Management of Urinary Calculi

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[edit] Management of Urinary Calculi

Fernando Coste Delvecchio

Glenn M. Preminger

[edit] EPIDEMIOLOGY

Nephrolithiasis is a relatively common disorder affecting 1% to 5% of the population in industrialized countries; it has a reported annual incidence rate as high as 1% in middle-aged Caucasian men.The most common type of renal calculus seen in industrialized countries contains primarily calcium oxalate occurring alone or in combination with hydroxyapatite.The frequency of stone composition is depicted in Table 147-1.

Table 147-1 Kidney Stone Composition

In several unselected population surveys, the life-time risk for stone formation in Caucasian men approaches 20%, whereas for Caucasian women, it is approximately 5% to 10%.In addition, the recurrence rate of nephrolithiasis has been reported to be as high as 50% within 5 years from the first stone occurrence.Overall, stone disease in African-American men is one-third to one-fourth less common than in Caucasian men.However, African-Americans demonstrate a higher prevalence of stones associated with infection by urea-splitting organisms.

Recent expansion in knowledge regarding the pathophysiologic mechanisms of calculus formation, paralleled by technologic advances, has allowed the identification of the physiologic or environmental causes of renal calculi in more than 97% of patients.Various diagnostic categories and their relative frequency are shown in Table 147-2.Low urinary volume is by far the most common combined abnormality and the single most important factor to be corrected to avoid recurrences of stones.^[1]

Table 147-2 Classification of Nephrolithiases

[edit] PATHOPHYSIOLOGY OF CALCIUM NEPHROLITHIASIS

[edit] Hypercalciuria

Hypercalciuria encountered in nephrolithiasis is heterogeneous in origin and comprises several entities.This condition is defined as the excretion of urinary calcium exceeding 200 mg in a 24-hour collection (or a calcium excess of 4 mg/kg/24 hours).Box 147-1 summarizes the causes of secondary hypercalciuria and Table 147-3 the hypercalciuric states.

Table 147-3 Summary of Hypercalciuric States

[edit] Absorptive Hypercalciuria.

The basic abnormality in absorptive hypercalciuria (AH) is the intestinal hyperabsorption of calcium,^[2] the exact cause of which is unknown.The resulting increase in the circulating concentration of calcium enhances the renal filtered load and suppresses parathyroid function.Hypercalciuria results from the combination of increased filtered load and reduced renal tubular reabsorption of calcium caused by parathyroid suppression.The excessive renal loss of calcium compensates for high calcium absorption from the intestinal tract and helps maintain serum calcium levels in the normal range.AH type I (AH-I) is a severe form, and the type II presentation (AH-II) is a mild to moderate form.Whereas urinary calcium levels are increased on both high-and restricted-calcium intakes in AH-I, hypercalciuria is present only during a high calcium intake in type II.(That is, in AH-II, a low-calcium diet corrects the hypercalciuria.)

[edit] Renal Hypercalciuria.

The primary abnormality in renal hypercalciuria is believed to be an impairment in the renal tubular reabsorption of calcium.^[2] The resulting reduction in the serum calcium concentration stimulates parathyroid function.There may be excessive mobilization ofcalcium from bone and enhanced intestinal absorption of calcium because of parathyroid hormone (PTH) excess and the ensuing stimulation of the renal synthesis of 1,25-hydroxyvitamin D, or 1,25-(OH)₂D.These effects increase the circulating concentration and renal filtered load of calcium, often causing significant hypercalciuria.Unlike primary hyperparathyroidism, the serum calcium concentration in renal hypercalciuria is normal, and the state of hyperparathyroidism is secondary.

[edit] Resorptive Hypercalciuria.

Resorptive hypercalciuria is characterized by primary hyperparathyroidism.The initial event is excessive resorption of bone resulting from the hypersecretion of PTH.The intestinal absorption of calcium is frequently increased because of PTH-dependent stimulation of the renal synthesis of 1,25-(OH)₂D.These effects increase the circulating concentration and renal filtered load of calcium, often causing significant hypercalciuria.Abnormally high levels of PTH enhance renal reabsorption of calcium and phosphate excretion.Fasting urinary calcium levels are elevated in spite of the enhanced calcium reabsorption because of the large increase in the filtered calcium load.

[edit] Pathogenesis of Other Causes of Calcium Stones

[edit] Hyperuricosuria.

Hyperuricosuria may be the only recognizable physiologic abnormality, occurring in about 10% of patients with calcium nephrolithiasis (hyperuricosuric calcium oxalate nephrolithiasis).Box 147-2 lists the possible etiologies of this condition.

It is believed that monosodium urate or uric acid is formed in the supersaturated environment of hyperuricosuric subjects.Monosodium urate or uric acid (colloidal or crystalline) may then initiate calcium oxalate stone formation by the direct induction of heterogeneous nucleation of calcium oxalate or by the adsorption of certain macromolecular inhibitors.

