Upper urinary tract obstruction can result from congenital or acquired conditions that impede urine flow from the kidneys to the bladder. Complete obstruction leads to hydronephrosis and retrograde pressure that damages kidney tissue over time through tubular atrophy and interstitial fibrosis. The degree and duration of obstruction determine the likelihood of recovering renal function after relief of obstruction. Emerging therapies aim to prevent obstruction-associated apoptosis and fibrosis by targeting growth factors and cytokines involved in renal injury pathways.

1. MANAGEMENT OF UPPER
URINARY TRACT OBSTRUCTION
BABALOLA R N
SENIOR REGISTRAR,
UROLOGY UNIT, OAUTHC, ILE-IFE.

3. • ETIOLOGY
• Upper urinary tract obstruction can result from a
• variety of both congenital and acquired conditions,
• impeding urinary flow from the renal pelvis to the
• bladder. Implicit in this statement is the fact that the
• structure affected is either the kidney (renal pelvis) or
• the ureter. Albeit that bilateral hydronephrosis resulting
• from bladder outlet obstruction shares many
• features of more proximal obstruction, we will restrict
• our discussion in this chapter to obstruction of the
• upper urinary tract.

4. • The nature of ureteric obstruction (UO) can be
• further delineated according to whether the obstruction
• is intraluminal or extrinsic. The degree of obstruction
• can also vary from partial, to progressively
• occluding to acutely presenting complete obstruction.
• Commonly, UO is unilateral (UUO) and may involve
• obstruction of proximal or distal segments.
• A major concern following obstruction is its effect
• on the proximal kidney, an effect which will depend on
• the site (renal pelvis, proximal or distal ureter), degree
• (partial, complete) and duration (acute or chronic). The
• combination of these considerations will determine the
• incidence of obstructive nephropathy in the affected
• kidney and in cases of UUO in individuals with a
• solitary kidney, the severity of acute renal failure
• encountered.

5. • Upper urinary tract obstruction is a frequently
• encountered diagnosis in urology. However, because
• of the fact its etiology is varied, reliable cumulative
• incidence rates do not exist.
• Starting with neonatal obstruction, the criteria
• for diagnosis requires that hydronephrosis is present,
• with the fetal kidney producing isoosmolar urine
• within the first trimester of pregnancy. Antenatally
• hydronephrosis id detectable via ultrasonography and
• its incidence is reported to be around 1% (1).
• The major cause of upper urinary tract obstruction
• in adult urology is intrinsic, intraluminal nephrolithiasis
• and urolithiasis. Calcium oxalate and calcium
• phosphate stone disease predominates, accounting for
• 80% of cases, with hypercalciuria a major risk factor,
• underpinned by both genetic and lifestyle factors. The
• lifetime incidence for men is reported at 12% versus 6%
• in women (2).

6. • CLINICAL PRESENTATION
• Presentation of upper urinary tract obstruction is not
• homogeneous, reflecting differences in etiology and
• degree of obstruction.
• Antenatal obstruction presents during routine
• imaging. In postnatal (inc. adult) obstruction, clinical
• presentation depends on the whether the obstruction is
• unilateral or bilateral, acute or chronic and partial or
• complete. Colicky flank pain is characteristic of acute
• UUO, with the presence of fever suggestive of infection.

7. • DIAGNOSIS AND TREATMENT
• Management of Neonatal Obstruction
• Neonatal hydronephrosis secondary to obstruction
• frequently has its origin in antenatal uretero-pelvic
• junction (UPJ) obstruction or uretero-vesicular junction
• (UVJ) obstruction, (primary megaureter) which
• can be visualized on antenatal ultrasound.
• Intrauterine management of obstruction is limited
• to close observation of the obstruction to decide the
• course of action in the neonate. While evidence of
• hydronephrosis per se does not exclude the possibility
• of meaningful renal function postnatally, evidence of
• renal hypoplasty and dysplasty predicts a poor outcome
• in the neonate, and reflects obstructive injury of

8. • first-trimester origin.
• Postnatal ultrasound revealing dilatation should
• lead to the ordering of a voiding cystourethrogram
• (VCUG) and/or diuretic renography. Sustained deterioration
• of split renal function indicates pyeloplastic
• surgical intervention in cases of UPJ obstruction. In
• cases of megaureter, if adequate ureteral drainage is
• observed a conservative approach of antibiotic theapy
• throughout the first year of life is indicated. However

