Urine is said to be saturated with, for example, calcium and oxalate when the product of th e concentrations of calcium and oxalate exceeds the solubility product (Ksp). Below Ksp, cr ystals of calcium and oxalate will not form and the urine is said to be undersaturated. Abo ve Ksp, crystals of calcium and oxalate should form, but they do not because of the presenc e of inhibitors of crystal formation. However, above a certain concentration of calcium and oxalate, inhibitors of crystallization become ineffective and crystals of calcium oxalate start to form. The concentration of calcium and oxalate at which this is reached (i.e. at w hich crystallization starts) is known as the formation product (Kf) and the urine is said t o be super- saturated with the substance or substances in question at concentrations above this level. Urine is described as being metastable for calcium and oxalate at concentration s between the Ksp of calcium and oxalate and the Kf (Box 9.1). The ability of urine to hold more solute in solution than can pure water is due partly to t he presence of various inhibitors of crystallization (e.g. cit- rate forms a soluble comple x with calcium, preventing it from combining with oxalate or phosphate to form calcium oxal ate or calcium phosphate stones). Other inhibitors of crystallization include magnesium, gl ycosamin- oglycans, and Tamm \200\223Horsfall protein. From a practical perspective, the on ly inhibitor of stone formation that is open to manipulation is citrate. Periods of intermittent supersaturation of urine with various substances can occur as a consequence of dehydration and following meals. The earliest phase of crystal formation is known as nucleation. Crystal nuclei usually form on the surfaces of epithelial cells or on other crystals. Crystal nuclei form into clumps \200\224a process known as aggregation. Citrate and magnesium not only inhibit crystallizat ion, but also inhibit aggrega- tion. Calcium oxalate stones form over a nucleus of calcium phosphate (Randall \200\231s plaques on the surface of a renal papilla). Box 9.1 Steps leading to stone formation - < solubility product l NO Calcium and oxalate concentration STONE FORMATION. Metastable calcium and oxalate concentra tions FORMATION. Calcium and oxalate concentrations l NO STONE > formation product l STONE. This page intentionally left blank CHAPTER 9 Stone disease 436 Factors predisposing to speci \201 c stone types Calcium oxalate (785% of stones) Although most patients with calcium oxalate stones have at least one met- abolic abnormality (e.g. hypercalciuria, hyperoxaluria, hypocitatruria), the majority of calcium oxalate stones are idiopathic, i.e. the cause of that metabolic abnormality is unknown. Hypercalciuria: excretion of >7mmol of calcium per day in men and >6mmol per day in women. The major metabolic risk factor for calcium oxalate stone formation is that it increases th e relative supersaturation of urine. Some series suggest that as many as 50% of patients wi th calcium stone disease have hypercalciuria although the proportion of hypercalciu- ric pa tients in other series is lower. There are three types: - Absorptive: increased intestinal absorption of calcium. - Renal: renal leak of calcium. - Resorptive: increased demineraliza tion of bone (due to hyper- parathyroidism). Diet has a major in \202 uence on hypercalciuria. Hypercalcaemia: almost all patients with hypercalcaemia who form stones have primary hyperparathyroidism. Of hyperparathyroid patie nts, about 1% form stones (the other 99% do not because of early detection of hyperparathyr oidism by screening serum calcium). Hyperoxaluria: is due to the following. - Altered membrane transportation of oxalate, leading to increased renal leak of oxalate. Pri mary hyperoxaluria: Increased oxalate absorption in short bowel syndrome or malabsorption ( enteric hyperoxaluria): the colon is exposed to more bile salts and this increases its perm eability to oxalate. increased hepatic oxalate production \200\224rare. Ascorbic acid and high protein intake increase oxalate production. Hypocitraturia: citrate forms a soluble complex with calcium (so-called chelation), thus preventing the complexing of calcium with oxalate to form calcium oxalate stones. Distal renal tubular acidosis, hypo kalaemia, and carbonic anhydrase inhibitors lead to hypocitatruria. Hyperuricosuria: high u rinary uric acid levels lead to the formation of uric acid crystals on the surface of which calcium oxalate crystals form. Uric acid (75 \200\22310% of stones) Humans (unlike birds) are unable to convert uric acid (which is rel- atively insoluble) into allantoin (which is very soluble). Human urine is supersaturated with insoluble uric acid. Uric acid exists in two forms in urine \200\224uric acid and sodium urate. Sodium urate is 20 times more solubl