephrolithiasis. The advantages of CT include detection of uric acid stones in
addition to the traditional radiopaque stones, no exposure to the risk of

NEPHROLITHIASIS
radiocontrast agents, and possible diagnosis of other causes of abdominal pain in a
patient suspected of having renal colic from stones.7
Ultrasound is not as sensitive as CT in detecting renal or ureteral stones.
Standard abdominal x-rays may be used to monitor patients for formation and
growth of kidney stones, as they are less expensive and provide less radiation
exposure than CT scans. Calcium, cystine, and struvite stones are all radiopaque
on standard x-rays, whereas uric acid stones are radiolucent. 7
Other Syndrome
Staghorn calculi
Struvite, cystine, and uric acid stones often grow too large to enter the
ureter. They gradually fill the renal pelvis and may extend outward through the
infundibula to the calyces themselves. Very large staghorn stones can have
surprisingly few symptoms and may lead to the eventual loss of kidney function.7
Nephrocalcinosis
Calcium stones grow on the papillae. Most break loose and cause colic,
but they may remain in place so that multiple papillary calcifications are found by
x-ray, a condition termed nephrocalcinosis. Papillary nephrocalcinosis is common
in hereditary distal renal tubular acidosis (RTA) and in other types of severe
hypercalciuria. In medullary sponge kidney disease, calcification may occur in
dilated distal collecting ducts.7
Infection
Although urinary tract infection is not a direct consequence of stone
disease, it can occur after instrumentation and surgery of the urinary tract, which

NEPHROLITHIASIS
are used frequently in the treatment of stone disease. Stone disease and urinary
tract infection can enhance their respective seriusness and interfere with
treatment.7
Obstruction of an infected kidney by a stone may lead to sepsis and
extensive damage of renal tissue, since it converts the urinary tract proximal to the
obstruction into a closed space that can become an abscess. Stones may harbor
bacteria in the stone matrix, leading to recurrent urinary tract infection, and
infection due to bacteria that have the enzyme urease can cause stones composed
of struvite.7
Activity of Stone Disease
In active disease, new stones are forming or preformed stones are
growing. Sequential radiographs are needed to document the growth or
appearance of new stones and ensure that passed stones are actually newly
formed, not pre-existent.7

NEPHROLITHIASIS
3.1 COMPOSITION OF KIDNEY STONE:
Kidney stones can be classified based on their composition. In broad
terms, stones are usually classified into calcium containing and non-calcium
containing stones.3
Calcium containing stones include calcium oxalate, hydroxyapatite and
brushite (calcium phosphate) stones. Non-calcium containing stones include uric
acid, struvite, cystine and medication related stones (Triamtrene, Silica). Calcium
oxalate stones are the most common and make up 60% of all stones.3
Table 3.1 - Stone Composition and Relative Occurrence8
Stone Composition Occurrence (%)
Calcium containing
Calcium Oxalate 60
Hydroxyapatite 20
Brushite 2
Non-calcium containing
Uric acid 7
Struvite 7
Cystine 1-3
Medications related <1

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*Occurrence (%) referenced from Pearle MS, Pak YC. Renal calculi: a practical
approach to medical evaluation and management.8
3.2 PATHOGENESIS OF STONE:
Urinary stones usually arise because of the breakdown of a delicate
balance between solubility and precipitation of salts. The kidneys must conserve
water, but they must excrete materials that have low solubility. These two
opposing requirements must be balanced during adaptation to diet, climate, and
activity.7
The problem is mitigated to some extent by the fact that urine contains
substances such as pyrophosphate, citrate, and glycoproteins that inhibit
crystallization. These protective mechanisms are less than perfect. When urine
becomes supersaturated with insoluble materials, because excretion rates are
excessive and/or because water conservation is extreme, crystals form and may
grow and aggregate to form a stone.7
Supersaturation
A solution in equilibrium with a solid phase is said to be saturated with
respect to that substance. If the concentration of a substance in a solution is above
the saturation point, the solution is said to be supersaturated and can support the
growth of crystals, and if supersaturation is excessive, new crystals can begin to
develop spontaneously.7
Excessive supersaturation is common in stone formation. Calcium,
oxalate, and phosphate form many soluble complexes among themselves and with
other substances in urine, such as citrate. As a result, their free ion activities are
below their chemical concentrations. Reduction in ligands such as citrate can

