Duke Internal Medicine Residency Curriculum
Kidney Stones
Wael AlJaroudi, MD
Editor: Amy Shaheen, MD, Assistant Professor
of Clinical Medicine
Duke University Medical Center
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Epidemiology
Epidemiology
•
Kidney stones (also called Nephrolithiasis or urolithiasis) are common
health problems
•
The prevalence of stone-forming disease rose from 3.8 percent in the
late 1970s to 5.2 percent in the late 1980s and early 1990s.
•
It is more common in men > women, white > African American
•
It is estimated that 12 % of men and 5 % of women will develop
symptomatic kidney stones by the age of 70
•
It has been estimated that for patients who have already had a stone,
the likelihood of forming a second stone is about 15 percent at one year,
35 to 40 percent at 5 years, and 80 percent at 10 years.
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Pathogenesis
Pathogenesis
For a stone to form, 3 processes occur:
1. Supersaturation: Cations and anions are charged soluble
molecules such as calcium and oxalate. However, at a specific
concentration and pH, the equilibrium state of these molecules
reach a critical point called supersaturation. Beyond this point,
these molecules cannot remain dissolved and will become
insoluble and precipitate
2. Nidus: A nidus represents a focus where crystals start
precipitating.
3. Aggregation: Aggregation is the process where precipitating
crystals accumulate on each others and form a bigger crystal in
a geometrical and organized fashion.
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Type of kidney stones
Type of kidney stones
1.Calcium stones account for 80 % of all kidney stones
-Calcium oxalate (monohydrate and dihydrate) are the
most common
-Calcium phosphate
2.Uric acid stones
3.Struvite stones (composed of magnesium, ammonium, calcium and
phosphate)
4.Cystine stones
5.Indinavir stones (limited to HIV-infected patients)
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Calcium Stones
Calcium stones
-Calcium stones are the most common
type of kidney stones
-Citrate is the most powerful inhibitor of Calcium oxalate stone formation
-Hyperoxaluria is the most important factor in the formation of calcium
oxalate stone
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Calcium Stones (cont.)
-Calcium phosphate stones are the second
most common calcium stones
after calcium oxalate: they are more common in patients with distal
RTA1, patients on acetozolamide ( alkaline pH which leads to CaPO4
precipitation).
-Calcium stones precipitate in alkaline urine.
-They are radio-opaque and are seen on xray films
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Calcium stones: Risk factors
Calcium stones:
Risk factors:
1.Low fluid intake/ Low urine Volume: Increases the concentration of
lithogenic factors in the urine.
2. Hypercalciuria: occurs with hypervitaminosis D, distal RTA 1, sarcoidosis,
primary hyperpathyroidism, excessive calcium intake.
3. Hypocitraturia: Occurs in patients with RTA 1 or chronic metabolic
acidosis. Citrate chelates calcium and prevent stone formation. Citrate is
the most powerful inhibitor of calcium stone formation
4. Hyperuricosuria: Occurs with high protein intake resulting in high uric
acid production/excretion. Uric acid act as a nidus for crystal formation
5. History of prior calcium stones
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Calcium stones: Risk factors (cont.)
Risk factors for calcium stones (continued)
6. Hyperoxaluria: Most important factor in calcium oxalate formation. It is
present in mildly elevated amount in up to 40 percent of male and 15
percent of female stone formers. Marked hyperoxaluria is usually
associated with inflammatory bowel disease and/or malabsorption: free
bile acid chelates calcium in the GI tract allowing more oxalate
absorption and hence urinary excretion.
High Vit C consumption, ethylene glycol are also associated with
hyperoxaluria
7. Medullary sponge kidney: Accounts for 10-20% of calcium stone formers
8. RTA type 1: It is associated with hypocitraturia and hypercalciuria and
alkaline pH
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Calcium stones: Risk factors (cont.)
