Urinary Tract Obstruction

C H A P T E R

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Urinary Tract Obstruction Kevin P.G. Harris, Jeremy Hughes

DEFINITIONS Obstructive uropathy refers to the structural or functional changes in the urinary tract that impede normal urine flow. Obstructive nephropathy refers to the renal disease caused by impaired flow of urine or tubular fluid. Hydronephrosis refers to dilation of the urinary tract. Importantly, hydronephrosis is not synonymous with obstructive uropathy as it can occur without functional obstruction to the urinary tract and can be absent in established obstruction. Obstructive uropathy and nephropathy frequently coexist, and their management requires close collabo­ ration between nephrologists and urologists. Some surgical aspects of obstruction to the urinary tract are discussed in Chapter 59. Obstructive uropathy is classified according to the site, degree, and duration of the obstruction. Acute or chronic obstruction can occur anywhere in the urinary tract and includes intrarenal causes (casts, crystals) and extrarenal causes. Acute or chronic obstruction is further subdivided into upper urinary tract obstruc­ tion (usually unilateral obstruction occurring above the vesico­ ureteral junction) and lower urinary tract obstruction (usually bilateral obstruction located below the vesicoureteral junction). Complete obstruction of the urinary tract is termed high grade, whereas partial or incomplete obstruction is termed low grade. Unilateral obstruction in a patient with two normal kidneys will not result in significant renal impairment because the con­ tralateral kidney compensates. However, bilateral obstruction or the obstruction of a single functioning kidney will result in renal failure. In acute urinary tract obstruction, changes are mainly functional, whereas structural damage to the kidney results from more chronic obstruction. The acute functional changes may recover after the effective release of the obstruction, but struc­ tural changes may be permanent and lead to chronic renal impairment. Urinary tract obstruction remains a major cause of renal impairment worldwide.

ETIOLOGY AND PATHOGENESIS The causes of obstructive uropathy affecting the upper and lower urinary tracts are summarized in Figures 58.1 and 58.2.

Congenital Urinary Tract Obstruction Congenital urinary tract obstruction occurs most frequently in males, most commonly as a result of either posterior urethral valves or pelviureteral junction obstruction. If obstruction occurs early during development, the kidney fails to develop and 702

becomes dysplastic. If the obstruction is bilateral, there is a high mortality rate as a result of severe renal failure. If the obstruction occurs later in gestation and is low grade or unilateral, hydrone­ phrosis and nephron loss will still occur, but renal function may be sufficient to allow survival, and such patients may not present until later in childhood. Pelviureteral junction obstruction, if it is mild, may not present until adulthood and in some patients may be an incidental finding (Fig. 58.3). However, with increased use and improved sensitivity of antenatal scanning, congenital abnormalities of the urinary tract are now frequently identified early, allowing prompt postnatal (and in some cases antenatal) intervention to relieve the obstruction and hence to preserve renal function. Congenital causes of obstruction are discussed further in Chapter 50.

Acquired Urinary Tract Obstruction Acquired urinary tract obstruction may affect either the upper or lower urinary tract and can result from either intrinsic or extrinsic causes. Intrinsic causes of obstruction may be intra­ luminal or intramural. Intrinsic Obstruction Intraluminal Obstruction  Intraluminal obstruction may result from tubular intrarenal obstruction, such as the deposition of uric acid crystals in the tubular lumen after treatment of hema­ tologic malignant neoplasms (tumor lysis syndrome). It may also occur with the precipitation of Bence Jones protein in myeloma and with the precipitation or crystal formation of a number of drugs, including sulfonamides, acyclovir, methotrexate, and indi­ navir (see Chapter 66). Extrarenal intraluminal obstruction in young adults is most commonly caused by renal calculi (see Chapter 57). Calcium oxalate stones are the most common and typically cause intermit­ tent acute unilateral urinary tract obstruction but rarely result in marked chronic renal impairment. Less common causes of urinary lithiasis, such as struvite stones, uric acid stones, and cystinuria, are often bilateral and hence more likely to cause long-term renal impairment. Renal calculi lodge more com­ monly in the calyx, pelviureteral junction, or vesicoureteral junc­ tion and at the level of the pelvic brim. Surgical management of stones is discussed in Chapter 59. Intraluminal obstruction can also result from a sloughed papilla after papillary necrosis or blood clots after macroscopic hematuria (clot colic). Papillary necrosis may occur in diabetes mellitus, sickle cell trait or disease, analgesic nephropathy, renal amyloidosis, and acute pyelone­ phritis. Clot colic can occur with bleeding from renal tumors or



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Causes of Upper Urinary Tract Obstruction Intrinsic Causes

Extrinsic Causes

Intraluminal Intratubular deposition of crystals (uric acid, drugs) Stones Papillary tissue Blood clots Fungal ball

Reproductive system Cervix: carcinoma Uterus: pregnancy, tumors, prolapse, endometriosis, pelvic inflammatory disease Ovary: abscess, tumor, cysts Prostate: carcinoma

Intramural Functional: pelvic-ureteral or vesicoureteral junction dysfunction Anatomic: tumors (benign or malignant) Infections, granulomas, strictures

Vascular system Aneurysms: aorta, iliac vessels Aberrant arteries: pelviureteral junction Venous: ovarian veins, retrocaval ureter Gastrointestinal tract Crohn’s disease Pancreatitis Appendicitis Diverticulitis Tumors Retroperitoneal space Lymph nodes Fibrosis: idiopathic, drugs, or inflammatory Tumors: primary or metastatic Hematomas Radiation therapy Surgical disruption or ureteral ligation

Figure 58.1  Causes of upper urinary tract obstruction. The most common causes are in italics.

Causes of Lower Urinary Tract Obstruction Urethral anatomic causes Urethal strictures: trauma, postinstrumentation, infections such as gonococcal urethritis, nongonococcal urethritis, tuberculosis Posterior urethral valves Stones Blood clots Periurethral abscess Phimosis Paraphimosis Meatal stenosis Urethral functional causes Anticholinergic drugs, antidepressants, levodopa Prostate Benign prostatic hypertrophy Prostatic carcinoma Prostatic calculi Prostatic infection Bladder anatomic causes Bladder cancer Schistosomiasis (Schistosoma haematobium infection) Bladder calculi Bladder trauma, pelvic fracture Bladder functional causes Neurogenic bladder: spinal cord defects or trauma, diabetes, multiple sclerosis, Parkinson’s disease, cerebrovascular accidents Figure 58.2  Causes of lower urinary tract obstruction. The most common causes are in italics.

