Watchful waiting In many instances, small ureteric stones will pass spontaneously within da ys or a few weeks, with analgesic supplements for exacerbations of pain. Data on the rate of spontaneous stone passage are surprisingly limited.2 Chances of spontan eous stone passage depend principally on stone size. Sixty-eight percent of stones 5mm or l ess will pass spontaneously (95% CI 46 \200\22385%; meta-analysis of 224 patients); 47% of stones 6 \200\22310mm in diameter will pass spontaneously (95% CI 36 \200\22359%; meta-anal ysis of 104 patients).2 Average time for spontaneous stone passage for stones 4 \200\2236mm in diam- eter is 3 weeks.3 Stones that have not passed in 2 months are unlikely to do so. Of those stones that do eventually pass, those 2mm or less do so within 30 days and those 2 \200\2236mm in size do so within 40 days (but not all stones do pass and we cannot predict the chance of spontaneous passage in the individual patient). Therefore, accurate determin ation of stone size (on plain abdominal X-ray or by CTU) helps predict chances of sponta- n eous stone passage. Medical expulsive therapy (MET) There is growing evidence for the ef \201 cacy of MET, the preferred agents being the smooth muscle relaxing A1-adrenergic adrenoceptor block- ers.2, 4 These increase spontaneous stone passage rates, reduce stone passage time, and reduce fre quency of ureteric colic.4 The EAU/AUA Nephrolithiasis Guideline Panel meta-analysis showed that 29% more URETERIC STONES: ACUTE MANAGEMENT 471 patients (CI: 20 \200\22337%) taking tamsulosin passed their stones compared with controls. 2 Tamsulosin has been most studied in this setting, but tera- zosin and doxazosin seem to b e equally effective. Whether stones in all segments of the ureter are equally responsive to A-blockers remains to be determined. Another meta-analysis (7 studies, 484 patients)5 suggests that tamsulosin also seems to enc ourage stone clearance after ESWL for ureteric (and possibly renal) stones, the pooled abso lute risk difference being between 16 \200\22319% (0.2 vs 0.4mg) in favor of tamsulosin (so if 70% pass their stones spontaneously without tamsulosin, 89% pass their stones while on 0.4mg tamsulosin). Five patients needed to be treated with tamsulosin to achieve stone clea rance in one. There was a mean difference of 8 days in terms of time to stone expulsion in favor of those on tamsulosin. In the same meta-analysis, there was no signi \201 cant difference in stone passage rates between those taking the calcium channel blocker, nifedi- pine, and control patients. Glyceryl trinitrate patches do not aid stone passage or reduce the frequency of pain episod es and corticosteroids are of minimal, if any, bene \201 t.4,6 A trial of MET is a very reasonable approach for many patients, but individual circumstance s may dictate \200\230up front \200\231 ESWL or ureteroscopy, e.g. the possible disruption to work and daily living activities from episodes of pain occurring while a stone is progr essing towards eventual spontaneous passage may prompt the patient to request ESWL or urete roscopy (e.g. commercial airline pilots cannot \202 y until stone-free nor can those who \202 y for leisure). MET is contraindicated where there is clinical evidence of sepsis (essen- tially fever) or deteriorating renal function. If you use a trial of MET, warn patients of the risks (drug s ide effects, possible need for intervention in the form of ESWL, ureteroscopy, or J stentin g) and mention it is an \200\230off-label \200\231 (i.e. non-licensed) therapy. Arrange pe riodic follow-up imaging (usually a plain X-Ray) to monitor stone position. Peristalsis, the forward propulsion of a bolus of urine down the ureter, can only occur if the walls of the ureter above the bolus of urine can coapt, i.e. close \201 rmly together . If they cannot, as occurs in a ureter distended with urine, the bolus of urine cannot mov e distally. 1 Springhart WP, Marguet CG, Sur RL, et al. (2006) Forced versus minimal intravenous hydrat ion in the management of acute renal colic: a randomized trial. J Endourol 20:713 \200\2236 . 2 Preminger GM, Tiselius HG, Assimos DG, et al. (2007) 2007 Guideline for the management of ureteral calculi (Joint EAU/AUA Nephrolithiasis Guideline Panel. J Urol 178:2418 \200\2233 4. 3 Miller OF, Kane CJ (1999) Time to stone passage for observed ureteral calculi. J Urol 162 :688 \200\22391. 4 Dellabella M, Milanese G, Muzzonigro G (2003) Ef \201 cacy of tamsulosin in the medical manage- ment of juxtavesical ureteral stones. J Urol 170:2202 \200\2235. 5 Zhu Y, Duijvesz D, Rovers MM, Lock TM (2009) Alpha blockers to assist stone clearance aft er extra-corporeal shock wave lithotripsy: a meta-analysis. BJU Int 106:256 \200\22361. 