e than uric acid. At a urine pH of 5, <20% of uric acid is present as soluble sodium urate. At urine pH 5.5, half of the uric acid is ionized as sodium urate (soluble) and half is no n-ionized as free uric acid (insoluble). At a urine pH of 6.5, >90% of uric acid is present as soluble sodium urate. FACTORS PREDISPOSING TO SPECIFIC STONE TYPES 437 Thus, uric acid is essentially insoluble in acid urine and soluble in alkaline urine. Human urine is acidic (because the end products of metabolism are acid) and this low pH, combine d with supersaturation of urine with uric acid, predisposes to uric acid stone formation. About 20% of patients with gout have uric acid stones. Patients with uric acid stones may have: - Gout forming a uric acid stone if you have gout is in the order of 1% per year from the tim e of the \201 rst attack of gout. Myeloproliferative disorders : particularly following t reatment with cytotoxic drugs, cell necrosis results in release of large quantities of nucl eic acids which are converted to uric acid. A large plug of uric acid crystals may form in the collecting system of the kidney in the absence of ureteric colic, causing oliguria or a nuria. Idiopathic uric acid stones : 50% of patients with uric acid stones have gout. The chance of : no associated condition. Calcium phosphate (calcium phosphate + calcium oxalate = 10% of stones) Occur in patients w ith renal tubular acidosis (RTA) \200\224a defect of renal tubular H+ secretion resulting i n an impaired ability of the kidney to acidify urine. The urine is, therefore, of high pH a nd the patient has a metabolic acidosis. The high urine pH increases supersaturation of the urine with calcium and phosphate, leading to their precipitation as stones. Types of renal tubular acidosis - Type 1 or distal RTA: the distal tubule is unable to maintain a proton gradient between the blood and the tubular \202 uid; 70% of such patients have stones. When the urine pH is > 5.5, the patient has a metabolic acidosis and hypokalaemia, urinary citrate is low, and hyp ercalciuria is present. Type 2 or proximal RTA: due to failure of bicarbonate resorption in the proximal tubule. There is associated increased urinary citrate excretion which protect s against stone formation. Type 3 Type 4 These patients do not make stones. : a variant of type 1 RTA. : seen in diabetic nephropathy and interstitial renal disease. If urine pH is >5.5, use the ammonium chloride loading test. Urine pH that remains above 5. 5 after an oral dose of ammonium chloride = incomplete distal RTA. Struvite (infection or triple phosphate stones) (2 \200\22320% of stones) These stones are composed of magnesium, ammonium, and phosphate. They form as a consequence of urease-produc ing bacteria which produce ammonia from the breakdown of urea (urease hydrolyses urea to ca rbon dioxide and ammonium) and in so doing, alkalinize urine as in the following equation: NH2 \200\223O \200\223NH2 + H2O l 2NH3 + CO2 Under alkaline conditions, crystals of magnesi um, ammonium, and phos- phate precipitate. CHAPTER 9 Stone disease 438 Cystine (1% of all stones) Occur only in patients with cystinuria \200\224an inherited (aut osomal reces- sive) disorder of transmembrane cystine transportation, resulting in decrease d absorption of cystine from the intestine and in the proximal tubule of the kidney. Cystin e is very insoluble so reduced absorption of cystine from the proximal tubule results in su persaturation with cystine and cys- tine crystal formation. Cystine is poorly soluble in ac id urine (300mg/L at pH 5, 400mg/L at pH 7). This page intentionally left blank CHAPTER 9 Stone disease 440 Evaluation of the stone former Determination of stone type and a metabolic evaluation allow s the iden- ti \201 cation of the factors that led to stone formation so advice can be giv en to prevent future stone formation. Metabolic evaluation depends, to an extent, on the stone type (Table 9.2). In many cases, a stone is retrieved. Stone type is analyzed by polarizing microscopy, X-ray diffraction, an d infrared spectroscopy rather than by chemical analysis. Where no stone is retrieved, its nature must be inferred from its radiological appearance (e.g. a completely radiolu- cent s tone is likely to be composed of uric acid) or from more detailed metabolic evaluation. In most patients, multiple factors are involved in the genesis of kidney stones and as a ge neral guide, the following evaluation is appropriate in most patients. Risk factors for stone disease - Diet : enquire about volume of \202 uid intake, meat consumption (causes hypercalciuria, high uric acid levels, low urine pH, low urinary citrate), multivitamins (vitamin D increas es intestinal calcium absorption, although in healthy post-menopausal women with no history of stone formation vitamin D supplementation does not increase