[edit] Gouty Diathesis.

The term gouty diathesis describes the formation of renal stones composed of uric acid or calcium oxalate in patients with primary gout, either manifesting fully with gouty arthritis and hyperuricemia or appearing in a latent form.The invariant feature of this condition is the passage of unusually acidic urine (pH below 5.5) in which uric acid is sparingly soluble in the absence of intestinal alkali loss ordietary acid load.Stone analysis discloses uric acid alone or in combination with calcium oxalate or calcium phosphate.In some patients the signs and symptoms of gouty diathesis, except for the lack of uric acid on stone analysis, may appear.The stones may be made up of only calcium oxalate or calcium phosphate.No specific cause has been detected for the unusually low urinary pH.The formation of uric acid stones is caused by undue acidity of urine, and that of calcium stones is caused by urate-induced crystallization of calcium salts.

[edit] Hyperoxaluria.

Hyperoxaluria is usually due to the intestinal hyperabsorption of oxalate.The major cause of increased intestinal absorption of oxalate (and subsequent hyperoxaluria) is ileal disease (enteric hyperoxaluria).This disturbance may be encountered in patients with inflammatory bowel disease, gastric or small bowel resection, or jejunoileal bypass.^[3]

Two factors probably act in concert to cause intestinal hyperabsorption of oxalate.Intestinal transport of oxalate may increase because of the action of bile salts and fatty acids on the permeability of intestinal mucosa to oxalate.The intestinal fat malabsorption characteristics of ileal disease may exaggerate calcium-soap formation, limit the amount of “free” calcium to complex oxalate, and thereby raise the amount of oxalate available for absorption.Stone formation in enteric hyperoxaluria is due to hyperoxaluria as well as other factors.Urinary output may be low as a result of fluid losses from the intestinal tract.The urinary citrate level is usually reduced due to hypokalemia and metabolic acidosis.Low urinary magnesium concentrations may result from impaired intestinal magnesium absorption.Other causes of hyperoxaluria include substrate excess (increased vitamin C ingestion), low calcium intake, and rarely, enzymatic disturbances in oxalate biosynthesis (primary hyperoxaluria).

Hyperoxaluria is defined by urinary oxalate excretion in excess of 45 mg/day.With levels higher than 80 mg/day, primary or enteric hyperoxaluria is probably present.A mild to moderate elevation (45 to 80 mg/day) may result from dietary noncompliance regarding oxalate-rich foods.

[edit] Hypocitraturia.

Among the factors that affect the renal handling of citrate, acid-base status probably plays the most important role.Acidosis reduces urinary citrate levels both by enhancing renal tubular reabsorption and by reducing the synthesis of citrate.This mechanism accounts for the occurrence of hypocitraturia in distal renal tubular acidosis, enteric hyperoxaluria, hypokalemia (from intracellular acidosis), strenuous physical exercise (from lactic acidosis), high-animal-protein diet (from elevated acid-ash content), and sodium excess (from bicarbonaturia).Hypocitraturia occurs with other causes of calcium nephrolithiasis (50%) and may exist as a solitary abnormality (10%).

Citrate lowers the urinary saturation of calcium salts by forming soluble complexes with calcium.Moreover, citrate directly inhibits the crystallization of calcium salts.Thus in the setting of low urinary citrate levels, the urinary environment is more supersaturated with respect to calcium salts; nucleation, growth, and aggregation are promoted.

[edit] PATHOPHYSIOLOGY OF NONCALCAREOUS STONES

[edit] Uric Acid Stones

Critical determinants for pure uric acid lithiasis are a urinary pH less than the dissociation constant for uric acid (5.5), hyperuricosuria, or both.In addition to gouty diathesis, uric acid stones may develop during secondary causes of purine overproduction, such as myeloproliferative states, glycogen storage disease, and malignancy (see Box 147-2).Chronic diarrheal syndromes (e.g., ulcerative colitis, regional enteritis) or jejunoileal bypass surgery may cause uric acid lithiasis by inducing net alkali deficit and lowering urine volume (thereby reducing urinary pH and augmenting urinary concentration of uric acid, respectively).

[edit] Cystine Stones.

Cystinuria is an inborn error of metabolism characterized by a disturbance in renal and intestinal handling of dicarboxylic acids, including cystine.Stone formation, occurring in a minority of patients, is the result of the excessive renal excretion of cystine and its low solubility in urine.Cystine solubility is pH dependent, with the lowest solubility at the low range of urinary pH, gradual in increase solubility with a rise in pH to 7.5, and rapid increasein solubility above a pH of 7.5.The main determinant of cystine crystallization is urinary supersaturation.Once the urinary saturation of cystine exceeds 250 mg/L, cystine will precipitate out of solution.If the cystine concentration can be maintained under 200 mg/L, cystine stones should not occur.Moreover, recent studies have demonstrated that 18% to 44% of patients with cystinuria have associated metabolic defects (e.g., hyperuricosuria, hypocitraturia), which may complicate their cystine stone disease.

