Urolithiasis (nephrolithiasis)

See kidney stones



Kidney stones occur in approximately 2-3% of general population.

Prevalence increasing in men and women and in whites and blacks.

Prevalence has dramatically increased in all demographic groups, especially among women, children, and non-whites.

Lifetime risk for kidney stone formation is estimated to be 1 in 11.

Symptomatic kidney stones are prevalent in 7.2-7.7% of the US adult population.

Estimated lifetime risk of developing a kidney stone is about 12% for white males and 6% for women.

Yearly incidence about 0.5%.

Incidence and prevalence steadily increasing across the world, especially among adolescents and women.

Annual cost for acute nephrolithiasis care $2 billion in the US.

Economic cost of Stone disease exceeds $10billion annually

Clinical hallmarks of kidney stone disease is severe pain from asymptomatic episode.

Sequelae of kidney stones may include: acute kidney injury, UTI, lower urinary tract symptoms, and less often progressive renal decline over time.

Stone formation can take place at any site in the urinary tract but is most common in the kidneys.

Stone size varies from crystal size to large stones.

A risk factor for bone fracture, cardiovascular disease, and chronic kidney disease.

Kidney stones are extremely painful because of the stretching, dilating, and spasm of the ureter and kidney caused by the acute obstruction.

The pain is unrelated to the size of the stone or its composition and is related only to the rapidity and degree of the obstruction.

The peak age range for calcium kidney stone production is generally 35-45 years.

The risk of subsequent symptomatic stone event varies with some patients only having one minimally symptomatic stone episode in their lifetime, while others may have multiple cycles of intense pain, emergency department visits, and operations.

Up to 22% of stone formers will have three or more stone events

Another peak incidence of hypercalciuria occurs in postmenopausal women, as many women are taking supplemental calcium for osteoporosis prophylaxis or therapy.

By age 70, 11% of men and 5.6% of women will have symptomatic kidney stones.l

White individuals have an approximate three times higher likelihood of having kidney stones than black persons.

80% of stones are composed of calcium oxalate with variable amounts of calcium phosphate.

The two most common types of calcium stones, calcium oxalate monohydrate and hydroxy apatite have increased over time.

Hypercalciuria is a shared risk factors of both calcium oxalate and hydroxy apatite stones.

Obesity is a risk factor for kidney stone disease in women but not in men.

Body size is a positive risk factor for kidney stone disease in women, but the correlation was much less significant in men.

High-dose vitamin B-6 appears to be beneficial in women with calcium oxalate stone disease but probably not in men.

Women who take large amounts of vitamin B-6 had a significantly lower incidence of new calcium oxalate stone formation, but a similar benefit was not noted in men.

Carbohydrate intake was found to be a kidney stone dietary risk factor for women but not for men.

Studies found no benefit to dietary vitamin-C modifications in either men or women.

Passage of a kidney stone requires an analysis or removal of such stone to diagnose a calcium stone.

Following the passage of a first stone, recurrence risk is 40% at five years and 75% at 20 years.

With recurrent calcium stones, new stones are formed in 43-80% of subjects within three years.

The Recurrence Of Kidney Stone (ROKS) tool identifies 13 clinical and radiographic predictors of symptomatic recurrence among community stone formers with one or more past stone episodes.

Factors included for recurrence risk: Younger age, male sex, higher BMI, family history of stones, pregnancy, incidental asymptomatic stones on imaging before the first episode, suspected stone episode before the first episode, history of a brushite,struvite, or uric acid stone, no history of calcium oxalate monohydrate stone, kidney pelvic or lower pole stone on imaging, no no uterovesicle junction stone on imaging, number of kidney stones on imaging, and diameter of the largest kidney stone on imaging.

Medical costs associated with kidney stones cost more than $5 billion annually in the US (Saigal CS).

Nephrolithiasis is associated with increased rates of chronic kidney disease, hypertension, and obesity.

In a meta-analysis studies a history of kidney stones is associated with an increased adjusted risk estimate for CHD and stroke, and data suggest that the risk may be higher in women than men.

In women with a history of kidney stones there is a modest increase risk of coronary artery disease while there was no association in men (F2241aro PM et al).

Most stones are idiopathic, and some are related to inherited and systemic diseases.

The majority of patients with idiopathic kidney stones have at least one metabolic abnormality, as identified by a 24 hour urine analysis.

Supersaturation, as expressed by the ratio of urinary calcium oxalate or calcium phosphate concentration to its solubility is the primary force in kidney stone formation.

With a supersaturation level below one crystals can dissolve in the urine, where levels above one, crystals can nucleate and promote growth to form a stone.