NEPHROLITHIASIS
increase ion activity and therefore supersaturation.7
Urine supersaturation can be increased by dehydration or by over
excretion of calcium, oxalate, phosphate, cystine, or uric acid. Urine pH is also
important; phosphate and uric acid are acids that dissociate readily over the
physiologic range of urine pH. Alkaline urine contains more dibasic phosphate,
favoring deposits of brushite and apatite. Below a urine pH of 5.5, uric acid
crystals predominate, whereas phosphate crystals are rare.7
The solubility of calcium oxalate is not influenced by changes in urine
pH. Measurements of supersaturation in a 24-h urine sample probably
underestimate the risk of precipitation. Transient dehydration, variation of urine
pH, and postprandial bursts of over excretion may cause spikes in
supersaturation.7
Crystallization
When urine supersaturation is excessive, crystals begin to nucleate. Once
formed, crystal nuclei will grow in size if urine is supersaturated with respect to
that crystal phase. Multiple crystals can then aggregate to form a kidney stone.7
For a kidney stone to form, crystals must be retained in the renal pelvis
long enough to grow and aggregate to a clinically significant size. Recent studies
have shown that common calcium oxalate kidney stones form as overgrowths on
apatite plaques in the renal papillae. These plaques, called Randall's plaques,
provide an excellent surface for heterogeneous nucleation of calcium oxalate
salts.7
The Randall's plaques begin in the deep medulla in the basement
membrane of the thin limb of the loop of Henle and then spread through the
interstitium to the basement membrane of the papillary urothelium.7

NEPHROLITHIASIS
If the urothelium becomes damaged, the plaque is exposed to the urine,
and calcium oxalate crystals form on the plaque, accumulating a clinically
significant mass to form a stone. Calcium phosphate stone formers, particularly
formers of brushite, do not follow this pattern.7
Inner medullary collecting ducts are plugged with apatite crystals, and
stones form as extension of those plugs. Unlike in calcium oxalate stone formers,
renal papillae are often fibrotic and deformed.7
3.3 PATHOPHYSIOLOGY:
Numerous pathophysiologic processes contribute to stone formation and
differ based on the stone composition. In the case of calcium stone formation the
pathophysiologic processes include hyperparathyroidism, increased
gastrointestinal calcium absorption, chronic diarrheal syndromes, distal renal
tubular acidosis, thiazide diuretics and primary hyperoxaluria, among many
others.3
Alternatively, uric acid stones form exclusively in acidic urine typically
with a pH≤5.5, which can result from a diet high in animal protein or diarrheal
states. In addition, both calcium containing stones and uric acid stones can form
as a result of inadequate fluid intake/low urine volume. Cystine stones form as a
result of impaired renal reabsorption of cystine due to an inherited autosomal
recessive disorder.3
Lastly, struvite stones, also known as infection stones, develop in alkaline
urine produced by certain bacterial infections of the urine (i.e., urease-producing
bacteria).3
3.4 EPIDEMOLOGY OF NEPHROLITHIASIS:

NEPHROLITHIASIS
Kidney stone disease is common with a lifetime prevalence estimated at
1% to 15%. The probability of developing kidney stones varies according to
numerous factors including age, gender, race, geographic location and body mass
index. Several studies support an increasing incidence and prevalence of stone
disease in numerous countries around the world.3
This increase is hypothesized to be mainly due to environmental factors
such as dietary habits and lifestyle, particularly an increase in the consumption of
animal protein. In addition, improvements in clinical diagnostic procedures,
specifically radiologic imaging, have likely also contributed.3
Age
Kidney stone disease is relatively uncommon before the age of 20, but the
incidence rises rapidly and peaks from 40-60 years of age and then declines from
65 years of age and beyond . The prevalence of kidney stone disease increases
with age up until the age of 70, at which point it begins to decrease.2
Gender
Typically, kidney stone disease affects males more commonly than females.
Based on studies that have examined inpatient admissions, outpatient clinic visits
and emergency department visits, men are approximately two to three times more
frequently affected than females. However, two recent studies provide evidence
that this difference is narrowing. Scales et al. (2005), demonstrated, using hospital
discharge data, that the prevalence, by gender, of treated stone disease decreased
from a 1.7:1 to a 1.3:1 male-to-female ratio, from 1997 to 2002.2
Race/Ethnicity
Several studies have reported differences in the prevalence of stone disease across
race/ethnicity. In the United States (US), studies have shown a higher prevalence

NEPHROLITHIASIS
of stone disease in whites as compared to Hispanics, Asians and African
Americans4,22. Outside of the US, individuals of Arabic, West Indian, West
Asian and Latin American origin have been shown to have a higher relative risk
for calcium stones disease relative to Caucasians, while those of East Asian and
African descent have been shown to have a lower risk.2
Geography
A higher prevalence of stone disease is typically found in hot, arid, or dry climates
such as the mountains, desert, or tropical areas, as geographic variability tends to
reflect environmental factors. Previously, it has been reported that areas of high
stone prevalence include the US, British Isles, Scandinavian and Mediterranean
countries, northern India and Pakistan, northern Australia, Central Europe,
portions of the Malay peninsula, and China.2
Body Mass Index
The association between body mass index (BMI) and risk for stone disease has
been demonstrated in two large prospective cohort studies. These two studies
revealed that the prevalent and incident risk of stone disease were directly
correlated with weight and BMI in both sexes, however the magnitude of the
association was greater in women than men.2
3.5 INCIDENCE:
Several population-based studies have demonstrated that incidence rates,
defined as the onset of an individual’s first kidney stone, vary by age, sex and
race. As with prevalence, the incidence rates are highest in the white males. For
men, the incidence begins to rise after the second decades of life and peaks
between 40 to 60 years at approximately 3 per 1000 per year and then begins to
decline.4

