Urinary Tract Obstruction in Children William
E. Smoyer, M.D.
Introduction
bstruction of the urinary tract is an important ~ of renal failure in children, and it is the underlying cause in approximately 33% of infants with renal failure. It can occur in a variety of clinical settings and is important to clinicians not only because it is a relatively common cause of renal failure but also because it is potentially reversible. Urinary tract obstruction (UTO) can also lead to many non-renal complications. Consequences of the oligohydramnios which often accompanies posterior urethral valves may include Potter facies; limb defects, such as talipes equinovarus and congenital hip dislocation; pectus excavatum and external ear anomalies.2-5 Severe oligohydramnios can also result in pulmonary hypoplasia with respicause
ratory insufficiency, pneumothoraces, and
death from
failure.&dquo; Urinary
with Eagle-Barrett syndrome has been attributed to urethral obstruction.’ Consequently, renal involvement should be considered in any neonate presenting with dysmorphic signs of poor abdominal musculature, external ear
patients
tract
respiratory obstruction
frequently may also be associated with congenital heart disease and anorectal malformations.6 In addition, the abdominal muscle deficiency (&dquo;prune belly&dquo;)
seen
Division of Nephrology, Children’s of Philadelphia. Address
Hospital
correspondence to: William E. Smoyer, M.D., Division of Nephrology, Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard,
Philadelphia, PA 19104 (215)590-2449
in
abnormalities, widely spaced nipples, imperforate anus, or spina bifida.’ There is evidence for the involvement of both genetic and enin vironmental factors the of pathogenesis congenital obstructive uropathy. Genetic involvement is suggested by the description of members of several families with hydronephrosis caused by obstruction of either the ureterovesical or ureteropelvic
junction.8S Hydronephrosis can also be with dominantly inherited syndromes, such as Ehlers-Danlos, Marfan’s, Apert’s acrocephalosyndactyly, and multiple lentigines, as well as with recessively inherited syndromes, such as Laurenceseen
Moon-Biedl, and
Fanconi’s
phropathy are most easily categorized according to the level of obstruction and whether they are intrinsic or extrinsic to the urinary In addition to structural causes, obstruction may be functract.
tional, due
to interference with in the urinary tract. peristalsis Table 1 shows the diversity of causes of UTO in children. The extent of irreversible renal damage resulting from UTO is, however, related to both the duration and severity of obstruction, as well as the rate of urine formation and the presence or absence of infection. 10 The following sections will review several aspects of UTO: the pathophysiology of UTO during and after relief of obstruction; the diagnosis of UTO, including signs, symptoms, and laboratory and radiologic findings; medical management of UTO; prenatal diagnosis and management of UTO; and the long-term outcome of children with UTO.
anemia,
ectromelia-ichthyosis.1 In con-
the involvement of environmental factors, the critical stage in the development of the human kidney is at 28 to 30 days, when the ureteric bud arises from the posteromedial wall of the wolffian duct.’Although no teratogens have been identified in humans, exogenous vitamin A, pantothenic acid or folic acid deficiency, and irradiation can all cause hydronephrosis in the rat.99 The causes of obstructive ne-
Pathophysiology
sidering
Urinary tract obstruction can be functionally defined as a disturbance in the normal pressure-flow relationships in the urinary tract, and it is only by an increase in presthat the effects of obstruction transmitted back to the kidney.’ Although the terms &dquo;obstructive nephropathy&dquo; and &dquo;obstructive sure are
uropathy&dquo; are often used interchangeably, they are not identical. Obstructive uropathy generally re109
fers
to the urinary result of obstruction, system whereas obstructive nephropathy is usually reserved specifically for damage to the kidneys as a result of obstruction. The pathophysiology of obstructive nephropathy is most easily understood by considering first the pathophysiology of the obstructive state, and then the pathophysiology of the postobstructive to
any
damage
as a
state.