Figure 58.3  Intravenous urogram demonstrating pelviureteral junction obstruction. The study was performed in a previously asymptomatic adult to investigate nonspecific right loin pain. There is unilateral (right side) dilation of the pelvicalyceal system. The ureter has not been visualized.

arteriovenous malformations, after renal trauma, and in patients with polycystic kidney disease. Intramural Obstruction  Intramural obstruction can result from either functional or anatomic changes. Functional disorders include vesicoureteral reflux, adynamic ureteral segments (usually at the junction of the ureter with the pelvis or bladder), and neurologic disorders. The last may result in a contracted (hyper­ tonic) bladder or a flaccid (atonic) bladder, depending on whether the lesion affects upper or lower motor neurons, and lead to impaired bladder emptying with vesicoureteral reflux. Bladder dysfunction is very common in patients with multiple sclerosis and after spinal cord injury and is also seen in diabetes mellitus, in Parkinson’s disease, and after cerebrovascular accidents. Some drugs (anticholinergics, levodopa) can alter neuromuscular activ­ ity of the bladder and result in functional obstruction, especially if there is preexisting bladder outflow obstruction (e.g., prostatic hypertrophy). Anatomic causes of intramural obstruction of the upper urinary tract include transitional cell carcinoma of the renal pelvis and ureter and ureteral strictures secondary to radio­ therapy or retroperitoneal surgery. Rarely, obstruction may result from ureteral valve malfunction, polyps, or strictures after therapy for tuberculosis. Intramural obstruction of the lower urinary tract can result from urethral strictures, which are usually secondary to chronic instrumentation or previous urethritis, or malignant and benign tumors of the bladder. Infection with Schistosoma haematobium, when the ova lodge in the distal ureter and bladder, is a common cause of obstructive uropathy world­ wide; up to 50% of chronically infected patients develop ureteral strictures and fibrosis, with contraction of the bladder. Extrinsic Obstruction The most common cause of extrinsic compression in women is pressure from a gravid uterus on the pelvic rim; the right ureter

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is more commonly affected. It is usually asymptomatic, and the changes resolve rapidly after delivery. Rarely, bilateral obstruc­ tion and acute kidney injury [AKI] may occur. Ureteral dilation may frequently be seen in pregnancy as a result of hormonal effects (especially progesterone) on smooth muscle, but this does not indicate functional obstruction (see Chapter 41, Fig. 41.1). Carcinoma of the cervix may also cause extrinsic obstruction because direct extension of the tumor to involve the urinary tract occurs in up to 30% of patients. Other pelvic pathologic pro­ cesses that can cause ureteral compression include benign and malignant uterine and ovarian masses, abscesses, endometriosis, and pelvic inflammatory disease. Compression of the ureters outside the bladder may also occur with uterine prolapse. Although rare (<0.5%), inadvertent ureteric ligation may occur during surgical procedures, particularly those related to obstet­ rics and gynecology. Unilateral ligation may go undetected, but AKI will result from bilateral ligation. In men, the most common cause of extrinsic obstruction of the lower urinary tract is benign prostatic hypertrophy. Carci­ noma of the prostate can also result in obstruction either from direct tumor extension to the bladder outlet or ureters or from metastases to the ureter or lymph nodes. Retroperitoneal disease may also result in extrinsic obstruc­ tion of the ureters, as can metastases or extension of tumors from the cervix, prostate, bladder, colon, ovary, and uterus. Primary tumors of the retroperitoneum, such as lymphomas and sarco­ mas, can commonly cause obstruction. Obstruction can also result from inflammatory conditions affecting the retroperito­ neum, such as Crohn’s disease and large bowel diverticulitis. In Crohn’s disease, the obstruction is usually right sided as a result of ileocecal disease. Less common pathologic processes include retroperitoneal fibrosis, in which thick fibrous tissue extends out from the aorta to encase the ureters and draw them medially (Fig. 58.4). Retroperitoneal fibrosis may be idiopathic but can result from inflammatory aortic aneurysms, certain drugs (e.g.,

Figure 58.4  Retrograde pyelogram showing idiopathic retroperitoneal fibrosis. Dilation of the pelvicalyceal system is clearly demonstrated. The ureters, however, are not dilated, and the left ureter can be seen being pulled medially as a result of encasement in thick fibrous tissue.

β-blockers, bromocriptine, and methysergide), previous irradia­ tion, trauma or surgery, and granulomatous disease (e.g., tuber­ culosis, sarcoidosis). Ureteral compression may also be a result of vascular abnormalities, including aneurysmal dilation of the aorta or iliac vessels, aberrant vessels, and anatomic variations in the location of the ureter (retrocaval ureter).

PATHOPHYSIOLOGY Obstruction to the renal tract causes profound functional and structural changes of the kidney.1 Initially, changes are predomi­ nantly functional and potentially reversible, but with time, chronic and irreversible structural changes occur. Our under­ standing of the consequences of urinary tract obstruction stem mainly from the study of animal models.2 Although many studies have focused on the effects of complete ureteral obstruction in rodents, investigators have also examined models of chronic complete, partial, or reversible obstruction in adult and neonatal animals.3 Available experimental data show little species to species variation in the response to acute obstruction, suggesting that similar changes are likely to occur in humans. The complex effects of urinary tract obstruction on the kidney affect both glomerular hemodynamics and tubular function.4

Changes in Glomerular Function Glomerular filtration rate (GFR) declines progressively after the onset of complete ureteral obstruction. Glomerular filtration is determined by the mean hydraulic pressure gradient between the glomerular capillary lumen and Bowman’s space, the renal plasma flow, the ultrafiltration coefficient of the glomerular cap­ illary wall, and the mean oncotic pressure difference across the glomerular wall. Obstruction can affect all of these, and the effects vary with the duration of the obstruction, the hydration state, and the presence or absence of a contralateral functioning kidney. After complete ureteral obstruction, there is an initial rise in proximal tubular pressure. At the same time, afferent arteriolar dilation occurs as a result of the generation of vasodilatory pros­ taglandins (e.g., prostacyclin, prostaglandin E2). Glomerular cap­ illary hydraulic pressure increases, but this does not offset the rise in tubular pressure, and there is a net decrease in the hydrau­ lic pressure gradient across glomerular capillaries, resulting in an 80% decline in GFR. About 2 to 5 hours after obstruction, renal blood flow begins to decline, whereas intratubular pressure continues to increase. Within 5 hours, proximal tubular pressure begins to decline toward control values. From this time, the main determinant of the decrease in GFR is the fall in intraglomerular capillary pres­ sure as a result of an increase in resistance of afferent arterioles. This results in a progressive fall in renal plasma flow, which reaches 30% to 50% of control values by 24 hours. Preferential constriction of the preglomerular blood vessels lowers both plasma flow and glomerular capillary pressure, resulting in a greater decrement in GFR than in plasma flow and a fall in filtration fraction. A falling filtration fraction also results from diversion of blood to nonfiltering areas of the kidney or a reduc­ tion in the ultrafiltration coefficient. The relative changes in ureteral pressure, renal plasma flow, and GFR are summarized in Figure 58.5. The intrarenal vasoconstriction results from the generation of angiotensin II and thromboxane A2, the release of vasopressin (antidiuretic hormone), and the decreased nitric oxide produc­



CHAPTER

Percentage of control values

The Effects of Complete Ureteral Obstruction 200 180 160 140 120 100 80 60 40 20 0

Ureteral pressure Renal plasma flow Glomerular filtration rate

0

2

4 6 8 10 12 14 Time postobstruction (hours)

