Townes \200\223Brock syndrome Genetic basis: mutation of SALL1 gene (16q12), which encodes a zinc \201 nger transcription factor. Inheritance pattern: AD; high proportion of cases are due to new mutations. General features: ear anomalies (dysplastic ears, pre-auric- ular tags) with sensorineural hearing loss; various hand malformations (notably triphalangeal t humb or hypoplastic thumb; preaxial polydactyly); imperforate anus. Nephrourological featur es: renal malformations (variable \200\223 may include: renal agenesis; unilateral or bila teral dysplas- tic/hypoplastic kidneys); lower urinary tract abnormalities (VUR; posterior urethral valves; urethral meatal stenosis; hypospadias; bi \201 d scrotum); CKD occurs in some cases; life-long monitoring of renal function is recommended. Turner syndrome Genetic basis: chromosomal (karyotype 45X in 50% of cases; remaining cases involve various combinations of mosaicism). General features: affects 1 in 2500 live femal e births; phe- notype is highly variable and features may be very subtle in some individual s; signi \201 cant short stature (may be treated with growth hormone therapy); neck may be broad and webbed, with low posterior hair-line; cardiovascular abnor- malities are present in 15 \200\22350% (notably aortic coarctation and ventricular septal defects; adults have an increased risk of aortic root dilatation and aortic dissection \200\223 regular sur- ve illance is advised); lymphatic abnormalities are associated with edema of hands and feet, s een most commonly in newborn period but may be present at any age; gonadal dysgenesis leads to absent or limited spontaneous puber- tal development and infertility in the majority of cases (estrogen treatment required from adolescence); other problems in adulthood include risk of osteoporosis and susceptibility to autoimmune diseases (hypothyroidism, diabetes me llitus, in \202 ammatory bowel disease, chronic liver disease); mosaic 45X/46XY individual s have an increased risk of gonadoblastoma. Nephrourological features: congenital renal ano malies are found in 1/3 of cases (notably horseshoe kidney; unilat- eral renal agenesis; r enal dysplasia/hypoplasia; pelviureteric duplication; VUR); hypertension may be more common than in the general adult population. Renal \200\223Coloboma syndrome Synonym: Papillorenal syndrome. Genetic basis: mutation of paired box gene 2 (PAX2, 10q24). Inheritance pattern: AD. General features: wide range of o cular abnormalities, from mild optic disc dysplasia (dif \201 cult to recognize, no func- tional consequences) to colobomas of optic nerve and retina; high frequency sensorineural h earing loss in some affected individuals; Chiari malformation with hydrocepha- lus has been reported. Nephrourological features: VUR; renal hypoplasia; CKD may progress to ESRD in ch ildhood or adult life. Senior \200\223L ken syndrome Synonym: juvenile nephronophthisis with Leber amaurosis; ren al \200\223retinal syndrome. Genetic basis: genetically heterogeneous; Senior \200\223L ke n syndrome 1 is due to mutations in the nephrocystin gene (NPHP1, 2q13); mutations in NPHP4 (1p36), NPHP5 (3q21) and possibly NPHP3 (3q22) are also associated with the Senior \200 \223L ken phenotype; other mutations in these genes may result in juvenile nephronophthisi s without ocular abnormalities. VATER/VACTERL association Genetic basis: unknown; more frequent in offspring of dia- betic mothers. Inheritance pattern: sporadic. R. HOLT 644 lateral renal agenesis; pelvic kidney; VUR; bladder diverticu- lae; urethral stenosis); hyp ercalciuria may be present even in the absence of hypercalcemia and may lead to nephro- cal cinosis; renal artery stenosis affects 40%; nonrenovascu- lar hypertension is also recogniz ed; ESRD has been successfully managed by renal transplantation. General features: incidence 1.6 in 10 000; VATER/ VACTERL are acronyms representing the pr incipal fea- tures: Vertebral defects (typically hemivertebrae or fused vertebrae in thorac ic or lumbar regions); Anal atresia; Cardiac abnormalities (80% of cases, various types); T racheo-esophageal \201 stula with Esophageal atresia; Renal anomalies; radial upper Limb defects; a secure diagnosis requires at least one defect each in limbs, thorax and lower ab domen/pelvis (probable diagnosis may be based upon two anomalies in each of two of these re gions). Nephrourological features occur in 80% of cases and may include: unilateral renal a genesis; renal dysplasia/hypoplasia; pelviureteric duplication; VUR; urethral atresia/steno sis; external genital defects (e.g. hypospadias, bi \201 d scrotum). Additional notes: ext ensive surgical treatment may be required over many years (neonatal repair of tracheo- esop hageal \201 stula and esophageal atresia, colostomy, uro- logical procedures), but most a ffected individuals achieve