NEPHROLITHIASIS
For women, incidence rates seem to be higher in the late 20’s
(2.5/1000/yr) and the decreases to 1/1000/yr by age 50. This rate then appears to
remain relatively constant for the next several decades.4
3.6 CLINICAL SIGNIFICANCE :
Pain
Without overstatement, the agonizing pain in the flank and lower abdomen
from kidney stone is the most often compared with the pain of normal labour and
delivery. However, kidney stone colicky pain usually appears suddenly, without
any warning sign, and cripples the patient owing to intense sharp, stabbing and
shooting pain. Besides, a victim of a kidney stone attack must endure pain for
days to weeks.9
Kidney stones can also cause nausea, vomiting, fever in addition to blood
in the urine, pain with urination, and probably other symptoms of infection as
well.9
Parenchymal Kidney Injury
In essence, kidney stones are not merely a mechanical disease or an
extreme painful condition, but they can cause parenchymal damage and reduce
kidney function by different mechanisms including direct kidney tissue injury or
indirectly by urinary obstruction, and infection.4
Iatrogenic renal injury by procedures needed to remove stones sometimes
cause serious problem. Evidence is accumulating that nephrolithiasis is associated
with decreased renal function. Two large studies reported that stone formers have
slightly, but significantly, lower glomerular filtration rates and creatinine
clearances than those who are not stone formers.4

NEPHROLITHIASIS
Nephrolithiasis and shockwave lithotripsy may increase the risk of chronic
kidney disease and hypertension. The relative contributions of nephrolithiasis, its
treatment and its underlying predispositions to these conditions have not studied
yet. Fortunately, most patient with renal colic are not at imminent risk of renal
failure since the stone does not completely obstruct the ureter. Furthermore, they
are likely to pass the stone so that the partial obstruction is short lived.4

NEPHROLITHIASIS
4.1 CAUSES:
Kidney stones may form when the normal balance of water, salts, minerals,
and other substances found in urine changes. How this balance changes
determines the type of kidney stone you have. Most kidney stones are calcium
type—they form when the calcium levels in your urine changes.
Things that change your urine balance include:
 Not drinking enough water. When you don't drink enough water, the salts,
minerals, and other substances in the urine can stick together and form a
stone. This is the most common cause of kidney stones.
 Medical conditions. Many medical conditions can affect the normal
balance and cause stones to form. Examples include gout and
inflammatory bowel disease, such as Crohn's disease.
Table 4.1 - Major Causes of Renal Stones7
Stone Type
and
Causes
Percent
of all
Stones
Percent
Occurre
nce of
Specific
Causes
Ratio of
Males to
Females
Etiology Diagnosis Treatment
Calcium
stones
75–85 2:1 to 3:1
Idiopathic
hypercalciu
ria
50–55 2:1 ?
Heredita
ry
Normocal
cemia,
unexplain
ed
hypercalci
Low-sodium,
low-protein
diet; thiazide
diuretics

NEPHROLITHIASIS
Stone Type
and
Causes
Percent
of all
Stones
Percent
Occurre
nce of
Specific
Causes
Ratio of
Males to
Females
uriab
Hyperuric
osuria
20 4:1 Diet Urine uric
acid >750
mg per 24
h
(women),
>800 mg
per 24 h
(men)
Allopurinol
or low-
purine diet
Primary
hyperparath
yroidism
3–5 3:10 Neoplasi
a
Hypercalc
emia with
nonsuppre
ssed
parathyroi
d
hormone
Surgery
Distal
renal
tubular
acidosis
Rare 1:1 Heredita
ry or
acquired
Hyperchlo
remic
acidosis,
minimum
urine pH
>5.5
Alkali
replacement
Dietary
hyperoxalur
ia
10–30 1:1 High-
oxalate
diet or
low-
calcium
diet
Urine
oxalate
>40 mg
per 24 h
Low-oxalate,
normal-
calcium diet
Enteric
hyperoxalur
ia
1–2 1:1 Bowel
surgery
Urine
oxalate
>75 mg
per 24 h
Low-oxalate
diet and oral
calcium pills
Primary
hyperoxalur
ia
Rare 1:1 Heredita
ry
Urine
oxalate
and
glycolic
or l-
glyceric
acid
Fluids,
pyridoxine,
citrate and
neutral
phosphate

