(<10% function on DMSA ureteric Secondary VUR - - VUR VUR cause \200\224relieve BOO, improve bladder compliance (options: intravesical botuli num toxin injections, augmentation cystoplasty, sacral deafferentation). VUR with no sympto ms, no UTI, no high bladder pressures, and no BOO: for grades I \200\223II re \202 ux, mon itor for infection, hypertension, and evidence of deterioration in the appearance and funct ion of the kidneys. For grades III \200\223V, some urologists would recommend ureteric reim plantation or an endoscopic injection of bulking agent at the ureteric ori \201 ce (see Fi g. 8.3 for VUR grading). into a transplanted kidney: no treatment is necessary. in association with the neuropathic bladder: treat the underlying CHAPTER 8 Miscellaneous urological diseases 410 Grade I II III IV V Grade I Contrast into non-dilated ureter Grade II Contrast into renal pelvis and calyces; n o dilatation Grade III Mild dilatation of ureter; pelvis, and calyces Grade IV Dilated uret er becomes slightly tortuous; moderate dilatation of pelvis and blunting of calyces Grade V Severe ureteric dilatation and tortuosity; gross dilatation of pelvis and calyces Fig. 8.3 International re \202 ux classi \201 cation. 1 Neuropathic disorders cause VUR because they lead to intermittently or chronically raised blad- der pressure (due to bladder outlet obstruction, poor compliance and/or detrusor ove ractivity). 2 The lower renal moiety ureter inserts into the bladder in a higher and more lateral locat ion as compared to the upper moiety ureter, which inserts distally and medially, i.e. neare r the bladder neck. The lower moiety ureter has a shorter intramural length and therefore c an be prone to re \202 ux. The upper moiety ureter has a longer intramural length and tend s to be at risk of obstruction. This page intentionally left blank CHAPTER 8 Miscellaneous urological diseases 412 Pelviureteric junction obstruction in adults De \201 nition PUJO is an obstruction of the proximal ureter at the junction with the re- nal pelvis, resulting in a restriction of urin e \202 ow (see b p. 672); known as \200\230uretero-pelvic junction obstruction \200\231 (UPJO) in North America. Etiology Congenital - Intrinsic: ureter at the PUJ. The ureter can insert high on the renal pelvis (which may be a primary abnormality or secondary to the pelvic dilatation). Extrins ic: over which the PUJ runs. It is unlikely that these vessels are the primary cause of the obstruction. It is more probable that PUJO leads to a dilated PUJ and ballooning of the re nal pelvis over the lower pole vessels, which may thus contribute to, but is not the primar y cause of, the obstruction. smooth muscle defect results in an aperistaltic segment of compression from the lower renal pole ( \200\230aberrant \200\231) vessel Acquired PUJ stricture secondary to ureteric manipulation (e.g. ureteroscopy); trau- ma fro m passage of calculi; \201 broepithelial polyps; TCC of urothelium at PUJ; external compr ession of ureter by retroperitoneal \201 brosis or malig- nancy. Presentation Flank pain precipitated by diuresis (high \202 uid intake, especially after con- sumption of alcohol); \202 ank mass; UTI; haematuria (after minor trauma). It may al so be associated with VUR. Investigation - Blood test: - MSU: - Renal ureter. for renal function (U&E, eGFR). to exclude infection. USS: shows renal pelvis dilatation in the absence of a dilated IVU- : demonstrates a delay of excretion of contrast and a dilated pelvicalyceal system. CT- : shows a dilated renal pelvis and non-dilated ureter. Also helpful in excluding a small, r adiolucent stone, urothelial TCC, or retroperitoneal pathology, which may be the cause of t he obstruction at the PUJ. MAG3 maximum diuresis): is the de \201 nitive diagnostic test f or PUJO. Radioisotope accumulates in the renal pelvis and following intravenous furosemide, it continues to accumulate (a \200\230rising \200\231 curve). Also useful as it provides split renal function. renogram (with administration of furosemide to establish PELVIURETERIC JUNCTION OBSTRUCTION IN ADULTS 413 Retrograde pyelography: obstruction \200\224often performed at the time of PUJ repair to av oid introducing infection into an obstructed renal pelvis. to establish the exact site of the Management Surgery is indicated for recurrent episodes of bothersome pain, renal impairment , where a stone has developed in the obstructed kidney and where infection