levo \202 oxacin 250mg od for 14 days. Alternatives include co-amoxiclav IVI, then PO, or a third-generation cephalosporin IVI, then PO for 14 days. \200 Consider additional single- dose gentamicin 3 \200\223 5mg/kg IVI. Rehydration with 0.9% NaCl. \200 Appropriate analgesia and antiemetics. CHAPTER 9 Essential urology 710 Urinary tract infection: miscellaneous Asymptomatic bacteriuria \200 Common (1% in young \231\200 vs 7 20% in \231\200 aged >80. Rare in \231\202 ). \200 De \201 nition ( \231\200 ): isolation of the same organism ( \211 105 cfu/mL) in two consecutive urine samples. Patient has no symptoms attributable to the urinary tract (by de \201 nition!). Associated with: sexual activity, diabetes, institutionalization, impaired urinary voiding, indwelling device (e.g. catheter or stent). 2 Important in: Pregnancy ( b p. 842). \200 Those about to undergo urinary tract instrumentation ( l muco sal bleeding, overt UTI, and bacteraemia). These are the only two groups where screening is appropriate, and treatment is not advocated outside these circumstances. Recurrent UTIs De \201 ned as >4 culture-proven UTIs in a year. A recurrence is not the sa me as a relapse (de \201 ned as return of symptoms with a culture of the same organism, fo llowing an initial UTI). Relapse can be treated with a pro- longed (e.g. 2 \200\223 4 week s \200\231 ) course of antibiotics. \200 Establish whether related to intercourse. \200 Advise to increase \202 uid intake >2L/day, with frequent voiding. \200 Double voidin g may help bladder emptying. \200 Spermicides or spermicide-coated condoms should be disc ouraged. \200 Consider topical estrogen creams (per vagina) in post-menopausal \231\200 . \200 Cranberry juice: in vitro data con \201 rm cranberry juice inhibits adherence of uropathogens to urothelial cells. Con \202 icting results in clinical studies (may be depe ndent on \200\230dose \200\231 and mode of administration (tablet vs drink). X Probiotics: alter vaginal \202 ora to inhibit colonization by uropathogens. Results from clinical trials to date have been disappointing. Consider investigations for an abnormal urinary tract: imaging (including bladder emptying), cystoscopy. For prophylaxis, see Box 9.1 . The following do not predispose to UTI: wiping patterns, voiding after intercourse, persona l hygiene, showering, hot baths or saunas, pantyhose or synthetic fabrics. Catheter-related UTI \200 Bacteriuria occurs in 3 \200\223 10% of patients with an indwe lling catheter/per day catheterized. There is no role for screening asymptomatic patients. Treatment is generally only required if signi \201 cant local symptoms or systemic upset. If required, continue antimicrobials for a minimum of 7 days, and remove the catheter, if p ossible, as a surface bio \201 lm will otherwise act as a reservoir of infection. Diagnosis: cultures positive for >10 5 cfu/mL and heavy pyuria (although pyuria is not always a reliable marker of infection in this context). Prevention is best: avoid catheterization or remove as soon as possible. URINARY TRACT INFECTION: MISCELLANEOUS 711 Box 9.1 Prophylaxis Prophylactic antibiotics are an option if no remediable underlying caus e is identi \201 ed and can reduce recurrence rates by 95%. Ensure any current infection i s successfully eradicated \201 rst. The optimum antibiotic regimen has not been establish ed. \200 If UTI related to sexual activity: trimethoprim 200mg, co-trimoxazole 480mg, or nitrofurantoin 50mg after intercourse. For others, offer nightly low-dose prophylaxis in a monthly rotation as: trimethoprim 100mg, then nitrofurantoin 50mg, then cefalexin 250mg. Alternativ es include co-trimoxazole 480mg or amoxicillin 250mg. These may be adapted, according to previous culture results. \200 Give prophylaxis for 1 year initially. \200 Warn against the potential development of oral or vaginal candida and how this may be treated if it occurs. Related disorders 2 Emphysematous pyelonephritis Caused by gas-forming Enterobacteriaceae a nd occurs predominantly in diabetic patients (90%). Presents as severe pyelonephritis. Gas usually vis- ible on KUB or CT. Mortality is high (20 \200\223 60%), but broad-spectrum an tibi- otics and urgent nephrectomy signi \201 cantly improve outcomes. Xanthogranulomatous pyelonephritis A chronic unilateral pyelonephritis associated with rena l calculi or obstruction and causing widespread parenchymal destruction. More common in dia betes mellitus. Presents as fever, nausea, anorexia, weight loss, \202 ank pain, and syst emic upset. The affected kidney is often palpa- ble. Urinalysis and MSU for M,C+S con \201 rm UTI (usually Proteus spp. or other Gram-negative organism). CT con \201 rms diagnosis. Treat initially as for pyelonephritis. Relapse is common. A nephrectomy is often required. May be confused for renal cell carcinoma. Acute bacterial prostatitis Probably