Pathophysiology of the Obstructive State In the normal state ureteral
peristalsis begins with electrical impulses originating at pacemaker sites located in the proximal portion of the collecting system.ll°12 These impulses result in changes in intracellular calcium concentration in the muscle cells of the ureter and thus initiate the peristaltic contraction waves which propel urine from the kidney to the bladder. These waves occur two to six times per minute 13 and are propagated at a rate of 2-6 cm/ sec.14 Nor-
mal baseline ureteral pressures range from 0-10 cm H20, with peristaltic wave pressures ranging from 20-60 cm H20Y Following the onset of acute UTO, there is of urine in the collecting system proximal to the site of obstruction and an increase in baseline ureteral and pressure dimensions.15,16 A transient increase in the amplitude and frequency of the peristaltic waves&dquo; is followed by discoordination of pelvic contractility and resultant incomplete emptying of the renal pelvis.18 In experimental models, although an obstructed ureter can
backup
circumferential contractile forces than a control ureter, the intraluminal pressure generated by the obstructed ureter can be little different from the resting pressure. As a result, the con-
develop greater
10
Table! 1
CAUSES OF UR~Nt~RI~
’~~~~~‘ I~B~~‘R1~~TItIN
lN ~H11DREN
traction
resulting
from
may be incapable of
peristalsis effectively pro-
pelling the urine bolus.’o Moreover, superimposed infection can lead to complete absence of contraction in an obstructed ureter and more severe impairment of urine transport.10 The renal functional changes which take place during UTO include changes in renal hemodynamics, impairment of urinary concentrating ability, and defects in urinary acidification and potassium excretion. Acute obstruction is accompanied by a transient increase in renal blood flow, which subsequently decreases to 40%50% of normal.&dquo; In addition, as the hydrostatic pressure within the proximal tubule increases, the net pressure across the glomerular capillary walls decreases, which results in a decrease in glomerular filtration rate (GFR) .’9 Despite this, however, there is considerable evidence that even complete obstruction of a ureter does not completely abolish glomerular filtration&dquo; and it appears that other factors are also involved in depressing GFR acutely.20 With chronic obstruction the reasons for the decreased GFR are even more complex than those for acute obstruction, as ureteral hydrostatic pressures are often normal or only slightly elevated, and the ureters are increased in both diameter and length. Patients with chronic partial obstruction, as well as patients with recent relief of obstruction, may also have defects in urinary acidification and
potassium excretion, leading
to
hyperkalemia and/or acidosis. In addition, these patients may also have a decreased urinary concentrating ability and present with polyuria and/or dehydration. The proposed mechanisms for these responses will be discussed in the next section.
Pathophysiology of the Postobstructive State The most important considerations of the postobstructive state relate to the recovery of renal function and the degree of postobstructive diuresis. Renal function after relief of UTO may vary from normal to advanced renal failure. Experiments in dogs, measuring the degree and rate of return of renal function after varying periods of complete unilateral ureteral obstruction, have suggested that the longer the duration of obstruction the less is the degree of recovery that can be expected.2’ The potential for recovery is usually better in partial than in complete obstruction and when obstruction is not complicated by urinary tract infection (UTI). 22,23 Various disorders of renal tubular function may be found following relief of UTO. Although a defect in proximal tubular function, with enhanced losses of magnesium, calcium, uric acid,
phosphate, alpha-amino-nitrogen, and bicarbonate in the postobstructive period has been re-
ported,24 have
an
commonly patients inability to acidify their
more
urine, and
studies have suggested they develop a form of distal renal tubular acidosis with an inability to lower the urine pH to normal minimum values in response to systemic acidosis.19 This defect can last from weeks to years following relief of obstruction. A syndrome of hyperkalemic, hyperchloremic metabolic acidosis (Type IV renal tubular acidosis) has been described in a group of adults with chronic renal insufficiency associated with obstructive uropathy. 2’ This was found to be caused by a distal defect in hydrogen ion and potassium secretion in some of the patients and a selective aldosterone deficiency in others. Distal tubular defects have also most
been demonstrated in infants and children. A group of infants with UTO and UTI who also presented with hyperkalemic metabolic acidosis has been reported.26 Unlike the adults, however, these infants had marked hyponatremia (serum Na 103-129 mmol/L) with urinary salt wasting in the face of elevated renin and aldosterone levels. These authors suggested that temporary aldosterone insensitivity can occur following an upper UTI in an anatomically abnormal urinary tract. In most of the infants the excessive urinary sodium losses gradually improved, but in some, polyuria persisted for as long as 10 years after relief of obstruction. This was thought to be caused by collecting tubule unresponsiveness to antidiuretic hormone This (ADH) . type of postobstructive defect appears to make sense
physiologically, since maximal concentrating ability, which is a function of the most distal segment of the nephron, should be the most vulnerable to increased intrapelvic
pressure. 27 A period of diuresis often occurs after relief of UTO. Although this is frequently thought of as an indicator of tubular dysfunction, a postobstructive diuresis may be
physiologically appropriate, or in some instances, even iatrogenic. Frequently, however, the postobstructive diuresis is associated with a decrease in maximal urinary concentrating ability. 28-32 This initial impairment of concentrating ability after the period of postobstructive diuresis is usually transient, and most patients regain the ability to concentrate urine appropriately over a period of days to months after relief of obstruction .29,30 A number of factors appear to contribute to postobstructive diuresis. Patients are often volume expanded prior to relief of the obstruction, and a
111
Figure 1: Effect of urinary tract obstruction on medullary prostagiandin
production,
with its subsequent effects on
urinary concentrating ability which culminates in polyuria. The inhibitory effect of prosta-
glandin synthetase inhibitors (PSis) on this sequence of events is shown by the dashed line. MTALH refers to medul-
larythickascending limbofthe loop of Henle.