has supervened ( an acutely infected obstructed kidney in a septic patient will require nephrostomy insertio n). In the absence of symptoms, consider watchful waiting with serial MAG3 renograms. If re nal function remains stable and the patient remains free of symptoms, there is no need to o perate. A non-functioning \200\230burnt-out \200\231 kidney with PUJO may require nephrect omy to avoid the complication of pyonephrosis. Pyeloplasty (see b p. 782) - Laparoscopic pyeloplasty: the dismembered pyeloplasty is the most commonly performed techni que using transperitoneal, retroperitoneal, or robotic-assisted approaches. Success rates a re 795%. Open pyeloplasty: success rates of 95%. Common techniques include dismembered or A nderson \200\223Hynes pyeloplasty. The narrowed area of PUJ is excised, the proximal ureter is spatulated and anastomosed to the renal pelvis. Alternative techniques include \202 a p pyeloplasty (Culp) and Y \200\223V-plasty (Foley). A double J ureteric stent is left for 6 weeks post-operatively, which can be removed with \202 exible cystoscopy as an outpatient procedure. Endopyelotomy (or pyelolysis) A minimally invasive technique to treat PUJO, but tends not t o be offered as \201 rst-line therapy other than in older or frail patients. It can be ut ilized after pyeloplasty has failed. A full thickness incision is made through the obstruct ing proximal ureter from within the lumen of the ureter down into the peripelvic and periur eteral fat, using a sharp knife or Holmium:YAG laser. The incision is stented for 4 weeks t o allow re-epithelialization of the PUJ. Generally not used for PUJO >2cm in length. The in cision may be made percutaneously or by a retrograde approach via a rigid or \202 exible ureteroscope or by using a specially designed endopyelotomy balloon, the Acucise techniqu e. Here, an angioplasty-type balloon (over which runs a cautery wire) is in \202 ated acro ss the PUJ. An electrical current heats the wire and this cuts through the obstructing ring of tissue at the PUJ. The presence of a combination of PUJO and a renal stone that is suitable for PCNL is an ind ication for combined PCNL and percutaneous endopyelotomy. Success rates in terms of relieving obstruction: percutaneous endopyelotomy, 60 \200\223100 % (mean 70%); cautery wire balloon endopyelotomy, 70%; ureteroscopic endopyelotomy, 80%. CHAPTER 8 Miscellaneous urological diseases 414 Follow-up Repeat MAG3 renogram is usually performed 3 months post-operatively. If there has been no improvement, this can be repeated 6 \200\22312 months post-operatively. Failure ma y need re-do surgery or endopyelotomy. Fig. 8.4 IVU demonstrating a right PUJO (dilated pelvicalyceal system and non-dilated urete r). Image kindly provided with permissions from Mr P. Malone. PELVIURETERIC JUNCTION OBSTRUCTION IN ADULTS 415 Fig. 8.5 Retrograde pyelogram demonstrating a right PUJO (circled). Image kindly provided w ith permissions from Mr P. Malone. Fig. 8.6 Contrast-enhanced CT (coronal section) image of a right PUJO (dilated pelvicalycea l system and non-dilated ureter). Image kindly provided with permission from Mr A. Wedderbu rn. CHAPTER 8 Miscellaneous urological diseases 416 Anomalies of renal fusion and ascent: horseshoe kidney, ectopic kidney Abnormalities of ren al fusion and ascent occur in weeks 6 \200\2239 of gestation, when the embryonic kidney is \200\230ascending \200\231 to its de \201 nitive lumbar position in the renal fossa ( \200\230ascending \200\231 as a result of rapid caudal growth of the embryo). Horseshoe kidney Most common example of renal fusion. Prevalence 1 in 400. Male to fe- male ratio 2:1. The kidneys lie vertically (instead of obliquely) and are joined at their lower poles (in 95%) by midline parenchymal tissue (the isthmus). The inferior mesenteric artery obstructs ascent of the isthmus. Consequently, the horseshoe kidney lies lower in the abdo men (L3 or L4 vertebral level). Normal rotation of the kidney is also prevented and therefo re, the renal pelvis lies anteriorly, with the ureters also passing anteriorly over the kid neys and isthmus (but entering the bladder nor- mally). Blood supply is variable, usually f rom one or more renal arteries or their branches or from branches off the aorta or inferior mesenteric artery (Fig. 8.7). A proportion of individuals with horseshoe kidneys have associated congenital abnormalities (Turner \200\231s syndrome, trisomy 18, genitourinary