6 Hussain Z, Inman RD, Elves AW, et al. (2001) Use of glyceryl trinitrate patches in patien ts with ureteral stones: a randomized, double-blind, placebo-controlled study. Urology 58:5 21 \200\2235. CHAPTER 9 Stone disease 472 Ureteric stones: indications for intervention to relieve obstruction and/or remove the ston e - Pain controlled with additional pain relief. : in the presence of an obstructing stone can lead to the Bacteriuria development of urosepsis. The EAU/AUA Nephrolithiasis Guideline Pan el recommends that patients with ureteric stones and bacteriuria be treated with appropriat e antibiotics (level IV evidence, i.e based on the opinions or clinical experience of respe cted authorities). Where intervention is planned (ESWL or ureteroscopy), appropriate antibi otics should be given in advance of the treatment. Fever percutaneous nephrostomy or JJ ste nt).1 Impaired renal function (solitary kidney obstructed by a stone, bilateral ureteric st ones, or pre-existing renal impairment which gets worse as a consequence of a ureteric ston e): threshold for intervention is lower. Prolonged unrelieved obstruction of renal function .1 How long it takes for this loss of renal function to occur is uncertain, but generally s peaking, the period of watchful waiting for spontaneous stone passage tends to be limited t o 4 \200\2236 weeks. Social reasons surgical treatment because they need to get back to wor k or because of their childcare duties whereas some patients will be happy to sit things ou t. Airline pilots and some other professions are unable to work until they are stone-free. : that fails to respond to analgesics or recurs and cannot be : have a low threshold for draining the kidney (either : this can result in long-term loss : young active patients may be very keen to opt for Emergency temporizing and de \201 nitive treatment of the stone Where the pain of a ureter ic stone fails to respond to analgesics or where renal function is impaired because of the stone, then temporary relief of the obstruction can be obtained by the insertion of a JJ st ent or percuta- neous nephrostomy tube. (Percutaneous nephrostomy tube can restore ef \201 cient peristalsis by restoring the ability of the ureteric wall to coapt.) JJ stent insertion or percutaneous nephrostomy tube can be done quickly, but the stone is s till present (Fig. 9.13). It may pass down and out of the ureter with a stent or nephrostom y in situ, but in many instances, it simply sits where it is and subsequent de \201 nitive treatment is still required. While JJ stents can relieve stone pain, they can cause bother some irrita- tive bladder symptoms (pain in the bladder, frequency, and urgency) (see Table 9.6). JJ stents do make subsequent stone treatment in the form of ureteroscopy technically easier by causing passive dilatation of the ureter. The patient may elect to proceed to de \201 nitive stone treatment by immediate ureteroscopy (for stones at any location in the ureter) or ESWL (if the stone is in the upper and lower ureter \200\224ESWL cannot be used for stones in the mid-ureter because this region is surrounded by bone, URETERIC STONES: INDICATIONS FOR INTERVENTION 473 which prevents penetration of the shock waves) (Fig. 9.14). Local facilities and expertise will determine whether de \201 nitive treatment can be offered immediately. Not all hospit als have access to ESWL or endoscopic sur- geons 365 days a year. Fig. 9.13 A JJ stent. Fig. 9.14 Ureteroscopic stone fragmentation for a lower ureteric stone. Emergency treatment of an obstructed infected kidney Antibiotic delivery into an obstructed collecting system is impaired and so the septic patient with an obstructing stone should u ndergo urgent decompression of the collecting system and de \201 nitive stone treatment (E SWL or ureteroscopy) should be delayed until the sepsis has resolved. CHAPTER 9 Stone disease 474 The rationale for performing percutaneous nephrostomy, rather than JJ stent insertion for a n infected obstructed kidney, is to reduce the like- lihood of septicaemia occurring as a c onsequence of showering bacteria into the circulation. It has been theorized that this is m ore likely to occur with JJ stent insertion than with percutaneous nephrostomy insertion, t hat J stent insertion might damage the ureter (unlikely), and that monitoring of urine outp ut and the facility for irrigation of a viscous pyonephrosis is possible with a nephrostomy , but with not a J stent. Nephrostomy inser- tion has the advantage that it avoids the need for a general anesthetic, but in fact, J stent insertion can be done with sedation and avo ids the risk of bleeding from inadvertent puncture of a branch of the renal artery.1 The EAU/AUA Nephrolithiasis Guideline Panel2 recommends that the system of drainage \200 \224J stent or percutaneous nephrostomy \200\224is left to the discretion of the urologist since both have been shown in a randomized trial of 42 patients with obstructing stones and a temperature of >38 C and/or WBC of 17 000/mm3* to be