normal cognitive development; dialysis and renal transplan- tat ion are established treatments for those patients who progress to ESRD. 22q11 deletion syndrome Synonyms: velocardiofacial syndrome; DiGeorge syndrome. Genetic bas is: 96% of patients have hemizygous 1.5 \200\2233 Mb deletions of 22q11, including 24 \200 \22330 genes; other patients have speci \201 c deletions, translocations or point mutation s of the TBX1 gene, which lies within this chromosomal region. Inheritance pattern: 94% of cases are due to new dele- tions; 6% inherited in AD pattern (although there is intrafa- m ilial variability in phenotypic expression). General features: growth retardation/short sta ture; char- acteristic facial appearance (prominent wide nasal bridge and root, small mouth , round ears); velopharyngeal insuf \201 - ciency cleft palate; congenital heart diseas e in 75% of cases (notably tetralogy of Fallot and other malformations of the cardiac out \202 ow tract); variable defect in cell-medi- ated immunity (usually mild and improving in \201 rst 2 years of life; a minority have a persistent profound T-cell dysfunc- tion); 60 % are hypocalcemic at some stage (notably during neonatal period, but also during later chi ldhood or preg- nancy); several of these features (velopharyngeal defects; thymic and parat hyroid abnormalities; cardiac out \202 ow tract malformations) are attributed to abnormal develop- ment of the derivatives of the third and fourth branchial arches. Nephrourological features: structural renal tract anomalies are found in 36% of cases (renal agenesis; mult icystic dys- plastic kidney; hydronephrosis; VUR). WAGR syndrome Genetic basis: microdeletion of chromosome 11p13, encompassing the Wilms \200 \231 tumor suppressor gene WT1 and the adjacent aniridia gene PAX6. Inheritance pattern: us ually new deletion, but familial occurrence has been reported. General features: WAGR is an acronym representing the principal features: Wilms \200\231 tumor predisposition; Aniridia ; Genitourinary abnormalities (hypospadias, cryptorchidism); mental Retardation. Nephrourol ogical features: Wilms \200\231 tumor occurs in up to 60% of cases; \211 20% develop CKD i n later life. Williams syndrome Genetic basis: microdeletion of chromosome 7q11, encom- passing 17 genes , including the elastin gene (ELN); hemizygosity of the elastin gene is thought to be respo nsi- ble for the vascular anomalies in this syndrome, while hemizygosity of other genes in this region may account for other features. Inheritance pattern: usually sporadic, but AD i nheritance has been reported. General features: short stature; characteristic facial appear - ance (periorbital fullness, wide nasal tip, long philtrum, wide mouth with full lips, sma ll widely spaced teeth; adults tend to develop a gaunt appearance); moderate \200\223severe learning dif \201 culties, but relatively good language skills and talkative personality; hypersensitivity to noise; congenital heart disease in 80% of cases (typically supravalvul ar aortic stenosis or supravalvular pulmonary stenosis; other arter- ies may also be affect ed by vascular stenosis \200\223 see below); 15% of infants develop hypercalcemia of unkn own cause (may require reduced dietary calcium intake; tends to improve during childhood). Nephrourological features: several structural anomalies are recognized (including asymmetry of renal lengths; uni- Further reading Firth HV, Hurst JA, Hall JG. Oxford desk reference: clinical genetics. Oxford: Oxford University Press; 2005. Jones KL. Smith \200\231s recognizable patterns of human malformation, 6th edn. Philadelphia: Elsevier/Saunders; 2006. Internet resources Online Mendelian Inheritance in Man (OMIM). www.ncbi.nlm.nih.gov See also Renal dysplasia, p. 646 Congenital abnormalities of the urinary tract, p. 658 Neph ronophthisis, p. 600 Congenital and infantile nephrotic syndrome, p. 616 Wilms \200\231 tum or, p. 672 645 Chapter 16 Structural and congenital abnormalities Chapter contents Renal dysplasia 646 Vesicoureteric re \202 ux and re \202 ux nephropathy 648 Urinary trac t obstruction 652 Congenital abnormalities of the urinary tract 658 Medullary sponge kidney 664 S. FEATHER 646 Renal dysplasia Introduction The term renal dysplasia is used to describe a speci \201 c type of parenchym al development due to abnormal metane- phric development and is a histological diagnosis. D ysplastic kidneys contain microscopic abnormalities that have been attributed to the persis tence of mesonephric tissue, developmental arrests and faulty differentiation leading to pe rsistence of primitive or fetal structures. Hypoplastic kidneys are considered to have a si gni \201 cant reduction in nephron number. A histological diagnosis is rarely made in clin ical practice, rather the presence of kidneys with lack of normal coti- comedullary