urinary calcium excretion), high doses of vitamin C (ascorbic acid causes hyperoxaluria). Drugs to hypercalciuria), ch emotherapeutic agents (breakdown products of malignant cells leads to hyperuricaemia). UTI Enterobacter) predispose to struvite stones. Mobility hypercalciuria. Systemic disease Fami ly history Renal anatomy with calcium-containing stones have MSK). Previous bowel resection or in \202 ammatory bowel disease intestinal hyperoxaluria. : corticosteroids (increase enteric absorption of calcium, leading : urease-producing bacteria (Proteus, Klebsiella, Serratia, : low activity levels predispose to bone demineralization and - : gout, primary hyperparathyroidism, sarcoidosis. : cystinuria, RTA. : PUJO, horseshoe kidney, MSK (up to 2% of patients : causes Metabolic evaluation of the stone former Patients can be categorized as low risk and high r isk for subsequent stone formation. High risk: previous history of a stone (i.e. multiple s tone form- ers), bilateral stones, family history of stones, GI disease, uric acid stones o r gout, chronic UTI, nephrocalcinosis, patients with solitary kidneys, stag- horn calculi, children and young adults. Low-risk patient evaluation U & E, FBC (to detect undiagnosed hematological malignancy), se rum calcium (corrected for serum albumin) and uric acid, urine culture, urine dipstick for pH. EVALUATION OF THE STONE FORMER 441 Table 9.2 Characteristics of stone types Mean urine pH ( SEM) Stone type Urine acidity Calcium oxalate Variable 6 ( 0.4) Calcium phosphate Tendency towards alkaline urine >5.5 Uric acid Acid 5.5 ( 0.4) Struvite Alkaline* \200\223 Cystine Normal (5 \200\2237) \200\223 Urine pH must be above 7.2 for deposition of struvite crystals. High-risk patient evaluation As for low-risk patients plus 24h urine for calcium, oxalate, uric acid, cystine; evaluation for RTA. Urine pH Urine pH in normal individuals shows variation from pH 5 \200\2237. After a meal, pH is initially acid because of acid production from metabolism of purines (nucleic acids i n, for example, meat). This is followed by an \200\230alkaline tide \200\231, pH rising to >6.5. Urine pH can help establish what type of stone the patient may have (if a stone is n ot available for analysis) and can help the urologist and patient in determining whether pr eventative measures are likely to be effective or not. - pH <6 in a patient with radiolucent stones suggests the presence of uric acid stones. pH co nsistently >5.5 suggests type 1 (distal) patients will form calcium phosphate stones). RTA (770% of such Evaluation for RTA Evaluate for RTA if: calcium phosphate stones, bilateral stones, nephro- calcinosis, MSK, hypocitraturia. - If fasting morning urine pH (i.e. \201 rst urine of the day) is >5.5, the patient has com plete distal RTA. First and second morning urine pH are a useful screening test for thedete ction of incomplete distal RTA, >90% of cases of RTA having a pH >6 on both specimens. The ammonium chloride loading test involves an oral dose of ammonium chloride (0.1g per kg; an acid load). If serum pH falls <7.3 or serum bicarbonate falls <16mmol/L, but urine pH remai ns >5.5, the patient has incomplete distal RTA. Diagnostic tests for suspected cystinuria Cyanide \200\223nitroprusside colorimetric test ( \200\230cystine spot test \200\231): if positive, a24h urine collection is done. A 24h cys tine >250mg is diagnostic of cystinuria.1 1 Millman S, Strauss AL, Parks JH, Coe FL (1982) Pathogenesis and clinical course of mixed calcium oxalate and uric acid nephrolithiasis. Kidney Int 22:366 \200\22370. CHAPTER 9 Stone disease 442 Kidney stones: presentation and diagnosis Kidney stones may present with symptoms or be fou nd incidentally dur- ing investigation of other problems. Presenting symptoms include pain or haematuria (microscopic or occasionally macroscopic). Struvite staghorn calculi classica lly present with recurrent UTIs. Malaise, weakness, and loss of appetite can also occur. Le ss commonly, struvite stones present with infective complications (pyonephrosis, perinephri c abscess, septicaemia, xanthogranulomatous pyelonephritis). Diagnostic tests - Plain abdominal radiography radiodense. Sulfur-containing stones (cystine) are relatively r adiolucent on plain radiography. Radiodensity of stones in decreasing order: calcium phosph ate > calcium oxalate > struvite (magnesium ammonium phosphate) >> cystine. Completely radi olucent stones (e.g. uric acid, triamterene, indinavir) are usually suspected on the basis of the patient \200\231s history and/or urine pH (pH <6 \200\224gout; drug history \200\224 triamterene, indinavir) and the diagnosis may be con \201 rmed by USS, CT-KUB, or MRU. Ren al depending on the series. Some series suggest 795% sensitivity for detecting stones, othe rs just 50%.1 A combination of plain abdominal radiography