equally effective for the manageme nt of presumed obstructive pyelonephritis or pyonephrosis3 in terms of time to normalizatio n of temperature and WBC (which takes approximately 2 \200\2233 days) and in-hospital stay. A 6 or 7 Ch J stent was used (with a Foley bladder catheter in 70%) or 8 Ch (occasionally larger) nephrostomy (plus a urethral catheter in 33%). Table 9.6 Complications of and problems associated with nephrostomy insertion and drainage (n = 169)4 and J stent5,6 (none performed for relief of obstructed, infected kidney; n=226) Complication J stent (%) Nephrostomy (%) Failure of insertion 16 2 Sepsis in previously non-septic patient 3 \200\2234 Hemorrhage requiring transfusion 2 Stent occlusion 1 \200\2237 Tube displacement (tube falling out or for J stent migrating up or down) 0.1 \200\2237 5 Pleural effusion 1 Pneumonia/atelectasis 2 Ureteric perforation 6% Stent symptoms Flank pain, 15 \200\22320; suprapubic pain, 20; urinary frequency, 40; haema-turia, 40 URETERIC STONES: INDICATIONS FOR INTERVENTION 475 An arbitrary de \201 nition of leukocytosis since patients with ureteric stones often have mildly elevated WBC. 1 Holm \200\223Nielsen A, Jorgensen T, Mogensen P, Fogh J (1981) The prognostic value of pr obe renog- raphy in ureteric stone obstruction. Br J Urol 53:504 \200\2237. 2 Preminger GM, Tiselius HG, Assimos DG, et al. (2007) 2007 Guideline for the management of ureteral calculi, Joint EAU/AUA Nephrolithiasis Guideline Panel. J Urol 178:2418 \200\2233 4. 3 Pearle MS, Pierce HL, Miller GL, et al. (1998) Optimal method of urgent decompression of the collecting system for obstruction and infection due to ureteral calculi. J Urol 160:126 0. 4 Lee WJ, et al. (1994) Emergency percutaneous nephrostomy: results and complications. J Va sc Intervent Rad 5:135. 5 Pocock RD, Stower MJ, Ferro MA, Smith PJ, Gingell JC (1986) Double J stents. A review of 100 patients. Br J Urol 58:629. 6 Smedlev FH, Rimmer J, Taube M, Edwards L (1988) J (pigtail) ureteric catheter insertions: a retrospective review. Ann R Coll Surg (Engl) 70:377. CHAPTER 9 Stone disease 476 Ureteric stone treatment Almost 70% of stones 5mm or less and almost 50% of stones 6 \200 \22310mm in diameter will pass spontaneously over a period of 3 \200\2236 weeks or there- a bouts.1 Stones that have not passed in 2 months are unlikely to do so, although much to the patient \200\231s and surgeon \200\231s surprise, large stones do sometimes drop out of th e ureter at the last moment. Indications for stone removal - Pain that fails to respond to analgesics or recurs and cannot be controlled with additional pain relief. Impaired renal function (solitary kidney obstructed by a stone, bilateral ure teric stones, or pre-existing renal impairment which gets worse as a consequence of a urete ric stone). 74 \200\2236 weeks). Prolonged unrelieved obstruction (generally speaking Socia l reasons: young active patients may be very keen to opt for surgical treatment because the y need to get back to work or because of their childcare duties whereas some patients will be happy to sit things out. Airline pilots and some other professions are unable to work un til they are stone-free. These indications need to be related to the individual patient \200\224their stone size, th eir renal function, the presence of a normal contralateral kidney, their tolerance of exace rbations of pain, their job and social situation, and local facilities (the availability of surgeons with appropriate skill and equip- ment to perform endoscopic stone treatment). Twenty years ago, when the only options were watchful waiting or open surgical removal of a stone (open ureterolithotomy), surgeons, and patients were inclined to \200\230sit it out \200\231 for a considerable time in the hope that the stone would pass spontaneously. Nowa days, the advent of ESWL and of smaller ureteroscopes with ef \201 cient stone fragmentati on devices (e.g. the holmium laser) has made stone treatment and removal a far less morbid procedure, with a far smoother and faster post-treatment recov- ery. It is easier for both the patient and the surgeon to opt for interven- tion, in the form of ESWL or surgery, as a quicker way of relieving them of their pain and a way of avoiding unpredictable and unplea sant exacerba- tions of pain. It is clearly important for the surgeon to inform the patient of the out- comes and potenti al complications of intervention, particularly given the fact that many of stones would pas s spontaneously if left a little longer, particularly now there is evidence for MET. 1 Preminger GM, Tiselius HG, Assimos DG, et al. (2007). 2007 Guideline for the management o f ureteral calculi. Joint EAU/AUA Nephrolituiasis Guideline Panel. J Urol 178: 2418 \200 \22334. This page intentionally left blank CHAPTER 9 Stone disease 478 Treatment options for ureteric stones - - - - - - ESWL Ureteroscopy. PCNL. Open ureterolithotomy. Laparoscopic ureterolithotomy. Percutaneous antegrade ureteroscopy. : in situ or after JJ stent insertion.