NEPHROLITHIASIS
Stone Type
and
Causes
Percent
of all
Stones
Percent
Occurre
nce of
Specific
Causes
Ratio of
Males to
Females
increased
Hypocitrat
uria
20–40 1:1 to 2:1 ?
Heredita
ry, diet
Urine
citrate
<320 mg
per 24 h
Alkali
supplements
Idiopathic
stone
disease
20 2:1 Unknow
n
None of
the above
present
Oral
phosphate,
fluids
Uric acid
stones
5–10
Metabolic
syndrome
30 1:1 Diet Glucose
intoleranc
e, obesity,
hyperlipid
emia
Alkali and
allopurinol if
daily urine
uric acid
>1000 mg
Gout 30 3:1 to 4:1 Heredita
ry
Clinical
diagnosis
Alkali and
allopurinol
Idiopathic 30 1:1 ?
Heredita
ry
Uric acid
stones, no
gout
Alkali and
allopurinol if
daily urine
uric acid
>1000 mg
Dehydrati
on
? 1:1 Intestina
l, habit
History,
intestinal
fluid loss
Alkali,
fluids,
reversal of
cause
Lesch-
Nyhan
syndrome
Rare Males
only
Heredita
ry
Reduced
hypoxanth
ine-
guanine
phosphori
bosyltrans
ferase
level
Allopurinol
Cystine
stones
1 1:1 Heredita
ry
Stone
type;
elevated
cystine
excretion
Massive
fluids, alkali,
D-
penicillamin
e if needed
Struvite 5 1:3 Infection Stone type Antimicrobia

NEPHROLITHIASIS
Stone Type
and
Causes
Percent
of all
Stones
Percent
Occurre
nce of
Specific
Causes
Ratio of
Males to
Females
stones l agents &
judicious
surgery
4.2 SYMPTOMS:
The symptoms of kidney stones include:10
 Waves of sharp pain that start in your back and side, and move towards the
groin or testicles.
 Inability to find a comfortable position, people with kidney stones often
pace up and down.
 Nausea and vomiting with ongoing pain.
 Blood in the urine.
 The frequent urge to urinate
 Some very small stones can be either asymptomatic or only cause mild
symptoms.
Sometimes an infection is also present and may cause these additional symptoms:
 Fever and chills.10
 Painful urination.10
 Cloudy or unpleasant-smelling urine.10

NEPHROLITHIASIS
A kidney stone may not cause symptoms until it moves around within your
kidney or passes into your ureter - the tube connecting the kidney and bladder. At
that point, you may experience these signs and symptoms:11
 Severe pain in the side and back, below the ribs
 Pain that spreads to the lower abdomen and groin
 Pain that comes in waves and fluctuates in intensity
 Pain on urination
 Pink, red or brown urine
 Cloudy or foul-smelling urine
 Nausea and vomiting
 Persistent need to urinate
 Urinating more often than usual
 Fever and chills if an infection is present
 Urinating small amounts of urine
Pain caused by a kidney stone may change -for instance, shifting to a different
location or increasing in intensity -as the stone moves through your urinary tract.11

NEPHROLITHIASIS
5.1 DIAGNOSIS:
The diagnosis of nephrolithiasis is often made on the basis of clinical
symptoms alone, although confirmatory tests are usually performed.
Clinical Presentation:
Clinical presentation is with costovertebral angle or flank pain which can
radiate to the scrotum or labia. Hematuria with nondysmorphic RBCs may be
noted. Oliguria and RTF are uncommon but can result if there is bilateral
obstruction or if a solitary functioning kidney is affected.6
Examination in patients with nephrolithiasis includes the following findings:
 Dramatic costovertebral angle tenderness; pain can move to upper/lower
abdominal quadrant with migration of ureteral stone
 Generally unremarkable abdominal evaluation: Possibly hypoactive bowel
sounds; usually absence of peritoneal signs; possibly painful testicles but
normal-appearing
 Constant body positional movements (eg, writhing, pacing)
 Tachycardia

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 Hypertension
 Microscopic hematuria
Diagnostic Testing:
Laboratories
 Metabolic evaluation should include urine culture, pH, and microscopy.
Serum calcium, phosphate, parathyroid hormones, and uric acid levels
complement routine studies. Urine should be strained and passed stones
analyzed for composition.6
 Recurrent stone formers should undergo a more extensive evaluation, with
24-hour urine collections for calcium, phosphate, uric acid, citrate, oxalate,
and cystine. This collection should not be done during an acute episode in
a hospitalized patient but rather reserved for when the patient is on his or
her normal outpatient diet.6
Other laboratory tests that may be helpful include the following:
 CBC with differential in febrile patients
 Serum electrolyte assessment in vomiting patients (eg, sodium, potassium,
calcium, PTH, phosphorus)
 Serum and urinary pH level: May provide insight regarding patient’s renal
function and type of calculus (eg, calcium oxalate, uric acid, cystine),
respectively
 Microscopic urinalysis
 24-Hour urine profil
Imaging