physiologic diuresis would be expected to occur following relief of obstruction.33 Accumulation of natriuretic factors in response to this volume expanded state may also play a role in postobstructive diureS1S.34 In addition, obstruction results in the accumulation of urea, which induce a may also solute diuresis with postobstructive large losses of sodium and water.35 Finally, there may be a relation between obstruction complicated by UTI and impaired urinary concentrating ability. In a group of adults with unilateral hydronephrosis sec-
ondary to ureteropelvic junction (UPJ) obstruction, some investigators
UTI
found that, in the absence of or
nephrolithiasis,
trating ability
was
not
concen-
reduced.31
Others, however, failed to find a strong correlation between impaired concentrating capacity and
112
UTI in a group of 11 infants and children with UTO.30 Although data on the relative involvement of each of these factors in humans are lacking, the pathogenesis of postobstructive diuresis is probably multifactorial. Postobstructive diuresis in some patients has also been associated
with increased din E2
urinary prostaglan-
(PGE2) excretion.36
Prosta-
glandins appear to modulate urine concentration by antagonizing ADH-sensitive adenylate cyclase in the collecting tubule and by decreasing medullary tonicity.&dquo; Intrarenal prostaglandins also inhibit urea transport from the collecting tubule, decrease sodium chloride transport in the thick ascending limb of the loop of Henle, and increase medullary blood flow.3’ This sequence of events is depicted in Figure 1. Although the
mechanism by which UTO induces increased prostaglandin production is not known, pressure-induced damage to distal and collecting tubule cells may stimulate an increase in medullary pros-
taglandin production directly
or
via cellular mediators (cytokines) which stimulate prostaglandin production by infiltrating interstitial cells such as macrophages. The precise mechanisms by which UTO causes the clinical features of obstructive nephropathy, however, must await further studies.
Diagnosis Signs and Symptom The clinical presentation of UTO can be variable and depends on the location of the obstruction, whether it develops acutely or
gradually, and whether it is unilateral or bilateral. Signs and symptoms suggestive of an obstructed urinary tract in a child are shown in Table 2. Neonates may present with an asymptomatic abdominal mass, a diminished urinary stream, or with abnormal voiding patterns,
such
as
oligoanuria
or
frequent
voiding of small volumes of urine. Isolated swelling of the penis or scrotum may be seen in infants with posterior urethral valves (PUV). Older children, however, may come to the attention of the pediatrician with complaints of urinary incontinence, nocturnal enuresis,
or
post-void dribbling.
Recurrent UTIs or UTIs resistant to treatment in a child of any age
should prompt an evaluation of the tract to exclude UTO or
urinary .
: ..
>=., .
- . , , ; ;
» .
; ;; .,
+.. ,,
; ;: .:
, j,% : : .