16

18

Figure 58.5  The effects of complete ureteral obstruction. The relative changes in ureteral pressure, renal plasma flow, and glomerular filtration rate are shown with data from experimental studies of unilateral ureteral obstruction in rats.

tion. Angiotensin II and thromboxane A2 may also reduce the ultrafiltration coefficient.4,5 The central role of these two vaso­ constrictors has been demonstrated by studies in rats, in which pretreatment with angiotensin-converting enzyme inhibitors and thromboxane synthase inhibitors virtually normalized renal function after the relief of short-term ureteral obstruction.6 Intrarenal angiotensin II generation occurs secondary to an increase in renin release either through reduced delivery of sodium and chloride to the distal nephron (macula densa mecha­ nism) or through a reduction in transmural pressure at the baro­ receptor as a consequence of the prostaglandin-dependent dilation of the afferent arteriole. Generation of thromboxane A2 occurs in both glomeruli and infiltrating interstitial cells. An interstitial leukocyte infiltrate, predominantly macro­ phages, develops in response to chemoattractants such as mono­ cyte chemoattractant protein 1 and osteopontin expressed by tubular cells. This infiltrate plays a key role in the acute func­ tional changes after ureteral obstruction7 and is implicated in the pathogenesis of the late structural changes that occur after obstruction as macrophage depletion limits interstitial fibrosis.8 The extent to which glomerular function recovers after the release of ureteral obstruction depends on the duration of the obstruction. Whole-kidney GFR may return to normal after short-term obstruction (days), whereas recovery may be incom­ plete after prolonged obstruction. Evidence from studies in rats now suggests that even with shorter periods of obstruction (72 hours), there may be a permanent loss of nephrons, and whole-kidney GFR returns to normal only at the expense of hyperfiltration (increase in single-nephron GFR) in the remain­ ing functional nephrons.9

Changes in Tubular Function Abnormalities in tubular function are common in urinary tract obstruction and are manifested as altered renal handling of elec­ trolytes and changes in the regulation of water excretion.4 The degree and nature of the tubular defects after obstruction depend in part on whether the obstruction is bilateral or unilateral. These differences could result from the dissimilar hemodynamic

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705

responses, different intrinsic changes within the nephron, differ­ ences in extrinsic factors (e.g., volume expansion and accumula­ tion of natriuretic substances in bilateral obstruction) between the two states, or a combination of all three. After ureteral obstruction, the ability to concentrate the urine is markedly impaired, with maximum values of 350 to 400 mOsm/kg reported in the rat. Causative factors include a loss of medullary tonicity, an overall decrease in GFR in deep nephrons, and a reduced expression of sodium transporters.10 Also, the col­ lecting duct is unresponsive to vasopressin because of a reduction in the expression of renal aquaporins that results from both cyclooxygenase 2 activity11 and angiotensin II.12 Rats exhibit reduced expression of multiple acid-base trans­ porters after ureteral obstruction,13 and patients with urinary tract obstruction often exhibit urinary acidification defects. This may be detected only by exogenous acid loading, but hyperchlo­ remic acidosis caused by impaired distal acid secretion, hypo­ reninemic hypoaldosteronism (type 4 renal tubular acidosis), and a combination of these findings have been described. This acidi­ fying defect results from a marked increase in bicarbonate excre­ tion or from a distal acidification defect, possibly as a result of abnormalities of the H+-ATPase activity of intercalated cells of the collecting duct after ureteral obstruction. Obstruction alters renal potassium handling. In the presence of a normal functioning contralateral kidney, potassium excre­ tion is reduced after relief of obstruction, either in proportion to or perhaps even greater than the fall in GFR (i.e., fractional excretion of potassium is unaltered or slightly reduced). There is a defect in the distal potassium secretory mechanism after unilateral obstruction that may be secondary to reduced respon­ siveness of that nephron segment to aldosterone. By contrast, after release of bilateral ureteral obstruction, there is a marked increase in both net and fractional potassium excretion. The major mechanism by which potassium losses occur in this setting is an increased delivery of sodium to the distal tubule, resulting in an accelerated sodium-potassium exchange. Recovery of tubular function after release of obstruction is slow and may remain abnormal even after whole-kidney GFR has returned to normal. In rats, acidification and potassium han­ dling abnormalities persist for at least 14 days and urinary con­ centrating ability is abnormal for up to 60 days after the release of 24 hours of unilateral ureteral obstruction. These observations are consistent with persistent alterations in distal tubular and collecting duct function or a loss in functioning juxtaglomerular nephrons after the release of the obstruction. Histopathologic Changes The morphologic alterations in renal architecture are similar irrespective of the cause of the obstruction. Initially, there is renal enlargement and edema with pelvicalyceal dilation (Fig. 58.6). Tubular dilation that predominantly affects the collecting duct and distal tubular segments develops microscopically, although cellular flattening and atrophy of proximal tubular cells can also occur. Glomerular structures are usually preserved ini­ tially, although Bowman’s space may be dilated and contain Tamm-Horsfall protein. Ultimately, some periglomerular fibro­ sis may develop. Inadequately treated obstruction to the urinary tract eventu­ ally causes irreversible structural changes to the renal tract. The renal pelvis becomes widely dilated, with the renal papillae either flattened or hollowed out. The cortex and medulla become grossly thinned, such that the kidney becomes a thin rim of renal tissue surrounding a large saccular pelvis (Fig. 58.7). Histologic

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transdifferentiation, and tubular cell apoptosis.3 However, it is pertinent that differences have been noted in the response of adult and neonatal rodents to experimental therapeutic interven­ tions, and it is unclear whether such differences might occur in humans.

EPIDEMIOLOGY

Figure 58.6  Autopsy specimen of a kidney showing the early effects of ureteral obstruction. The kidney is enlarged and edematous with pelvicalyceal dilation. There is good preservation of the renal parenchyma.

Figure 58.7  Chronic ureteral obstruction. Surgical specimen of a kidney showing gross dilation of the pelvicalyceal system and the reduction of the renal cortex to a thin fibrotic rim of tissue. There would have been no prospect for any significant functional recovery in this kidney after the relief of the obstruction.

examination demonstrates tubulointerstitial fibrosis and oblit­ eration of nephrons. There is tubular proliferation and apoptosis, epithelial-mesenchymal transition, (myo)fibroblast accumula­ tion, increased extracellular matrix deposition, and tubular atrophy. Ischemia as a result of the decreased renal blood flow contributes to the parenchymal damage after obstruction. In both genetic and interventional studies, an important pathologic role for angiotensin II and transforming growth factor β (TGFβ) has been established.14,15 Infiltrating macrophages play a pivotal role in the chronic tissue injury and fibrosis that result from prolonged ureteral obstruction (Fig. 58.8).8,16 Interstitial macrophages release profi­ brogenic factors such as TGF-β and galectin-3, which promote progressive fibrosis. Local angiotensin II generation may also stimulate the production of TGF-β by tubular cells. Treatments shown to ameliorate chronic interstitial damage in experimental obstructive uropathy include angiotensin receptor blockers, pentoxifylline, simvastatin, and growth factors (such as bone morphogenetic protein 7, hepatocyte growth factor, and epider­ mal growth factor); beneficial effects include a reduction in tubu­ lointerstitial inflammation and fibrosis, epithelial-mesenchymal