differe ntiation (sometimes containing cysts) is often assumed clinically to denote renal dysplasia (Fig. 16.1.1). Often, but not always, the kidneys are small. Some authors prefer to group renal dysplasia and hypopla- sia together as renal hypodysplasia. external ear malformations, pre-auricular pits, branchial cysts and hearing loss (branchio- oto-renal syndrome); imperforate anus, thumb abnormalities, hearing defects, hypospadias (T ownes \200\223Brock syndrome); diabetes and uterus malformations (RCAD syndrome). Management Management of renal dysplasia depends on the level of renal function which may b e variably impaired. Isolated renal dysplasia may be difficult to detect on antenatal scree ning. In children born with signi \201 cantly impaired renal function the glomerular \201 ltration rate may improve over the \201 rst year of life and sometimes up to 3 years of age. Puberty is typically a time when renal insuf \201 ciency may need closer monitori ng as renal function may decrease associated with growth. Milder cases of renal dysplasia m ay not be detected in childhood and present later in life with established renal impairment . Clinically when associated with other malformations including VUR it may be dif \201 cul t to differentiate from scarring associated with ascending infections. Clinical follow-up i s required to assess renal function, renal growth as assessed by USS and monitoring for dev el- opment of hypertension. Classi \201 cation Renal dysplasia is considered to be a common form of CAKUT (congenital abnormalities of the kidney and urinary tract). Renal dysplasia can occur in isolation or t ogether with other congenital abnormalities of the urinary tract. CAKUT are an important ca use of ESRD in child- hood (accounting for almost half of patients with ESRD in childhood). Renal dysplasia may occur less commonly as part of a complex syndrome with malformations o f other organ systems or external features. Multicystic dysplastic kidney (MCDK) This is a developmental abnormality of the kidney in w hich the renal parenchyma is non-functioning and replaced by many large cysts of differing sizes which appear to be non-communicating. It is nearly always associated with proximal ur eteral atresia. Epidemiology Overall dysplastic kidneys are common malformations affecting 1 in 1000 of th e general population. Severe forms of renal dysplasia account for 20% of pediatric ESRD ca ses. Epidemiology The incidence is considered to be between 1 in 2000 and 1 in 4500. MCDK occurs twice as often in males as in females. Genetics Usually renal dysplasia occurs sporadically. There are also >100 syndromes which i nclude renal dys- plasia and therefore clinical genetics advice should be con- sulted in ca ses with dysmorphic features or family history. For example there may be a chromosomal abno rmality or mutations in a single gene that may be helpful. It is possible that a genetic di agnosis may be possible in some cases in association with syndromes: \200 \200 \200 Genetics MCDK is usually sporadic although there are reported families with many affected i ndividuals with MCDK in the literature. Unusually, MCDK may occur in association with a num ber of rare syndromes: \200 Meckel \200\223Gruber; \200 Jeune thoracic dystrophy; \200 Zellweger cerebro-hepato-renal syndrome. SALL1 mutations (Townes \200\223Brock); PAX2 (renal coloboma syndrome); EYA1 or SIX1 mutati ons. Hence an assessment for external dysmorphic features should be undertaken. Clinical features The presenting sign of a multicystic kidney is usually a uni- lateral mas s. They are unilateral in 90% of cases. Abnormalities of the contralateral kidney may be pr esent in up to 30% of cases, including vesicoureteric re \202 ux, renal agenesis and pelvi ureteric junction obstruction. Currently the prevalence of mutations in developmental genes in children with renal hypodys plasia is 16%. Clinical features Clinical examination of patients with suspected renal dysplasia should in clude looking for dysmorphic features, for example: \200 fundoscopy examination to look for optic nerve colobo- mas even in the absence of visual im pairment (PAX2 renal coloboma syndrome); CHAPTER 16.1 Renal dysplasia 647 Fig. 16.1.1 Featureless renal ultrasound of renal dysplasia. Investigations MCDK are usually diagnosed on antenatal USS and con \201 rmed by postnatal USS (Fig. 16.1.2) although histori- cally they used to present as an abdominal mass. DMSA i sotope renogram postnatally will demonstrate absence of function in the multicystic dysplas tic kidney (Fig. 16.1.3). The micturating cystourethrogram (if performed) may show a blind- ending ureter and vesicoureteric re \202 ux in the contralateral kidney. Fig. 16.1.3 DMSA isotope renogram in the same 3-month-old infant with left MCDK and no func tion on left side. Management The management