caused by re \202 ux of infected urine into the prost atic ducts. Presents with symptoms of lower tract infection, associated with fever and, occ asionally, with urethral obstruction. The prostate is swollen and tender on DRE. Urine cult ure will often demonstrate pyuria and bacteriu- ria. Treatment: \202 uoroquinolones (prol onged \211 4 weeks). Interstitial cystitis A sterile in \202 ammatory cystitis, presenting in \231\200 aged >4 0 (often with a prior history of recurrent UTI). Symptoms include frequency, dysuria, and ( often disabling) suprapubic or pelvic pain. May be associated with sterile pyuria. Sensitiv ity to intravesical potassium solutions may help to con \201 rm the diagnosis. Cystoscopy and bladder biopsy may show characteristic in \202 ammation and ulceration. Treatment can be dif \201 cult. Tricyclic antide- pressants can help with neuropathic pain. Oral (or int ravesical) pentosan polysulfate sodium is ef \201 cacious in some cases. CHAPTER 9 Essential urology 712 Re \202 ux nephropathy Re \202 ux nephropathy (RN) is a progressive lesion caused by repe ated infec- tions in the kidneys and almost always develops in childhood in the con- text o f an abnormal urinary tract. The long-term renal scarring and CKD resulting from this early injury is called RN or chronic pyelonephritis . 5 \200\223 12% of the ESRD population in the developed world is generally considered to have RN (although the diagnosis is often pre sumed in a patient presenting with scarred kidneys). The main anatomical abnormality of the urinary tract is usually vesi- coureteric re \202 u x (VUR), but RN can also occur with incomplete bladder emptying or out \202 ow obstruction . The ureter inserts obliquely through the bladder wall, forming a com- pressible tunnel that acts as a one-way valve to prevent re \202 ux of urine. A short or incompetent tunnel may allow re \202 ux of urine into the ureters, as the bladder contracts during micturition. Superinfection is the norm. By late childhood, the bladder base thickens; the ureteric tunn el elongates, and free re \202 ux generally no longer occurs. Vesicoureteric re \202 ux \200 Genetically heterogeneous but: \200 Affects 0.1 \200 \223 1% of newborns. \200 Underlies 12 \200\223 50% of children with a proven UTI. Is almost always present in children with proven renal scarring. \200 It may be associate d with renal dysplasia and hypoplasia (and 6 childhood i BP, CKD, and ESRD). Unilateral or bilateral (unilateral will not cause signi \201 cant CKD). \200 Ceases aro und puberty when anatomical changes mean that free re \202 ux is no longer possible. Essentially a radiological diagnosis, classi \201 ed grades I \200\223 V by severity (see Table 9.1). Surgical correction of incompetent valves offers no bene \201 t over simple antibiotic prophylaxis and prompt treatment of UTIs in terms of long-term outcome. Table 9.1 Classi \201 cation of VUR Grade I Re \202 ux into ureter, with no dilatation Grade II Re \202 ux into ureter, pelvis, and calyces, with no dilatation Grade III Mild or moderate dilatation of the pelvis No, or only slight, blunting of the fornices Grade IV Moderate dilatation and/or tortuosity of the ureter and moderate dilatation of the pelvis a nd calyces. Complete obliteration of the sharp angles of the fornices but maintenance of th e papillary impressions of most calyces Grade V Gross dilatation and tortuosity of the ureter, pelvis, and calyces Papillary impressions ar e no longer seen in the majority of calyce REFLUX NEPHROPATHY 713 RN: a new paradigm More recently, however, the belief that re \202 ux alone directly leads to renal scarring has been questioned. It is thought that VUR may simply be a marker of ab normal renal development, including renal dysplasia and hypoplasia. It is proposed that it is this abnormal renal development that predisposes to CKD. Evidence: renal lesions may be present antenatally in the absence of infection, and treatment of childhood VUR-associated UTIs often does not alter long-term renal outcomes. RN may 6 be better thought of as the sequelae of a developmental abnormality (renal hypoplasia or dysplasia), with associated VUR. Clinical presentation \200 In children, all UTIs should be subsequently evaluated for RN. \200 In adulthood, the presentation is usually with unexplained CKD. i BP ( 7 50% of adu lts). Proteinuria is low grade (<1g/day) unless progressive CKD ( s FSGS). Adults with UTI and a NORMAL renal tract will not develop RN. \200 Pregnant women with RN may develop UTIs, functional deterioration, or i BP 9 pre-eclampsia and should be referred for specialist care. Investigations \200 99m Tc-DMSA scintigraphy (DMSA is taken up in functioning renal tubul es) will demonstrate renal scars as areas of reduced uptake. \200 IVU: classically renal scarring (as parenchymal loss) and \200\230clubbed calyces \200\231 . Localized