Supersaturation is generally higher in recurrent kidney stone patients than those without this condition.

Urinary supersaturation varies with the type of kidney stone that is formed.

Most ureteral stones are less than 5 mm and located in the distal ureter.

For small ureteral stones less than 5 mm in size spontaneous passage rates of 71-98% have been noted (Segura JW et al).

For small stones conservative treatment is indicated with control of pain and if there is no infection present.

In 2000 nearly 2 million outpatient visits for this problem.

Supersaturation is created by imbalances in the excretion of calcium, oxalate and water.

Calcium oxalate supersaturation is independent of urine pH.

Calcium phosphate supersaturation increases as urine pH rises from 6 to 7.

Calcium oxalate stones form over an initial calcium phosphate layer.

Treatment of calcium kidney stones should attempt to lower the supersaturation of both calcium oxalate and calcium phosphate.

Specialized laboratories can calculate supersaturation values.

Increasing urinary citrate can slow the growth of calcium crystals.

Ascorbic acid supplements of 1000 mg a day is associated with a two fold increase the risk of kidney stone formation.

Urinary stasis with horseshoe kidneys, polycystic kidneys may precipitate or worsen stone formation.

Hypercalciuria is the most common metabolic abnormality found in patients with recurrent calcium stones and is strongly influenced by diet.

Hypercalciuria is most often familial and idiopathic.

Idiopathic hypercalciuria is associated with increased gastrointestinal calcium absorption, but serum calcium remains normal, as absorb calcium is promptly excreted.

Approximately 50% of patients with previous urinary calculi have a recurrence within 10 years and 75% by 20 years.

Once there is a stone recurrence the risk of subsequent relapse is increased and the interval between such recurrences is shortened.

Recurrence of stones associated with young age, positive family history, presence of infection induced stones, and associated medical conditions like hyperparathyroidism.

Patients usually present between 30 and 60 years of age.

Between the ages of 30-60 years the incidence for men who never had a stone is 3-4 cases per 1000 per year and declines with age.

The highest incidence for women is between the age of 20 and 30 years and is about 2 per 1000 women per year, it then declines to 1 per 1000 women per year for the next 4 decades.

Two to three times more frequent in males than females.

In the sixth decade of life the incidence falls in men and rises in women resulting in a trend towards gender equivalence.

Whites affected more than Asians, who are affected more often than blacks.

More common in hot, arid areas than in temperate zones.

Genetics, diet, employment, geography, history of urinary tract infection, hypercalciuria, hyperuricosuria associated with stone formation.

Decreased fluid intake associated with stone formation.

Patients on a DASH diet have a 45% lower risk of developing kidney stones compared to individuals with eating habits least reflective of this type of diet.

Associated with diets high in sucrose or fructose.

Health Professionals Follow-up Study involving 45,821 men and 18 years of follow-up , and the Nurses’ Health Study I  with 94,108 older women followed for 18 years , and Nurses’ Health study II with 101,837 younger women with 14 years of follow-up: the DASH diet high scorers had significantly less likelihood to develop kidney stones than those with lower scores.

Patients who have kidney stones may be at increased risk of fracture.

In a retrospective cohort study, men with a history of kidney stones had a higher risk of fracture than men who don’t have urolithiasis (Denburg M et al).

In the above study the risk of fracture is also elevated among women ages 30 to 79 with a history of renal stones.

Because a large number of patients with recurrent kidney stones have hypercalciuria, which can lead to negative calcium balance and compromised bone remodeling.

In the above study the median time from kidney stone diagnosis to first fracture was 10 years.

Medications such as triamterene, indinavar, acetazolamide are associated with urolithiasis.

Patients with uric acid stones usually present with an acidic urine, and those with stone formation resulting from infection have an alkaline urine.

Uric acid stones are associated with gout and with rapid cell turnover seen with leukemias and myeloproliferative syndromes.

Although 90% of urinary calculi have historically been considered radiopaque, the sensitivity and specificity of KUB radiography alone remain poor 45:59 percent respectively.

A number of types of stones are radiolucemt on plain films and include uric acid stones and medication related stones such as those need of pseudoephedrine, guaifenesin and protease inhibitors.

IVP considered the standard imaging modality for urinary tract calculi.

Non-contrast helical CT is fast and accurate in identifying all types stones in all types of locations.

CT scan has the highest sensitivity (95%) and specificity (98%) for urinary stone detection.

Abdominal CT has become most common initial imagining test for nephrolithiasis with high sensitivity for diagnosis.