of MCDK is controversial. The outcome in children with unilateral MCDK and a normal contralateral kidney is excellent as the normal contralateral kidney dev elops compensatory hypertrophy. Surgical removal of the unilateral mass has been advocated for many years because of an anticipated risk of hyperten- sion and malignancy. Currently, if the renal diagnosis of MCDK is clear, conserv- ative management with sequential renal US S is usually advocated unless symptoms develop. Patients should be followed up regularly wi th measure- ment of BP and urinalysis and annual renal USS to ensure that the MCDK has regressed. This usually occurs at age \211 5 years. Indications for surg ery would include obstruction/gross abdominal distension or hypertension. A few centers sti ll advocate nephrectomy even if cysts have regressed because of a small chance of late comp lications. Further reading Firth HV, Hurst JA, Hall JG. Clinical genetics. Oxford: Oxford University Press; 2005. Jones KL. Smith \200\231s recognizable patterns of human malformation, 6th edn. Philadelphia: Elsevier/Saunders; 2006. Postlethwaite RJ, Webb N. Clinical pediatric nephrology, 3rd edn. Oxford: Oxford University Press; 2003. Internet resources Online mendelian inheritance in man: http://www.ncbi.nlm.nih.gov/omim Genetic & Rare Diseases Information Center: http://rarediseases.info.nih.gov See also Vesicoureteric re \202 ux and re \202 ux nephropathy, p. 648 Investigation of in herited renal disease, p. 582 Polycystic kidney disease in children, p. 586 Rare syndromes with renal involvement, p. 640 Fig. 16.1.2 Renal ultrasound of a 3-month-old infant with left MCDK. S. FEATHER 648 Vesicoureteric re \202 ux and re \202 ux nephropathy Introduction Vesicoureteric re \202 ux (VUR) This is the retrograde passage of urine from the bladder towards the kidneys as demonstrated on radiological imaging. Overall VUR is het erogeneous but can be de \201 ned as: Primary: \200 A family history of VUR or recurrent UTI should be sought. Most centers would not advocate routine screening of siblings with micturating cystograms to look for VUR but would focus o n: \200 \200 \200 awareness of urine infection symptoms; prompt diagnosis and treatment of infections; renal USS to look for dilating degrees of VUR/major renal tract abnormality. generally considered to be due to abnormal/more lateral insertion of the ureter into the bl adder wall. Since VUR can occur in association with a malformed urinary tract in a genetic syndrome, ca reful examination of the patient for features of a syndrome is important (e.g. ear abnormal ities, optic disc abnormalities). There is no genetic diagnosis available unless VUR occurs as part of a syndrome in which the genetic defect is already known. Secondary: \200 to obstruction or bladder dysfunction. VUR may be considered to be one feature of a malformed urinary tract. Re \202 ux nephropathy Re \202 ux nephropathy is de \201 ned as the renal disease result - ing from VUR. At least three different renal patterns of re \202 ux nephro pathy are see n: \200 \200 \200 Clinical features The two main presenting features of VUR are: \200 \200 antenatal diagnosis: hydronephrosis on fetal USS; urinary tract infection in childhood. congenital dysplasia; focal defects associated with pyelonephritis; glomerular sclerosis as sociated with proteinuria and hypertension. Febrile urinary tract infections are particularly important as they are more likely to be a ssociated with VUR. Other more unusual presentations include: \200 \200 \200 \200 It is important to appreciate that the small shrunken kidney associated with urinary tract infections (UTIs) is not neces- sarily scarred due to infection and VUR and could equally r epresent renal dysplasia. VUR is known to regress with age. loin pain; hypertension; proteinuria; enuresis. Clinical examination of the spine and nervous system is important if there is inadequate bl adder emptying due to a neuropathic bladder. In bladder out \202 ow obstruction, especiall y in boys, posterior urethral valves should be excluded. Classi \201 cation According to the International Re \202 ux Study Committee (1981), VUR is classi \201 ed according to severity (Fig. 16.2.1 and Table 16.2.1). VUR can be classi \201 ed as active (occurring during micturi- tion) and passive (without micturition). Investigations VUR is a radiological diagnosis. Epidemiology The incidence of VUR is estimated to be 1 \200\2232%. Re \202 ux nephropathy accounts for 15% of ESRD in teenag- ers and adults. VUR is less common in Afro-Caribbean c hildren compared with Caucasian children. In older children VUR is reported in greater freq uency in females but, in children who present with UTI, VUR is found in similar frequencies in both males and females. The prenatal diagnosis of VUR is more common in males than fema les and