Obstructive uropathy is a common entity and can occur at all ages. The prevalence of hydronephrosis at autopsy is 3.5% to 3.8%, with about equal distribution between males and females,17 although this underestimates the true incidence as these figures exclude transient obstruction. The frequency and etiology of obstruction vary in both sexes with age. Antenatal ultrasound has significantly increased the detection rate of lower urinary tract obstruction in the fetus.18 In children younger than 10 years, obstruction is more common in boys; congenital urinary tract anomalies, such as urethral valves and pelviureteral junction obstruction, account for most cases. In North America, obstruc­ tive uropathy remains the most common cause of end-stage renal disease (ESRD) in pediatric patients registered for renal trans­ plantation, accounting for 16% of cases. In addition, congenital obstructive uropathy accounts for 0.7% of all patients (median age, 31 years) maintained with renal replacement therapy, dem­ onstrating the continued impact of this disease into adult life.19 In young adults (<20 years of age), the frequency of urinary tract obstruction is similar in males and females. Beyond 20 years of age, obstruction becomes more common in women, mainly as a result of pregnancy and gynecologic malignant neoplasms. The peak incidence of renal calculi occurs in the second and third decades of life with a threefold increased incidence in men. After the age of 60 years, obstructive uropathy occurs more frequently in men secondary to benign prostatic hypertrophy and prostatic carcinoma. About 80% of men older than 60 years have some symptoms of bladder outflow obstruction, and up to 10% have hydronephrosis. In Europe, acquired urinary tract obstruction accounts for 3% to 5% of the cases of ESRD in patients older than 65 years, with most resulting from prostatic disease.20 In the United States, the number of patients receiving renal replace­ ment therapy as a result of acquired obstruction continues to increase, accounting for 1.4% of prevalent patients, although the rise is not as rapid as with other causes of ESRD.19

CLINICAL MANIFESTATIONS Obstruction of the urinary tract can present with a wide range of clinical symptoms, depending on the site, degree, and duration of obstruction.4 The clinical manifestations of upper and lower urinary tract obstruction differ. Symptoms can be caused by mechanical obstruction of the urinary tract (usually pain) or can result from the complex alterations in glomerular and tubular function that may occur in obstructive nephropathy. The latter commonly present as alterations in urine volume and as renal failure, which can be acute or chronic. For example, patients with complete obstruction present with anuria and AKI, whereas those with partial obstruction may present with polyuria and polydipsia as a result of acquired vasopressin resistance. Alterna­ tively, there may be a fluctuating urine output, alternating from oliguria to polyuria. However, obstructive uropathy and hence obstructive nephropathy can occur without symptoms and with minimal clinical manifestations. Thus, obstruction of the urinary tract must be considered in the differential diagnosis of any patient with renal impairment.



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Impairment of Function and Structural Damage in Obstructive Nephropathy Obstruction of urinary tract

Abrupt fall in GFR

Mechanical stimulation Membrane stretch

Release of chemoattractants

Stimulation of intrinsic renal cells

Macrophage infiltration and interstitial inflammation

Generation of vasoactive substances, e.g., Ang II, TXA2

Mediator and cytokine generation, e.g., nitric oxide, TNF-α, TGF-β

Altered renal hemodynamics

Peritubular capillary loss and ischemia

Tubular cell apoptosis and tubular atrophy

Myofibroblast accumulation and interstitial fibrosis

Acute kidney injury Nephron loss

Irreversible renal injury and scarring with resultant chronic renal failure

Figure 58.8  Events leading to acute impairment of renal function and chronic structural damage in obstructive nephropathy. Ang II, angiotensin II; GFR, glomerular filtration rate; TGF-β, transforming growth factor β; TNF-α, tumor necrosis factor α; TXA2, thromboxane A2.

Pain

Lower Urinary Tract Symptoms

Pain is a frequent complaint in patients with obstructive uropa­ thy, particularly in those with ureteral calculi. The pain is believed to result from stretching of the collecting system or the renal capsule. Its severity correlates with the degree of distention and not with the degree of dilation of the urinary tract. On occasion, the location of the pain helps determine the site of obstruction. With upper ureteral or pelvic obstruction, flank pain and tenderness typically occur, whereas lower ureteral obstruction causes pain that radiates to the groin, the ipsilateral testicle, or the labia. Acute high-grade ureteral obstruction may be accompanied by a steady and severe crescendo flank pain radiating to the labia, the testicles, or the groin (“classic” renal colic). The acute attack may last less than half an hour or as long as a day. In contrast, pain radiating into the flank during micturition is said to be pathognomonic of vesicoureteral reflux. By comparison, patients with chronic, slowly progressive obstruction may have no pain or minimal pain during the course of their disease. In such patients, any pain that does occur is rarely colicky in nature. In pelviureteral junction obstruction, pain may occur only after fluid loading to promote a high urine flow rate.

Obstructive lesions of the bladder neck or bladder disease may cause a decrease in the force or caliber of the urine stream, intermittency, post-micturition dribbling, hesitancy, or nocturia. Urgency, frequency, and urinary incontinence can result from incomplete bladder emptying. Such symptoms commonly result from prostatic hypertrophy and are frequently referred to as prostatism, but they are not pathognomonic of this condition.

Urinary Tract Infections Urinary stasis resulting from obstruction predisposes to urinary tract infections, and patients may develop cystitis with dysuria and frequency or pyelonephritis with loin pain and systemic symptoms. Infection occurs more often in patients with lower urinary tract obstruction than in those with upper urinary tract obstruction. Urinary tract infection in men or young children of either sex, recurrent or persistent infections in women, infections with unusual organisms such as Pseudomonas species, and a single attack of acute pyelonephritis require further investigation to exclude obstruction. Also, the presence of obstruction makes

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effective eradication of the infection difficult. Infections of the urinary tract with a urease-producing organism such as Proteus mirabilis predispose to stone formation. These organisms gener­ ate ammonia, which results in urine alkalinization and favors the development of magnesium ammonium phosphate (struvite) stones. Struvite calculi can fill the entire renal pelvis to form a staghorn calculus that eventually leads to loss of the kidney if it is untreated. Thus, stone formation and papillary necrosis can also be a consequence of urinary tract obstruction as well as a cause of obstruction.

Hematuria Calculi may cause trauma to the urinary tract uroepithelium and result in either macroscopic or microscopic hematuria. Any neo­ plastic lesion that obstructs the urinary tract, especially uroepi­ thelial malignant neoplasms, may bleed, resulting in macroscopic hematuria. Urinary tract bleeding may also result in obstruction, giving rise to clot colic when it is in the ureter or clot retention when it is in the bladder.

Changes in Urine Output Complete bilateral obstruction or unilateral obstruction of a single functioning kidney such as a renal transplant will result in anuria. However, when the lesion results in partial obstruction, urine output may be normal or increased (polyuria). A pattern of alternating oliguria and polyuria or the presence of anuria strongly suggests obstructive uropathy.