Risk factors for calcium stones (continued)
9. Primary hyperparathyroidism: Associated with hypercalciuria
10. Gout: associated with hyperuricosuria which acts as a nidus
11. HTN: associated with hyperuricosuria
12.High animal protein: results in high uric acid production and hence
excretion
13. High NaCl intake: leads to increased urinary calcium excretion
14. Low calcium intake: Results in less oxalate chelation in the GI tract,
more oxalate absorption and hence hyperoxaluria
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Uric Acid Stone
Uric Acid Stone:
-Uric acid stones precipitate
in acidic urine, mainly with a pH <5.5
-They are radiolucent and do not show on a regular xray film
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Uric Acid Stone (cont.)
Uric acid Stone
Risk factors:
1.Hyperuricosuria
- 10-20 % of gout patients overproduce uric acid leading to increased
excretion
-Inherited enzyme defects leading to purine overproduction (eg.
Lych Nyhan syndrome)
-Urate overproduction: (myeloproliferative disorders, obesity,
lymphoma,hemolysis, glycogen storage disease, ethanol, vit b12
deficiency, chemotherapy..)
2. Chronic diarrhea: Results in bicarbonate loss, acidic concentrated urine
which precipitates uric acid stone
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Struvite Stones
Struvite Stones
-Struvite stones occur in patients with chronic urinary infections due to a urease
producing organism
-The urease enzyme splits urea into ammonium.
-Ammonium binds with phosphorus, magnesium and calcium and form the struvite
stone
-Urease producing bacteria include proteus (most common), pseudomona, yeast, and
Staph (PPYS = piss)
-They are rapid forming and often cause staghorn calculi
-They precipitate faster in alkaline urine
-They are less radio-opaque then calcium stones
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Cystine Stones
Cystine Stones:
-Cystine stones develop in patients with cystinuria,
an autosomal recessif
disease associated with increased excretion of cystine.
-They tend to recur very frequently and often can cause urinary obstrcution
and compromise kidney function
-Heterozygote/carriers of the disease do not form stones
-They precipitate faster in acidic urine
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Clinical Symptoms
• Clinical symptoms:
-Kidney stones often are asymptomatic
-Usually, the first symptom of a kidney stone is pain. Pain occurs when
there is obstruction of the urinary tract and spasm. Pain is colicky,
waxes on/off, sharp, often associated with nausea/vomiting. Its location
varies with the location of the stone and can migrate to the suprapubic
area and groin as the stone moves down the ureter.
-Microscopic/macroscopic hematuria
-Dysuria
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Evaluation of Kidney stones
Evaluation of kidney stones
-Workup on initial kidney stone includes:
calcium level (r/o
hyperparathyroidism, hypervitaminosis D), phopsphorus, electrolytes
such as bicarbonate (r/o RTA type 1), U/A with culture, and an imaging
modality. Although IVP has been the standard, current data shows that
CT renal protocol is as sensitive and specific and does not require
contrast.
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Evaluation of kidney stones
Evaluation of kidney stones (continued)
-Urinary
pH. A pH >7 (alkaline) is usually associated with calcium
phosphorus stones and struvite stones.
A pH <5.5 (acidic) is usually associated with cystine and uric
acid stones
-Crystal morphology is helpful in determining the type of stone
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Calcium oxalate crystals
Calcium oxalate crystals:urine sediment shows envelop
shape dihydrate stone (small arrow), and dumbbell shape
monohydrate crystals (long arrow) which could also have
a needle appearance.
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Uric Acid Stone
Uric acid stone: Urine sediment shows pleomorphic
Rhombic plates or diamond shape crystals
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Struvite Stone
Struvite stone: Urine sediment shows “coffin lid” crystals
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Cystine Crystal
Cystine crystal: Urine sediment shows hexagnal
Crystals which are pathognomonic of cystine stone
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Recurrent kidney stones
For recurrent kidney stones, additional work up includes checking for 24 hr
urine volume, cystine, calcium, Na, citrate, urea, uric acid, and
creatinine excretion.