.
vesicoureteral reflux (VUR). It should be noted, however, that partial or gradual obstruction may cause significant damage to the urinary tract, despite being undetected for many years in an asymptomatic patient. When UTI supervenes, a child may present acutely ill with renal failure and possibly sepsis and meningitis.&dquo; In fact, infection is often the event which draws attention to an obstruction, and it is one of the major factors that causes loss of renal function in such cases.’ For this reason, when a child is diagnosed with a UTI in certain clinical situations, a renal ultrasound may be indicated to exclude UTO. Conversely, when UTO is diagnosed, the urine should always be cultured. When UTO is identified, the most com-
%.., ,:o . eo=
.,» ;. , oi . =° ’7. &dquo;i’,,
< j,
#. -> ; ’ I ’
°
1_~;± ._±.~° ,i j,; (=’_ .g~).j gjl(#fl=igi~,: [§j( )#f~ /j/T Q’.I.~il&dquo;I§:I%/((I]%I ; .°’&dquo; &dquo; _)&dquo;. ..;’/.~E_fl/(,/ ~’ l ©/§i~’i ~j
jfl@fyj@§]I;~l~.ij,,gl:.i/Egg.igEj>g§§(g; . ~ ° - . , &dquo;r . ° ’‘ , ~ ° . , °, ‘ , ~ F ‘ ~a ., , .~ .&dquo;?-° ‘ ~,sea ,.h ~ ma ° y;a,
~~3
urinary pathogens seen are gram-negative bacilli, Staphylococci, and Streptococci. Urinary tract obstruction must mon
be considered in the differential diagnosis if a child presents with renal failure associated with either anuria (absence of urine after bladder catheterization) or alternating oligoanuria and polyuria. Improvement in urine output and renal function with catheterization suggests obstruction at or below the level of the bladder. Urinary tract obstruction should also be considered in all cases of unexplained acute or chronic renal failure, as well as acute deterioration of renal function in patients with known renal disease of any cause.
Ureteropelvic junction (UPJ) obstruction is the most common cause of UTO in infancy.39 It occurs more frequently in males and more commonly involves the left kidney. The usual presentation is with an abdominal mass, but UTI and emesis also are frequently seen. In older children, however, UPJ obstruction may present with intermittent flank or abdominal pain, symptoms of or hematuria. UTI, Posterior urethral valves (PUV) are another important cause of UTO in children. The most common clinical finding in this disorder, regardless of the age of presentation, is a palpably enlarged bladder.4° The parents may report the presence of an abnormal urinary stream, sometimes described as urinary &dquo;dribbling.&dquo; These patients may also present with azotemia, sepsis, meningitis, hyponatremia, hyperkalemia, dehydration, or acidosis. Approximately 90% of infants with PUV have hydronephrosis&dquo; and 40% have an accompanying UTI.42 Half of these patients are also found to have VUR at diagnosis.4° Although delayed diagnosis is unusual,
school-age boys present most com-
113
monly with a history of daytime urinary incontinence or nocturnal
Also, although not routinely evaluated, impairment of maximal uri-
enuresis.
nary concentrating ability is the earliest functional abnormality in obstructive nephropathy.’9 Because obstruction of the urinary tract often results in decreased urine flow, these patients are also at increased risk for UTI and may have pyuria or bacteriuria. When chronic UTO presents as acute renal failure, the urine diagnostic indices are often similar to acute tubular necrosis, with decreased
Laboratory Findings Patients with UTO may present with a wide range of blood and urine abnormalities (Table 3). Conversely, even severe obstruction can present with a relatively normal urinalysis. More often, however, some degree of proteinuria and/or hematuria is noted. _) ~N , , ~ ~ ’ j $ ~ ’ ’ £ ’ ~ ) ’ ’ &dquo; ’ ~ £. ; , ~ ; ’~~~W §=jjs%;,, ~.&dquo;~j _=*-’j#,~;~%,%£,__ju=.jg= [§#§&dquo;&dquo;fi ’-,’,~;Q,§&dquo; ’ ’
&dquo;
...
-
_
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’&dquo;
’
.:&dquo;§&dquo;fi
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-_
§
_ g b’=
(?_
m ~ = £; .#
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8_
~ _ _.)