NEPHROLITHIASIS
A plain abdominal film may reveal the radiopaque stones composed of
calcium salts, struvite, or cystine. However, noncontrast CT scanning has replaced
other imaging modalities as the study of choice is for suspected nephrolithiasis.6
The European Association of Urology recommends the following laboratory tests
in all patients with an acute stone episode:
 Urinary sediment/dipstick test: To demonstrate blood cells, with a test for
bacteriuria (nitrite) and urine culture in case of a positive reaction
 Serum creatinine level: To measure renal function
The following imaging studies are used in the evaluation of nephrolithiasis:
 Noncontrast abdominopelvic CT scan: The imaging modality of choice for
assessment of urinary tract disease, especially acute renal colic.
 Renal ultrasonography: To determine presence of a renal stone and the
presence of hydronephrosis or ureteral dilation; used alone or in
combination with plain abdominal radiography.
 Plain abdominal radiograph (flat plate or KUB): To assess total stone
burden, as well as size, shape, composition, location of urinary calculi;
often used in conjunction with renal ultrasonography or CT scanning.
 IVP (urography) (historically, the criterion standard): For clear
visualization of entire urinary system, identification of specific
problematic stone among many pelvic calcifications, demonstration of
affected and contralateral kidney function.
 Plain renal tomography: For monitoring a difficult-to-observe stone after
therapy, clarifying stones not clearly detected or identified with other

NEPHROLITHIASIS
studies, finding small renal calculi, and determining number of renal
calculi present before instituting a stone-prevention program.
 Retrograde pyelography: Most precise imaging method for determining
the anatomy of the ureter and renal pelvis; for making definitive diagnosis
of any ureteral calculus.
 Nuclear renal scanning: To objectively measure differential renal function,
especially in a dilated system for which the degree of obstruction is in
question; reasonable study in pregnant patients, in whom radiation
exposure must be limited.
5.2 MANAGEMENT:
Supportive care and pharmacotherapy:
Medical treatment of nephrolithiasis involves supportive care and
administration of agents, such as the following:2
 IV hydration
 Nonnarcotic analgesics (eg, APAP)
 PO/IV narcotic analgesics (eg, codeine, butorphanol, morphine sulphate,
oxycodone/APAP, hydrocodone/APAP, meperidine, nalbuphine)
 NSAIDS (eg, ketorolac, ketorolac intranasal, ibuprofen)
 Uricosuric agents (eg, allopurinol)
 Antiemetics (eg, metoclopramide)
 Antidiuretics (eg, DDAVP)
 Antibiotics (eg, ampicillin, gentamicin, ticarcillin/clavulanic acid,
ciprofloxacin, levofloxacin, ofloxacin)

NEPHROLITHIASIS
 Alkalinizing agents (eg, potassium citrate, sodium bicarbonate): For uric
acid and cysteine calculi
 Corticosteroids (eg, prednisone, prednisolone)
 Calcium channel blockers [CCB] (eg, nifedipine)
 Alpha blockers (eg, tamsulosin, terazosin)
Surgical Option:
Stones that are 7 mm and larger are unlikely to pass spontaneously and
require some type of surgical procedure, such as the following:4
 Stent placement
 Percutaneous nephrostomy
 Extracorporeal shockwave lithotripsy
 Ureteroscopy
 Percutaneous nephrostolithotomy
 Open nephrostomy
5.3 EVALUATION & TREATMENT OF NEPHROLITHIASIS:
Most patients with nephrolithiasis have remediable metabolic disorders
that cause stones and can be detected by chemical analyses of serum and urine.
Adults with recurrent kidney stones and children with even a single kidney stone
should be evaluated.7
A practical outpatient evaluation consists of two 24-h urine collections,
with a corresponding blood sample; measurements of serum and urine calcium,

NEPHROLITHIASIS
uric acid, electrolytes, and creatinine, along with urine pH, volume, oxalate, and
citrate should be made. Since stone risks vary with diet, activity, and environment,
at least one urine collection should be made on a weekend when the patient is at
home and another on a workday.7
When possible, the composition of kidney stones should be determined
because treatment depends on stone type (Table 4-1). No matter what disorders
are found, every patient should be counselled to avoid dehydration and drink
copious amounts of water. The efficacy of high fluid intake was confirmed in a
prospective study of first-time stone formers. Increasing urine volume to 2.5 L per
day resulted in a 50% reduction of stone recurrence compared with the control
group.7
5.4 TREATMENT OF NEPHROLITHIASIS:
The management of stones already present in the kidneys or urinary tract
requires a combined medical and surgical approach. The specific treatment
depends on the location of the stone, the extent of obstruction, the nature of the
stone, the function of the affected and unaffected kidneys, the presence or absence
of urinary tract infection, the progress of stone passage, and the risks of operation
or anaesthesia in light of the clinical state of the patient.7
Medical therapy can enhance passage of ureteral stones. Oral 1-adrenergic
blockers relax ureteral muscle and have been shown to reduce time to stone
passage and the need for surgical removal of small stones. Severe obstruction,
infection, intractable pain, and serious bleeding are indications for removal of a
stone.7
There are now three alternatives for stone removal. Extracorporeal
lithotripsy causes the in situ fragmentation of stones in the kidney, renal pelvis, or