anomalies, ureteric duplication), VU R, PUJ obstruction, and renal tumors (including Wilms \200\231 tumors). Most patients with horseshoe kidneys remain asymptomatic; however, infection and calculi ma y develop and cause symptoms. The diagnosis is usually suggested on renal USS and con \201 rmed by IVU (calyces of the lower renal pole are seen to point medially and lie medially i n relation to the ureters) or CT. Renal function is usually normal. Ectopic kidney The kidney fails to achieve its normal position and may be located in the th orax, abdomen, lumbar (in iliac fossa), or pelvis (on the contralateral side or crossed). T he prevalence of renal ectopia is 1 in 900, with both sexes affected equally. The left kidn ey is affected more often than the right and bilateral cases are seen in <10%. The affected kidney is smaller, with the renal pelvis positioned anteriorly (instead of medially) and t he ureter is short, but enters the bladder normally. Pelvic kidneys occur in 1 in 2000 \200 \2233000 and lie opposite the sacrum and below the aortic bi- furcation and are supplied by adjacent (aberrant) vessels (Fig. 8.8). Renal ectopia has an increased risk of congenital anomalies, including contralateral renal agenesis and genital malformations. Most are asymptomatic. Diagnosis is made on renal USS, IVU, or renog- raphy. Complications include hydronephrosis (secondary to VUR, VUJ obstruction, and PUJO), stones, and infection . ANOMALIES OF RENAL FUSION AND ASCENT 417 Horseshoe kidney (vertical orientation) Anterior renal pelvis Ureter (running anterior to kidney) Isthmus Bony pelvis Bladder (a) Horseshoe kidney (b) Fig. 8.7 (a) Horseshoe kidney; (b) Axial section of a CT scan demonstrating a horseshoe kid ney. CHAPTER 8 Miscellaneous urological diseases 418 Smaller pelvic kidney Anterior renal pelvis Short ureter (a) (b) Fig. 8.8 (a) Ectopic (pelvic) kidney; (b) IVU demonstrating ectopic kidneys. Sterilization clips are also seen. Image kindly provided with permission from Prof. S. Reif. This page intentionally left blank CHAPTER 8 Miscellaneous urological diseases 420 Anomalies of renal number and rotation: renal agenesis and malrotation Renal agenesis Unila teral renal agenesis is the absence of one kidney due to embryologi- cal abnormality or abs ence of the ureteric bud. This results in failure of the ureteric bud to contact the metane phric blastema with failed induction of nephrogenesis. The incidence is 1 in 1000, left sid e > right, males > females. Absence of a kidney may also be caused by involution of a multi cystic dys- plastic kidney in utero or post-natally. Many patients are asymptomatic; howeve r, it is associated with Turner \200\231s syndrome and cardiac, respiratory, gastrointestin al, and musculoskeletal abnormalities. Associated genitouri- nary anomalies include absence of the ipsilateral ureter, abnormal trigone, VUR, PUJO, VUJO, uterine abnormalities (unico rnuate \200\224one side has failed to develop; bicornuate \200\224partially divided uterus; didelphys \200\224double uterus), vaginal agenesis, anomalies of seminal vesicles, and abs ence of vas deferens. Often discovered as an incidental \201 nding on USS performed for o ther reasons or during investigation of associated abnormalities. Long- term follow-up of r enal function, urinalysis, and BP should be considered. Bilateral renal agenesis is rare an d incompatible with life. It is associated with complete ureteric atresia, bladder hypoplas ia or absence, intrauterine growth retardation, pulmonary hypoplasia, and oligohydramnios ( reduced amniotic \202 uid), causing characteristic \200\230Potter \200\231 facial featur es (blunted nose, low set ears, depression on the chin) and limb abnormalities. Malrotation The kidney is located in a normal position, but the renal pelvis fails to ro- t ate to the normal medial orientation. Often seen with horseshoe kidneys and renal ectopia a nd associated with Turner \200\231s syndrome. The incidence is 71 in 1000, with a male to f emale ratio of 2:1. The renal shape may be altered ( \202 attened, oval, triangular, or el ongated) and the kidney retains its fetal lobulated outline (Fig. 8.9). It is associated wi th increased deposition of \201 brous tissue around the renal hilum, which can produce sy mptoms due to ureteric or PUJ obstruction (causing hydronephrosis, infection, or stone form ation). Most patients, however, remain asymptomatic. The diagnosis is made on USS, IVU, or