Sensitivity (95-100%) and specificity (94 to 96%) with the use of non-contrast helical CT. Imaging of modalities for nephrolithiasis:

Plain films: widely available, low-cost, minimal radiation exposure and rapid evaluation.

Disadvantages to plain films is a low sensitivity of 45-58%, lacks anatomical detail, does not assess ureteral obstruction, it has limitations because of body habitus, overlying bowel gas and extrarenal calcifications.

Plain films have difficulty to visualize uric acid stones, matrix stones, protease inhibitor inducedvstones, triamterene stones, xanthine stones and pseudoephedrine/guaifenesin stones.

Ultrasonography: widely available, low-cost, no radiation, they detect hydroureter and hydronephrosis.

Ultrasonic disadvantages include variable sensitivity, poor ability to find renal stones and define small renal stones <5 mm.

Noncontrast CT scans:

Has high sensitivity and specificity, wide availability, can determine stone density, size, location, and obstruction, provides good anatomic detail and it is a rapid test.

CT scans can detect stones as small as 1 mm and can provide information on location and possibly composition, and can detect the presence of other asymptomatic stones.

Disadvantage of CT scans include high radiation dosage, high cost and incidental findings, difficult to visualize protease inhibitor induced stones.

MRI: Associated with no radiation, provides good anatomic details and can assess urinary tract obstruction.

Disadvantages include limited experience and availability, high cost, stones are not directly detected, small stones may be difficult to visualize and cannot differentiate stones from tumor or clot.

In a randomized study of US vs CT scan as initial study for patients with suspected nephrolithiasis resulted in no need fot CT scan in most patients, lower cumulative radiation exposure, with no significant differences in risk of adverse events, pain, return ED visits or hospitalizations (Smith-Bind,an B et al).

In the above study US was less sensitive than CT scan for the diagnosis of

Noncontrast helical CT is the most common initial imaging test with the highest sensitivity and specificity of all imaging modalities.

CT scans detects the vast majority of urinary stones including uric acid stones and stones created by most medications.

Kidney stones are composed of inorganic and organic crystals which are amalgamated with proteins.

Laboratory tests are non-diagnostic.

Urine analysis occasionally reveals crystals, but more commonly will be nonspecific, with findings of white blood cells in the urine and hematuria.

Calcium stones are the most common accounting form more than 80% of stones.

Most common types of stones contain calcium oxalate and phosphate (34% of all stones), pure calcium oxalate (33%), pure calcium phosphate (6%), mixed struvite and apatite (15%), uric acid (6%), and cystine (3%).

Previous studies classified stone composition of the following groups: any calcium oxalate monohydrate 40-60%, any calcium oxalate dihydrate 40-60%, any hydroxyapatite 20-60%, any brushite 2-4%, any Uris acid 5-10% , anynstruvite 5-15%, any cystine 1-2.5%.

Calcium oxalate, phosphate stones occur when the absorption of more calcium in the gut than is excreted in the urine, or have a primary renal defect of calcium reabsorption, or less commonly have hyperkalemia secondary to hyperparathyroidsism, vitamin D intoxification or sarcoidosis.

Oxalate excretion is modestly higher in patients with recurrent calcium kidney stones than among those without this condition, probaly due to increaded gastrointestinal oxalate absorption.

Ascorbic acid intake and high level of protein intake may increase oxalate production.

Struvite stones account for approximately 15% of kidney stones and they can develop after infections-these stones can harbor bacteria, usually Proteus, Pseudomonas and Klebsiella.

Struvite stones composed of magnesium ammonium phosphate and occur in patients with persistently alkaline urine from urinary tract infections caused by urease-positive organisms.

Urease production and alkalinization of the urine leads to precipitation of organic and inorganic compounds, which leads to struvite stones which are composed of a combination of magnesium ammonium phosphate (struvite) and calcium carbonate-apatite.

Struvite stone formation can be sustained by ammonia production is increased and the urine pH is elevated to decrease the solubility of phosphate.

Staghorn kidney stone refers to a stone that creates a cast of the renal pelvis and calyceal system.

Cystine stones seen with genetic abnormalities in cystine metabolism, ornithine, lysine or arginine and are more likely to form in acidic urine.

Sepsis in conjunction with an obstructing stone represents a true emergency.

Sepsis with obstruction needs to be treated with percutaneous nephrostomy or retrograde ureteral stent insertion.

Percutaneous nephrostomy reduces mortality from 40% to 8% when there is obstruction associated with gram-negative septicemia.

Hematuria is the most common lab finding but is absent in up to 15% of patients, usually due to a completely obstructed stone.