fl. ’o ; ..(_ flS- ;
-;_g~ ~
gj_~%’&dquo;£>_j_’ , j ,, ~:i ’ll lig§;% #§;; :§lj=§’, %)&dquo;>j§:%:. I;#§%##°##’##I##*I+ Z=.*’.lill#~§$ #l’#’ §;;.I._##§£il§z %§§it,) g
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z
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t):.I&dquo;,.lilifl#1#&dquo;]# ’~’&dquo;&#l ,=b. :.&dquo;.&dquo; ’Z I&dquo;I.E§(:I;k.~~%~#~’* #, ’&dquo;.~ % +°&dquo;&dquo; *&dquo; ~ # &dquo;#&dquo; ’ i@g i’ ~ ’ %#~’I = I*s.*§,’&dquo;.%%#&dquo;k -~ ’ %£ % ~§£ i §§ % &dquo;%*&dquo; w©ow&dquo; #h’ ’ %i ,O E’ #* ;.I -;b ,,fl, -j * =&dquo;w©&, w ~- = &dquo; ?* - _ , _ . - ;, -z’s g#,§ =’ I %Zo’ &dquo;&dquo;&dquo;# 0 -’g & dquo;&dquo; &-iS ’& - i y’ l%I M#I 1ii I&dquo; ’’*% # ~~~.*~*~’ Ya§ ’&dquo;Q ’ &dquo;&dq~uo;iw %= #~’~&dquo;~~&dquo;~~ N:, 53 8~~ l_~ # ~ k ~.#~#~ ~ ~ ’&dquo;~~&dquo;# ORI 0* ’ 0&dquo; ’~i$$~f$IAT£D , &dquo;&dquo;
’*
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~-$~#~#~~~%$ AO’ -’ ’ &dquo; **&dquo;&dquo;’* .
p
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.=
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&dquo;&dquo;’I#*# f
&dquo; - - .
0~
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N
--
&dquo; , ;
tl ’Xi;l’E.0’&dquo;©%#N0)10k#°&dquo;5z§#m%&dquo;ia%%%I#.#flilll §§£I,[ [&dquo; ~
~
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fr‘
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§b’## #.##’811#§jil
urine osmolality (500 mOsm/kg) and urine to plasma creatinine ratio (>40) and decreased urinary sodium (
E. Smoyer, M.D.
Introduction
bstruction of the urinary tract is an important ~ of renal failure in children, and it is the underlying cause in approximately 33% of infants with renal failure. It can occur in a variety of clinical settings and is important to clinicians not only because it is a relatively common cause of renal failure but also because it is potentially reversible. Urinary tract obstruction (UTO) can also lead to many non-renal complications. Consequences of the oligohydramnios which often accompanies posterior urethral valves may include Potter facies; limb defects, such as talipes equinovarus and congenital hip dislocation; pectus excavatum and external ear anomalies.2-5 Severe oligohydramnios can also result in pulmonary hypoplasia with respicause
ratory insufficiency, pneumothoraces, and
death from
failure.&dquo; Urinary
with Eagle-Barrett syndrome has been attributed to urethral obstruction.’ Consequently, renal involvement should be considered in any neonate presenting with dysmorphic signs of poor abdominal musculature, external ear
patients
tract
respiratory obstruction
frequently may also be associated with congenital heart disease and anorectal malformations.6 In addition, the abdominal muscle deficiency (&dquo;prune belly&dquo;)
seen
Division of Nephrology, Children’s of Philadelphia. Address
Hospital
correspondence to: William E. Smoyer, M.D., Division of Nephrology, Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard,
Philadelphia, PA 19104 (215)590-2449
in
abnormalities, widely spaced nipples, imperforate anus, or spina bifida.’ There is evidence for the involvement of both genetic and enin vironmental factors the of pathogenesis congenital obstructive uropathy. Genetic involvement is suggested by the description of members of several families with hydronephrosis caused by obstruction of either the ureterovesical or ureteropelvic
junction.8S Hydronephrosis can also be with dominantly inherited syndromes, such as Ehlers-Danlos, Marfan’s, Apert’s acrocephalosyndactyly, and multiple lentigines, as well as with recessively inherited syndromes, such as Laurenceseen
Moon-Biedl, and
Fanconi’s
phropathy are most easily categorized according to the level of obstruction and whether they are intrinsic or extrinsic to the urinary In addition to structural causes, obstruction may be functract.
tional, due
to interference with in the urinary tract. peristalsis Table 1 shows the diversity of causes of UTO in children. The extent of irreversible renal damage resulting from UTO is, however, related to both the duration and severity of obstruction, as well as the rate of urine formation and the presence or absence of infection. 10 The following sections will review several aspects of UTO: the pathophysiology of UTO during and after relief of obstruction; the diagnosis of UTO, including signs, symptoms, and laboratory and radiologic findings; medical management of UTO; prenatal diagnosis and management of UTO; and the long-term outcome of children with UTO.