retrograde pyelography. ANOMALIES OF RENAL NUMBER AND ROTATION 421 Altered renal shape (with fetal lobulations) Anterior renal pelvis Ureter Bladder Fig. 8.9 Malrotation of the kidney. CHAPTER 8 Miscellaneous urological diseases 422 Upper urinary tract duplication De \201 nitions A duplex kidney has an upper renal moiety and a lower renal moiety, each with its own separate pelvicalyceal system and ureter. The t wo ureters may join to form a single ureter at the PUJ (bi \201 d system; Fig. 8.10) or mo re distally (bi \201 d ureter) before entering the bladder through one ureteric ori \201 ce. Alternatively, the two ureters may pass down individually to the bladder (complete dupl ication; Fig. 8.11). In this case, the Weigert \200\223Meyer rule states that the upper moi ety ureter always opens onto the bladder medially and inferiorly to the ureter of the lower moiety, thereby predis- posing to ectopic placement of the ureteric ori \201 ce and obstr uction (due to the longer intramural course of the ureter through the bladder wall). The lo wer moiety ureter opens onto the bladder laterally and superiorly, reducing the intramural ureteric length which predisposes to VUR (in up to 85%; Fig. 8.2). Epidemiology Ureteric duplication occurs in 1 in 125 individuals. Female to male ra- tio is 2:1. Unilateral cases are more common than bilateral, with right and left sides affected e qually. Risk of other congenital malformations is increased. Embryology In duplication, two ureteric buds arise from the mesonephric duct (week 4 of ges tation). The ureteric bud situated more distally (lower moi- ety ureter) enters the bladder \201 rst and so migrates a longer distance, resulting in the superior and lateral positi on of the ureteric ori \201 ce. The proximal bud (upper moiety ureter) has less time to mi grate and con- sequently, the ureteric ori \201 ce is inferior and medial (ectopic) (see b p. 668). Interaction of each ureteric bud with the same metanephric tis- sue creates separ ate collecting systems within the same renal unit. With bi \201 d ureters, a single ureter ic bud splits after it has emerged from the mesonephric duct. Complications Ectopic ureters are associated with upper renal moiety hydronephrosis (second ary to obstruction), renal hypoplasia or dysplasia (maldevelop- ment of the kidney correlat ing with the degree of ectopic displacement of ureteric ori \201 ce)1, and ureteroceles (F ig. 8.10). Lower moiety ureters are prone to re \202 ux, resulting in hydroureter and hydr onephrosis. Bi \201 d ureters can get urine continuously, passing from one collecting syst em to the oth- er (yo-yo re \202 ux), causing urinary stasis (and predisposing to infectio n). Presentation Symptoms of UTI, \202 ank pain, or an incidental \201 nding. UPPER URINARY TRACT DUPLICATION 423 Investigation - Renal USS: hydronephrosis. decreased contrast excretion from renal upper po le 9 IVU: hydronephrosis (which may displace the lower pole downwards and outwards, produci ng a \200\230drooping lily \200\231 appearance). Contrast in a ureterocele gives the appea rance of a \200\230cobra head \200\231 (Fig. 8.10). Micturating cystourethrography (MCUG): re \202 ux is present. Enhanced CT and MRI: demonstrates ureteric duplication 9 dilatation and will determine whether 99mTc-DMSA renogram: assesses individual renal moiety function. reveals detailed anatomical information. Management Uncomplicated complete or incomplete ureteric duplication does not require any i ntervention. In symptomatic patients, the aim is to reduce obstruction and re \202 ux and improve function. Where renal function is rea- sonable, common sheath ureteric reimplantati on (where a cuff of bladder tissue is taken that encompasses both duplicated ureters) can t reat both conditions. A poorly functioning renal moiety (i.e. upper moiety associ- ated wit h ectopic ureter and/or re \202 ux or lower moiety associated with a ureterocele) may requ ire heminephrectomy and ureterectomy. Where both renal moieties have poor function or dyspl asia, nephroureterectomy is indicated. 