NEPHROLITHIASIS
ureter by exposing them to shock waves.7
After multiple shock waves, most stones are reduced to powder that moves
through the ureter into the bladder. Percutaneous nephrolithotomy requires the
passage of a nephroscope into the renal pelvis through a small incision in the
flank. Stones are then disrupted by a small ultrasound transducer or holmium
laser. The third method is ureteroscopy with stone disruption using a holmium
laser. Ureteroscopy generally is used for stones in the ureter, but some surgeons
are now using ureteroscopy for stones in the renal pelvis as well.7
 General treatment of nephrolithiasis is with hydration to increase urine
output and with analgesia (Ketorolac or narcotics such as meperidine). If
the stone is obstructing outflow or is accompanied by infection, removal is
indicated with urgent urologic or radiologic intervention.6
 After passage of a stone, treatment is directed at prevention of recurrent
stone formation. Regardless of stone type, the foundation of therapy is
maintenance of high urine output (2 to 3 L/d) with oral hydration and a
low-salt diet (<2 g/d).6
 For calcium oxalate stones, a low-calcium diet is no longer recommended
given the risks of osteoporosis. A normal-calcium diet with no added
calcium supplements is now in favour. Patients should avoid oxalate-rich
foods (e.g., spinach, rhubarb). Thiazide diuretics may reduce calciuria and
potassium citrate may be added in patients with hypocitraturia.6
 Uric acid stones can be prevented or reduced in size by allopurinol. A low-
protein diet may be helpful as can urinary alkalinization with citrate,
bicarbonate, or acetazolamide.6

NEPHROLITHIASIS
 Strucite calculi frequently require surgical intervenation for their removal.
Extracorporeal shock-wave lihotripsy can be used as adjunctive therapy.
Aggressive antibiotic treatment is indicated if monthly urine cultures
become positive.6
 Cystine stones require extensive urinary alkalinization to a pH of 7 o 7.5 to
induce solubility. D-penicillamine and mercaptopropiomylglycine can
further increase solubility through breakage and exchange of disulfide
bonds.6
5.5 CURRENT INDIACATION OF NEPHROLITHIASIS:
Many patients with renal or ureteral calculi will not require intervention.
Small (<5mm), non-obstructive, asymptomatic renal calculi generally do not
require prophylactic treatment. Exceptions to this include paediatric patients,
patients with a solitary kidney, patients in high-risk professions (e.g., pilots), and
women considering pregnancy. For ureteral calculi, if the width is ≤5mm then
approximately 68% will pass spontaneously, and as such conservative
management should also be considered in these patients.12
5.6 DETERMINENTS OF TREATMENT:
A number of factors must be considered to determine the optimal
treatment for patients with renal or ureteral calculi. These factors may be grouped
into four broad categories: stone factors (location, size, composition, obstruction
and duration of presence), clinical factors (symptom severity, patient’s
expectations, associated infection, obesity, coagulopathy, hypertension and
solitary kidney), anatomic factors (horseshoe kidney, ureteropelvic junction

NEPHROLITHIASIS
obstruction, renal ectopia) and technical factors (available equipment, expertise,
cost).2
Surgical Management:
Three main modalities are presently utilized in an attempt to achieve the
goal of maximal stone clearance with minimal morbidity to the patient. These are
extracorporeal shockwave lithotripsy (SWL), URS and percutaneous
nephrolithotomy (PCNL).2
Each modality along with its indications for use is described below.
Treatment outcomes for these modalities are typically reported by two different
terms: stone-free rate and success rate. Stone free means the absence of any
radiological evidence of stone, whereas success includes patients who are stone
free, as well as those with clinically insignificant residual fragments. The lack of
consensus regarding the definition of clinically insignificant residual fragments
makes comparisons across studies with this definition difficult. As such, for
consistency only the stone-free rates have been reported below in describing each
of the three modalities.2
Extracorporeal Shockwave Lithotripsy (E.S. Lithotripsy):
SWL involves the generation of relatively weak, non-intrusive
shockwaves externally that are transmitted through the body. The shockwaves
build to sufficient strength only at the target (i.e., the stone) where they generate
enough force to fragment the stone.2
SWL is an outpatient procedure performed under conscious sedation, and
doesn’t require a general aesthetic. It represents the least invasive of three surgical
options for the management of kidney stone disease, but also the least effective at
achieving stone-free status, in certain situations.2