papillary scars do not take up contrast well, blunting the no rmal appearance of the renal calyx. In children, the gold standard for diagnosis of VUR is a micturating cystogram, although is otope cystography (which avoids a urinary catheter) is often preferred, particularly in old er children ( b p.54 \200\2236). Pathology Kidney biopsies are rarely undertaken, as kidneys are often small at pres- entati on. Characteristic appearances are chronic tubulointerstitial scars, with dilated, atrophie d tubules and often an in \202 ammatory cell in \201 ltrate. Secondary hyper \201 ltrati on injury develops over time, with compensa- tory hypertrophy of unaffected segments, vesse l changes, and glomerular collapse and sclerosis. Management (in adults) Given that re \202 ux has ceased and that there is no new scar form ation in adulthood, treatment is aimed at preventing CKD progression. \200 Treat i BP and proteinuria, with ACE-I or ARB as \201 rst line (target BP <130/80mmHg). Treat any new urine infections vigorously. CHAPTER 9 Essential urology 714 Congenital abnormalities of the kidney and urinary tract Introduction A group of well-recog nized developmental anomalies that are now col- lectively referred to as congenital abnorma lities of the kidney and urinary tract (CAKUT) (see Table 9.2). Variations of these disorde rs are identi \201 - able in 1 in 500 antenatal USS, and they are responsible for 7 30% of all fetal abnormalities. Prior to routine antenatal scanning, these conditions were diagno sed when symptoms developed in childhood and, occasion- ally, adult life. They account for the majority of CKD (and ESRD) in infants. Various gene mutations have been described, incl uding SALL1, SIX1, HNF-1 B , and PAX2. The conditions appear polygenic, with variable penet rance. Clinical evaluation Thorough post-natal assessment, as for any congenital abnormality. This should include maternal drug use (prescribed or recreational), family his- tory, and a com prehensive physical examination (targeted at important dysmorphic features, such as ear mal formations, hearing loss, optic nerve colobomas, digital anomalies, and abnormal external g enitalia). Investigation Suspected urinary tract abnormalities typically require a post-natal USS and micturating cystography. MAG3 renography or DMSA scanning will determine split function. Cy stoscopy may be necessary. It is important to appreciate that several abnormalities may be present together (e.g. VUR in an ectopic kidney). Genetic testing may be possible for sever al CAKUT-associated syndromes, e.g. CHARGE ( C olobomas, H eart defects, A tresia choanae, R etardation of growth and development, G enital abnor- malities and hypogonadism, E ar abn ormalities 9 deafness). Table 9.2 Important CAKUT disorders Abnormality Features Renal agenesis The ureteric bud fails to communicate with the metanephric blastema in 1st trimester. Often associated with other malformations, including VUR, and with genetic syndromes (e.g. Potte r \200\231 s syndrome l bilateral renal agenesis). Outcomes depend on these associations. Renal ectopia Failure of renal ascent during embryogenesis. The kidneys are usually abnormally shaped and often functionally impaired. 7 60% are pelvic kidneys. Often associated with ureteric abno rmalities. >90% are horseshoe kidneys where there is fusion of the lower poles by a narrow isthmus (us ually comprises functioning renal tissue). The kidneys are sited more caudally than normal. Often missed on USS. Commoner in \231\202 (although associated with Turner \200\231 s sy ndrome in \231\200 ). Renal fusion CAKUT 715 Table 9.2 (Continued) Abnormality Features Usually asymptomatic but may be associated with haematuria, abdominal pain, abdomi nal mass, UTI, i BP. Concomitant ureteric abnormalities often present (esp. PUJ and VUJ obs truction). Associated with nephrolithiasis and malignancy (TCC in adults, Wilm \200\231 s tumor in children). Crossed fusion ectopia occurs when one kidney crosses the midline and l ies in an abnormally rotated position. Associated with ureteric and cloacal abnormalities. The development of an accessory ureteric bud causes a duplex kidney and collecting system. May be complete or partial. If complete, there are two renal moieties with separate collect ing systems and ureters. These may drain aberrantly, e.g. into the vagina or posterior uret hra ( l re \202 ux and obstruction). If incomplete, the ureters usually join along their l ength. Common 7 1% normal population. Familial. Associated with chromosomal abnormalities, e.g. Turner \200\231 s syndrome. Usually asymptomatic. Failure of the ureteric bud and ren al mesenchyme to unite, resulting in a multiloculated mass, comprising thin-walled cysts wi th atresia of the proximal ureter. 