* Basketing of stones (blind or under radiographic \200\230control \200\231) is a historical treatment (the potential for serious ureteric injury is signi \201 cant). For the purposes of decision making with regard to treatment options, the ureter can be div ided into two halves (proximal and distal to the iliac vessels) or in thirds (upper third f rom the PUJ to the upper edge of the sacrum; middle third from the upper to the lower edge of the sacrum, i.e. the extent of the sacroiliac joint; lower third from the lower edge of the sacrum to the VUJ). EAU/AUA Nephrolithiasis Guideline Panel recommendations 20071 These should be interpreted i n the light of local facilities and expertise. Some hospitals have access to and expertise in the whole range of treat- ment options. Others may have limited access to a lithotriptor or may not have surgeons skilled in the use of the ureteroscope. Smaller ureteroscopes with improved optics and larger instrument channels and the advent of holmium laser lithotripsy have improved the ef \201 cacy of ureteroscopic stone fragmenta tion (to 795% stone clearance) and reduced its morbidity. As a consequence, many surgeons a nd patients will opt for ureteroscopy, with its potential for a \200\230one-off \200\231 treatment, over ESWL where more than one treatment will be required and post-treat- ment im aging is required to con \201 rm stone clearance (with ureteroscopy, you can directly see that the stone has gone). Many urology departments do not have unlimited access to ESWL and patients may, therefore, opt for ureteroscopic stone extraction. The stone clearance rates for ESWL are stone size-dependent. ESWL is more ef \201 cient fo r stones <1cm in diameter compared with those >1cm in size. Conversely, the outcome of uret eroscopy is somewhat less depen- dent on stone size. The bottom line seems to be that for stones <1cm in diameter, ESWL and ureteroscopy are abl e to achieve virtually equivalent stone-free rates, but ureteroscopy has the edge over ESWL for stones >1cm (although the differ- ence in stone-free rates is not huge between these t wo treatments).2,3 ESWL after \200\230push-back \200\231 of the stone into the kidney (i.e. into the renal pe lvis or calyces) is a historical treatment for two reasons: (1) In situ ESWL (ESWL of the s tone located within the ureter) is very effective in most cases without the need to push th e stone back into the kidney; (2) If the ESWL fails to fragment the stone, a relatively str aightforward operation of ureteroscopy has been converted into the technically more challen ging one of \202 exible ureterorenoscopy. So try to avoid pushing the stone back into the kidney when inserting a J stent, but warn the patient of this possibility. TREATMENT OPTIONS FOR URETERIC STONES 479 Ef \201 cacy outcomes (i.e. stone-free rates) of EAU/AUA Nephrolithiasis Guideline Panel 2 007 Table 9.7 Median stone-free rates of ESWL and ureteroscopy ( \201 gures in brackets are 95 % CI)1 Stone position and size ESWL Ureteroscopy Distal ureter <10mm 86% (73 \200\22375) 97% (96 \200\22398) Distal ureter >10mm 74% (80 \200\22390) 93% (88 \200\22396) Mid ureter <10mm 84% (65 \200\22395) 91% (81 \200\22396) Mid ureter >10mm 76% (36 \200\22397) 78% (61 \200\22390) Proximal ureter <10mm 90% (85 \200\22393) 80% (73 \200\22385) Proximal ureter >10mm 68% (55 \200\22379) 79% (71 \200\22387) RCTs comparing ESWL and ureteroscopy are generally lacking. The EAU/AUA Nephrolithiasis Gui deline Panel 2007 meta-analysis suggests that: - Proximal ureter <10mm than ureteroscopy. Proximal ureter >10mm rate than ESWL. For all mid- ureteric stones higher stone-free rate than ESWL, but small patient numbers make comparison dif \201 cult. For all distal stones ureteroscopy ESWL. : ESWL marginally higher stone-free rate : ureteroscopy marginally higher stone-free : ureteroscopy has a marginally : has a higher stone-free rate than Thus, there are no great differences in stone-free rates between ESWL and ureteroscopy (see Table 9.7). Precisely which technique one uses will depend to a considerable degree on loc al resources (e.g. ready access to ESWL) and local expertise at performing ureteroscopy, pa rticularly for upper tract stones. Failed initial ESWL is associated with a low success rat e for subsequent ESWL.4 Therefore, if no effect after one or two treat- ments, change tacti cs. Open ureterolithotomy and laparoscopic ureterolithotomy (less inva- sive than open ureterol ithotomy) are used in the rare cases (e.g. very impacted stones) where ESWL or ureteroscopy have been tried and failed or were not feasible.1 Laparoscopic ureterolithotomy for large, impacted stones has a stone-free rate averaging almost 90%. Should a stent be inserted after ureteroscopic stone removal? The