anemia,
ectromelia-ichthyosis.1 In con-
the involvement of environmental factors, the critical stage in the development of the human kidney is at 28 to 30 days, when the ureteric bud arises from the posteromedial wall of the wolffian duct.’Although no teratogens have been identified in humans, exogenous vitamin A, pantothenic acid or folic acid deficiency, and irradiation can all cause hydronephrosis in the rat.99 The causes of obstructive ne-
Pathophysiology
sidering
Urinary tract obstruction can be functionally defined as a disturbance in the normal pressure-flow relationships in the urinary tract, and it is only by an increase in presthat the effects of obstruction transmitted back to the kidney.’ Although the terms &dquo;obstructive nephropathy&dquo; and &dquo;obstructive sure are
uropathy&dquo; are often used interchangeably, they are not identical. Obstructive uropathy generally re109
fers
to the urinary result of obstruction, system whereas obstructive nephropathy is usually reserved specifically for damage to the kidneys as a result of obstruction. The pathophysiology of obstructive nephropathy is most easily understood by considering first the pathophysiology of the obstructive state, and then the pathophysiology of the postobstructive to
any
damage
as a
state.
Pathophysiology of the Obstructive State In the normal state ureteral
peristalsis begins with electrical impulses originating at pacemaker sites located in the proximal portion of the collecting system.ll°12 These impulses result in changes in intracellular calcium concentration in the muscle cells of the ureter and thus initiate the peristaltic contraction waves which propel urine from the kidney to the bladder. These waves occur two to six times per minute 13 and are propagated at a rate of 2-6 cm/ sec.14 Nor-
mal baseline ureteral pressures range from 0-10 cm H20, with peristaltic wave pressures ranging from 20-60 cm H20Y Following the onset of acute UTO, there is of urine in the collecting system proximal to the site of obstruction and an increase in baseline ureteral and pressure dimensions.15,16 A transient increase in the amplitude and frequency of the peristaltic waves&dquo; is followed by discoordination of pelvic contractility and resultant incomplete emptying of the renal pelvis.18 In experimental models, although an obstructed ureter can
backup
circumferential contractile forces than a control ureter, the intraluminal pressure generated by the obstructed ureter can be little different from the resting pressure. As a result, the con-
develop greater
10
Table! 1
CAUSES OF UR~Nt~RI~
’~~~~~‘ I~B~~‘R1~~TItIN
lN ~H11DREN
traction
resulting
from
may be incapable of
peristalsis effectively pro-
pelling the urine bolus.’o Moreover, superimposed infection can lead to complete absence of contraction in an obstructed ureter and more severe impairment of urine transport.10 The renal functional changes which take place during UTO include changes in renal hemodynamics, impairment of urinary concentrating ability, and defects in urinary acidification and potassium excretion. Acute obstruction is accompanied by a transient increase in renal blood flow, which subsequently decreases to 40%50% of normal.&dquo; In addition, as the hydrostatic pressure within the proximal tubule increases, the net pressure across the glomerular capillary walls decreases, which results in a decrease in glomerular filtration rate (GFR) .’9 Despite this, however, there is considerable evidence that even complete obstruction of a ureter does not completely abolish glomerular filtration&dquo; and it appears that other factors are also involved in depressing GFR acutely.20 With chronic obstruction the reasons for the decreased GFR are even more complex than those for acute obstruction, as ureteral hydrostatic pressures are often normal or only slightly elevated, and the ureters are increased in both diameter and length. Patients with chronic partial obstruction, as well as patients with recent relief of obstruction, may also have defects in urinary acidification and
potassium excretion, leading
to
hyperkalemia and/or acidosis. In addition, these patients may also have a decreased urinary concentrating ability and present with polyuria and/or dehydration. The proposed mechanisms for these responses will be discussed in the next section.