NEPHROLITHIASIS
5.7 INDICATION FOR E. S. LITHOTRIPSY:
Summary of Surgical Management:
Considering all of the above, SWL is still believed to be the most
commonly used and primary treatment modality for management of
uncomplicated kidney stones. The minimally-invasive nature, ease of performance
and low perceived morbidity contribute to the frequent use of this modality.2
The most important drawback is the need for repeat treatment in a
substantial proportion of patients. URS offers patients a minimally invasive
approach with an equal or greater likelihood of achieving stone-free status
compared to SWL, but with fewer treatments needed.2
This comes at the expense of needing a general aesthetic and the
possibility of greater post-treatment morbidity. Lastly, PCNL the most invasive
treatment modality is reserved for the largest and most complex renal stones,
where the high success rate balances the more significant procedure related
morbidity.2
Non Surgical Management:
Conservative/Expectant
As previously mentioned, many patients with renal or ureteral calculi will
not require intervention. In the case of small (<5mm), non-obstructive,
asymptomatic renal stones or ureteral stones ≤5mm conservative management
should be considered.2
Patients undergoing conservative management for renal stones require
regular follow-up, as based on one study 77% of asymptomatic renal stones will
progress and 26% of patient will ultimately require surgical intervention. For

NEPHROLITHIASIS
ureteral stones if significant progress or passage of the stone has not occurred
within 4 weeks of observation intervention is usually required.2
Medical Expulsive Therapy
Medical expulsive therapy (MET) is the use of pharmacologic agents to
promote ureteral stone passage by relaxing ureteral smooth muscle. Both α
adrenergic blockers and calcium-channel blockers have been shown to increase
the likelihood of spontaneous stone passage.2
A recent meta-analysis found that α-adrenergic blockers were superior to
the calcium-channel blocker Nifedipine and as such may be the preferred agent for
MET. MET is commonly utilized now in patients who undergo
conservative/expectant management for ureteric calculi.2
6.1 RISK FACTORS :
Family History:
There are many major factors which have been linked to the development
of kidney stone disease. However, some of these risk factors are modifiable but
some are not modifiable. The risk of becoming a stone former is more than 2.5
times greater in individuals who have a family history of stone disease. This
increased risk has been attributed both to genetic, environmental, and dietary
factors.13
Systemic Disorders:
There are many systemic disorders, which have been linked to kidney
stone formation including; primary hyperparathyroidism, renal tubular acidosis
and Crohn’s disease. Interestingly, primary hyperparathyroidism may be found in
5% of stone formers. Increased body mass index (BMI > 30 kg/m2) and weight
gain are now recognized risked factors for the development of kidney stones.14

NEPHROLITHIASIS
In addition, a history of gout increases the likelihood of forming kidney
stones; both uric acid and calcium oxalate (50% more likely to have a history of
stones). Moreover, a history of type II diabetes mellitus increases the risk of stone
formation by 30 to 50% in women but not in men.14
Environmental Factors:
Some environmental factors have been implicated for example:
working in a hot environment, lack of access to water or lower fluid intake all
have been shown to predispose to rental stone formation.15
Dietary Factors:
Some dietary factors have been linked to kidney stones formation.
Nutrients that have been implicated include calcium, animal protein, oxalate,
sodium, sucrose, magnesium, and potassium.13
 Calcium: Although high dietary calcium had been strongly suspected of
raising the risk of stone disease in the past, a recent cohort study of more
than 50,000 male health professionals aged 40 to 75 years, has shown that
very low calcium intake can actually predispose to kidney stone formation
as well.17,18
 Oxalate: Up to one-third of patients with calcium oxalate nephrolithiasis
may have increased absorption of dietary oxalate, and in some cases a
deficiency of oxalate degradation by the Bacterium Oxalobacter
formigenes in the gut could be the culprit.19

NEPHROLITHIASIS
 Other Nutrients: Several other nutrients have been reported to be
implicated in the development of stone formation, including; high animal
protein intake, high sodium intake, high sucrose intake, low potassium
intake and low calcium intake. Furthermore, potassium supplementation
decreases calcium excretion and many potassium-rich foods increase
urinary citrate due to their alkali content.13
Recently, phytate (the principal storage form of phosphorus in
many plants) was also found to reduce the likelihood of stone formation in
younger women substantially. Magnesium can make complexes with
oxalate, thereby potentially reduces oxalate absorption in the
gastrointestinal tract and decreases calcium oxalate supersaturation in the
urine. High vitamin C intake and vitamin B6 deficiency could increase the
risk of calcium oxalate stone formation as well. Vitamin B6 deficiency
increases oxalate production, whereas vitamin C can be metabolized to
oxalate, and both can cause hyperoxuluria.16
 Fluid Intake and Beverages: Observational studies and a randomized
controlled trial in almost all types of kidney stones have demonstrated,
when the urine output is less than 1 L/day, the risk of stone formation is
higher than those with higher urine output. On the other hand, some
beverages have been shown to increase the risk of stone formation (for
instance grapefruit juice and soft drinks). Grapefruit juice intake has been
associated with a 40% higher risk of stone formation. Other studies
suggested an increased risk of kidney stone formation with soda
consumption.20,21