standard advice, based on a number of RCTs, is that routine J stent- ing after an \200\230uncomplicated \200\231 ur eteroscopy is unnecessary.5 \200\230Uncomplicated ureteroscopy \200\231 has not been preci sely de \201 ned. De \201 nitions include minimal or no ureteral trauma during the proces s of stone extraction, minimal or no ureteral dilatation required in order to allow uretero scope access, and no or minimal residual stone burden. CHAPTER 9 Stone disease 480 Meta-analyzes of post-ureteroscopy complications (emergency room visit, readmission to hosp ital, requirement for secondary procedures) showed no signi \201 cant difference in outcom e in those stented post- ureteroscopy compared with those not stented.6,7 Whether there are subgroups of patients who do bene \201 t from stenting post-ureteroscopy remains to be de termined. It has been suggested that post-ureteroscopy stenting reduces ure- teric stricture rates, b ut there is no convincing evidence to support this assertion.6,7 1 Preminger GM, Tiselius HG, Assimos DG, et al. (2007) 2007 Guideline for the management of ureteral calculi, Joint EAU/ AUA Nephrolithiasis Guideline Panel. J Urol 178:2418 \200\223 34. 2 Kijvikai K, Haleblian GE, Preminger GM, de la Rosette J (2008) Shock wave lithotripsy or ureteroscopy for the management of proximal ureteral calculi: an old discussion revisited. J Urol 178:1157 \200\22363. 3 Verze P, Imbimbo C, Cancelmo G, et al. (2010) Extracorporeal shock wave lithotripsy vs ur et- eroscopy as \201 rst line therapy for patients with single, distal ureteric stones: a prospective random- ized study. BJU Int 106:1748 \200\22352. 4 Pace KT, Weir MJ, Tariq N, Honey RJ (2000) Low success rate of repeat shock wave lithotri psy for ureteral stones after failed initial treatment. J Urol 164:1905 \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 Nabi G, Cook J, N \200\231Dow J, McClinton S (2007) Outcomes of stenting after uncomplica ted ureteroscopy: systematic review and meta-analysis. BMJ 334:572. 7 Makarov DV, Trock BJ, Allaf ME, Matlaga BR (2008) The effect of ureteral stent placement on post-ureteroscopy complications: a meta-analysis. Urology 71:796 \200\223800. This page intentionally left blank CHAPTER 9 Stone disease 482 Prevention of calcium oxalate stone formation The recurrent nature of stone disease emphasi zes the importance of pre- vention. Recurrence is more likely in those with an onset of sto ne disease at a young age, a family history for stones, those with an underlying meta- boli c predisposition (cystinuria, gout), and in those who have had an infec- tion stone (especi ally in those with neuropathic bladders). A series of landmark papers from Harvard Medical School1 and other groups allows us to give rational advice on reducing the risk of future stone formation. The Harvard studies were c arried out in those with no prior history of stone disease, but are likely to be relevant t o those who have already formed a stone (which, of course, is the group most inter- ested i n how to avoid the unpleasantness of another stone). The Harvard studies strati \201 ed th e risk of stone formation based on intake of calcium and other nutrients (Nurses Health Stu dy, n = 81 000 women; equivalent male study, n = 45 000). Low \202 uid intake Low \202 uid intake may be the single most important risk factor fo r recurrent stone formation. High \202 uid intake is protective,2 by reducing urinary sat - uration of calcium, oxalate, and urate. Time to recurrent stone formation is prolonged fr om 2 to 3y in previous stone formers randomized to high \202 uid vs low \202 uid intake (averaging 72.5 vs 1L/day) and over 5y, the risk of recurrent stones was 27% in low-volume controls compared with 12% in high-volume patients.2 Dietary calcium Conventional teaching was that high calcium intake increases the risk of ca lcium oxalate stone disease. The Harvard Medical School studies have shown that low calcium intake is paradoxically associated with an increased risk of forming kidney stones in both men and women (relative risk of stone formation for the highest quintile of dietary calciu m intake vs the lowest quintile = 0.65; 95% CI 0.5 \200\2230.83, i.e. high calcium intake w as associated with a low risk of stone formation). Calcium supplements In the Harvard studies,1,3 the relative risk of stone formation in wome n on supplemental calcium (most calcium supplements contain calcium carbo- nate) compared w ith those not on calcium was 1.2 (95% CI 1.02 \200\2231.4) and for men, it was 1.23 (95% CI 0.84 \200\2231.79). In 67% of women and 49% of men on supplements, the calcium was either not consumed with a meal or was consumed with a meal with low oxalate content. It is possib le that con- suming calcium supplements with a meal or with oxalate-containing foods could reduce this small risk of inducing kidney stones. A total of 650mg of calcium