and renal ultrasonography is a u seful screening test for renal calculi. : calculi that contain calcium are USS: its sensitivity for detecting renal calculi is variable IVU- : virtually a historical investigation now having, to all intents and purposes, been replaced by CT-KUB. Useful for the rare patient with suspected indinavir sto nes (which are not visible on CT). : a very accurate method of diagnosing renal and ureteri c stones CTU (except) indinavir stones. Allows accurate determination of stone size and loc ation and good de \201 nition of pelvicalyceal anatomy. MRU of hydronephrosis. : cannot visualize stones, but is able to demonstrate the presence 1 Haddad MC, Sharif HS, Abomelha ME, et al. (1992) Management of renal colic: rede \201 ni ng the role of the urogram. Radiology 184:35 \200\2236. This page intentionally left blank CHAPTER 9 Stone disease 444 Kidney stone treatment options: watchful waiting and the natural history of stones The trad itional indications for intervention are pain, infection, and obstruc- tion. Haematuria cau sed by a stone is only very rarely severe or frequent enough to be the only reason to warra nt treatment. Before embarking on treatment of a stone which you think is the cause of the patient \200 \231s pain or infections, warn them that though you may be able to remove the stone success fully, their pain or infections may persist (i.e. the stone may be coincidental to their pa in or infections which may be due to something else). Remember, UTIs are common in women as are stones and it is not, therefore, surprising that the two may coexist in the same patie nt, but be otherwise unrelated. Options for stone management are watchful waiting, ESWL, \202 exible ureteroscopy, PCNL, open surgery, and medical \200\230dissolution \200\231 therapy. When to watch and wait \200\224and when not to It is not necessary to treat every kidney st one. As a rule of thumb, the younger the patient, the larger the stone and the more symptom s it is causing, the more inclined we are to recommend treatment. Thus, one would be inclin ed to do nothing about a 1cm symptomless stone in the kidney of a patient aged 95y. On the other hand, a 1cm stone in a symp- tomless patient aged 20y runs the risk over the remainin g (many) years of the patient \200\231s life of causing problems. It could drop into the ur eter, causing ureteric colic or it could increase in size and affect kidney function or cau se pain. The results of observational studies are con \202 icting, some suggesting most renal stone s progress \200\224increase in size, cause symptoms, or require intervention while others s uggest many do not. In a series of 80 calyceal stones followed over 7.5y (stone size not re ported), 45% of the stones increased in size and the authors concluded that 80% would requi re inter- vention within 5y.1 Conversely, 68% of patients with small renal stones remained asymptomatic over 2.5y in Glowacki \200\231s study2 and in Keeley \200\231s RCT of ESWL vs watchful waiting for small calyceal stones, only 9% required surgery over an average follow -up of 2y.3 Burger \200\231s paper4 is helpful because it relates the risk of intervention to stone siz e and location, allowing a more tailored approach to decision making. Asymptomatic stones f ollowed over a 3y period were more likely to require intervention (surgery or ESWL) or to i ncrease in size or cause pain if they were >4mm in diameter or if located in a middle or lo wer pole calyx.4 The approximate risks over 3y of follow-up of requiring interven- tion, de veloping pain, or of increase in stone size relative to stone size is shown in Table 9.3. Another factor determining the need for treatment is the patient \200\231s job. Airline pil ots are not allowed to \202 y if they have kidney stones for fear that the stones could d rop into the ureter at 30 000 ft with disastrous conse- quences! They will only be deemed \201 t to \202 y when they are radiologically KIDNEY STONE TREATMENT OPTIONS 445 stone-free. It is sensible to warn any one whose job entrusts them with the safety of other s (pilots, train drivers, drivers of busses and lorries) that they are not \201 t to carr y out these occupations until stone-free or, at the very least, that they should contact th e relevant regulatory authority to seek guidance (the Civil Aviation Authority (CAA) for pi lots and the Drivers Vehicle Licensing Agency (DVLA) for drivers).5 Some stones are de \201 nitely not suitable for watchful waiting. Untreated struvite (i.e. infection-related) staghorn calculi will eventually destroy the kidney if untreated and ar e a signi \201 cant risk to the patient \200\231s life. Watchful waiting is, therefore, NO T recommended for staghorn calculi unless patient comorbidity is such that surgery would be a higher risk than watch- ful waiting. Historical