2 \231\202 > 1 \231\200 . The renal tissue is non-func tioning. Renal dysplasia is the term used when there is some functioning tissue within an a bnormal kidney, with the two conditions part of a spectrum of developmental abnormality. 2 90% are unilateral but may be associated with contralateral abnormalities, such as VUR in 2 5%. Usually involute during childhood (and 6 labeled as a \200\230solitary kidney \200 \231 in later life). No intervention is required unless recurrent UTIs, bleeding or suspect ed malignancy. Weak association with i BP. Duplication Multicystic dysplastic kidneys Polycystic kidneys See b p. 592. Obstruction Antenatal renal tract dilatation is present in 1 in 200 antenatal scans but will resolve sp ontaneously in 50%. See also posterior urethral valves, PUJ and VUJ obstruction ( b p. 736) . Either primary (majority) or secondary to distal obstruction. \231\202 > \231\200 . Lef t > right. 25% bilateral. (cid:2) Urinary sepsis. Cystic dilatation of the terminal ureter. Intra- or extravesical (latter often more problematic, e.g. obstruction). Triad: de \201 cient or absent anterior abdominal wall musculature, bilateral cryptorchidism (empty scrotu m), plus urinary tract abnormalities (esp. megacystis and megaureter). Abnormalities in oth er organ systems in 75%. 95% are \231\202 . Genetic basis has not been established. Causes 1 \200\223 3% of ESRD. Also associated with renal dysplasia, VUR, PUJ/VUJ obstruction, ab normally thickened bladder, GI abnormalities (e.g. malrotation), congenital heart disease, and hip dysplasia. Failure of development of the urorectal septum in \231\200 leads to a s ingle opening of urethra, vagina, and colon. Associated with obstruction which requires sur gical correction. Megaureter Ureterocele Prune belly syndrome (Eagle \200\223 Barrett or triad syndrome) Cloacal abnormality CHAPTER 9 Essential urology 716 Nephrolithiasis Introduction Urinary tract stones affect 8 \200\223 15% of people (2 \231 \202 : 1 \231\200 , typical age 20 \200\223 60 years). The incidence is increasing in dev eloped countries. After a single stone, the likelihood of a second within 7 years is 7 50% (>75% after a sec- ond). However, preventative measures are highly effective in most cases. Nephrolithiasis refers to stone formation within the renal tubules or collecting system, a lthough calculi are also commonly found in the ure- ters and/or bladder. Diffuse parenchyma l calci \201 cation with the kidney is termed nephrocalcinosis ( b p.45). In the absence o f nephrolithiasis, most patients with nephrocalcinosis are asymptomatic (and renal function cor- relates poorly with the degree of calci \201 cation visible on imaging). Stone formation Stone formation around a crystal nidus is encouraged when the solubility of a urinary salt is exceeded in certain situations (termed \200\230supersatura- tion \200 \231 ). These include high solute delivery, concentrated urine (low vol- ume), areas of sta sis (anatomically abnormal urinary tract), and an excess of stone promoters over inhibitors . Supersaturation is dependent on free ion state, rather than absolute concentration, so wi ll be signi \201 cantly in \202 u- enced by the other constituents and characteristics of urine, such as pH. Aggregation of crystals into stones involves a process of epithelial ce ll anchoring within the renal tubules. Stone composition An important part of management is to identify stone constituents and any metabolic predisposition to formation. Stone composition varies, accord- ing to geography. In the Mediterranean, >70% are uric acid, whilst, in the UK and USA, the majority are calc ium oxalate or calcium phosphate. Both environmental and genetic factors in \202 uence thi s distribution. Stone composition and incidence (UK) \200 Calcium oxalate/phosphate: 60 \200\22380% (ofte n mixed stones \200\224pure calcium phosphate stones are uncommon). Struvite (magnesium ammonium phosphate) 10 \200\223 20% \200 Uric acid 5 \200\223 10% Stone types Calcium-based stones \200 Most are calcium oxalate , either alone or in combi nation with calcium phosphate or urate . An associated metabolic abnormality (or other predisposing factor) can be identi \201 ed i n many patients with recurrent stones, although some are truly idiopathic. NEPHROLITHIASIS 717 Risk factors (see Table 9.3): Excessive excretion of calcium (hypercalciuria), oxalate (hyperoxaluria), or uric acid (hyperuricosuria). Uric acid crystals often form the nidus th at progresses to a calcium-based stone. \200 Factors that cause insolubility, e.g. insuf \201 cient citrate excretion (hypocitraturia). Citrate forms a soluble complex with calciu m. Low-volume, or concentrated, urine. \200 Abnormal urinary tract, e.g. medullary sponge ki dney. \200 Renal tubular acidosis ( b p. 824). Table 9.3 Important metabolic risk factors for stone formation Hypercalciuria Hyperoxaluria Secondary to either i dietary oxalate or enhanced oxalate uptake High vitamin C intake Mala bsorption disorders (fat malabsorption l i colonic fatty acid delivery l i oxalate absorpti on): Crohn \200\231 s disease Coeliac disease Chronic pancreatitis Jejuno-ileal bypass Pri mary hyperoxaluria * Common. Secondary to either i GI absorption or reduced renal reabsorption With normal serum Ca 2+ : Idiopathic hypercalciuria (this is a polygenic disorder, \231\202 > \231\200 ) W ith i serum Ca 2+ : Hyperparathyroidism Granulomatous disease, e.g. sarcoid Immobilization Malignancy Hyperthyroidism Hypocitraturia Hyperuricosuria Metabolic acidosis ( i citrate absorption) Hypokalaemia Hypomagnesaemia Diarrhea UTI Exerci se High dietary purine or protein intake Cellular breakdown: Tumor lysis, haemolysis Myeloprol iferative disorders Gout Uricosuric drugs, e.g. loop diuretics Ketosis-promoting diets Inherited metabolic conditions (e.g. Lesch \200\223 Nyhan syndrome) An inherited enzyme defect associated with systemic calcium oxalate deposition from childho od ( l cardiomyopathy, bone marrow failure, CKD). Two distinct liver enzyme defects are des cribed (types I and II). Type II (enzyme: glyoxylate reductase/hydroxypyruvate reductase) t ends to be a milder disorder than type I (enzyme: alanine-glyoxalate aminotransferase). Uric acid stones Hyperuricosuria is most commonly associated with the formation of cal- ciu m oxalate stones! Pure uric acid stones are less common and are radio- lucent on KUB X-rays . Three key factors in \202 uence their formation: low urine volume, elevated serum uric a cid concentration, and low urine pH ( < 5.5). Low urine pH results from high animal protein intake and impaired CHAPTER 9 Essential urology 718 ammoniagenesis ( l excess secretion of unbuffered H + ). An increase in uric acid stone for mation has been seen in parallel with obesity and insulin resistance (perhaps s to d urine pH). Struvite stones ( \200\230triple phosphate \200\231 or \200\230infection \200\231 sto nes) Struvite (magnesium ammonium phosphate) stones are typically large stones associated w ith urease-producing ( 6 urea-splitting) bacteria and an alkaline urine. Urea breakdown pro duces excess ammonium and hydroxyl ions, a rise in urinary pH, and a decrease in phosphate solubility \200\224 thus encouraging the precipitation of insoluble magnesium ammonium pho s- phate. These stones can act as a reservoir for further infection and can rapidly expand to \201 ll much of the collecting system (termed \200\230staghorn calculi \200\231 beca use of their characteristic appearance on imaging). Many common bacteria are urease producers, particularly Proteus (oth- ers: Haemophilus , Ps eudomonas , Klebsiella , Yersinia , Staphylococcus epider- midis , Citrobacter , Serratia , and Ureaplasma urealyicum ). Note: E. coli does not produce urease. Risk factors: \231\200 > \231\202 ( s to i incidence of UTI), long-term catheteriza- tion, urinary stasis (e.g. neurogenic bladder). Antibiotic therapy (often long-term) and urological intervention, such as nephrolithotomy o r open surgery, are usually required (although surgery may not always be possible, as patie nts are often complex with multiple comorbidities). Eradication of infection can be extreme ly dif \201 cult. Any available stone material should be cultured for antibiotic sensitivi ties. Distal renal tubular acidosis ( b p. 824) \200 Characterized by impaired distal tubular e xcretion of H + , a non-anion gap metabolic acidosis, and an alkaline urine. Acidosis causes: Skeletal release of calcium and phosphate ( l i urinary excretion of both). i citrate reabsorption in the proximal tubule. High urinary pH + hypocitraturia + i urinary excretion of Ca 2+ and PO 4 l a \200\230perfect storm \200\231 for calcium phosphate precipitation. Nephrocalcinosis is not uncommon, in addition to nephrolithiasis. Stone prevention: sodium bicarbonate and potassium citrate (correct metabolic acidosis and increase urinary citrate excretion). Avoid urine pH >6.5, as this encourages calcium phosph ate precipitation. Large doses are often required. Bladder stones Usually arise include in abnormal bladders. Predisposing post-surgical recon struction, UTI, bladder diverticulae, neurogenic blad- der 9 bladder out \202 ow obstructi on. factors NEPHROLITHIASIS 719 Cystine \200 Cystinuria is an autosomal recessive disorder, causing a tubular defect in t he uptake of dibasic amino acid (cystine, ornithine, arginine, and lysine). There are two sources of cystine: (i) dietary and (ii) synthesized from methionine. Most cystine is reabsorbed in the renal tubules, with only 7 20mg per day excreted in the urine under normal circumstances. In cystinuria, failure of uptake leads to excretion of >250mg/day. \200 Cystine is poorly soluble, so this larger amount inevitably leads to insoluble crystal formation and stone development. Autosomal inheritance was \201 rst described in the 1950s. Initially, three types were proposed (types I \200\223 III). However, this terminology is now less po pular, as types II and III have proved dif \201 cult to differentiate. The type II/III for m has a more complex mode of inheritance (described as \200\230incompletely recessive \200\231 ). Clinically, even carriers of type II/III cystinuria may be stone formers. The genes (so far) associated with type I and types II/III are SLC3A1 and SLC7A9, respectively, with multiple mutations identi \201 ed. Although available, gene tic testing is not in routine clinical use. \200 Note: avoid cysteine/cystine confusion. Methionine is an essential amino acid. It can be converted to cyst e ine in the body. Two cyst e ine molecules then co mbine together (via a strong disulphide bond) to form one cystine molecule (hence cystine = \200\230dimeric \200\231 or \200\230dibasic \200\231 ). When cystine stones are broken with a laser, they give off a characteristic sulphuric rotten egg odor (the disulphide bond is broken, and sulfur is rele ased). Cystinuria should be suspected in all childhood stone formers. \200 The disorder usually presents during a patient \200\231 s teens or 20s, often with multiple and bilateral stones. Management: Maintain high urine volumes ( b p. 722). \200 Lower urinary pH (with potassium citrate) ( b p. 723). \200 Restrict sodium intake (reduces calciuria) ( b p. 722). \200 The precu rsor of cystine (methionine) is an essential amino acid, so complete dietary exclusion is n ot possible, but restriction, combined with reduced animal protein intake, is desirable (an excellent recipe book is available free at M http://www.cystinuriauk.co.uk ). Drug therapy is required in only a minority of patients. Mechanism: combine with cystine (at the disulphide bond) and increase solubility. Tiopronin (alpha mercaptopropionylglycine) is the most commonly used, as it has fewer side effects than older alternatives. A typical regimen is 1,000mg/day in three divided doses (d epending on urinary cystine levels and tolerability). Unlicensed in the UK but often used u nder specialist supervision. \200 Penicillamine; generally less well tolerated. Typical r egimen: 1 \200\223 3g/ day in divided doses. X Captopril: if others unsuitable. Ef \201 cacy uncertain. CHAPTER 9 Essential urology 720 Stone disease: evaluation Clinical presentation The clinical presentation of stone disease will vary, according to stone type, location, and size \200\224 ranging from small, asympt omatic, stones through to large infected and obstructing staghorn calculi. Pain ( b p. 724), haematuria (macroscopic and microscopic), infection (may be relapsing), a nd obstruction ( (cid:2) l AKI if single functioning kidney) are the key clinical considera tions. Progressive CKD is also possible from recurrent obstruction, infection, and renal in terstitial damage ( s to the \201 brosis incited by microcrystals). Who to evaluate? In patients presenting with a \201 rst urinary stone, detailed metabolic inves- tigation is not usually justi \201 ed or cost-effective. However, that is not to s ay that no evaluation should be undertaken. A basic assessment (history, physical examinati on, limited dietary assessment, limited blood testing, urinalysis, urine culture, and appro priate imaging) should be undertaken in all cases, with a more thorough metabolic evaluatio n (e.g. detailed 24h urine testing and comprehensive dietetic review) reserved for all recu r- rent stone formers and those known to have non-calcium-based stones. Where stone materia l is available, it should always be sent for analysis. \200 History: Age at \201 rst onset (younger age makes a metabolic abnormality, such as cystinuria or primary hyperoxaluria, more likely). Number and frequency of stones to date (and previous interventions, such as lithotripsy, undertaken). Site (recurrence at same site suggests a urinary tract abnormality). \200 Family history. \200 Stone type (if known). Non-calcium stones mandate closer scrutiny. \200 Associate d urinary tract infection. \200 Relevant systemic disease (e.g. Crohn \200\231 s disease , hypercalcaemic disorder, obesity, and insulin resistance (uric acid stones)). Drug history: Calcium stones: loop diuretics, calcium supplements, antacids, vitamin D preparations, corticosteroids, theophylline, acetazolamide. Uric acid stones: salicylates, probenecid. \200 Crystalluria: indinavir, nel \201 navir (both antiretrovirals), and triamterene can cause crystalluria as a precursor to stone formation. Diet ( b p. 723). \200 Lifestyle: those who restrict their \202 uid intake to avoid inc onvenient bathroom breaks, e.g. taxi drivers, surgeons. Exercise intensity. \200 Obvious systemic predisposition, e.g. gouty tophi, spinal injury with bladder dysfunction. Urinalysis: Microscopic haematuria. Proteinuria. Leucocytes and nitrites. Urinary pH: Usually high if struvite or calcium phosphate stones. \200 