Abnormal Physical Findings Physical examination findings can be completely normal. Some patients with upper urinary tract obstruction may have flank tenderness. Long-standing obstructive uropathy may result in an enlarged kidney that may be palpable. Hydronephrosis is a common cause of a palpable abdominal mass in children. Lower urinary tract obstruction causes a distended, palpable, and occa­ sionally painful bladder. A rectal examination and, in women, a pelvic examination should be performed because they may reveal a local malignant neoplasm or prostatic enlargement. Acute or chronic hydronephrosis, either unilateral or bilat­ eral, may cause hypertension as a result of impaired sodium excretion with expansion of extracellular fluid volume or from the abnormal release of renin. On occasion, in patients with partial urinary tract obstruction, hypotension occurs as a result of polyuria and volume depletion.

Abnormal Laboratory Findings Urinalysis may show hematuria, bacteriuria, pyuria, crystalluria, and low-grade proteinuria, depending on the cause of obstruc­ tion. However, urinalysis may be completely negative despite advanced obstructive nephropathy. In the acute phase of obstruc­ tion, urinary electrolyte values are similar to those seen in a “prerenal” state, with a low urinary sodium (<20 mmol/l), a low fractional excretion of sodium (<1%), and a high urinary osmolality (>500 mOsm/kg). However, with more prolonged obstruction, there is a decreased ability to concentrate the urine and an inability to reabsorb sodium and other solutes. These changes are particularly marked after the release of chronic obstruction and give rise to the syndrome commonly referred to as postobstructive diuresis. Obstructive nephropathy may cause

secondary polycythemia as a result of increased erythropoietin production. Increases in serum urea and creatinine are the most significant laboratory abnormalities in patients with obstructive uropathy. Electrolyte abnormalities may also occur, including a hyperchlo­ remic hyperkalemic (type 4) metabolic acidosis or hypernatremia as a result of acquired nephrogenic diabetes insipidus. The devel­ opment of obstruction in patients with underlying chronic kidney disease may accelerate the rate of progression. ESRD may occa­ sionally be caused by chronic obstructive uropathy that had been asymptomatic.

Obstruction in Neonates or Infants With the advent of routine antenatal scanning, the diagnosis of hydronephrosis and genitourinary abnormalities is now fre­ quently made antenatally; however, unsuspected obstructive uropathy may present in the postnatal period with failure to thrive, voiding difficulties, fever, hematuria, or symptoms of renal failure. Oligohydramnios at the time of delivery should raise the suspicion of obstructive uropathy, as should the pres­ ence of congenital anomalies of the external genitalia. Nonuro­ logic anomalies, such as ear deformities, a single umbilical artery, imperforate anus, or a rectourethral or rectovaginal fistula, should prompt investigation for urinary tract obstruction. Any infant with neurologic abnormalities may have a neurogenic bladder with associated obstructive uropathy.

DIAGNOSIS Prompt diagnosis of urinary tract obstruction is essential to allow treatment to limit any long-term adverse consequences. Symp­ toms such as “renal colic” may suggest the diagnosis and prompt appropriate investigation. However, urinary tract obstruction should be actively considered in any patient with unexplained acute or chronic kidney impairment. The diagnostic approach has to be tailored to the clinical presentation (Fig. 58.9), but a careful history and thorough physical examination are manda­ tory in all patients. Urinalysis may provide valuable diagnostic information. Hematuria suggests that the obstructing lesion is a calculus, sloughed papilla, or tumor. Bacteriuria suggests urinary stasis, especially in men or in pregnant women, but it may also be a complication of chronic obstruction. The presence of crystals in the urine sediment (cystine or uric acid) may be an indication of the type of stone causing the ureteral obstruction or the intra­ renal obstruction resulting in AKI. Laboratory studies should include an assessment of renal function (serum creatinine and urea) and the measurement of serum electrolytes.

Imaging Because the sites, causes, and consequences of obstruction to the renal tract are so variable, no single imaging investigation can diagnose renal tract obstruction with certainty. Thus, no single imaging investigation should be relied on to definitively exclude obstruction, especially if the clinical suspicion of obstruction is high. Therefore, the approach to the patient with suspected obstruction may require the complementary use of a number of different imaging techniques. Ultrasound is the most widely used imaging modality, but the imaging approach to investigation of obstruction is chang­ ing. Computed tomography (CT) and magnetic resonance (MR)



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Investigation and Management of Suspected Urinary Tract Obstruction Suspected obstruction

History/examination Urinalysis and urine culture Assessment of renal function Lower tract symptoms

Flank pain ? Renal colic

Ultrasound scan ± plain abdominal x-ray

Bladder ultrasound scan

CT scan (or IVU)

Dilation of PC system

Large residual volume

Impaired renal function

Normal renal function

Nephrostomy

Further imaging to define lesion (CT or MR scan)

Catheterize

Nondilated PC system

Obstruction still suspected

Consider retrograde pyelography

Consider diuresis renogram

Nephrostogram to define lesion

Plan definitive therapy Figure 58.9  Investigation and management of suspected urinary tract obstruction. A full history and examination should be performed, together with urinalysis, urine microscopy and culture, and measurement of renal function and serum electrolytes. Ultrasound is a useful first-line investigation for any patient with suspected urinary tract obstruction. Helical (spiral) computed tomography (CT) is now the preferred imaging technique when renal calculi are suspected. Either CT or magnetic resonance (MR) urography can accurately diagnose both the site and the cause of obstruction in most cases. If there is renal impairment, insertion of a nephrostomy allows the effective relief of the obstruction and time for renal function to recover while definitive therapy is planned. IVU, intravenous urography; PC, pelvicalyceal.

urography are useful in accurately diagnosing both the site and the cause of obstruction, but the availability and expertise in the use of different imaging techniques vary from center to center, and older imaging techniques, such as intravenous urog­ raphy (IVU), can still be used effectively to evaluate patients with obstructive uropathy. The role of imaging techniques is shown in Figure 58.9. Imaging is also discussed further in Chapter 5. Ultrasound Ultrasound can define renal size and demonstrate calyceal dila­ tion21 (Fig. 58.10) but depends on the expertise of the operator. Although it is sensitive for detection of hydronephrosis, ultra­ sound will often not detect its cause. Pathologic change within the ureter is difficult to demonstrate, and tiny stones will not generate acoustic shadows. However, unilateral hydronephrosis suggests obstruction of the upper urinary tract by stones, blood clots, or tumors. Bilateral hydronephrosis is more likely to result from a pelvic problem obstructing both ureters or obstruction of the bladder outlet, in which case the bladder will also be enlarged.