[edit] Infection (Struvite) Stones.

Infection of the urinary tract with urea-splitting organisms may be associated with renal stones composed of struvite (magnesium-ammonium phosphate) or calcium carbonate apatite.The critical determinant is the formation of ammonia in urine resulting from the enzymatic degradation of urea by bacterial urease.The ammonia undergoes hydrolysis to form ammonium and hydroxyl ions.The resulting alkalinity of the urine augments dissociation of phosphate to form triphosphate ions, which reduce the solubility of struvite.Thus the urinary environment becomes supersaturated with struvite.Certain bacterial species, most commonly Proteus, Klebsiella, Pseudomonas, and Staphylococcus, produce urease.However, E.coli does not.Struvite stones are most common in patients with chronic infections and in those with anatomic or functional abnormalities of the urinary tract that favor the stasis of urine, such as urinary diversions, neurogenic bladder, strictures, and diverticuli.

[edit] PATIENT EVALUATION

[edit] History and Physical Evaluation

A thorough past medical history may provide clues to the etiology of stone disease.A history of skeletal fracture and peptic ulcer disease suggests primary hyperparathyroidism.Intestinal disease such as chronic diarrheal states, ileal disease, or intestinal resection may predispose the patient to enteric hyperoxaluria or hypocitraturia, resulting in calcium oxalate stones.Patients with gout may form uric acid stones or calcium oxalate stones.A history of recurrent urinary tract infections may suggest infection nephrolithiasis.A physical examination should be performed but is rarely helpful unless the etiology of the stone disease has extrarenal manifestations (such as band keratopathy in hypercalcemia and tophi or gout in hyperuricemia).

A family history of stones is obtained to ascertain etiologies that express a familial tendency (e.g., AH, cystinuria, renal tubular acidosis, primary hyperoxaluria).Medical regimens that have been attempted in the past for stone disease should be discussed in detail.The failure of certain therapeutic modalities may indicate that the etiology is different than that initially suspected and that a more specific approach to treatment is needed.

A careful history of dietary habits, fluid ingestion, and over-the-counter and prescription drug use is obtained.Foods high in calcium, oxalate, and purines can aggravate existing stone disease, as can inadequate fluid ingestion.Implicated medications include vitamins A and D, calcium supplements, and antacids (hypercalciuria), acetazolamide (hypercalciuria, hypocitraturia, and pH increase), vitamin C (hyperoxaluria), furosemide (hypercalciuria), triamterene and indinavir (triamterene and indinavir stones), and hyperuricosuric drugs.

[edit] Radiologic Evaluation

A thorough radiologic evaluation is one of the most important aspects of the overall investigation of urinary stone disease.These studies are necessary for determining stone burden and location, urinary tract anatomy, and renal function.Information about these three factors must be obtained before an appropriate treatment can be selected.

[edit] Kidney, Ureter, and Bladder X-Ray Studies.

Over 90% of stones within the urinary tract are radiopaque.Calcium phosphate and calcium oxalate are the most radiodense stones.A plain film of the abdomen (kidney, ureter, and bladder [KUB]) should be the initial image obtained in all patients with nephrolithiasis.A KUB study should be performed before any subsequent films that use contrast media, since contrast may obscure the presence of even large calculi.

Abdominal films are obtained to document the number, size, and location of all stones within the urinary tract.The radiopacity of any existing stones may suggest the type of stones present.The plain abdominal film is also useful in identifying nephrocalcinosis (suggestive of renal tubular acidosis, sarcoidosis, hyperparathyroidism, or primary hyperoxaluria).

It is important not to overlook stones that may be obscured when they overlie bony structures such as the sacrum or transverse processes of the lumbar vertebrae.These stones can be more easily identified using oblique or anteroposterior views.In addition, nephrotomograms can also be used to assist in the identification of small, less radiopaque calculi within the kidneys.

[edit] Intravenous Pyelogram.

The intravenous pyelogram (IVP) is instrumental in defining the relationship of the calculus to the pyelocaliceal system and ureter.The exact location of stones, the presence or absence of obstruction, hydronephrosis, caliectasis, and renal and ureteral anomalies are all important pieces of information that must be gleaned from the IVP.In addition, the IVP can approximate the function of an affected or “normal” contralateral kidney as suggested by the promptness of contrast excretion, thickness of renal parenchyma, and amount of pyelocaliectasis.(For more precise information on renal function, a differential renal scan should be performed.) In patients with an apparent obstructing ureteral calculus, it is imperative that delayed films be obtained as long as necessary to specifically identify the location of small obstructing calculi.Finally, an IVP may confirm the presence of radiolucent stones and also identify anatomic abnormalities that may be responsible for stone formation, such as a ureteropelvic junction obstruction or calyceal diverticulum.