Hydronephrosis and infection proximal to the obstructive site can occur with prolonged impairment of the urine flow.

If patients do not have a single kidney, or obstructing pyelonephritis and pain relief can be achieved the patients presenting with a painful stone do not need renal pelvis decompression, but can be managed with medical treatment, since many of such stones will pass spontaneously.

90% of stones smaller than 4 mm and 50% of stones 4-7 mm diagnosis diameter will pass spontaneously.

Stones 8 mm in diameter or larger rarely pass spontaneously.

Urinary stone size and location are the most important predictors of stone passage.

Primary treatment for symptomatic urolithiasis is extracorporeal shock-wave lithotripsy.

With shock wave lithotripsy perirenal fluid accumulation and subcapsular bleeding reported in 15-32% of cases.

Retreatment rate for lithotripsy ranges from 4-50%.

Complication rate after ureteroscopic removal of stones 10-20%, with ureteral perforation, avulsion, and stricture formation accounting for 3-5% of events.

Treatment with calcium channel blockers or α-blockers results in a 65% greater likelihood of spontaneous passage of a stone than in patients not given such drugs.

Relaxation of ureteral smooth muscle can be achieved by inhibiting active calcium channel pumps and adrenergic α-1 receptors.

Relaxing ureteral muscles in the region of the stone and increasing hydrostatic pressure proximal to the stone facilitates passage.

Expulsive therapy with calcium channel blockers or α-blockers significantly reduces time to the passage of stones, associated with lower pain scores and utilizes less analgesics.

A 5 mm stone in the distal ureter as a 50-60% chance of spontaneous passage.

In the absence of unmanageable pain, infection or renal failure 5mm stones can be managed conservtively for up to 4 weeks.

Average time to passage of such stones is 22 days and expulsive therapy is warranted.

Tamsulosin, 0.4mg/d for ureteral stones 5-7 mm, results in passage of such stones an average 2-6 days earlier than placebo (Lojanapiwat B et al).

Meta-analysis of tamsulosin in ureteral stones resulted in a mean time to expulsion less than 14 days (Singh et al).

Nifedipine slighly less effective than tamulosin in stone expulsion.

Higher intake of dietary calcium in young women associated with a decreased risk of stone formation.

Calcium supplements are not associated with an increased risk of kidney stones in younger women.

Can rarely present asymptomatically and result in giant hydronephrosis, which is defined as the presence of more than 1 L of fluid in the collecting system.

In patients with idiopathic hypercalciuria patients often excrete more calcium than they eat.

In patients with idiopathic hypercalciuria urinary calcium excretion increases markedy after intake of calcium free nutrients.

Because kidney stones are associated with chronic kidney disease preventing recurrence is a major goal and is largely specific to the type of stone identified

Urine pH and 24-hour urine assessment provide information about stone formation that can guide prevention.

Medications including protease inhibitors, antibiotics, and some diuretics, increase the risk of some types of kidney stones.

Managing diet, medication use, and nutrient intake can help prevent the formation of kidney stones.

Obesity increases the risk of renal stones but weight efforts could undermine prevention of stones if associated with a high animal protein intake, laxatives, rapid loss of lean tissue, and poor hydration.

Kidney stone prevention of calcium oxalate, cystine, and uric acid stones, urine alkanization by eating a diet high in fruits and vegetables, taking supplemental or prescription citrate, or drinking alkaline mineral waters.

Preventing kidney stones of calcium phosphate and struvite, urine should be acidified with cranb2241y juice or betaine to lower urine pH.

Symptoms attributable to struvite stones are uncommon.

Gram negative organisms which split urea and Proteus infections are associated with staghorn calculi of the urinary tract.

Silodosin may ease the passage of distal ureteral stones

Silodosin may aid the passage of a unilateral distal ureteral stone 4 to 10 mm in diameter (Sur RL et al).

The rate of stone passage was about 23% higher with silodosin compared with placebo.

An 8 mg daily dose for up to 4 weeks of treatment.

Results with silodosin were similar for men and women.

The distal ureter contains the highest concentration of alpha-1 adrenergic receptors and silodosin is an alpha-blocker.

Bockage of the alpha-adrenergic receptors relaxes the ureter and potentially providing a spasmolytic effect,

But silodosin performed no better than placebo at eliminating ureteral stones generally, including medial and proximal stones.

Silodosin had no significant advantages in patient use of pain relievers, emergency room visits, or hospital admissions.

Adverse effects of solodosin included retrograde ejaculation, nausea, dizziness, headache, and nasal congestion.

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