carbonate tak en immediately after a meal is associated with a lower urinary oxalate and higher urinary c itrate than when taken at bed- time. Urinary calcium excretion increased, but the net effec t was a reduc- tion in the activity product for calcium oxalate crystal formation.4 The bot tom line seems to be \200\230take your calcium supplement at mealtimes \200\231. PREVENTION OF CALCIUM OXALATE STONE FORMATION 483 In post-menopausal women, calcium citrate, 400 mg twice daily, increases urinary calcium an d citrate excretion, reduces oxalate excre- tion, and does not change urine calcium oxalate saturation, which suggests calcium citrate neither increases nor decreases stone risk.5 Those few studies exploring the risk of calcium supplementation in those who have already f ormed a stone recruited so few subjects that few conclusions can be drawn. A reduction in u rine saturation with calcium and oxalate was reported in 22 hyperoxaluric stone formers adv ised to consume calcium-containing foods or supplemental calcium citrate with meals (300 \200\223500mg of calcium), entirely in keeping with the protective effect of calcium noted in the Harvard studies (the risk of actual stone formation was not assessed).6 The critical factor may be taking the supple- ment at meal times. Other dietary risk factors related to stone formation Increased risk of stone formation (re lative risk of stone formation shown in brackets for highest to lowest quintiles of intake of particular dietaryfactor): - - Sucrose (1.5). Sodium (1.3): high sodium intake (leading to natriuresis) causes hypercalciu ria. Potassium (0.65). Animal proteins High intake of animal proteins causes increased urinary excretion of cal- c ium, reduced pH, high urinary uric acid, and reduced urinary citrate, all of which predispo se to stone formation.7,8 Alcohol Curhan \200\231s studies from Harvard9 suggest small quantities of wine decrease th e risk of stones. Vegetarian diet Vegetable proteins contain less of the amino acids, phenylalanine, tyro- si ne, and tryptophan, that increase the endogenous production of oxalate. A vegetarian diet m ay protect against the risk of stone formation.10 A low animal protein, low sodium, and low oxalate diet with normal calcium intake (1200mg daily) is associated with a reduction in r isk of stone for- mation of almost 50% over 5y when compared with a diet low in calcium (40 0mg daily) and oxalate7. Dietary oxalate A small increase in urinary oxalate concentration increases calcium oxa- la te supersaturation much more than does an increase in urinary calcium concentration. Mild h yperoxaluria is one of the main factors leading to calcium stone formation.11 CHAPTER 9 Stone disease 484 Potassium citrate Potassium citrate results in a substantial reduction in the risk of stone for- mation.12,13 Gastrointestinal side effects (nausea, vomiting, bloating, diar- rhoea) are common. Calcium phosphate stones may form in the alkaline urine induced by citrate supp lements (keep urine pH <6.5). Thiazide diuretics Reduce calcium stone disease by reducing urinary calcium excretion.14 Hy pokalaemia, glucose intolerance, hyperuricaemia, and increased total cholesterol, LDL and t riglycerides are potential side effects, the latter pre- disposing to cardiovascular diseas e. Allopurinol Allopurinol 50 \200\223100mg daily reduces calcium oxalate stone recurrence in both urate stone formers and calcium oxalate stone formers.15 Calcium salts or calcium supplementation May be helpful in those with hyperoxaluria or exce ssive GI oxalate absorp- tion (in \202 ammatory bowel disease, small bowel resection). Magnesium and phosphate Magnesium (an inhibitor of crystallization) and phosphate (which re duces GI calcium absorption) are probably not effective. The bottom line in calcium stone prevention \200 High \202 uid intake (aiming for >2.5L urine output daily); normal calcium intake; low sodium, oxalate, and protein; potassium ci trate (e.g. lemon squash). Prevention of other stone types - Uric acid stones : high \202 uid intake aiming for urine output >3L/day; alkalinize urine (e.g. citrate), allopurinol (xanthine oxidase inhibitor). Calcium phosphate stones appropr iately acidify the urine). Citrate increases urinary pH and helps reduce stone risk. Cystin e stones urine to pH >7 with citrate and bicarbonate) and reduce its urinary concentration to <500micromol/L (increase \202 uid intake to >4L/day; night time \202 uids help). Pen icillamine, A-mercaptopropionlyglycine (Tiopronin), and captopril bind with cystine to form soluble dimers. Infection stones patient since sterilizing the urine may be impossible in the context of indwelling catheters. Consider low-dose antibiotics although whether they re duce stone recurrence rates is debatable (warn of rare, but serious, side effects: nitrofur antoin \200\224pulmonary \201 brosis; trimethoprim \200\224hematological). : usually due to RTA (inability to : aim to increase free cystine solubility (by alkalinizing : a dif \201 cult one, especially in the neuropathic PREVENTION OF CALCIUM OXALATE STONE FORMATION 485 1 Curhan GC, Willett WC, Rimm EB, Stampfer MJ (1993) A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med 328:833 \200 \2238. 