series suggest that somewhere between 9 and 30% of patients with staghorn calculi who did not undergo surgical removal (from choice or because of comorbidity) died of renal-related causes \200\224 renal failure, urosepsis (septicaemia, pyonephrosis, perinephric abscess).6-8 A combination of a neurogenic bladder and staghorn calculus seems to be particularly associated with a poor outcome.9 Table 9.3 Approximate 3-year risk of intervention, pain, or increase in stone size (from Bu rger 2004)4 Stone size <5mm 5 \200\22310mm 11 \200\22315mm >15mm % Requiring intervention 20 25 40 30 % Causing pain 40 40 40 60 % Increasing in size 50 55 60 70 1 Hubner WA, Porpaczy P (1990) Treatment of calyceal calculi. Br J Urol 66:9 \200\22311. 2 Glowacki LS, Beecroft ML, Cook RJ, Pahl D, Churchill DN (1992) The natural history of asy mp- tomatic urolithiasis. J Urol 147:319 \200\22321. 3 Keeley FX, Tilling K, Elves A, et al. (2001) Preliminary results of a randomized controll ed trial of prophylactic shock wave lithotripsy for small asymptomatic renal calyceal stone s. BJU Int 87:1 \200\2238. 4 Burgher A, Beman M, Holtzman JL, Monga M (2004) Progression of nephrolithiasis: long-term outcomes with observation of asymptomatic calculi J Endourol 18:534 \200\2239. 5 Borley NC, Rainford D, Anson KM, Watkin N. (2007) What activities are safe with kidney st ones? A review of occupational and travel advice in the UK. Br J Urol Int 99:494 \200\2236. 6 Blandy JP, Singh M (1976) The case for a more aggressive approach to staghorn stones. J U rol 115:505 \200\2236. 7 Rous SN, Turner WR (1977) Retrospective study of 95 patients with staghorn calculus disea se. J Urol 118:902. 8 Vargas AD, Bragin SD, Mendez R (1982) Staghorn calculi: clinical presentation, complicati ons and management J Urol 127:860 \200\2232. 9 Teichmann J (1995) Long-term renal fate and prognosis after staghorn calculus management. J Urol 153:1403 \200\2237. CHAPTER 9 Stone disease 446 Stone fragmentation techniques: extracorporeal lithotripsy (ESWL) The technique of focusing externally generated shock waves at a target (the stone). First used in humans in 1980. Th e \201 rst commercial lithotriptor, the Dornier HM3, became available in 1983.1 ESWL revo lutionized kidney and ureteric stone treatment. Three methods of shock wave generation are commercially available \200\224 electrohydraulic, electromagnetic, and piezoelectric. Electrohydraulic: application of a hi gh voltage electrical current between two electrodes about 1mm apart under water causes dis charge of a spark. Water around the tip of the electrode is vaporized by the high temper- a ture, resulting in a rapidly expanding gas bubble. The rapid expansion and then the rapid c ollapse of this bubble generate a shock wave that is focused by a metal re \202 ector shap ed as a hemiellipsoid. Used in the original Dornier HM3 lithotriptor. Electromagnetic: two electrically conducting cylindrical plates are sepa- rated by a thin membrane of insulating material. Passage of an electri- cal current through the plates generates a strong magneti c \201 eld between them, the subsequent movement of which generates a shock wave. An \200\230acoustic \200\231 lens is used to focus the shock wave. Piezoelectric: a spherical dish is covered with about 3000 small ceramic elements, each of which expands rapidly when a high voltage is applied across them. This rapid expansion generates a shock wave. X-ray, USS, or a combination of both are used to locate the stone on which the shock waves are foc used. Older machines required general or regional anesthesia because the shock waves were p owerful and caused severe pain. Newer lithotriptors generate less powerful shock waves, all owing ESWL with oral or parenteral analgesia in many cases, but they are less ef \201 cien t at stone fragmentation. Ef \201 cacy of ESWL The likelihood of fragmentation with ESWL depends on the stone size a nd location, anatomy of renal collecting system, degree of obesity, and stone composition. Most effective for stones <1cm in diameter and in favorable anatomical locations. Less effe ctive for stones >1cm diameter, in lower pole stones in a calyceal diverticulum (poor drain age), and those com- posed of cystine or calcium oxalate monohydrate (very hard). Randomized studies show that a lower shock wave rate (60 vs 120 per min) achieves better st one fragmentation and clearance. Animal studies also demonstrate less renal injury and a sm aller decrease in renal blood \202 ow from lower shock wave rates.2 There have been no randomized studies comparing stone-free rates between different lithotri ptors. In non-randomized studies, rather surpris- ingly, when it comes to the ef \201 cacy of stone fragmentation, older (the original Dornier HM3 machine) is better (but with a hig her requirement for analgesia and sedation or