NEPHROLITHIASIS
 Urinary Factors: Some urinary factors have been suggested as the risk
factors for renal stones formation namely: hypercalciuria, hyperoxaluria
and hyperuricosuria and hypocitraturia, have been associated with
increased risk of stone formation. This will be discussed in detail in the
urinary composition and stone formation sections.13
RESOURCES & REFERENCES:
1. http://en.wikipedia.org/wiki/Urinary_system
2. The Surgical Management of Kidney Stone Disease in the Province of
Ontario: A Population Based Time Series Analysis By Michael Ordon,
2013.
3. Pearle MS, Lotan, Y. Urinary Lithiasis: Etiology, Epidemiology, and
Pathogeneis. In: Wein AJ, Kavoussi, L.R., Novick, A.C., Partin, A.W.,
Peters, C.A., ed. Campbell-‐Walsh Urology. Vol 2. 9th ed. Philadelphia:
Saunders Elsevier; 2007.
4. Urinary Composition and Stone Formation, By Mohammad Ali Shafiee,
2010.

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5. Monk RD. Proportion of stone types. Clinical approach to adults with
nephrolithiasis. Semin Nephrol. 1996; 16:375-88.
6. Foster C, Mistry NF, Peddi PF, Sharma S. The Washington Manual of
Medical Theraputics. ISBN-13:978-81-8473-397-6.
7. Longo, Fauci, Kasper, Hauser, Jameson, Loscalzo. Harrison’s Principles
of Internal Medicine. ISBN- 978-0-07-177509-0.
8. Pearle MSP, Y.C. Renal calculi: a practical approach to medical
evaluation and management. In: Andreucci VEF, L.G., ed. International
yearbook of nephrology. New York: Oxford University Press; 1996:69.
9. National Kidney and Urologic Diseases Information Clearinghouse
(NIKUDIC) website:
http://kidney.niddk.nih.gov/Kudiseases/pubs/stonesadults
10. http://www.webmd.boots.com/digestive-disorders/kidney-stones
11. http://www.mayoclinic.org/diseases-conditions/kidney-
stones/basics/symptoms/con-20024829.
12. Matlaga BR, Lingeman, J.E. Surgical Management of Upper Urinary Tract
Calculi. In: Wein AJ, Kavoussi, L. R., Novick, A. C., Partin, A.W., and
Peters, C. A., ed. Campbell- ‐Walsh Urology. Vol 2. 10th ed. Philadelphia:
Elsevier Saunders; 2012:1357--‐1410.
13. Curhan GC. Epidemiology of stone disease. Urol Clin North Am. 2007
Aug; 34(3):287-93.
14. Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of
nephrolithiasis. Kidney Int 2005; 68(3):1230–5.

NEPHROLITHIASIS
15. Atan L, Andreoni C, Ortiz V, Silva EK, Pitta R, Atan F, et al. High kidney
stone risk in men working in steel industry at hot temperatures. Urology
2005; 65(5):858-61.
16. Curhan GC, Willett WC, Speizer FE, Stampefer MJ. Intake of Vitamins
B6 and C and the risk of kidney stones in women. J Am Soc Nephrol.
1999; 10:840-845.
17. Curhan G, Willett W, Speizer F, Spiegelman D, Stampfer M. Comparison
of dietary calcium with supplemental calcium and other nutrients as
factors affecting the risk for kidney stones in women. Ann Intern Med
1997; 126:497–504.
18. Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the
risk of incident kidney stones in younger women (Nurses’ Health Study
II). Arch Intern Med 2004; 164:885–91.
19. Holmes RP, Assimos DG. The impact of dietary oxalate on kidney stone
formation. Urol Res 2004; 32 (5):311–6.
20. Curhan GC, Willett WC, Rimm EB, Spiegelman D, Stampfer MJ.
Prospective study of beverage use and the risk of kidney stones. Am J
Epidemiol 1996; 143(3):240–7.
21. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Beverage use and risk
for kidney stones in women. Ann Intern Med 1998; 128(7):534–40.
22. http://www.mucmn.com/kidney-stones/causes-and-symptoms/urinary-
tract-diagram/

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