Ultrasound is often combined with radiographic examination of the kidneys, ureters, and bladder (often known as KUB) to ensure that ureteral stones or small renal stones are not overlooked. Ultrasound produces false-negative results in cases of nondi­ lated obstructive uropathy.21 Immediately after acute obstruction (<24 hours), the relatively noncompliant collecting system may not have dilated, such that an ultrasound examination may be normal. Furthermore, if urine flow is low, as in severe dehydra­ tion or renal failure, there may be little dilation of the urinary tract. Dilation may also be absent in slowly progressive obstruc­ tion when the ureters are encased by fibrous tissue (as in retro­ peritoneal fibrosis) or by tumor. The acoustic shadow of a staghorn calculus can also mask dilation of the upper urinary tract. The sensitivity of ultrasound for diagnosis of obstruction can be improved by measuring the resistive index with color Doppler ultrasound. A resistive index above 0.7 reflects the increased vascular resistance present in obstruction and effec­ tively discriminates between obstructed and nonobstructed kidneys.21 Such ultrasound techniques are particularly useful when it is especially important to minimize radiation exposure,

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Figure 58.10  Renal ultrasound scan of a patient with obstruction of the urinary tract causing hydronephrosis. The kidney is hydronephrotic with dilation of the pelvicalyceal system; dilation of the upper ureter is also clearly seen (arrows).

for example, in pregnant women and children, and in the follow-up of patients requiring repeated imaging, such as after extracorporeal shock wave lithotripsy. Even in experienced hands, ultrasound may have a significant false-positive rate, especially if minimal criteria are adopted to diagnose obstruction. In addition, the echogenicity produced by multiple renal cysts may be mistaken for hydronephrosis. Ultrasound scanning can be used to assess bladder emptying and should be undertaken in patients with lower urinary tract symptoms. A large post-micturition residual volume suggests bladder outflow obstruction, which should prompt further uro­ logic investigation and treatment. The investigation of neonates with hydronephrosis diagnosed antenatally depends on the grade of hydronephrosis identified. Neonates with grade 1 or 2 hydronephrosis (no calyceal dilation) undergo ultrasound scanning; neonates with grade 3 to 5 hydro­ nephrosis (indicating increasingly severe pelvicalyceal dilation) require both ultrasound scanning and voiding cystourethrogra­ phy. This combination can distinguish megaureter resulting from obstruction or reflux and diagnose posterior urethral valves and ureteropelvic junction obstruction. Plain Abdominal Radiography A plain abdominal radiograph (or KUB) allows an assessment of kidney size and contour and frequently demonstrates renal calculi because about 90% of calculi are radiopaque. Intravenous Urography IVU was formerly the first-choice investigation for suspected upper urinary tract obstruction. In patients with normal renal function, it can usually define both the site and the cause of the obstruction. However, the excretion of contrast material may be poor or delayed in patients with low GFR because of a decreased filtered load of the contrast agent, which is potentially nephro­ toxic. IVU is no longer a first-line investigation to diagnose urinary tract obstruction, especially in patients with impaired renal function.

Figure 58.11  CT scan of the abdomen showing a grossly hydronephrotic kidney on the left (arrows mark dilated renal pelvis). Dilated loops of small bowel are seen in the right hypochondrium. Sequential sections demonstrated that the ureter was dilated along its length and that there was a pelvic mass, which was responsible for both bowel and left ureteral obstruction. The mass was subsequently shown to be arising from a carcinoma of the colon.

Computed Tomography Non–contrast-enhanced helical (spiral) CT scanning is used increasingly as the primary imaging modality for the evaluation of patients with acute flank pain.22 Stones are easily detected because of their high density, and CT can provide an accurate and rapid diagnosis of an obstructing ureteral calculus. In addition, it provides useful information about the site and nature of the obstructing lesion, especially when this is extrinsic to the urinary tract (Fig. 58.11; see also Chapter 59, Fig. 59.2). CT demon­ strates retroperitoneal disease, such as para-aortic and paracaval lymphadenopathy; retroperitoneal fibrosis is evident as increased attenuation within the retroperitoneal fat, with encasement of one or both ureters. Hematomas, primary ureteral tumors, and polyps are also detectable. The diagnostic potential of CT is enhanced by the administration of contrast material, but this may limit its use in patients with renal impairment. In addition, it involves considerable exposure to ionizing radiation. Magnetic Resonance Urography MR urography (combined with KUB) can diagnose ureteral obstruction due to renal calculi with accuracy similar to that of spiral CT scanning but without exposure to contrast medium or ionizing radiation. The technique has less observer variability and is more accurate than CT in detecting indirect evidence of obstruction, such as perirenal fluid.23 MR urography can rapidly and accurately depict the morphologic features of dilated urinary tracts and provide information about the degree and level of obstruction (Fig. 58.12).24 MR urography is a particularly attrac­ tive imaging modality for the evaluation of hydronephrosis in children as it provides both anatomic and functional data and can indicate whether the hydronephrosis is compensated (symmetric changes of signal intensity of the nephrogram) or decompen­ sated.25 Signs of decompensation (acute on chronic obstruction) include edema of the renal parenchyma, a delayed and increas­ ingly dense nephrogram, a delayed calyceal transit time, and a more than 4% difference in the calculated differential renal func­ tion. MR urography is likely to be increasingly used in the future. Retrograde Pyelography Retrograde pyelography (Fig. 58.13; see also Fig. 58.4) may be particularly useful to identify both the site and the cause of the



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711

Diuretic Isotopic Renography

Renal isotope activity

Normal uptake and excretion of isotope

Time

Renal isotope activity

Obstruction: delayed excretion

Furosemide

Time

Figure 58.12  MR urography showing obstructive uropathy. T2-weighted MR image shows a proximal right-sided ureteral obstruction with an associated mild hydronephrosis. The obstruction was secondary to a ureteral calculus.

Renal isotope activity

Dilation without obstruction

Furosemide

Time Figure 58.14  Diuretic isotopic renography. Idealized tracings for normal, obstructed, and dilated kidneys without obstruction of the upper urinary tract. In obstruction, there is delayed excretion of 99mTc-MAG3 despite administration of furosemide. When there is dilation of the upper urinary tract without obstruction, the isotope is retained but is rapidly excreted after the administration of furosemide.

obstruction. It is also helpful when nondilated urinary tract obstruction is suspected or when there is a history of allergic reactions to contrast material. Urinary tract infection that may become overwhelming if obstruction is present is a contraindica­ tion to retrograde pyelography. Diuresis Renography A diuresis renogram using technetium Tc 99m mercaptoacetyl­ triglycine (99mTc-MAG3), combined with intravenous furose­ mide administered 20 to 30 minutes after injection of the isotope (diuretic isotopic renography), can be used to distinguish between simple dilation of the collecting system and true obstruction.26 Normally, there is a rapid washout of the isotope from the kidney, and persistence of the isotope suggests a degree of obstruction (Fig. 58.14). Poor renal function significantly limits the usefulness of renography as the diuretic response to furose­ mide may be absent. Diuresis renography may also be used for follow up of patients who have undergone surgical procedures to relieve obstruction, such as a pyeloplasty. Figure 58.13  Ureteral obstruction by a tumor. A retrograde pyelogram shows that the tumor is within and obstructing the ureter (arrows). Above the tumor, there is dilation of the ureter; but below it, the ureter is of a normal caliber.