general anesthesia). Less powerful (modern) l ithotriptors have lower stone-free rates and higher retreatment rates. STONE FRAGMENTATION TECHNIQUES: ESWL 447 Side effects of ESWL (see Fig. 9.3) ESWL causes a certain amount of structural and function al renal dam- age (found more frequently the harder you look). Haematuria (micro- scopic, m acroscopic \200\224due to the rupture of intraparencyhmal vessels) and oedema are common, p erirenal haematomas less so (0.5% detected on USS with modern machines, although reported i n as many as 30% with the Dornier HM3). Effective renal plasma \202 ow (measured by renog raphy) has been reported to fall in 730% of treated kidneys. Renal injury during ESWL is signi \201 cantly reduced by slowing the rate of shock wave delivery from 120 to 30 shock waves per min.3 There are data suggesting that ESWL may increase the likelihood of development of hypertens ion. Acute renal injury may be more likely to occur in patients with pre-existing hypertens ion, prolonged coagulation time, coexisting coronary heart disease, diabetes, and in those withsoli- tary kidneys. A retrospective case control study with 19y follow-up has raised th e possibility that ESWL may cause pancreatic damage, leading to a higher risk of diabetes \200\224diabetes developed in 16.8% of patients undergo- ing ESWL vs 6.6% of controls.4 Fig. 9.3 Side effects of ESWL: steinstrasse (= Stone Street) or \200\230log-jam \200\231. CHAPTER 9 Stone disease 448 Should a stent be inserted prior to ESWL to renal (or ureteric) calculi? Is ESWL more effec tive in the absence of pre-ESWL stenting? Probably yes.5 Does pre-ESWL stenting reduce the risk of ESWL complications? Probably not. When ESWL was \201 rst introduced, stones of al l sizes were treated. It soon became apparent that multiple fragments from large stones cou ld obstruct the ureter, causing a so-called steinstrasse (inci- dence of steinstrasse 2 \200\2233% for stones 1.5 \200\2232cm diameter; 56% for stones 3 \200\2233.5cm). Whether stenting prior to ESWL can reduce the risk of steinstrasse remains controversial. P re-ESWL stenting does not reduce the chances of spontaneous resolution of the steinstrasse (spontaneous passage of the stones). We nowadays see steinstrasse only rarely because ESWL tends to be reserved for smaller stones (<2cm) and PCNL for larger stones. Steinstrasse is managed expectantly (since 50% will resolve spontane- ously), with ESWL of the so-called \200\230lead \200\231 fragment or ureteroscopy being required where the stones fail to pass . The overall consensus is that pre-ESWL stenting is probably not neces- sary in most cases. For patients with solitary kidneys undergoing ESWL, prestenting is an option to reduce the risk of renal obstruction. The alter- native is closer monitoring in the days and weeks aft er ESWL and emer- gency ureteroscopy where anuria develops. Contraindications to ESWL Absolute contraindications: pregnancy, uncorrected blood clotting disor- ders (including anticoagulation); known renal artery. BAUS procedure-speci \201 c consent form: potential complications after ESWL Common - - - Bleeding on passing urine for short period after procedure. Pain in the kidney as small fra gments of stone pass after fragmentation. UTI treatment. from bacteria released from the stone, needing antibiotic Occasional - - - Stone will not break as too hard, requiring an alternative treatment. Repeated Recurrence o f stones. ESWL treatments may be required. Rare - - Kidney damage (bruising) or infection, needing further treatment. Stone fragments occasiona lly get stuck in the tube between the kidney and the bladder, requiring hospital attendance and sometimes surgery to remove the stone fragment. Severe infection requiring kidney by a small drain placed through the back into the kidney. IV antibiotics and sometimes drainage of the STONE FRAGMENTATION TECHNIQUES: ESWL 449 Alternative therapy Telescopic surgery, open surgery, or observation to allow spontaneous p assage. What is the fate of the \200\230clinically insigni \201 cant fragment \200\231 after ESWL ? Clinically insigni \201 cant residual fragments (CIRFs) are residual stone frag- ments 4 mm in size or less after ESWL. \200\230Clinically insigni \201 cant \200\231 is something of a misnomer for 12 \200\22346% of such fragments will increase in size over a period of 2 \200\2233y.6-10 Given that there is a signi \201 cant risk of increase in stone size and given our knowledge that stones that grow are likely to continue to do so and, therefore, require intervention or to become symptomatic and so require intervention, radiological fol low-up of such patients seems to be sensible. How (plain X-ray if the stones are visible, U SS or CT), how often and by whom (in primary care or by urologists) are contentious issues? 