[edit] Renal Ultrasound.

Ultrasonography (US) can be used as a screening tool for hydronephrosis or stones within the collecting system.Additional information provided by sonographic examination of the kidneys is the amount of parenchyma present in an obstructed kidney and identification of radiolucent calculi.The classic “sonographic shadow” clearly identifies stones that may not be visualized on radiographic examinations.However, the middle and distal ureter are not satisfactorily seen on US because of the presence of bowel gas anteriorly and bony pelvis posteriorly.US may be helpful in the acute setting to rule out other causes of abdominal pain and during follow-up of patients with recurrent nephrolithiasis to avoid excessive x-ray exposure.

[edit] Computed Tomography.

Computed tomography (CT) is particularly useful in helping identify the etiology of radiolucent filling defects within the renal pelvis or ureter.In addition, anatomic abnormalities, obstruction, and other conditions that mimic ureteral colic can be easily identified.

Nonenhanced spiral CT is currently being used as the preferred diagnostic tool in the assessment of patients with acute flank pain.^[4] This technique is more sensitive than simple radiography and US.All stones, independent of their composition, are visualized by this fast and cost-effective method.Moreover, other manifestations of obstructive stones, such as periureteric and perinephric stranding and periureteric edema and hydronephrosis, are easily visualized.Finally, a spiral CT scan can identify other causes of acute flank or abdominal discomfort, such as appendicitis and diverticulitis.

[edit] Radionuclide Evaluation.

Renal radionuclide studies provide rapid and safe information about total and differential renal function.These tests are specifically advantageous because the radionuclide evaluation is not invasive, requires no bowel preparation or specific preoperative preparation, subjects the patient to only minimal radiation exposure, and is apparently free of allergic complications.

[edit] METABOLIC EVALUATION

The decision to investigate thoroughly a first-time stone former should ideally be shared by the physician and the patient.One approach is to gauge the extent of evaluation according to the estimation of the potential or the risk for new stone formation (Fig.147-1).Patients at high risk might be middle-aged, Caucasian men with a familial history of stones or those with intestinal disease (chronic diarrheal states), pathologic skeletal fractures, osteoporosis, urinary tract infection, or gout.In these patients, an extensive evaluation is recommended.Any patients with stones composed of cystine, uric acid, or struvite should undergo a complete metabolic workup.Because stone disease is uncommon in African-Americans, a search for underlying derangements in these individuals is recommended.

Figure 147-1 Schema for diagnostic evaluation.

[edit] Abbreviated Protocol for Low-Risk Single-Stone Formers

In single-stone formers without risk, the following abbreviated protocol may be applied.A multichannel blood screen can be helpful in identifying certain systemic problems, including primary hyperparathyroidism (high serum calcium and low serum phosphorus levels), renal phosphate leak (hypophosphatemia), uric acid lithiasis (hyperuricemia), and distal renal tubular acidosis (abnormalities in the serum electrolytes [e.g., low serum bicarbonate and potassium levels]).

Voided urinary specimens should be obtained for comprehensive urinalysis and culture.The urinalysis should include pH determination (by electrode), since a pH of greater than 7.5 is compatible with possible infection lithiasis, whereas a pH of less than 5.5 may suggest uric acid lithiasis.The urine sediment is also examined for crystalluria, since particular crystal types may give a clue as to the composition of stones.Urine cultures positive for urea-splitting organisms such as Proteus, Pseudomonas, and Klebsiella are suggestive of infection lithiasis.In addition, urine should be examined for the presence of cystine using a qualitative examination (nitroprusside test).Abdominal x-ray films should be obtained to search for residual stones within the urinary tract.

Finally, all available stones should be analyzed to determine their crystalline composition.The presence of uric acid and cystine crystals suggests the presence of gouty diathesis and cystinuria, respectively.The finding of carbonate apatite or magnesium ammonium phosphate suggests infection lithiasis.A predominance of hydroxyapatite suggests the presence of distal renal tubular acidosis or primary hyperparathyroidism.A finding of stones composed purely or predominantly of calcium oxalate is less useful diagnostically because such stones may occur in several entities, including AH, renal hypercalciuria, hyperuricosuric calcium nephrolithiasis, enteric hyperoxaluria, hypocitraturic calcium nephrolithiasis, and low urine volume.

[edit] Extensive Diagnostic Evaluation

A metabolic evaluation directed at the identification of underlying physiologic derangements should be performed in patients with recurrent nephrolithiasis as well as in stone formers at increased risk for further stone formation or with evidence of multisystem involvement.