1 Mackie GG, Stephens FD (1975) Duplex kidneys: a correlation of renal dysplasia with posit ion of the ureteric ori \201 ce. J Urol 114:274 \200\22380. CHAPTER 8 Miscellaneous urological diseases 424 Left ureterocele Fig. 8.10 IVU demonstrating bilateral (bi \201 d system) renal duplication and a left uret erocele in the bladder ( \200\230cobra head \200\231 sign). UPPER URINARY TRACT DUPLICATION 425 Fig. 8.11 IVU demonstrating complete left-sided renal and ureteric duplication. Upper renal moiety Lower renal moiety Fig. 8.12 Diagrammatic representation of the Weigert \200\223Meyer rule with complete urete ric duplication. This page intentionally left blank 427 Chapter 9 Stone disease Kidney stones: epidemiology 428 Kidney stones: types and predisposing factors 432 Kidney st ones: mechanisms of formation 434 Factors predisposing to speci \201 c stone types 436 Eva luation of the stone former 440 Kidney stones: presentation and diagnosis 442 Kidney stone treatment options: watchful waiting and the natural history of stones 444 Stone fragmentation techniques: extracorporeal lithotripsy (ESWL) 446 Intracorporeal techniques of stone fragmentation 450 Flexible ureteroscopy and laser treatm ent 454 Kidney stone treatment: percutaneous nephrolithotomy (PCNL) 456 Kidney stones: open stone surgery 462 Kidney stones: medical therapy (dissolution therapy) 464 Ureteric stones: presentation 466 Ureteric stones: diagnostic radiological imaging 468 Ureteric stones: acute management 470 Ureteric stones: indications for intervention to reli eve obstruction and/or remove the stone 472 Ureteric stone treatment 476 Treatment options for ureteric stones 478 Prevention of calciu m oxalate stone formation 482 Bladder stones 486 Management of ureteric stones in pregnancy 488 CHAPTER 9 Stone disease 428 Kidney stones: epidemiology What is the risk of de novo stone formation? Previous editions of this book have stated that 710% of Caucasian men will develop a kidney stone by the age of 70. This is very much an average \201 gure since lifetime stone risk is multifactorial , being dependent on a vari- ety of intrinsic (inherent to the patient \200\224sex, age, fa mily history, comorbid conditions) and extrinsic factors ( \202 uid intake, diet, lifestyl e, climate, coun- try of residence). In the United States of America (USA), the lifetime pr ev- alence of stones is 712% for men and 77% for women. In other western countries, the lif etime risk is probably lower, but the gap between lifetime risk in the USA and that in othe r countries is probably narrowing as our lifestyles move closer to a USA one. The prevalence of stone disease is increasing in all western societies. In the USA, the pre valence of stone disease increased from affecting 3.6% of the population in the period 1976 \200\2231980 to 5.2% between1988 and 1994.1 While some of this increase may re \202 ect b etter diagnostic tests (e.g. the advent of CTU) diagnosing asymptomatic stones, much of thi s increase is likely to be real. Certainly in the UK, rates of treatment for stones have sh own a very substantial rise over the last 10y at a time when there have been no substantial changes in technology or technique of stone treat- ment. Thus, the use of ESWL for treatin g upper tract stones increased by 55% between 2000 and 2010 with a 127% increase in the num ber of ureteroscopic stone treatments, 49% of this increase occurring between the periods 2 007 \200\2238 and 2009 \200\22310.2 Of 5047 men and women (mean age 57y) undergoing CT colonography screening in 2004 \200\2232 008 and with no symptoms of stone disease, a stagger- ing 395 (7.8%) had stones (an average of 2 stones per patient, mean stone size 3mm).3 The prevalence in men was 9.7% and in wome n 6.3%, but was not (surprisingly) related to diabetes, obesity, and age >60. A substantial proportion of these initially asymptomatic stones became symptomatic over time. Over 10y o f follow-up, 81 of these 395 patients (21%) went on to develop at least one symptomatic sto ne event. What is the risk of recurrent stone formation in those who have already had a stone? Once a stone has formed, the risk of future stone disease is very substan- tially increased. With in 1y of a calcium oxalate stone, 10% of men will form another calcium oxalate stone, 727 \200\22350% will have formed another stone within a mean of 7.54 to 9y.5 Once a second stone has formed, the frequency of recurrences increases and the interval between relapses becomes smaller. Factors affecting stone formation The prevalence of renal tract stone disease is determined by factors intrin- sic to the individual and by extrinsic (environmental) factors. A combi na- tion of factors often contributes to risk of stone formation. KIDNEY STONES: EPIDEMIOLOGY 429 Intrinsic factors The prevalence of stone disease and incidence of new