Pathophysiology of the Postobstructive State The most important considerations of the postobstructive state relate to the recovery of renal function and the degree of postobstructive diuresis. Renal function after relief of UTO may vary from normal to advanced renal failure. Experiments in dogs, measuring the degree and rate of return of renal function after varying periods of complete unilateral ureteral obstruction, have suggested that the longer the duration of obstruction the less is the degree of recovery that can be expected.2’ The potential for recovery is usually better in partial than in complete obstruction and when obstruction is not complicated by urinary tract infection (UTI). 22,23 Various disorders of renal tubular function may be found following relief of UTO. Although a defect in proximal tubular function, with enhanced losses of magnesium, calcium, uric acid,
phosphate, alpha-amino-nitrogen, and bicarbonate in the postobstructive period has been re-
ported,24 have
an
commonly patients inability to acidify their
more
urine, and
studies have suggested they develop a form of distal renal tubular acidosis with an inability to lower the urine pH to normal minimum values in response to systemic acidosis.19 This defect can last from weeks to years following relief of obstruction. A syndrome of hyperkalemic, hyperchloremic metabolic acidosis (Type IV renal tubular acidosis) has been described in a group of adults with chronic renal insufficiency associated with obstructive uropathy. 2’ This was found to be caused by a distal defect in hydrogen ion and potassium secretion in some of the patients and a selective aldosterone deficiency in others. Distal tubular defects have also most
been demonstrated in infants and children. A group of infants with UTO and UTI who also presented with hyperkalemic metabolic acidosis has been reported.26 Unlike the adults, however, these infants had marked hyponatremia (serum Na 103-129 mmol/L) with urinary salt wasting in the face of elevated renin and aldosterone levels. These authors suggested that temporary aldosterone insensitivity can occur following an upper UTI in an anatomically abnormal urinary tract. In most of the infants the excessive urinary sodium losses gradually improved, but in some, polyuria persisted for as long as 10 years after relief of obstruction. This was thought to be caused by collecting tubule unresponsiveness to antidiuretic hormone This (ADH) . type of postobstructive defect appears to make sense
physiologically, since maximal concentrating ability, which is a function of the most distal segment of the nephron, should be the most vulnerable to increased intrapelvic
pressure. 27 A period of diuresis often occurs after relief of UTO. Although this is frequently thought of as an indicator of tubular dysfunction, a postobstructive diuresis may be
physiologically appropriate, or in some instances, even iatrogenic. Frequently, however, the postobstructive diuresis is associated with a decrease in maximal urinary concentrating ability. 28-32 This initial impairment of concentrating ability after the period of postobstructive diuresis is usually transient, and most patients regain the ability to concentrate urine appropriately over a period of days to months after relief of obstruction .29,30 A number of factors appear to contribute to postobstructive diuresis. Patients are often volume expanded prior to relief of the obstruction, and a
111
Figure 1: Effect of urinary tract obstruction on medullary prostagiandin
production,
with its subsequent effects on
urinary concentrating ability which culminates in polyuria. The inhibitory effect of prosta-
glandin synthetase inhibitors (PSis) on this sequence of events is shown by the dashed line. MTALH refers to medul-
larythickascending limbofthe loop of Henle.
physiologic diuresis would be expected to occur following relief of obstruction.33 Accumulation of natriuretic factors in response to this volume expanded state may also play a role in postobstructive diureS1S.34 In addition, obstruction results in the accumulation of urea, which induce a may also solute diuresis with postobstructive large losses of sodium and water.35 Finally, there may be a relation between obstruction complicated by UTI and impaired urinary concentrating ability. In a group of adults with unilateral hydronephrosis sec-
ondary to ureteropelvic junction (UPJ) obstruction, some investigators
UTI
found that, in the absence of or
nephrolithiasis,
trating ability
was
not
concen-
reduced.31
Others, however, failed to find a strong correlation between impaired concentrating capacity and
112
UTI in a group of 11 infants and children with UTO.30 Although data on the relative involvement of each of these factors in humans are lacking, the pathogenesis of postobstructive diuresis is probably multifactorial. Postobstructive diuresis in some patients has also been associated
with increased din E2
urinary prostaglan-
(PGE2) excretion.36
Prosta-
glandins appear to modulate urine concentration by antagonizing ADH-sensitive adenylate cyclase in the collecting tubule and by decreasing medullary tonicity.&dquo; Intrarenal prostaglandins also inhibit urea transport from the collecting tubule, decrease sodium chloride transport in the thick ascending limb of the loop of Henle, and increase medullary blood flow.3’ This sequence of events is depicted in Figure 1. Although the
mechanism by which UTO induces increased prostaglandin production is not known, pressure-induced damage to distal and collecting tubule cells may stimulate an increase in medullary pros-
taglandin production directly
or
via cellular mediators (cytokines) which stimulate prostaglandin production by infiltrating interstitial cells such as macrophages. The precise mechanisms by which UTO causes the clinical features of obstructive nephropathy, however, must await further studies.