Before and during the evaluation, the patient is instructed to discontinue any medication that is known to interfere with the metabolism of calcium, uric acid, or oxalate.Three 24-hour urine samples are collected.Two are obtained with the patient on a random diet, which is reflective of usual dietary intake.The third 24-hour sample is collected after a week of a diet restricted in calcium (less than 400 mg/day), sodium (less than 100 mEq/day), and oxalate (less than 50 mg/day).This dietary restriction is imposed to standardize the diagnostic tests, to better assess the etiology of hypercalciuria, and to prepare for the “fast and calcium load” test, which is performed on the second visit.Blood samples are obtained on both visits (Table 147-4).

Table 147-4 Outline of Extensive Ambulatory Protocol

✢History and physical examination, diet history, radiologic evaluation, two 24-hour urine tests on a random diet are performed and dietary instruction for a restricted diet is given.

†The 24-hour urine tests after restricted diet (400 mg of calcium and 100 mEq of sodium a day), or the fast-and-load-test, is performed.

The fasting urinary calcium level is expressed in milligrams per deciliter of glomerular filtrate, since it isreflective of renal function.To obtain this unit of measurement, the urinary calcium level (in milligram per milligram of creatinine) is multiplied by the serum creatinine level (in milligram per deciliter).The normal fasting urinary calcium level is less than 0.11 mg per deciliter of glomerular filtrate.A calcium load of 1 gm is then administered orally.The post-load urinary calcium level is best expressed in milligrams per milligram of creatinine because it is a function of a fixed oral calcium load.The normal value for this measurement is less than 0.2 mg of calcium per milligram of creatinine.

[edit] MANAGEMENT

[edit] Acute Stone Episode

Classic symptoms associated with an acutely obstructing urinary stone include colicky flank pain with radiation to the groin, ipsilateral testicle, or labia, and hematuria (gross or microscopic).Stones in the distal ureter may also present with frequency, urgency, and dysuria.Nausea and vomiting are common.If the obstruction is infected, high-grade fevers or even sepsis may ensue.

If a patient demonstrates these classic findings and has a previous history of recurrent radiopaque nephrolithiasis, a KUB study is warranted to address the size and location of the stone to decide the best course of treatment.Stones no more than 4 mm in size (largest diameter) have a rate of spontaneous passage greater than 90% with conservative measures alone; however, stones larger than or equal to 6 mm pass alone only 10% of the time.^[5]

In patients who lack the classic findings, who are experiencing their first stone episode, or who are known to form radiolucent stones, either a nonenhanced spiral CT or an IVP should be performed.US may be used to assess hydronephrosis and intrarenal calculi but is not very accurate for the diagnosis of ureteral stones.

If the patient is clinically stable and there is no evidence of systemic infection, complete obstruction leading to renal deterioration, or obstruction of a solitary kidney, then conservative management may be offered with pain medication alone (usually nonsteroidal antiinflammatory drugs and narcotic analgesics).However, in the presence of such impending problems, urinary drainage should be performed on an emergency basis, either as ureteral stent placement or percutaneous nephrostomy.In the case of infection, antibiotics should be started promptly.The size of the stone on imaging studies determines the need for intervention.If there is no evidence of movement or passage of a ureteral stone that has been treated conservatively after 3 to 4 weeks or if pain is intractable, surgical intervention is warranted.

[edit] PREVENTION OF STONE RECURRENCES

[edit] Medical Management of Nephrolithiasis

[edit] Conservative Medical Treatment.

Certain conservative recommendations are made for all patients regardless of the underlying etiology of the stone disease.These measures include increased fluids to maintain a urine output above 2000 ml/day.In addition, all patients should be placed on a diet limited in oxalate and sodium, which should help decrease the urinary excretion of oxalate and calcium.In patients with suspected AH without evidence of bone loss, a dietary limitation of dairy products may also be enforced.A restriction of animal proteins in patients with “purine gluttony” and hyperuricosuria should be encouraged.

After 3 to 4 months on conservative management, patients should be reevaluated.If the metabolic or environmental abnormalities have been corrected by the conservative dietary and fluid manipulations alone, conservative therapy should be continued and the patient followed every 6 months with 24-hour urine testing.Follow-up is essential not only for monitoring the efficiency of treatment but also for encouraging patient compliance.If, however, a metabolic or environmental defect persists while the patient is on conservative therapy, more selective medical therapy may be instituted.

[edit] Selective Medical Treatment

[edit] Sodium Cellulose Phosphate.

Currently, no treatment program is capable of correcting the basic abnormality of AH-1.When sodium cellulose phosphate (SCP) is given orally, this nonabsorbable ion-exchange resin binds calcium and inhibits calcium absorption.However, this inhibition is caused by limiting the amount of intraluminal calcium available for absorption, not by correcting the basic disturbance in calcium transport.