•
Men: Calcium <300 (7.5 mmol/day)/ Female: <250 (6.25 mmol/day)
Men: Uric acid <800 (4.8 mmol/day)/ Female: <750 (4.5 mmol/day)
Men and Female: Oxalate <45 (0.5 mmol/day)
•
The standard lower limit of normal for citrate is 320 mg for men and
women.
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Imaging Modality
• Imaging modality
-IVP used to be the gold standard.
-Non-contrast-enhanced helical CT scan has proven to be accurate in
detecting of kidney stones
-It is important to appreciate that ureteral dilatation without a stone on
radiologic examination could represent recent passage of the stone
- Renal ultrasonography is an alternative in pregnant women, but this
cannot localize ureteral stones, which can often be detected by
transvaginal ultrasonography
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Imaging Modality (cont.)
Imaging Modality:
- The stone characteristics on CT scan may suggest the type of stone that
is present:
-
Although magnesium ammonium phosphate and cystine stones are often
radiopaque, they are not as dense as stones comprised of calcium
oxalate or calcium phosphate.
-
Calcium phosphate stones are more likely found in the presence of
nephrocalcinosis, which is suggestive of renal tubular acidosis. Bilateral
calcifications at the corticomedullary junction is typically seen in
medullary sponge kidney and in this setting calcium oxalate or calcium
phosphate stones may be found
-
The presence of staghorn calculi favors struvite stones
-
Uric acid stones are radio-lucent on xray but visible on CT scan
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Treatment
• Treatment
A. Non obstructing stone
Calcium stone:
-Increase fluid intake to 2 L per day. Decrease
dietary protein and Na.
-If urinary calcium is elevated, evaluate for high Vit D, hyperparathyroidism
and treat accordingly
Thiazide diuretic decrease hypercalciuria
-If hypocitraturia is present, supplement with potassium citrate. If the pH is
>6, citrate supplementation should be avoided because of the increased
pH alkalanization and higher risk of stone precipitation
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Treatment (cont.)
• Treatment
A. Medical management
-If hyperoxaluria is present, the approach to intervention depends
on the diet and the urine calcium. If the urine calcium is not
high, increasing dietary calcium should be considered along with
a low oxalate diet.
Food with high oxalate content include:
• beets
rhubarb
• chocolate
spinach
• coffee
strawberries
• cola
tea
• nuts
wheat bran
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Treatment: Medical Management (cont.)
• Treatment
A. Medical management (continued)
-If hyperuricosuria is present, lifestyle modification with the aim of reducing
uric acid production (i.e. decreased purine intake and weight loss)
should be implemented.
However, if the urine pH is 6 or higher, the high urine uric acid may not
be playing a role as it will stay in solution.
Allopurinol can help decrease uric acid in patients who are
overproducers.
-Do not decrease calcium intake; this will increases oxaluria
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Treatment: Medical Management (cont.)
Medical management (continued)
Uric acid stone
-Allopurinol
+/- urine alkalinization
-Low purine diet
-High fluid intake
-Avoid urine alkalinization if there is superimposed hypercalciuria
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Treatment: Medical Management (cont.)
Medical management (continued)
Struvite stone
-Acidification of the urine
-Antibiotics
-Removal of the stone
-If stones cannot be removed, acetohydroxamic acid (AHA) can be used
with long-term antibiotic drugs to prevent the infection that leads to
stone growth.
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Treatment: Medical Management (cont.)
Medical management (continued)
Cystine stone
-Increased fluid intake
-Alkalinization of the urine
-Penicillamine forms soluble complexes with cystine but not well tolerated
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Surgical Treatment
B. Surgical treatment
-Surgery should be reserved as an option for cases where other approaches have
failed. Surgery may be needed to remove a kidney stone if it:
•
does not pass after a reasonable period of time and causes constant pain
•
is too large to pass on its own or is caught in a difficult place
•
blocks the flow of urine
•
causes ongoing urinary tract infection
•
damages kidney tissue or causes constant bleeding
•
has grown larger (as seen on follow-up x ray studies).