1 Chaussy CG, Brendel W, Schmidt E (1980) Extracorporeal induced destruction of kidney ston es by shock waves. Lancet 2:1265 \200\2238. 2 Semins MJ, Trock BJ, Matlaga BR (2008) The effect of shock wave rate on the outcome of sh ock wave lithotripsy: a meta-analysis. J Urol 179:194 \200\2237. 3 Evan AP, McAteer JA, Connors BA, Blomgren PM, Lingeman JE (2007) Renal injury during shoc k wave lithotripsy is signi \201 cantly reduced by slowing the rate of shock wave delivery . BJU Int 100:624 \200\2237. 4 Kramback AE, Gettman MT, Rohlinger AL, et al. (2006) Diabetes mellitus and hypertension a ssociated with shock wave lithotripsy of renal and proximal ureteric stones at 19y of follo w-up. J Urol 175:1742 \200\2237. 5 Haleblian, Kijvikai K, de la Rosette J, Preminger G (2008) Ureteral stenting and urinary stone management: a systematic review. J Urol 179:424 \200\22330. 6 Candau C, Saussine C, Lang H, Roy C, Faure F, Jacqmin D (2000) Natural history of residua l renal stone fragments after ESWL. Eur Urol 37:18 \200\22322. 7 Streem SB, Yost A, Mascha E (1996) Clinical implications of clinically insigni \201 cant stone frag- ments after extracorporeal shock wave lithotripsy. J Urol 155:1186 \200\22390. 8 El-Nahas AR, El-Assmy AM, Madbouly K, Sheir KZ. (2006) Predictors of clinical signi \201 cance of residual fragments after extracorporeal shockwave lithotripsy for renal stones. J Endourol 20:870 \200\2234. 9 Zanetti G, Seveso M, Montanari E, et al. (1997) Renal stone fragments following shock wav e lithotripsy. J Urol 158:352 \200\2235. 10 Buchholz N, Meier-Padel S, Rutishauser G (1997) Minor residual fragments after extracor- poreal shockwave lithotripsy: spontaneous clearance or risk factor for recurrent stone for mation. J Endourol 11:227 \200\22332. CHAPTER 9 Stone disease 450 Intracorporeal techniques of stone fragmentation Electrohydraulic lithotripsy (EHL) The \201 rst technique developed for intracorporeal lithotripsy. A high volt- age applied acros s a concentric electrode under water generates a spark. This vaporizes water and the subseq uent expansion and collapse of the gas bubble generates a shock wave. An effective form of stone fragmentation. The shock wave is not focused so the EHL probe must be applied within 1mm of the stone to optimize stone fragmentation. EHL has a narrower safety margin than pneumatic, ultrasonic, or laser lithotripsy and shoul d be kept as far away as possible from the wall of the ureter, renal pelvis, or bladder to limit damage to these structures and at least 2mm away from the cystoscope, ureteroscope, o r nephroscope to prevent lens fracture. Principal uses: bladder stones (wider safety margin than in the narrower ureter). Pneumatic (ballistic) lithotripsy A metal projectile contained within the handpiece is prop elled backwards and forwards at great speed by bursts of compressed air (Fig. 9.4a). It str ikes a long, thin, metal probe at one end of the handpiece at 12Hz (12 strikes per second) transmitting shock waves to the probe which, when in contact with a rigid structure such as a stone, fragments the stone. Used for stone fragmentation in the ureter (using a thin pro be to allow insertion down a ureteroscope) or kidney (a thicker probe may be used, with an inbuilt suction device \200\224 \200\230Lithovac \200\231 \200\224to remove stone fragments ). Pneumatic lithotripsy is very safe since the excursion of the end of the probe is about 1mm and it bounces off the pliable wall of the ureter. Ureteric perforation is, therefore, rar e. Also low cost and low mainte- nance. However, its ballistic effect has a tendency to cau se stone migra- tion into the proximal ureter or renal pelvis where the stone may be inacce ssible to further treatment. The metal probe cannot bend around corners so it cannot be use d for ureteroscopic treatment of stones within the kidney. Principal uses: ureteric stones. Ultrasonic lithotripsy An electrical current applied across a piezoceramic plate located in the ultrasound transducer generates ultrasound waves of a speci \201 c frequency (23 000 \200\22325 000Hz). The ultrasound energy is transmitted to a hollow metal probe which, in t urn, is applied to the stone (Fig. 9.4b). The stone resonates at high frequency and this ca uses it to break into small fragments (the opera singer breaking a glass) which are then su cked out through the center of the hollow probe. Soft tissues do not resonate when the prob e is applied to them and, therefore, are not damaged. Can only be used down straight instru ments. Principal uses: fragmentation of renal calculi during PCNL. INTRACORPOREAL TECHNIQUES OF STONE FRAGMENTATION 451 (a) probe metal projectile to generator (b) GENERATOR piezoceramic elements USS probe (longitudinal vibration) acoustic end parts suction foot pedal Fig. 9.4 (a) The Lithoclast: a pneumatic lithotripsy device (b) The Calcuson: an