this is usually in the context of a congeni- tally abnormal renal tract. Renal ultrasound scan In the context of UTI, renal USS is a useful initial investiga- tion to look for renal size, presence of hydronephrosis and hydroureter, bladder wall thickness and extent of bladder empyting. Cystogram The gold standard for diagnosis of VUR is a cystogram. Micturating cystourethrogram (MCUG) This is the method of choice for infants who are unable to void to command and in those in whom it is important to delineate anatomy (Fig. 16.2.2) . A catheter is inserted into the bladder, \201 lled with contrast and then withdrawn. In male infants with VUR it is important to obtain a view of the urethra to exclude obstructi on due to posterior urethral valves. It is important to cover this investigation with antib iotic prophylaxis. The timing of the MCUG with respect to UTI is not crucial in terms of fa lse-positive VUR \201 ndings. Genetics Screening studies of relatives of children with VUR using micturating cystograms s uggest that VUR occurs more fre- quently in \201 rst-degree relatives of individuals comp ared with the general population. Overall the etiology of VUR is multifactorial and the gen etic component likely to be polygenic (due to many different genes) although in some famili es a single gene may play a major role. CHAPTER 16.2 Vesicoureteric re \202 ux and re \202 ux nephropathy 649 I II III IV V Fig. 16.2.1 Classi \201 cation of grades of vesicoureteric re \202 ux used by the Interna tional Re \202 ux Study Committee. Isotope cystogram In older children (able to micturate when requested and in whom urethral catheter insertion is more traumatic) an indirect isotope cystogram using MAG3 radioisotope can be used instead although it is recognized that this investiga- tion can be less sensit ive (Fig. 16.2.3). In this investigation, radioactive contrast is injected IV. Uptake of th e contrast occurs in the kidneys, excretion can be followed into the bladder and then on mi cturition, con- trast can be seen to re \202 ux back towards the kidneys if VUR is present . Indirect cystography is not available in all centers. Table 16.2.1 Classi \201 cation of vesicoureteric re \202 ux (International Re \202 ux S tudy Committee, 1981) Re \202 ux into ureter only with no dilatation. Grade I Re \202 ux into ureter, pelvis and calyces with no dilatation. Grade II 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 and calyces. Complete obliteration of the sharp angles of the fornices but maintenance of the papillary impressions of the majority of the calcyces. Gross dilatation and tortuosity of the ureter, pelvis and calcyces. Grade V The papillary impressions are no longer seen in the majority of calyces. Fig. 16.2.3 MAG3 isotope renogram showing unilateral right-sided vesicoureteric re \202 ux . Fig. 16.2.2 MCUG showing grade IV/V vesicoureteric re \202 ux on the right-hand side in an infant with recurrent febrile UTI. S. FEATHER 650 The most important aspect of management is to correctly diagnose and promptly treat UTI in children, especially if they are known to have VUR. It is important to be aware that UTI in small children can present with a nonspeci \201 c range of symptoms including fever, fail ure to thrive, vomiting. Simple measures Advice regarding prevention of urine infections including: \200 \200 \200 \200 \200 good \202 uid intake; regular voiding (including double voiding if VUR present); avoidanc e of constipation; perineal hygiene; advice to avoid perineal irritation (including avoidan ce of bubble baths and scented soaps). Other options are: \200 \200 antibiotic prophylaxis; surgical management (reimplantation of ureters or endoscopic correc tion of VUR). Antibiotic prophylaxis Antibiotic prophylaxis is usually the \201 rst-line management. Ty pically trimethoprim (1 \200\2232 mg/kg) once a day is used as \201 rst line although thi s may need to be changed if resistance to trimethoprim develops. If no further infection oc curs prophylaxis can eventually be discontinued. There is no clear guidance as to when this should be done and a reasonable time to do this is when the child comes out of nappies and urine collection becomes easier. Prophylaxis may need to be stopped if there are evolving problems with antibiotic resistance. There is controversy as to whether it is necessary to per- form a cystogram before stopping antibiotic prophylaxis. It would seem reasonable not to do this providing the child remains well. Repeated DMSA isotope renograms may not be nee ded unless there are problems with ongoing urine infections. Fig. 16.2.4 DMSA isotope renogram showing bilateral focal defects and reduced function on t he right-hand side (15% R, 85% L). Further investigations if VUR con \201 rmed If VUR is demonstrated, some assessment of ren al imaging needs to be made. Renal USS is