Usually low if uric acid or ca lcium oxalate stones. STONE DISEASE: EVALUATION 721 Urine speci \201 c gravity: a high reading on a random sample suggests inadequate \202 uid intake. Urine microscopy for crystals ( b p.28). \200 MSU for M,C+S (? concomitant infection). \200 Blood tests: U&E, bicarbonate, SCr, calcium (and PTH if calcium elevated), phosphate, serum urate. Stone analysis if possible. This is highly desirable \200\224 patients should be encouraged to retrieve stones. Urinary stone screen ( b see below). \200 Imaging ( b see below). Urinary values for 24-hour \200\230stone screen \200\231 Ensure that the collection is ade quate. Urine creatinine of >88 mol/ kg (10mg/kg) in \231\200 and 132 mol/kg (15mg/kg ) in \231\202 implies a complete sample. Collect stone screen in acidi \201 ed container for all investigations listed, except urin ary uric acid which requires a plain container. Two 24h col- lections may be required to al leviate intrapatient variability. The collec- tion should be undertaken on a typical day wi th a typical diet. Optimal ranges: \200 Volume 2 \200\223 2.5L. \200 Calcium <0.1mmol/kg/day (4mg/kg/day) . \200 Oxalate <0.36mmol/day (40mg/day). \200 Uric acid <4.4mmol/day (750mg/day). \200 Citrate >1.67mmol/day (320mg/day). \200 Phosphate <35mmol/day (1,100mg/day). \200 Sod ium <3,000mg (130mmol/day). \200 Cystine negligible (can 6 be measured on a spot sample). Some specialist laboratories may also be able to provide supersaturation analysis (the rat io between ion activity product and its solubility product). Imaging in nephrolithiasis 2 Calcium-containing or struvite stones are radio-opaque, while uric acid and cystine stones are radiolucent, i.e. not visible on a plain X-ray. However, t hey will be visible as an acoustic shadow on USS and as a \201 lling defect on contrast C T or IVU. \200 CT-KUB offers the single best test. It can be rapidly performed, is more sensitive and speci \201 c than an IVU, and avoids the administration of contrast (al though radiation dose is higher). A subsequent CT contrast study may help to identify an un derlying urinary tract abnormality. Plain KUB allows monitoring of radio-opaque stones. \200 IVU offers an alternative if CT unavailable. \200 USS may be helpful if obstruction suspected and is also sensitive for stones in the renal pelvis but often misses ureteric stones. For considerations when stones occur in pregnancy, see b p. 860. CHAPTER 9 Essential urology 722 Stone disease: management Prevention of recurrent nephrolithiasis General measures: \200 Consider a specialist referral. Attendance at a stone clinic has been shown to reduce stone recurrence, independent of other factors! \200 Increase \202 uid intake for daily UO > 2.5L/day. Urine should appear clear, not dark and concentrated. Advise to: \200 Drink a large glass of water at speci \201 c times during the day, e.g. upon waking, arriving at work, etc. Drink a glass of fruit juice with breakfast. \200 Keep a large bottle of water at their w orkplace and sip from it regularly throughout the day. Drink a glass of water each hour, on the hour. \200 Add slices of lemon, lime, or orange to water. It improves \202 avour and helps to alkalinize the urine. Drink two full glasses of water at each meal (one before, one after). \200 Carry a re \201 llable water bottle everywhere \200\224 walking, shopping, driving, watching television, etc. Eat fruits and vegetables (contain a high amount of water). \200 Include more liquid and \200\230wet \200\231 foods in the diet, e.g. soups, stew, jellies, etc. Drink before bedtime. Aim to provoke nocturia at least once per night. Reduce animal protein intake: Protein ingestion l i acid formation l reduced urinary citrate excretion l less citrate available to form a soluble complex with calcium. It also generates sulfate ions that decrease calcium solubility. \200 Acidosis also decre ases tubular calcium absorption. \200 Protein metabolism increases uric acid production a nd encourages uric acid stone formation in low pH urine. Aim 0.8 \200\223 1.0g/kg/day animal protein (meat, poultry, \201 sh, eggs, cheese, yogurt), and advise regarding non-animal protein substitutes (lentils, chickpeas, k idney beans, butter beans, baked beans, quorn). Reduce Na + intake <3g/day (<6g/day NaCl). Na + enhances calciuria (partly explaining the increased incidence of hypercalciuria in hypertensive patients). Educate patients to understand salt content labeling on foods. Recommend a normal calcium intake of 7 700 \200\223 1,000mg/day. (cid:2) Many patients are erroneously told to reduce calcium ingestion. This risks osteopor osis (esp. \231\200 ) and may actually promote stone formation (low Ca 2+ intake l i oxala te absorption and excretion). Calcium supplement supplements should be avoided, however. Reduce dietary oxalate (see Table 9.4). \200 If uric acid stones, reduce dietary