ultrasonic lithotripsy device. (Reproduced from Walsh PC, Retik AB, Vaughan D, et al. (2002) Campbell \200\231s Urology, 8th edn. Amsterdam: W.B. Saunders/Elsevier, pp. 3395 \200\2237 with per mission from Elsevier). CHAPTER 9 Stone disease 452 Laser lithotripsy The holmium:YAG laser. Principally, a photothermal mechanism of action, c ausing stone vaporization. Minimal shock wave generation and, therefore, less risk of causi ng stone migration. The laser energy is delivered down \201 bres which vary in diameter f rom 200 to 360 m. The 200 m \201 bre is very \202 exible and can be used to gain acce ss to stones even within the lower pole of the kidney (Figs. 9.5 and 9.6). A 275 m \201 bre delivers more laser energy at the expense of a reduction in \202 exibility and, there fore, a reduced chance of lower pole access. The zone of thermal injury is limited from 0.5 to 1mm from the laser tip. No stone can withstand the heat generated by the Ho:YAG laser. Laser lithotripsy takes time, however, since the thin laser \201 bre must be \200\230pai nted \200\231 over the surface of the stone to vaporize it. Principal uses: ureteric stones, small intrarenal stones. INTRACORPOREAL TECHNIQUES OF STONE FRAGMENTATION 453 Fig. 9.5 A laser \201 bre. Fig. 9.6 Access to the lower pole of the kidney with a \202 exible ureteroscope. CHAPTER 9 Stone disease 454 Flexible ureteroscopy and laser treatment The development of small caliber ureteroscopes wi th active de \202 ecting mechanisms and instrument channels, in combination with the devel op- ment of laser technology, small diameter laser \201 bres, and stone baskets and grasp ers, has opened the way for intracorporeal, endoscopic treat- ment of kidney stones. Access to virtually the entire collecting system is possible with modern instruments. The holmium :YAG laser has a minimal effect on tissues at distances of 2 \200\2233mm from the laser tip and so \200\230collat- eral \200\231 tissue damage is minimal with this laser type. Flexible ureteroscopy and laser fragmentation offer a more effective treatment option compa red with ESWL, with a lower morbidity than PCNL, but usually requires a general anesthetic (some patients will toler- ate it with sedation alone). It can also allow access to areas o f the kidney where ESWL is less ef \201 cient or where PCNL cannot reach. It is most suite d to stones <2cm in diameter. Indications for \202 exible ureteroscopic kidney stone treatment - - ESWL Lower pole stone (reduces the likelihood of stone passage post- ESWL \200\224fragments have to pass \200\230uphill \200\231). Cystine stones. Obesity such that (nephroscopes ma y not be long enough to reach the stone). Obesity such that ESWL is technically dif \201 c ult or impossible. BMI >28 is associated with lower ESWL success rates. Treatment distance may exceed the focal length of the lithotripter. Musculoskeletal deformities such that ston e access by is dif \201 cult or impossible (e.g. kyphoscoliosis). Stone in a calyceal dive rticulum (accessing stones in small diverticulae in upper and anterior calyces is dif \201 cult and carries signi \201 cant risks). Stenosis of a calyceal infundibulum or \200\230 tight \200\231 angle between the renal pelvis and infundibulum. The \202 exible ureterosc ope can negotiate acute angles and the laser can be used to divide obstructions. Bleeding d iathesis where reversal of this diathesis is potentially dangerous or dif \201 cult. Horse shoe or pelvic kidney. ESWL fragmentation rates are only 50% in such cases1 due to dif \201 culties of shock wave transmission through overlying organs (bowel). PCNL for such kid neys is dif \201 cult because of bowel proximity and variable blood supply (blood supply d erived frommultiple sources). Patient \200\231s preference. failure. PCNL access is technically dif \201 cult or impossible PCNL or ESWL Disadvantages Ef \201 cacy diminishes as stone burden increases \200\224it simply takes a long time to \200\230paint \200\231 the surface of the stone with laser energy so destroyi ng it. A dust cloud is produced as the stone fragments and this temporarily obscures FLEXIBLE URETEROSCOPY AND LASER TREATMENT 455 the view until it has been washed away by irrigation. Stone fragmentation rates for those e xpert in \202 exible ureteroscopy (not every stone surgeon will be able to achieve these results) are 770 \200\22380% for stones <2cm in diameter and 50% for those >2cm in diameter 2 and 710% of patients will require two or more treatment sessions.2 1 Kupeli B, Isen K, Biri H, et al. (1999) Extracorporeal shockwave lithotripsy in anomalous kid- neys. J Endourol 13:39 \200\22352. 2 Dasgupta P, Cynk MS, Bultitude MF, Tiptaft RC, Glass JM. (2004) Flexible ureterorenoscopy : prospective analysis of the Guy \200\231s experience. Ann R Coll Surg 86:367 \200\22370. CHAPTER 9 Stone disease 456