stone events is incr eas- ing. Much of this change may relate to the epidemic of obesity sweeping western societ ies (obesity is associated with increased urinary excretion of stone-promoting substances, e.g. calcium, oxalate, uric acid, and decreased excretion of stone-preventing substances, e .g. citrate). Obese patients have a lower urinary pH which encourages urate stone formation . - - Age Sex three times as frequently as females, but the gender gap is closing, at least in th e USA so that between 1997 and 2002, the male : female ratio for treated stones fell from 1 .7:1 to 1.3:1.6 Testosterone may cause increased oxalate production in the liver (predispos ing to calcium oxalate stones) and women have higher urinary citrate concentrations (citrat e inhibits calcium oxalate stone formation). Genetic : kidney stones are relatively uncommo n in Native Americans, Black Africans, and American Blacks and more common in Caucasians an d Asians. About 25% of patients with kidney stones report a family history of stone disease (the relative risk of stone formation remaining high after adjusting for dietary calcium i ntake). Familial renal tubular acidosis (predisposing to calcium phosphate stones) and cyst inuria (predisposing to cystine stones) are inherited.7 : the peak incidence of stones occurs between the ages of 20 \200\22350y. : previous editio ns of this book have stated that males are affected Extrinsic (environmental) factors - Geographical location, climate, and season between these factors and stone risk is complex. While renal stone disease is more common in hot climates, some indigenous populations of h ot climates have a low incidence of stones (e.g. Black Africans, Aborigines) and many tempe rate areas have a high incidence of stones (e.g. Northern Europe and Scandinavia). This may relate to western lifestyle \200\224excess food, inadequate \202 uid intake, limited exe rcise \200\224 combined with a genetic predisposition to stone formation. Ureteric stones b ecome more prevalent during the summer : the highest incidence occurs a month or so after p eak summertime temperatures, presumably because of higher urinary concentration in the summ er (encourages crystallization). The number of patients presenting acutely with urinary cal culi increases by 2.8% for each degree increase in temperature and 0.2% for each hour incre ase in sunlight hours.8 Concentrated urine has a lower pH, encouraging cystine and uric aci d stone formation. Exposure to sunlight may also increase endogenous vitamin D production, leading to hypercalciuria. Water intake : low \202 uid intake (<1200mL/day) predisposes t o stone formation9 and patients who relapse after experiencing a stone are less likely to h ave increased their \202 uid intake than those who remain stone- free. Increasing water \200\230hardness \200\231 (high calcium content) may reduce the risk of stone formation, by decreasing urinary oxalate.10 : the relationship CHAPTER 9 Stone disease 430 Diet (high urinary oxalate, low pH, low urinary citrate).11,12 High salt intake causes hype rcalciuria (through a sodium:calcium co-transportation mechanism). Contrary to conventional teaching, epidemiological studies show that in populations, low calcium diets predispose t o calcium stone disease and high calcium intake is protective.13 Occupation with manual wor kers. : high animal protein intake increases the risk of stone disease : sedentary occupations predispose to stones compared 1 Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC (2003) Time trends in reported prevalence of kidney stones in the United States: 1976 \200\2231994. Kidney Int 63:1817 \200\22323. 2 Turney BW, Reynard JM, Noble JG, Keoghane SR. Trends in urological stone disease. Br J Ur ol Int 2011. 3 Boyce CJ, Pickhardt PJ, Lawrence EM, Kim DH, Bruce RJ (2010) Prevalance of urolithiasis i n asymptomatic adults: objective determination using low dose non-contrast computerized tom og- raphy. J Urol 183:1017 \200\22321. 4 Trinchieri A, Ostini F, Nespoli R, Rovera F, Montanari E, Zanetti G (1999) A prospective study of recurrence rate and risk factors for recurrence after a \201 rst renal stone. J Urol 162:27 \200\22330. 5 Sutherland JW, Parks JH, Coe FL (1985) Recurrence after a single stone in a community pra ctice. Mineral Electrolyte Metab 11:267 \200\2239. 6 Scales CD, Curtis LH, Norris RD, et al. (2007) Changing gender prevalence of stone diseas e. J Urol 177:979 \200\22382. 