a useful initial assessment. An isotope renogram using DMSA radioisotope is usually performed. This investigation gives an assessment of rel a- tive contribution to renal function of each kidney and whether or not there are focal de fects due to scarring or dysplasia (Fig. 16.2.4). The timing of DMSA isotope renogram with respect to urinary tract infection is important; at least 3 \200\2236 month delay after UTI is recommended so that acute changes have an opportunity to resolve. An IV pyelogram is no w not routinely used as an investiga- tion for re \202 ux nephropathy. It is likely that n ew guidelines for the investigation of UTI will suggest less frequent use of MCUG in childr en with UTI. Surgical management Controversy exists as to the appropriate surgical manage- ment for VUR. There is no clear evidence base that either reimplantation of the ureters or endoscopic co rrection of VUR provide a better outcome in terms of prevention of renal failure or symptom s (although some studies have suggested that sur- gery may be better for symptoms). Usually invasive surgery (reimplantation of the ureters) is reserved for cases in which repeated s ymptomatic UTI occur despite antibiotic prophylaxis. Newer methods such as noninvasive endo scopic correc- tion may be used as an early alternative to antibiotic prophylaxis. Shared m anagement with a pediatric nephrol- ogist and urologist may be indicated. Management Secondary causes of VUR should be sought and managed as appropriate. The rationa le for management of VUR is aimed at two objectives: \200 Follow-up The presence of persistent focal defects on DMSA isotope renograms indicates the possible need for indefinite follow-up of BP and urinalysis to look for proteinuria. preventing further renal damage due to scarring with ascending urinary tract infection; imp roving symptoms of recurrent urine infection which can be debilitating for infants (e.g. ma y affect growth). CHAPTER 16.2 Vesicoureteric re \202 ux and re \202 ux nephropathy 651 When bilateral focal defects on DMSA isotope renogram are present, continued follow-up and regular assessment of renal function is required. Great Ormond Street Hospital Family Factsheet on VUR: http://www.ich.ucl.ac.uk/factsheets/families/ F000277/index.html UK Vesicoureteric re \202 ux DNA collection: Further reading Cochrane Renal Group. Interventions for primary vesicoureteric http://www.vur.org.uk/ re \202 ux. Review. See also Urinary tract infections in infancy and childhood, p. 252 Lower and upper urinary tract infection in the adult, p. 244 Renal dysplasia, p. 646 Congenital abnormalities of th e urinary tract, p. 658 Postlethwaite RJ, Webb N. Clinical pediatric nephrology, 3rd edn. Oxford: Oxford University Press; 2003. Internet resources Cochrane Renal Group: http://www.cochrane-renal.org/ The Renal Registry: http://www.renalreg.org K. HARRIS 652 Urinary tract obstruction Introduction Obstruction of the urinary tract remains a major but pre- ventable cause of ch ronic kidney disease (CKD) worldwide. Urinary tract obstruction can result from a number of dif- ferent pathologies with the causes of obstruction varying according to the patient \200\231s age and sex. Immediately follow- ing acute obstruction, the changes within the ki dney are mainly functional and potentially fully reversible. However, longstanding obstruct ion results in irreversible functional and structural damage. In order to avoid long-term s truc- tural and functional damage to the kidney, prompt investiga- tion is required along w ith effective relief of the obstruction. Close collaboration between nephrologists, radiolo gists and urologists is essential for optimal investigation and management of the patient w ith urinary tract obstruction. unilateral (will not result in signi \201 cant renal impairment as there is a functioning contralateral kidney) or bilateral (will result in renal impairment); affecting the lower o r upper urinary tract (lower urinary tract obstruction always has the potential to result i n signi \201 cant renal impairment as it can inevitably affect the drainage of both kidney s). The common sites and causes of obstruction are shown in Fig. 16.3.1. Congenital urinary tract obstruction This is commonest in males. Causes include: \200 \200 \200 posterior urethral valves; meatal strictures; ureteropelvic junction obstruction \200\223 this is bilateral in 20% of cases but, if low grade and unilateral, may not present until a dulthood or as an incidental \201 nding on abdominal USS. De \201 nitions Obstructive uropathy The structural or functional changes in the urinary t ract which impede normal urinary \202 ow. It is classi \201 ed according to the site, th e degree, and the duration of the obstruction. It may be complete (high grade) or partial o r incomplete (low grade). Acquired urinary tract