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Surgical options
Surgical options include:
-Extracorporeal shockwave lithotripsy (ESWL): It is the most frequently
used procedure for the treatment of kidney stones. In ESWL, shock
waves that are created outside the body travel through the skin and
body tissues until they hit the denser stones. The stones break down
into sand-like particles and are easily passed through the urinary tract
in the urine.
-Percutaneous nephrolithotomy: It is recommended to remove a stone that
is quite large or in a location that does not allow effective use of ESWL.
-Ureteroscopic Stone Removal: If a stone is located low in the urether, it
might not be amenable to ESWL. A small fiberoptic instrument called a
ureteroscope is passed through the urethra and bladder into the ureter
and the stone is either mechanically extracted or fragmented with shock
wave impulse
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POP QUIZ
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2. Which of the following factors is not associated with
calcium stones
a.
b.
c.
d.
e.
High uricosuria
High Na diet
High oxaluria
High citraturia
Alkaline pH
Go to the next slide for the answer
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Answer: d.
Uric acid acts as a nidus for calcium stones. High Na diet
leads to increased urinary calcium. Oxalate binds to
calcium in the urine and precipitates calcium-oxalate
crystals if present at high concentrations. Alkaline pH
precipitates calcium stones. Citrate is the most powerful
inhibitor of calcium oxalate stones
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3. True or False. In patients with calcium oxalate stones,
decreasing calcium intake will lower urinary calcium
excretion and will result in less stone formation.
Go to the next slide for the answer
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Answer: False.
Lowering calcium intake will result in less calcium chelating
oxalate in the GI tract, more oxalate absorption and thus
urinary excretion. Hyperoxaluria will cause more calcium
stone precipitations
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4. True/False: Potassium citrate is routinely used in patients
with calcium oxalate stones and low urinary citrate.
Go to the next slide for the answer
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• 4. Answer: False.
Although citrate is a powerful inhibitor of calcium oxalate
formation and needed in the urine to prevent stones, it
also raises the pH which might cause more calcium stone
precipitation, especially calcium phosphate. If the urine
pH >6, it should be avoided.
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References:
1.
Pictures of kidney stone crystal morphology are taken from the following site:
www.Uptodate.com / Clinical evaluation of kidney stones
2. Straub M. Hautmann RE. Developments in stone prevention. Curr Opin Urol. 2005
Mar;15(2):119-26.
3. Knoll T, Zollner A. Cystinuria in childhood and adolescence: recommendations for diagnosis,
treatment, and follow-up. Pediatr Nephrol. 2005 Jan;20(1):19-24.
4. Rao PN. Imaging for kidney stones. World J Urol. 2004 Nov;22(5):323-7.
5. Caramia G, Di Gregorio L, et. al. Uric acid, phosphate and oxalate stones: treatment and
prophylaxis. Urol Int. 2004;72 Suppl 1:24-8.
6. Marangella M, Bagnis C, et. al. Crystallization inhibitors in the pathophysiology and treatment of
nephrolithiasis. Urol Int. 2004;72 Suppl 1:6-10
7. Amato M, Lusini ML. Epidemiology of nephrolithiasis today. Urol Int. 2004;72 Suppl 1:1-5.
8. Putmann SS, Hamilton BD. The use of shock wave lithotripsy for renal calculi. Curr Opin Urol.
2004 Mar;14(2):117-21
9. Sandhu C, Anson KM. Urinary tract stones--Part I: role of radiological imaging in diagnosis and
treatment planning. Clin Radiol. 2003 Jun;58(6):415-21.
10. Sandhu C, Anson KM Urinary tract stones--Part II: current status of treatment.
Clin Radiol. 2003 Jun;58(6):422-33. Review.
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