2 Borghi L, Meschi T, Amato F, Briganti A, Novarini A, Giannini A. (1996) Urinary volume, w a- ter and recurrences in idiopathic calcium nephrolithiasis: A 5-year randomized prospecti ve study. J Urol 155:839 \200\22343. 3 Curhan G, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ (1997) Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kid ney stones in women. Ann Int Med 126:497 \200\223504. 4 Domrongkitchaiporn S, Sopassathit W, Stitchantrakul W, Prapaipanich S, Ingsathit A, Rajat anavin R (2004) Schedule of taking calcium supplement and the risk of nephrolithiasis. Kidn ey Int 65:1835-41. 5 Sakhaee K, Poindexter JR, Grif \201 th CS, Pak CY (2004) Stone forming risk of calcium c itrate supplementation in healthy postmenopausal women. J Urol 172:958 \200\22361. 6 Penniston KL, Nakada SY (2009) Effect of dietary changes on urinary oxalate excretion and calcium oxalate supersaturation in patients with hyperoxaluric stone formation. Urology 73 :484 \200\2239. 7 Borghi, L (2002) Comparison of two diets for prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 346:77 \200\22384. 8 Kok DJ (1990) The effects of dietary excesses in animal protein and in sodium on the comp osi- tion and crystallization kinetics of calcium oxalate monohydrate in urines of healthy men. J Clin Endocrinol Metab 71:861 \200\2237. 9 Curhan G, Willett WC, Speizer FE, Stampfer MJ (1998) Beverage use and risk for kidney sto nes in women. Ann Intern Med 128:534 \200\22340. 10 Robertson WG, Peacock M, Marshall DH (1982) Prevalence of urinary stone disease in veg- etarians. Eur Urol 8:334 \200\2239. 11 Robertson WG, Peacock M, Ouimet D, et al. (1981) The main risk for calcium oxalate stone disease in man: hypercalciuria or mild hyperoxaluria? In: Smith LH, Robertson WG, Finlayso n B (eds) Urolithiasis: Clinical and Basic Research. New York: Plenum Press, pp. 3 \200\223 12. 12 Ettinger B, Pak CY, Citron JT, Thomas C, Adams-Huet B, Vangessel A (1997) Potassium magn esium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis . J Urol 158:2069 \200\22373. 13 Barcelo P, Wuhl O, Servitge E, Rousaud A, Pak CY (1993) Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis. J Urol 150:1761 \200\2234. 14 Pearle MS, Roehrborn CG, Pak CY (1999) Meta-analysis of randomized trials for medical pr evention of calcium oxalate nephrolithiasis. J Endourol 13:679. 15 Ettinger B, Tang A, Citron JT, Livermore B, Williams T (1986) Randomized trial of allopu rinol in th eprevention of calcium oxalate calculi. N Engl J Med 315:1386-9. CHAPTER 9 Stone disease 486 Bladder stones Composition Struvite (i.e. they are infection stones) or uric acid (in non-i nfected urine). Adults Bladder calculi are predominantly a disease of men aged >50 and with BOO due to BPE. They also occur in the chronically catheterized patient (e.g. SCI patients), where the cha nce of developing a bladder stone is 25% over 5y (similar risk whether urethral or suprapub ic location of the stone).1 Children Bladder stones are still common in Thailand, Indonesia, North Africa, the Middle E ast, and Burma. In these endemic areas, they are usually com- posed of a combination of amm onium urate and calcium oxalate. A low phosphate diet in these areas (a diet of breast milk and polished rice or millet) results in high peaks of ammonia excretion in the urine. Symptoms May be symptomless (incidental \201 nding on KUB X-ray or bladder USS or on cyst oscopy) \200\224the common presentation in spinal patients who have limited or no bladder s ensation). In the neurologically intact patient \200\224 suprapubic or perineal pain, haema turia, urgency, and/or urge inconti- nence, recurrent UTI, LUTS (hesitancy, poor \202 ow) . Diagnosis If you suspect a bladder stone, they will be visible on KUB X-ray or renal USS (F ig. 9.15). Treatment Most stones are small enough to be removed cystoscopically (endoscopic cystolitho lapaxy), using stone-fragmenting forceps for stones that can be engaged by the jaws of the forceps and EHL or pneumatic lithotripsy for those that cannot. Large stones (Fig. 9.15) ca n be removed by open sur- gery (open cystolitholapaxy).1 1 Ord J (2003) Bladder management and risk of bladder stone formation in spinal cord injure d patients. J Urol 170:1734 \200\2237. BLADDER STONES 487 Fig. 9.15 A bladder stone. CHAPTER 9 Stone disease 488 Management of ureteric stones in pregnancy While hypercalciuria and uric acid excretion inc reases in pregnancy (pre- disposing to stone formation), so too do urinary citrate and magn esium levels (protecting against stone formation). The \200\230net \200\231 effect \200 \224incidence of ureteric colic is the same as in non-pregnant women.1 Ureteric stones occu r in 1 in 1500 \200\2232500 pregnancies, mostly during second and third tri- mesters. They are associated with a signi \201 cant risk of preterm labor2 and the pain caused by ureter ic stones can be dif \201 cult to distinguish from other causes. Differential diagnosis of \202 ank pain in pregnancy Ureteric stone, placental abruption, appendicitis, pyelonephritis, and all the other (many) causes of \202 ank pain in non-pr egnant women. Diagnostic imaging studies in pregnancy Exposure of the fetus to ionizing radiation can cau se fetal malformations, intrauterine growth retardation, malignancies in later life (leukem ia), and mutagenic effects (damage to genes, causing inherited disease in the off- spring o f the fetus). The fetus is most at risk during organogenesis (weeks 4 \200\22310 of gestati on). Fetal radiation doses during various procedures are shown in Table 9.8. Radiation dose s of <100mGy are reported as unlikely to have an adverse effect on the fetus.3 In USA, the National Council on Radiation Protection has stated that \200\230fetal risk is considered to be negligible at <50mGy when compared to the other risks of pregnancy and the risk of ma lformations is signi \201 cantly increased above control levels at doses >150mGy \200\231. 4 The American College of Obstetricians and Gynecologists has stated that \200\230X-ray ex posure to <50mGy has not been associated with an increase in fetal anomalies or pregnancy l oss \200\231.5 However, every effort should be made to limit exposure of the fetus to radia tion. Table 9.8 Fetal radiation dose after various radiological investigations (note lcGy is equi valent to 10mGy) Risk of inducing cancer (up to age 15y) Procedure Fetal dose (mGy) KUB X-ray 1.4 1 in 24 000 IVU 6 shot 1.7 1 in 10 000 IVU 3 shot \200\223 \200\223 CT: abdominal 8 1 in 4000 CT: pelvic 25 1 in 1300 Fluoroscopy for JJ stent insertion 0.4 1 in 42 000 Adapted from the Joint Guidance from the National Radiographic protection Board, College of Radiographeres Royal College of Radiologists, 1998. MANAGEMENT OF URETERIC STONES IN PREGNANCY 489 Plain radiography and IVU Limited usefulness (fetal skeleton and the enlarged uterus obscur e ureteric stones; delayed excretion of contrast limits opaci \201 cation of ureter; theo- retical risk of fetal toxicity from the contrast material). Recommendations are for a limi ted IVU (e.g. control \201 lm followed by a 30min \201 lm) with fetal shielding. CT-KUB Very accurate method for detecting ureteric stones, but most radiologists and urolog ists are unhappy to recommend this form of imaging in preg- nant women due to increased fet al radiation exposure. Low and ultra-low dose CT protocols are being developed. MRU The American College of Obstetricians and Gynecologists and the US National Council on Radiation Protection state that \200\230although there is no evidence to suggest that the embryo is sensitive to magnetic and radio- frequency at the intensities encountered in MRI, it might be prudent to exclude pregnant women during the \201 rst trimester \200\231.5,6 MRU can, therefore, potentially be used during the second and third trimesters, but not du r- ing the \201 rst trimester. Involves no ionizing radiation. Very accurate (100% sensit ivity for detecting ureteric stones)7, but expensive and not readily available in most hosp itals, particularly out of hours. Management Most (70 \200\22380%) will pass spontaneously.3 - Pain relief premature closure of the ductus arteriosus by blocking prostaglandin synthesis) . Indications for intervention pain refractory to analgesics, suspected urinary infection ( high fever, high WBC), high-grade obstruction, and obstruction in a solitary kidney). : opiate-based analgesics; avoid NSAIDs (can cause : the same as in non-pregnant patients \200\224 Options for intervention Depend on the stage of pregnancy and on local facilities and exper tise: - 4 requires regular changing (approximately JJ stent urinary diversion: 6 \200\2238 weeks to avoid encrustation). Nephrostomy urinary d iversion. Ureteroscopic stone removal with laser fragmentation. Aim to minimize radiation exposure to the fetus and to minimize the risk of miscarriage and preterm labor. General anesthesia can precipitate preterm labor and many urologists and ob stetricians will err on the side of temporizing options such as nephrostomy tube drainage o r JJ stent placement, rather than on operative treatment in the form of uretero- scopic sto ne removal. Avoid PCNL; ESWL is contraindicated. CHAPTER 9 Stone disease 490 1 Coe FL, Parks JH, Lindhermer MD (1978) Nephrolithiasis during pregnancy. N Engl J Med 298 :324 \200\2236. 2 Hendricks SK (1991) An algorithm for diagnosis and therapy of urolithiasis during pregnan cy Surg Gynecol Obst 172:49 \200\22354.