The aforementioned mode of action accounts for the three potential complications of SCP therapy.First, this medication may cause a negative calcium balance and parathyroid stimulation when used in patients with normal intestinal calcium absorption or with renal or resorptive hypercalciuria.Second, the treatment may cause magnesium depletion bybinding magnesium.Third, SCP may produce secondary hyperoxaluria by binding divalent cations in the intestinal tract, reducing divalent cation-oxalate complexation, and making more oxalate available for absorption.These complications may be overcome by using the drug only in documented cases of AH-I, providing oral magnesium supplementation (given independent from SCP), and imposing a moderate dietary restriction of oxalate.

When these precautions are followed, SCP, 10 to 15 gm/day (given with meals), reduces urinary calcium levels and the saturation of calcium salts (calcium phosphate as well as calcium oxalate), maintains stable bone density, and is clinically effective.

[edit] Thiazide.

Thiazide is ideally indicated for the treatment of renal hypercalciuria.This diuretic corrects the renal leak of calcium by augmenting calcium reabsorption in the distal tubule and by causing extracellular volume depletion and stimulating proximal tubule reabsorption of calcium.The ensuing correction of secondary hyperparathyroidism restores normal serum 1,25-(OH)₂D levels and intestinal calcium absorption.Thiazide provides a sustained correction of hypercalciuria commensurate with a restoration of normal serum 1,25-(OH)₂D levels and intestinal calcium absorption for up to 10 years of therapy.Physiochemically, the urinary environment becomes less saturated with respect to calcium oxalate and brushite during thiazide treatment, largely because of the reduced calcium excretion.Moreover, urinary inhibitor activity, as reflected in the limit of metastability, is increased by an unknown mechanism.These effects are shared by hydrochlorothiazide, 50 mg twice a day; chlorthalidone, 50 mg/day; or trichlormethiazide, 4 mg/day.Potassium supplementation (approximately 40 mEq/day) is required to prevent hypokalemia and attendant hypocitraturia with all of these agents.Potassium citrate is effective in averting hypokalemia and in increasing urinary citrate when administered to patients with calcium nephrolithiasis who are taking thiazide.Concurrent use of triamterene, a potassium-sparing agent, should be undertaken with caution because of recent reports of triamterene stone formation.Thiazide is contraindicated in primary hyperparathyroidism because of a potential aggravation of hypercalcemia.

Thiazide is not considered a selective therapy for absorptive hypercalciuria, since it does not decrease intestinal calcium absorption in this condition.However, it has been used widely to treat absorptive hypercalciuria because of its hypocalciuric action and the high cost and inconvenience of alternative therapy (SCP).

Current studies indicate that thiazide may have a limited long-term effectiveness in AH-I.^[6] Despite an initial reduction in the urinary calcium excretion rate, the intestinal calcium absorption rate remains persistently elevated.These studies suggest that the retained calcium level may be accreted in bone at least during the first few years of therapy.Bone density may increase during thiazide treatment in absorptive hypercalciuria.With continued treatment, however, the rise in bone density stabilizes, and the hypocalciuric effect of thiazide becomes attenuated.The results suggest that thiazide treatment has caused a low turnover state of bone that interferes with continued calcium accretion in the skeleton.The “rejected” calcium would then be excreted in urine.In contrast, bone density is not significantly altered in renal hypercalciuria in which thiazide causes a decline in intestinal calcium absorption commensurate with a reduction in urinary calcium.

[edit] Guidelines for the use of sodium cellulose phosphate or thiazide in absorptive hypercalciuria type I.

Neither SCP nor thiazide corrects the basic, underlying physiologic defect in AH.SCP might be used in patients with severe AH-I (urinary calcium level greater than 350 mg/day) or in those resistant to or intolerant of thiazide therapy.In patients with AH-I who may be at risk for bone disease (growing children, postmenopausal women) or who already have bone loss, thiazide may be the first choice.When thiazide loses its hypocalciuric action (after long-term treatment), SCP may be temporarily substituted for approximately 6 months; thiazide treatment may then be resumed.

[edit] Allopurinol.

Allopurinol is the drug of choice in patients with hyperuricosuria (with or without hyperuricemia) because of its ability to reduce uric acid synthesis and lower urinary uric acid levels by inhibiting the enzyme xanthine oxidase.Allopurinol is preferred in patients with marked hyperuricosuria (higher than 1,000 mg/day), especially if hyperuricemia coexists.The usual dose is 300 mg/day, but it should be lowered in patients with renal insufficiency.

[edit] Potassium Citrate.

Potassium citrate is used as a treatment for primary hypocitraturia and hypocitraturia secondary to metabolic acidosis (i.e., renal tubular acidosis, chronic diarrheal states) and as an alkali in patients with uric acid and cystine stones.It is also used in the prevention of potassium depletion and hypocitraturia induced by thiazides.