7 Curhan GC, Willett WC, Rimm EB, Stampfer MJ (1997) Family history and risk of kidney ston es. J Am Soc Nephrol 8:1568 \200\22373. 8 Lo SS, Johnston R, Al Sameraaii A, et al. (2009) Seasonal variation in the acute presenta tion of urinary calculi over 8y in Auckland, New Zealand. BJU Int 106:96 \200\223101. 9 Borghi L, Meschi T, Amato F, Briganti A, Novarini A, Giannini A (1996) Urinary volume, wa - ter and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospectiv e study. J Urol 155:839 \200\22343. 10 Strauss AL, Coe FL, Deutsch L, Parks JH (1982) Factors that predict relapse of calcium n eph- rolithiasis during treatment. Am J Med 72:17 \200\22324. 11 Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ (1997) Comparison of di- et ary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Int Med 126:497 \200\223504. 12 Borghi L, Schianchi T, Meschi T, et al. (2002) Comparison of 2 diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 346:77 \200\22384. 13 Curhan GC, Willett WC, Rimm EB, Stampfer MJ (1993) A prospective study of dietary calciu m and other nutrients and the risk of symptomatic kidney stones. N Engl J Med 328:833 \200 \2238. This page intentionally left blank CHAPTER 9 Stone disease 432 Kidney stones: types and predisposing factors Stones may be classi \201 ed according to co mposition (Table 9.1), X-ray appearance, size, and shape. Table 9.1 Composition of stones Stone composition % of all renal calculi* Calcium oxalate 80 \200\22385 Uric acid** 5 \200\22310 Calcium phosphate + calcium oxalate 10 Pure calcium phosphate Rare Struvite (infection stones) 2 \200\22320 Cystine 1 The precise distribution of stone types will vary depending on the characteristics of the s tudy population (geographical location, racial distribution, etc.). Hence, the quoted \201 gures do not equate to 100. ** 80% uric acid stones are pure uric acid, and 20% contai n some calcium oxalate as well. Other rare stone types (all of which are radiolucent): indinavir (a prote- ase inhibitor us ed for treatment of HIV), triamterene (a relatively insoluble potassium-sparing diuretic, m ost of which is excreted in urine), xanthine. Radiodensity on X-ray Three broad categories of stones are described, based on their X-ray appearance. This gives some indication of the likely stone composition and helps, to some e xtent, to determine treatment options. However, in only 40% of cases is the stone compositi on correctly identi \201 ed from visual estimation of the radiodensity on plain X-ray.3 Radio-opaque Opacity implies the presence of substantial amounts of calcium within the ston e. Calcium phosphate stones are the most radiodense stones, being almost as dense as bone. Calcium oxalate stones are slightly less radiodense. Relatively radiolucent on plain X-ray Cystine stones are relatively radiodense because they contain sulfur (Fig. 9.1). Magnesium ammonium phosphate (struvite) stones are less radiode nse than calcium-containing stones. Completely radiolucent on plain X-ray Uric acid, triamterene, xanthine, indinavir (cannot b e seen even on CTU, hence if suspected, con \201 rm by IVU). KIDNEY STONES: TYPES AND PREDISPOSING FACTORS 433 Size and shape Stones can be characterized by their size, in mm or cm. Stones which grow to occupy the renal collecting system (the pelvis and one or more renal calyces) are known as staghorn calculi since they resemble the horns of a stag (Fig. 9.2). They are most commonl y composed of struvite \200\224 magnesium ammonium phosphate (being caused by infection and forming under the alkaline conditions induced by urea-splitting bacteria), but may be comp osed of uric acid, cystine, or calcium oxalate monohydrate. Fig. 9.1 A left cystine stone, barely visible, just below the midpoint of the 12th rib. Fig. 9.2 A large, right staghorn calculus. 1 Ramakumar S, Patterson DE, LeRoy AJ, et al. (1999) Prediction of stone composition from p lain radiographs: a prospective study. J Endo Urol 13:397 \200\223401. CHAPTER 9 Stone disease 434 Kidney stones: mechanisms of formation The driving force behind stone formation is the supe rsaturation of urine. Supersaturation is expressed as the ratio of urinary calcium oxalate (for example) to its solubility. Below a supersaturation of 1, crystals of calcium oxalate remain soluble. Above a supersaturation of 1, crystals of calcium oxalate nucleate and grow , thereby promoting stone formation. 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