Pressure-Flow Studies A pressure-flow study (Whitaker test27) involves puncture of the collecting system with a fine-gauge needle to perfuse fluid (at 10 ml/min) with concurrent measurement of the differential

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pressure between the bladder and the collecting system; a pres­ sure above 20 cm H2O indicates obstruction. This test is now rarely required. Other Evaluations Lower urinary tract obstruction may be evaluated by cystoscopy, which allows a visual inspection of the entire urethra and the bladder. Urodynamic studies (see Chapter 50, Fig. 50.17) can assess bladder outlet obstruction, measure the residual urine volume after voiding, and detect functional bladder abnormali­ ties. Although IVU with oblique films of the bladder and urethra during voiding (excretory cystography) and after voiding can also evaluate the site of lower urinary tract obstruction and the amount of residual urine, this has now largely been superseded by the use of ultrasound, CT, and MR urography.

DIFFERENTIAL DIAGNOSIS Diagnostic uncertainty arises with nonobstructive dilation of the upper urinary tract that may be seen with vesicoureteral reflux, diuretic administration, diabetes insipidus, congenital megacaly­ ces, chronic pyelonephritis, and postobstructive atrophy. Diure­ sis renography or retrograde pyelography may be required to exclude obstruction.

NATURAL HISTORY Obstructive uropathy is potentially curable but will result in progressive irreversible loss of nephrons and renal scarring if it is left untreated (Fig. 58.15). ESRD will result if both kidneys are affected or if there is only a solitary kidney. Outcome data for obstructive uropathy are limited, but the exact prognosis will depend on the pathologic process responsible for the

Figure 58.15  Pathology of chronic ureteral obstruction. This is a section of the rim of renal tissue from the kidney shown in Figure 58.7. The renal capsule is at the top, the urinary space at the bottom. The cortex is considerably thinned, and only a few atrophic tubules remain (arrows) within an interstitium comprising dense fibrous tissue and a mononuclear cell infiltrate (blue-staining nuclei). No glomeruli can be seen. This demonstrates why there would be no prospect for any significant functional recovery in this kidney even after the relief of the obstruction.

obstruction, the duration of the obstruction, and the presence or absence of urosepsis. Relief of short-term obstruction (<1 to 2 weeks) usually results in an adequate return of renal function. With chronic progressive obstruction (>12 weeks), there is often irreversible and severe renal damage, and renal functional recov­ ery may be limited even after relief of the obstruction. A singlecenter study identified 104 patients who presented with obstruc­ tive nephropathy.28 The mean GFR at presentation and at 3, 12, and 36 months was 9 ml/min, 28 ml/min, 29 ml/min, and 30 ml/ min (patients on dialysis excluded), demonstrating significant but nonprogressive renal impairment after relief of obstruction. It is likely that the prognosis for renal functional recovery is better the earlier the obstruction is diagnosed and relieved.

TREATMENT General Considerations Treatment is dictated by the location of the obstruction, the underlying cause, and the degree of any renal impairment. If renal impairment is present, the treatment of obstruction requires close collaboration between nephrologists and urologists to reduce the risks associated with the metabolic and electrolyte consequences of renal failure and to optimize the chances for long-term recovery of renal function. For example, complete bilateral ureteral obstruction presenting as AKI is a medical emergency and requires rapid intervention to salvage renal func­ tion. Prompt intervention to relieve the obstruction should result in a rapid improvement in renal function. Dialysis should rarely be required in patients with AKI secondary to obstruction except to make the patient fit for intervention, for example, by improv­ ing life-threatening hyperkalemia or severe fluid overload. The rapid relief of obstruction will limit permanent renal damage, but renal function may not recover immediately if acute tubular necrosis has resulted from obstruction or any accompanying sepsis. Some surgical aspects of the management of obstructive urop­ athy are discussed in Chapter 59. The site of obstruction fre­ quently determines the approach. If the obstruction is distal to the bladder, a urethral catheter or, if this cannot be passed, a suprapubic cystostomy will effectively decompress the kidneys. Placement of nephrostomy tubes or cystoscopy and passage of a retrograde ureteral catheter will relieve upper urinary tract obstruction. Percutaneous nephrostomy (PCN) is generally the appropriate emergency treatment of upper urinary tract obstruc­ tion, especially in the setting of AKI. PCN can be achieved with local anesthesia and should allow rapid recovery of renal function in most patients (>70%), avoiding the need for dialysis. After relief of the obstruction by PCN, the exact site and nature of the obstructing lesion can be determined by an antegrade study infusing radiographic contrast material into the nephrostomy tube (nephrostogram, Fig. 58.16), and time can be taken to plan definitive therapy. Major complications of nephrostomy inser­ tion (abscess, infection, and hematoma) occur in less than 5% of patients. If both kidneys are obstructed, the nephrostomy should initially be placed in the kidney with the most preserved renal parenchyma, although bilateral nephrostomies may be required to maximize the potential for the recovery of renal function. If infection occurs above a ureteral obstruction (pyonephrosis), drainage of the kidney by PCN can play an important therapeu­ tic role together with appropriate antibiotics. A nephrostomy can be used to gauge the potential for func­ tional recovery in patients with chronic obstruction. Failure of



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C

Figure 58.16  Nephrostogram. A nephrostomy has been placed percutaneously into the dilated collecting system of the kidney under ultrasound control (A). After infusion of contrast material down the nephrostomy, the dilated pelvicalyceal system and upper ureter (B) and the lower ureter (C) are outlined. The ureter is dilated along its length but tapers abruptly at the vesicoureteral junction (arrow). In this case, the obstruction was caused by a radiolucent stone.

renal recovery after several weeks of nephrostomy drainage strongly suggests irreversible structural damage and thus no likely benefit from undertaking a more definitive surgical correction of the obstructing lesion. Long-term nephrostomy is increasingly used as a definitive therapy for patients who are unsuitable for major surgical intervention and those with incurable malignant disease (see Chapter 59 for further discussion). Ureteral obstruction requiring intervention occurs in approx­ imately 3% of renal transplant recipients.29 It can be treated by nephrostomy and ureteric stenting, percutaneous incision or balloon dilation of the stricture, or open surgical repair (see Chapter 99).