The use of potassium citrate in hypercalciuric and hyperuricosuric calcium nephrolithiasis is warranted, since citrate has an inhibitory activity with respect to calcium oxalate (and calcium phosphate) crystallization, aggregation, and agglomeration.

The administration of potassium citrate (30 to 60 mEq/day in divided doses) to patients with hypercalciuric calcium oxalate nephrolithiasis may reduce the urinary saturation of calcium oxalate (by complexing calcium) and inhibit the urate-induced crystallization of calcium oxalate.Potassium citrate may be particularly useful in patients with mild to moderate hyperuricosuria (less than 800 mg/day) and uric acid lithiasis in whom hypocitraturia is also present.It is the drug of choice in the management of patients with gouty diathesis, in whom the major goal of management is to increase the urinary pH above pH 5.5, preferably to approximately 6.5.Potassium citrate is capable of maintaining urinary pH at approximately 6.5 at a dose of 30 to 60 mEq/day in two divided doses.Attempts at alkalinizing the urine to a pH of greater than 7.0 should be avoided.At a higher pH, there is a possibility of precipitating calcium phosphate (hydroxyapatite) and therefore increasing the risk of calcium stone formation.

[edit] Calcium.

The oral administration of large amounts of calcium (0.25 to 1.0 gm four times a day) or magnesium has been recommended for the control of enteric hyperoxaluria.Although urinary oxalate levels may decrease (probably from binding of oxalate by divalent cations), the concurrent rise in urinary calcium levels may obviate the beneficial effect of this therapy, at least in some patients.

Calcium citrate may theoretically have a role in the management of enteric hyperoxaluria.This treatment may lower urinary oxalate concentrations by binding oxalate in the intestinal tract.Calcium citrate may also raise the urinarycitrate values and pH by providing an alkali load.Finally, calcium citrate may correct the malabsorption of calcium and adverse effects on the skeleton by providing efficiently absorbed calcium.If hypercalciuria develops during calcium citrate treatment, thiazide (e.g., trichloromethiazide 2 to 4 mg/day) may be added.

[edit] α-Mercaptopropionylglycine.

The object of treatment for cystinuria is to reduce the urinary concentration of cystine to below its solubility limit (200 to 250 mg/L).The initial treatment program includes a high fluid intake and oral administration of soluble alkali (potassium citrate) at a dose sufficient to maintain the urinary pH at 6.5 to 7.0.When this conservative program is ineffective,d-penicillamine or α-mercaptopropionylglycine (1000 to 2000 mg/day in divided doses) has been used.This treatment increases cystine solubility in urine via the formation of a more soluble mixed-disulfide.Penicillamine has been associated with frequent side effects, including nephrotic syndrome, dermatitis, and pancytopenia.This profile appears to be less marked with α-mercaptopropionylglycine.

[edit] Captopril.

Recent studies have suggested that captopril may work in the same way as penicillamine and α-mercaptopropionylglycine, forming a captopril-cysteine disulfide that is 200 times more soluble in urine than cystine.However, further investigations are needed to confirm the long-term effectiveness of captopril for the management of cystinuria.

[edit] Acetohydroxamic acid.

The gold standard for the treatment of infection stones is complete surgical removal and treatment of infection with adequate antibiotics.When the former therapies are contraindicated or unsuccessful, acetohydroxamic acid (AHA) may be used.AHA, a urease inhibitor, reduces the urinary saturation of struvite and retards stone formation.When given at a dose of 250 mg three times a day, AHA may prevent the recurrence of new stones and inhibit the growth of stones in patients with chronic urea-splitting infections.In addition, in a limited number of patients, AHA has caused the dissolution of existing struvite calculi.However, some patients on chronic AHA therapy have experienced minor side effects, and a few developed deep venous thrombosis.Additional long-term studies must be done to determine the benefit risk ratio of AHA.

[edit] SURGERY

[edit] Surgical Management

Indications for the surgical management of urinary stones include symptomatic calculi, obstruction, staghorn calculi (even if asymptomatic), and stones in high-risk patients who must not experience an episode of kidney colic (i.e., airplane pilots) or infection (patients who have undergone transplants and patients receiving prostheses).Surgical therapy for urinary tract calculi has changed significantly over the previous 10 years.The advent of shock wave lithotripsy (SWL) and advances in fiberoptics with the subsequent development of flexible instruments as well as small-caliber rigid endoscopes have allowed minimally invasive treatment of urinary calculi and the development of the subspecialty of endourology (“the closed, controlled manipulation of the entire urinary tract”).Determination of the composition, location, and burden of the stone, and renal function and anatomic structures are all important factors in planning the appropriate approach for stone removal.

[edit] Selecting the Adequate Treatment Strategy

[edit] Shock Wave Lithotripsy.