obstruction Intrinsic causes of obstruction Renal calculi: can be fo und anywhere along the renal tract but typically lodge at the ureteropelvic junction or ves i- coureteric junction causing obstruction. Renal calculi affect 1 \200\2235% of the popula tion and occur most commonly during the 2nd and 3rd decades of life. (male:female >3:1). Sl oughed papilla resulting from papillary necrosis which can occur in: \200 \200 \200 \200 \200 Obstructive nephropathy The renal disease resulting from impaired urine \202 ow. Hydronephrosis Dilatation of the upper urinary tract. Obstruction is the commonest cause. I t may also occur without obstruction (as in re \202 ux nephropathy) and rarely can be abse nt in established obstruction. diabetes mellitus; sickle cell trait or disease; analgesic nephropathy; renal amyloidosis; acute pyelonephritis. Epidemiology The frequency and etiology of obstruction varies with age and sex. Antenatal U SS commonly detects urinary tract dilatation in the fetus although the exact long-term sign i \201 cance of many such observations remains to be determined. In children aged <10 year s obstruction is commoner in males due to congenital anomalies of the urinary tract (urethr al valves, PUJ obstruction). Congenital obstructive uropathy is a common cause of ESRD in t his age group (up to 16%). With improved survival the impact of this disease can now be see n in adult life. Between 10 and 20 years of age, the frequency of urinary tract obstruction is similar in males and females. After 20 years of age, obstruction occurs more commonly i n females, as a result of pregnancy and gynecologic malignancies. >60 years of age obstruct ion is more common in males as a result of either benign or malignant prostatic disease. 80 % of men >60 years of age have some symptoms of bladder out \202 ow obstruction, and up to 10% have hydronephrosis. The postmortem prevalence of hydronephrosis is 3.5 \200\2233.8%, with approximately equal distribution between males and females. Blood clots seen in: \200 \200 \200 \200 bleeding renal tumors; arteriovenous malformations; following renal trauma; patients with p olycystic kidney disease. Uroepithelial malignancy: may occur in the renal pelvis, ureter and bladder. Ureteral stric tures: secondary to radiotherapy or retro- peritoneal surgery. Worldwide infection with Sch istosoma haematobium is an important cause. Ova may lodge in the distal ureter and bladder causing ureteral strictures, and contraction of the bladder in up to 50% of chronically inf ected patients. Urethral strictures: usually only in males secondary to urethral instrument ation or infection. Neurological conditions: can result in either a contracted (spastic) or a flaccid (atonic) bladder (depending on whether the lesion affects upper or lower motor n eurons) and cause impaired bladder emptying, e.g. multiple sclero- sis, spinal cord trauma. Extrinsic causes of obstruction Females: \200 Etiology It is useful to consider whether the obstruction is: \200 \200 carcinoma of the cervix: direct extension of the tumor to involve the urinary tract occurs in up to 30% of patients; congenital or acquired; due to disease intrinsic or extrinsic to the renal tract; CHAPTER 16.3 Urinary tract obstruction 653 Extrinsic causes of obstruction Intrinsic causes of obstruction Stricture Tumors Calculi Renal pelvis Retroperitoneal pathology Fibrosis Aortic aneurysm Malignancy (1 or 2 ) Inflammation Granuloma Calculi Clot Tumor Strictures Ureters Gravid uterus Female Benign ovarian mass Malignant ovarian mass Endometriosis Carcinoma of cervix Tumors Neurological conditions Bladder Male Benign prostatic hypertrophy Carcinoma of the prostate Posterior urethral valves Urethral strictures Urethra Fig. 16.3.1 Diagrammatic representation of urinary tract showing the common sites and cause s of obstruction. \200 benign and malignant uterine and ovarian masses; pelvic pathology: abscesses, endometriosis , and pelvic in \202 ammatory disease; inadvertent ligation of the ureter during surgical proce- dures; pressure from a gravid uterus on the pelvic rim: right ureter more commonly a ffected than the left. It is usually asymptomatic and the changes resolve rapidly following delivery (non-obstructed ureteral dilatation is also seen in pregnancy as a result of horm onal effects, especially progesterone on smooth muscle). Glomerular \201 ltration The glomerular effects of obstruction are complex. Obstruction c an alter all the determinants of glomerular \201 ltration: \200 mean hydraulic pressure gradient between the glomerular capillary lumen and Bowman \200\231 s space; renal plasma \202 ow; ultra \201 ltration coef \201 cient of the glomerular ca pillary wall; mean oncotic pressure difference across the glomerular wall. \200 Males: \200 \200 Early obstruction is typically characterized by: \200 progressive