Specific Therapies Calculi are the most common cause of ureteral obstruction, and their treatment includes relief of pain, elimination of obstruc­ tion, and treatment of infection (see Chapter 59). Ureteral obstruction by papillary tissue, blood clots, or a fungus ball is treated by procedures similar to those used for calculi. When obstruction is caused by neoplastic, inflammatory, or neurologic disease, there is unlikely to be spontaneous remission of the obstruction, and some form of urinary diversion, such as an ileal conduit, should be considered. Some obstructing neoplastic lesions, such as lymphadenopathy from lymphoma, may respond to chemotherapy. Management of malignant urinary tract obstruction is discussed further in Chapter 59. In idiopathic retroperitoneal fibrosis, ureterolysis (in which the ureters are surgically freed from their fibrous encasement) may be beneficial, especially in combination with corticosteroid therapy to prevent recurrence. A retrospective study demon­ strated the effectiveness of ureteric stent insertion and cortico­ steroids in idiopathic retroperitoneal fibrosis.30

Functionally significant pelviureteral junction obstruction should be corrected surgically by either an open (AndersonHynes) pyeloplasty or a laparoscopic approach. The laparoscopic approach results in significantly less morbidity and has good long-term outcomes that are identical to those of the open pro­ cedure. Balloon dilation of the abnormal segment of ureter is also possible, but the recurrence rate is high. Benign prostatic hypertrophy is the most common cause of lower urinary tract obstruction in men and may be mild and nonprogressive. A patient with minimal symptoms, no infection, and a normal upper urinary tract can continue with assessment until he and his physician agree that further treatment is desir­ able. Medical therapy with either α-adrenergic blockers (e.g., tamsulosin) or 5α-reductase inhibitors (e.g., finasteride) may be used in patients with moderate symptoms.31 α-Blockers relax the smooth muscle of the bladder neck and prostate and decrease urethral pressure and outflow obstruction. 5α-Reductase inhibi­ tors inhibit the conversion of testosterone to the active metabo­ lite dihydrotestosterone and reduce prostatic hypertrophy. Combination therapy with these agents may be synergistic. Sur­ gical intervention with transurethral resection of the prostate is generally required for failed medical treatment, debilitating symptoms, urinary retention, recurrent infection, or evidence of renal parenchymal damage. Holmium laser enucleation of the prostate is a less invasive alternative to transurethral resection of the prostate with good short-term and long-term outcomes.32 Urethral strictures in men can be treated by dilation or directvision internal urethrotomy. The incidence of bladder neck and urethral obstruction in women is low and treatment rarely required. Suprapubic cystostomy may be necessary for bladder drainage in patients unable to void after injury to the urethra or in those who have an impassable urethral stricture. When obstruction results from neuropathic bladder function, urodynamic studies are essential to determine therapy. The goals

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of therapy are to establish the bladder as a urine storage organ without causing renal parenchymal injury and to provide a mech­ anism for bladder emptying that is acceptable to the patient. Patients may have either a flaccid atonic or an unstable hyper­ tonic bladder. Ureteral reflux and parenchymal damage may develop in both cases, although it is more common in patients with a hypertonic bladder. Asking the patient to void at regular intervals may achieve satisfactory emptying of the bladder. Patients with an atonic bladder and significant residual urine retention associated with recurrent urosepsis need to undertake clean intermittent self-catheterization. The aim should be to catheterize four or five times per day to ensure that the amount of urine drained from the bladder on each occasion is less than 400 ml. External sphincterotomy has also been used in men with an atonic bladder and may relieve outlet obstruction and promote bladder emptying, but it may cause urinary incontinence and the need to wear an external collection device. In patients with a hypertonic bladder, improvement in the storage function of the bladder may be obtained with anticholinergic agents. On occa­ sion, chronic clean intermittent self-catheterization is necessary. Whenever possible, chronic indwelling catheters should be avoided in patients with a neurogenic bladder because they may lead to the formation of bladder stones, urosepsis, and urethral erosion, and they predispose to squamous cell carcinoma of the bladder. Patients who have chronic indwelling catheters for more than 5 years should have annual cystoscopic examinations. If deterioration in renal function occurs despite conservative mea­ sures or there is intractable incontinence or a small contracted bladder, an upper urinary tract diversion procedure such as an ileal conduit may be required.

Management of Postobstructive Diuresis Marked polyuria (postobstructive diuresis) is frequently seen after the release of bilateral obstruction or obstruction of a single functioning kidney. Release of unilateral obstruction rarely results in a postobstructive diuresis33 despite the presence of tubular dysfunction and a concentrating defect. This is due to intrinsic differences in the tubular response to unilateral and bilateral obstruction and, more important, the salt and water retention and renal impairment that occurred in bilateral obstruc­ tion (not evident in unilateral obstruction because of the contra­ lateral normal kidney). The resultant increase in natriuretic factors (including atrial natriuretic peptide) and substances able to promote an osmotic diuresis, such as urea,34 promote an appropriate postobstructive diuresis to excrete water and electro­ lytes that were retained during the period of obstruction. However, the postobstructive diuresis may also be inappropriate as a result of tubular dysfunction, and if it is not managed cor­ rectly, this may cause severe volume depletion and electrolyte imbalance with continued renal dysfunction. Intravenous and oral fluid replacement is usually required, with careful and regular clinical assessment of fluid balance and serum electrolytes to tailor the fluid replacement regimen appropriately. Once the patient is deemed euvolemic, urine losses plus an allowance for insensible losses should be replaced. Urine volume should be measured regularly (hourly) to facilitate fluid administration, and serum electrolytes should be measured at least daily and as fre­ quently as every 6 hours when there is a massive diuresis. Daily weighing of the patient is also helpful. Replacement fluid regi­ mens should include sodium chloride, a source of bicarbonate, and potassium. Calcium, phosphate, and magnesium replace­ ment may also be necessary.

If fluid administration is overzealous, the kidney will not recover its concentrating ability, and a continued “driven” diure­ sis will result. It may then be necessary to decrease fluid replace­ ment to levels below those of the urine output and to observe the patient carefully for signs of volume depletion.

Future Prospects Understanding of the pathophysiologic changes that follow ure­ teral obstruction has allowed the development of rational inter­ ventional therapies to hasten the recovery of renal function and to limit permanent renal damage. Although the best treatment option in humans remains the prompt and effective relief of the obstruction, the development and implementation of improved imaging modalities that provide more sophisticated anatomic and functional information (including intrarenal oxygen content35) will undoubtedly refine management and increase the data available for making key clinical decisions, such as whether and when surgical intervention is required.

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29. Faenza A, Nardo B, Catena F, et al. Ureteral stenosis after kidney trans­ plantation. A study on 869 consecutive transplants. Transplant Int. 1999; 12:334-340. 30. Fry AC, Singh S, Gunda SS, et al. Successful use of steroids and ureteric stents in 24 patients with idiopathic retroperitoneal fibrosis: A retrospec­ tive study. Nephron Clin Pract. 2008;108:c213-c220. 31. Beckman TJ, Mynderse LA. Evaluation and medical management of benign prostatic hyperplasia. Mayo Clin Proc. 2005;80:1356-1362. 32. Suardi N, Gallina A, Salonia A, et al. Holmium laser enucleation of the prostate and holmium laser ablation of the prostate: Indications and outcome. Curr Opin Urol. 2009;19:38-43. 33. Gillenwater JY, Westervelt FBJ, Vaughan EDJ, et al. Renal function after release of chronic unilateral hydronephrosis in man. Kidney Int. 1975;7:179-186. 34. Harris RH, Yarger WE. The pathogenesis of post-obstructive diuresis. The role of circulating natriuretic and diuretic factors, including urea. J Clin Invest. 1975;56:880-887. 35. Thoeny HC, Kessler TM, Simon-Zoula S, et al. Renal oxygenation changes during acute unilateral ureteral obstruction: Assessment with blood oxygen level–dependent MR imaging—initial experience. Radiology. 2008;247:754-761.