Currently, most symptomatic renal and proximal ureteric stones are treated by SWL.This procedure uses high-energy shock waves that are transmitted through water and are directly focused onto renal and ureteral stones with the aid of fluoroscopy or US.The change in tissue density between the soft renal tissue and the hard stone causes a release of energy at the stone surface, with subsequent stone fragmentation.Multiple shock waves applied to the stone ideally pulverize the stone into small pieces (between 2 and 3 mm), which can then be passed down the ureter and out of the body with the urine.

To diminish the incidence of postprocedural residual fragments and of procedures aimed at treating complications caused by retained fragments, SWL should be reserved for stones that are highly likely to be broken into small, easy-to-pass fragments.Several authors have already proved the long-term negative impact on stone recurrence of untreated residual fragments after surgery.^[7]

Therefore SWL should not be considered in cases in which the stone is associated with an obstruction (i.e., primary or secondary ureteropelvic junction obstruction, ureteral stricture, the presence of a distally impacted second stone).Other relative contraindications to SWL treatment are severe hydronephrosis, impaired renal function, and stones within calyceal diverticulum or hydrocalyxes, since stone fragments may not pass in these clinical settings, even when adequately fragmented.SWL should not be considered for stones larger than 1 cm when renal anomalies are present (e.g., pelvic kidney, horseshoe kidney, malrotated kidneys) or in transplanted kidneys.

SWL therapy provides poor results with stones composed of calcium oxalate monohydrate or cystine, since their hard composition may preclude adequate fragmentation.Using other treatment modalities (i.e., percutaneous stone removal, ureteroscopy) may salvage inadequate fragmentation after a technically sound SWL.

Similarly, SWL management of lower-pole kidney stones may not be successful because of inadequate drainage of stone fragments within a gravity-dependent calyx.Other contraindications to SWL are uncontrolled hypertension and bleeding diathesis, since SWL in this setting may cause bleeding around the kidney.

In properly selected patients, SWL should be the procedure of first choice for low-volume stone disease of the upper urinary tract because of its reduced patient morbidity, noninvasiveness, and cost-efficiency.

[edit] Percutaneous Nephrostolithotomy.

The technique of percutaneous nephrostolithotomy (PNL) relies on access to the intrarenal collecting system through a percutaneous nephrostomy tract (Fig.147-2).A fiberoptic telescope is passed directly into the renal collecting system, where stones are visualized, fragmented, and extracted.For stones located in calyces that cannot be reached using rigid fiberoptic telescopes, a flexible fiberoptic endoscope and instruments can be used.

Figure 147-2 Percutaneous ultrasonic stone disintegration. A, Nephroscopic sheath with a closed, continuous-flow irrigation system: using the working channel as an outflow port (open arrows) keeps the fragments around the tips of the sonotrode, even if it is clogged. B, Open system with a nephrostomy sheath; debris is flushed out continuously alongside the nephroscope. (From Krane R, Siroky M, Fitzpatrick J, editors:Clinical urology, Philadelphia, 1994, JB Lippincott.)

PNL is ideally suited for all patients who have renal stones and who are not candidates for SWL.PNL is currently indicated for the treatment of hard calculi, stones larger than 2 cm, stones within the lower-pole calyx or within a calyceal diverticulum, and staghorn calculi; it is also used as a salvage procedure after failed SWL.

[edit] Ureterorenoscopy.

Another endourologic method for the management of ureteral and renal calculi uses rigid or flexible ureteroscopes.These instruments can be advanced under direct vision or fluoroscopic guidance directly to the level of the stone, which may be fragmented or extracted intact.Various modalities of intracorporeal stone fragmentation, such as electrohydraulic lithotripsy, pneumatic lithotripsy, and laser lithotripsy, may be used to break up stones too large for intact extraction.

Although ureteroscopy requires specific expertise and specialized equipment, its major advantage is decreased morbidity and trauma for the patient undergoing stone removal.Most ureteroscopies are performed as out-patient procedures, with the patient returning to work within 1 to 2 days.

Ureteroscopy is a versatile technique that can be used to treat stones throughout the urinary tract.As with all calculi, the location and size of stones are the most important factors in planning the approach for ureteral stone removal (Fig.147-3).Upper ureteral calculi can be approached by direct SWL, antegrade percutaneous stone extraction, or ureteroscopy.However, the success rate of SWL treatment for ureteral stones has not been as good as with stones located within the renal pelvis.Current experience reveals that lower ureteral calculi may be best approached with a ureteroscopic technique.

Figure 147-3 Management of ureteral calculi. SWL, Shock wave lithotripsy;PNL, percutaneous nephrostolithotomy.

[edit] Open Surgery.

For only a very small number of patients (less than 1%) with extremely large or complex calculi, an open surgical procedure, most commonly an anatrophic nephrolithotomy, can be used for stone removal.

[edit] References