intrarenal vasoconstric tion; \200 shunting of blood to non \201 ltering areas; \200 proportionately greater f all in GFR; \200 fall in \201 ltration fraction. benign prostatic hyperplasia: commonest cause; carcinoma of the prostate: either from direc t extension of the tumor to the bladder outlet or ureters or from metastases to the ureter or lymph nodes. Either sex: \200 These changes are modulated by generation of vasocon- strictors such as thomboxane and angi otensin II, a decrease in the generation of vasodilatory prostaglandins and nitric oxide an d an in \201 ltrate of macrophages \200\223 the latter has also been implicated in the pa thogenesis of the structural changes that occur following prolonged obstruction. Whole kidn ey GFR will usually return to normal after short- term obstruction (days). However, even re latively short periods of obstruction may lead to a permanent loss of nephrons with whole k idney GFR recovering at the expense of hyper \201 ltration in the remaining functional nep hrons. Once extensive chronic structural changes have occurred within the kidney the patien t will be left with a decreased GFR and CKD even after the effective relief of the obstruct ion. retroperitoneal malignancy: either primary (lymphoma and sarcoma) or metastases; retroperit oneal \201 brosis: either idiopathic (rare) or second- ary to in \202 ammatory aortic an eurysms, drugs (methy- sergide, B-blockers bromocriptine), radiation, trauma or granulomato us disease (TB, Crohn \200\231s, sarcoid, Wegener \200\231s); vascular abnormalities: aneur ysmal dilatation of the aorta or iliac vessels, aberrant vessels, or anatomic varia- tions in the location of the ureter (retrocaval ureter). Acquired urinary tract obstruction (most ly prostatic dis- ease in men) accounts for 3 \200\2235% of the cases of ESRD in patients a ged >65 years. Pathophysiological changes within the kidney Obstruction of the renal tract rapidly results in alteration in both glomerular and tubular function. These changes depend on the duratio n of the obstruction, the patient \200\231s hydration state and whether there is a con- tra lateral functioning kidney. Ultimately irreversible structural damage leads to CKD. Tubular function Abnormalities in tubular function are common in urinary tract obstruction and may include: \200 \200 \200 \200 altered renal handling of electrolytes; changes in the regulation of water excretion; impai rment of urinary concentrating ability; urinary acidi \201 cation defects. K. HARRIS 654 Investigations General investigations Urinalysis This is commonly negative but depending on the cause of obstruction can show: \200 \200 \200 \200 \200 Recovery of tubular function following release of obstruc- tion is slow and it may remain a bnormal even after whole kidney GFR has returned to normal. Clinical features Symptoms Symptoms depend on the patient \200\231s age and the site, dura- tion, degree and cause of the obstruction. Congenital obstruction may cause: \200 \200 \200 \200 hematuria; bacteriuria; pyuria; crystalluria; low grade proteinuria. oligohydramnios; distended bladder; failure to thrive; vomiting. Full blood count Anemia may be found if obstruction has resulted in CKD, but polycythemia h as been described in short-term obstruction from erythropoetin release. Acquired obstruction may cause: \200 \200 \200 \200 \200 \200 changes in urine output; \202 ank pain; hematuria; lower urinary tract symptoms; urinary tract infections; no symptoms. Renal function tests These may range form near normal (especially if the obstruction is uni lateral or partial without damage to the upper renal tract) to advanced CKD. Electrolytes These may demonstrate a hyperchloremic hyperkalemic (type IV) metabolic acidos is and hypernatremia. Changes in urine output: anuria occurs following complete bilateral obstruction or unilater al obstruction in patients with a single functioning kidney. In partial obstruction, urine output may be normal or increased (polyuria). Flank pain and tenderness are typical of uppe r tract obstruction and may be severe and crescendo in nature radiating to the labia, the t esticles, or the groin (renal colic) if the obstruction is acute. Hematuria: trauma to the uroepithelium from calculi or a uroepithelial malignancy can result in either visible (macr o) or invisible (microscopic) hematuria. Lower urinary tract symptoms are typical of bladde r out \202 ow obstruction: \200 \200 \200 \200 Imaging investigations Imaging is key to diagnosing the site and cause of obstruc- tion and may require complementary use of a number of different modalities. No single investigation should be relied upon to rule out obstruction if the clinical suspicion is high. The imagi ng techniques below have largely replaced the use of IVU in the evaluation of suspected ren al tract obstruction.