purine i ntake (see Table 9.4). \200 Increase intake of citrus fruits (a source of potassium citra te). \200 Avoid excessive vitamin C supplementation (increases urine oxalate). \200 Mon itor urinary stone screen for ef \201 cacy of therapy. STONE DISEASE: MANAGEMENT 723 Table 9.4 Dietary sources of oxalate and purine High oxalate Greens (e.g. spinach and kale), green beans, rhubarb, \201 gs, beetroot, cel ery, spring onions, leeks, okra, cocoa and chocolate, berries (including strawberries, blac kberries, etc.), plums, kiwi fruit, tangerines, lemons, tofu, soy milk, nuts, seeds, tea, c offee High purine (uric acid) Meat (particularly viscera, e.g. liver, kidney, heart), meat extrac ts (e.g. stock, broth, or gravy), anchovies, crab, oily \201 sh, such as sardines and mac kerel, shrimp, certain vegetables (including asparagus, cauli \202 ower, peas, spinach, mu shrooms), lentils, kidney beans, beer Speci \201 c measures Calcium oxalate/phosphate stones \200 If u-Ca 2+ normal: Potassium citrate 15 \200\223 30mmoL PO tds. \200 Potassium citrate increases urinary ci trate and urinary pH. Aim for a pH of 6.5. Higher might encourage calcium phosphate stones. Liquid preparations can be unpalatable, but tablet formulations (e.g. Urocit -K wax tablet ) are available (although more expensive). \200 The potassium salt is favored over the so dium salt, as the latter promotes calciuria. If u-Ca 2+ raised: Potassium citrate as for normal + either indapamide 2.5 \200\223 5mg PO daily or hydrochlo rothiazide 25 \200\223 50mg PO daily (monitor K + with both). \200 Thiazide diuretics in crease tubular Ca 2+ reabsorption (note: avoid triamterene, as it causes crystalluria itself). If d K + develops, add amiloride (for potassium). Recheck urinary citrate and calcium excretion after several weeks, and adjust appropriately. Hyperoxaluria \200 In malabsorption disorders, ensure adequate hydration. Hypocitraturia and hypokalaemia can occur and should be corrected. Colestyramine binds fatty acids and pre vents their delivery to the colon (where they would otherwise increase oxalate absorption). Pyridoxine (vitamin B6) can be helpful, although large doses may be required. Calcium carbonate 500 \200\223 1,500mg tds before meals may reduce oxalate absorption. Primary hyperoxaluria can only be cured by liver transplantation. Struvite stones Require vigorous eradication of infection; antibiotic therapy is often pro- longed, e.g. 3 \200\223 6 months, directed by cultures and sensitivities. Cystine stones (see b p. 719). Hyperuricosuria Complete dissolution of uric acid stones can often be achie ved, using a combination of high \202 uid intake, urinary alkalinization (pH >6.5), reduc ed dietary purine intake, and, if necessary, allopurinol 100 \200\223 300mg PO daily. CHAPTER 9 Essential urology 724 Acute renal colic Presentation The syndrome caused by stone(s) passage down the urinary tra ct. Typically \231\202 aged 20 \200\223 40. Colicky abdominal pain ( 2 often very severe) , radiating from loin to groin (especially as the stone moves toward the vesicoure- teric j unction). Often abrupt onset, with progressive increase in inten- sity. Nausea and vomiting common. Renal angle tenderness, haematuria (often macroscopic), dysuria, strangury, freque ncy 9 symptoms of UTI. 2 Patients may be systemically unwell at presentation, with dehydrat ion and d BP. Predisposing factors include dehydration and exercise. Renal colic may also b e caused by ureteric clots and papillary necrosis ( b p. 585). Investigations \200 Dipstick urine for haematuria (microscopic haematuria is almost universal) as well as leucocytes and nitrites. \200 Urine microscopy for crystals. MSU fo r M,C+S. \200 SCr, U&E, CRP, FBC ( 2 blood cultures if signs of infection). \200 CT-KUB to con \201 rm diagnosis, locate the stone, exclude obstruction, and predict response to lithotripsy. IVU if CT unavailable. Plain AXR may reveal radio-opaq ue stones ( 7 80%). (cid:2) A stone may be an incidental \201 nding. Have you considered other causes of pain? Management \200 3 Infection 9 obstruction are indications for urgent intervention. \200 Analgesia: NSAIDs (e.g. diclofenac 75mg IM or via suppository) are often very effective (use with caution, i.e. correct dehydration; monitor renal function wi th prolonged use). Opiates may also be necessary, e.g. diamorphine 2.5 \200\223 10mg SC/IM ) (with antiemetic, e.g. metoclopramide 10mg IM/IVI or cyclizine 50mg IM). Desmopressin can reduce pain in many patients (antidiuretic effect ameliorates proximal ure teric distension). It acts quickly and has minimal adverse effects. Usually 1 x 40 microgra ms dose administered nasally. Oral rehydration. If vomiting, IVI 0.9% NaCl for UO >2L/day. No role for \200\230forced hydration \200\231 to assist stone passage. If stone \211 5mm, 7 70 \200\223 80% will pass spontaneously. 50% if 5 \200\223 10mm.