Diagnosis Signs and Symptom The clinical presentation of UTO can be variable and depends on the location of the obstruction, whether it develops acutely or
gradually, and whether it is unilateral or bilateral. Signs and symptoms suggestive of an obstructed urinary tract in a child are shown in Table 2. Neonates may present with an asymptomatic abdominal mass, a diminished urinary stream, or with abnormal voiding patterns,
such
as
oligoanuria
or
frequent
voiding of small volumes of urine. Isolated swelling of the penis or scrotum may be seen in infants with posterior urethral valves (PUV). Older children, however, may come to the attention of the pediatrician with complaints of urinary incontinence, nocturnal enuresis,
or
post-void dribbling.
Recurrent UTIs or UTIs resistant to treatment in a child of any age
should prompt an evaluation of the tract to exclude UTO or
urinary .
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vesicoureteral reflux (VUR). It should be noted, however, that partial or gradual obstruction may cause significant damage to the urinary tract, despite being undetected for many years in an asymptomatic patient. When UTI supervenes, a child may present acutely ill with renal failure and possibly sepsis and meningitis.&dquo; In fact, infection is often the event which draws attention to an obstruction, and it is one of the major factors that causes loss of renal function in such cases.’ For this reason, when a child is diagnosed with a UTI in certain clinical situations, a renal ultrasound may be indicated to exclude UTO. Conversely, when UTO is diagnosed, the urine should always be cultured. When UTO is identified, the most com-
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urinary pathogens seen are gram-negative bacilli, Staphylococci, and Streptococci. Urinary tract obstruction must mon
be considered in the differential diagnosis if a child presents with renal failure associated with either anuria (absence of urine after bladder catheterization) or alternating oligoanuria and polyuria. Improvement in urine output and renal function with catheterization suggests obstruction at or below the level of the bladder. Urinary tract obstruction should also be considered in all cases of unexplained acute or chronic renal failure, as well as acute deterioration of renal function in patients with known renal disease of any cause.
Ureteropelvic junction (UPJ) obstruction is the most common cause of UTO in infancy.39 It occurs more frequently in males and more commonly involves the left kidney. The usual presentation is with an abdominal mass, but UTI and emesis also are frequently seen. In older children, however, UPJ obstruction may present with intermittent flank or abdominal pain, symptoms of or hematuria. UTI, Posterior urethral valves (PUV) are another important cause of UTO in children. The most common clinical finding in this disorder, regardless of the age of presentation, is a palpably enlarged bladder.4° The parents may report the presence of an abnormal urinary stream, sometimes described as urinary &dquo;dribbling.&dquo; These patients may also present with azotemia, sepsis, meningitis, hyponatremia, hyperkalemia, dehydration, or acidosis. Approximately 90% of infants with PUV have hydronephrosis&dquo; and 40% have an accompanying UTI.42 Half of these patients are also found to have VUR at diagnosis.4° Although delayed diagnosis is unusual,
school-age boys present most com-
113
monly with a history of daytime urinary incontinence or nocturnal
Also, although not routinely evaluated, impairment of maximal uri-
enuresis.
nary concentrating ability is the earliest functional abnormality in obstructive nephropathy.’9 Because obstruction of the urinary tract often results in decreased urine flow, these patients are also at increased risk for UTI and may have pyuria or bacteriuria. When chronic UTO presents as acute renal failure, the urine diagnostic indices are often similar to acute tubular necrosis, with decreased
Laboratory Findings Patients with UTO may present with a wide range of blood and urine abnormalities (Table 3). Conversely, even severe obstruction can present with a relatively normal urinalysis. More often, however, some degree of proteinuria and/or hematuria is noted. _) ~N , , ~ ~ ’ j $ ~ ’ ’ £ ’ ~ ) ’ ’ &dquo; ’ ~ £. ; , ~ ; ’~~~W §=jjs%;,, ~.&dquo;~j _=*-’j#,~;~%,%£,__ju=.jg= [§#§&dquo;&dquo;fi ’-,’,~;Q,§&dquo; ’ ’
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