10. • THE EFFECT OF URETERIC OBSTRUCTION ON
• URETERIC FUNCTION
• Normal Pyelourteric Peristalsis
• The peristaltic propulsion of a urine bolus from the
• renal pelvis to the bladder depends on coordinated
• contractions of the renal pelvis and ureter. In times of
• low urine output, renal pelvic contractions outnumber
• ureteric contraction. During diuresis however, contractility
• in the renal pelvis is increased to a point
• where it instigates myogenic transfer of action potentials
• to the ureteric muscularis, leading to coordinated
• pelvic/ureteric contractions, which have the combined

11. • effect of propelling urine to the bladder. Despite
• existence of evidence of both sympathetic and parasympathetic
• input and receptor expression in the
• renal pelvis and proximal ureter, central integrative
• control of ureteric peristalsis remains poorly understood.
• It is currently believed that the primary oscillator
• of ureteric peristalsis is renal pelvic urine
• volume and its effect on pyeloureteric pacemaker
• activity (7).
• As mentioned above, peristalsis in the distal
• ureter is more dependent on adrenergic control of

12. • peristalsis making medically expulsive therapy an
• exciting emerging field in the treatment of distally
• located calculi.
• Pacemaker coordination of pyelourteric peristalsis
• has been suggested to depend primarily on the
• activity of atypical smooth muscle cells and interstitial
• cells of Cajal-like cells which predominate in the renal
• pelvis, have a low depolarization threshold and act to
• drive depolarization (and peristalsis) in naturally
• more refractory typical smooth muscle cells (8).
• The tonic effect of urothelium-derived factors on
• contractility remains an interesting area. Diclofenac is
• effective in preventing obstruction-associated colic
• and is a nonspecific inhibitor of prostaglandin producing
• cycloxygenase enzymes, which are localized to
• the urothelium. No consensus has been reached on the
• effect of individual prostaglandin species on ureteric
• contractility (

13. • OBSTRUCTIVE NEPHROPATHY
• Obstructive Nephropathy Following UUO
• in Animal Models
• The above description of the changes in ureteric
• function in obstructive injury has important implications
• for the upstream kidney.
• To explain the pathophysiology of obstructive
• nephropathy, it is best to examine the findings of
• acute UUO in adult animals, which approximates
• most accurately to acute and complete stone mediated
• obstruction of the ureter in the adult human. While
• doing so, it is imperative to keep in mind that the
• results of such studies may have important differences
• to obstruction in divergent clinical settings (e.g., partial
• obstruction, bilateral affectation, neonatal vs.
• adult).
• Overview of Macroscopic and Microscopic

14. • Changes in Acute, Complete UUO
• With complete obstruction comes associated urinary
• pooling which, in combination with changes in ureteric
• contractility, gives rise to retrograde pressure
• transfer to the proximal kidney and hydronephrosis.
• These events set in motion the major gross morphological
• and microanatomical changes observed in
• renal structure. With increasing time post obstruction,
• the kidney becomes swollen because of pooling of
• urine proximal to the site of obstruction. As the renal
• pelvis expands, the renal parenchyma becomes affected.
• Flattening of the renal papilla and back filling of the
• collecting system occurs. This leads to compression of
• the renal cortex causing the characteristic cortical
• thinning observed in obstruction. When obstruction

15. • is sustained, tubular swelling extends to the more
• proximal portions of the nephron where flattening of
• the tubular epithelium can be observed. These
• mechanical changes are associated with renal tubular
• cell stress, which is associated with increased oxidative
• stress (12), the induction of cell death by apoptosis,
• and the initiation of both proinflammatory and
• profibrotic signaling (13) (Fig. 1). The result of sustained
• UUO is therefore progressive tubular atrophy
• accompanied by the development of tubulointerstitial
• fibrosis.
• Following UUO there is relative preservation of
• renal microvascular structure and glomerulosclerosis

16. • LINK BETWEEN CHANGES IN RENAL PELVIC
• PRESSURE AND BLOOD FLOW POST UUO
• A well-defined phasic response to UUO is known to
• occur. In the first phase (0–90 minutes) there is an
• increase in intrapelvic pressure from values of 6 to 7 to
• 50 to 70 mmHg (16). Initial elevations in ipsilateral
• renal pelvic pressure induce a reno-renal reflex characterized
• by substance P release from renal sensory
• neurons that leads to decreased efferent sympathetic
• output (17,18). This neural adaptation underpins the
• contralateral diuresis observed in UUO. In chronic
• UUO in rats, artificial elevation of ipsilateral intrapelvic
• pressure fails to induce a further reno-renal
• reflex (18).
• Accompanying these phasic pressure changes
• are nitric oxide/prostaglandin mediated decreases in
• afferent arteriolar resistance, which in turn raise glomerular
• capillary pressure to the extent that glomerular
• filtration rate (GFR) is maintained at around 80% of
• normal values despite large increases in intratubular
• pressure (19).

17. • In the second phase, occurring approximately
• between 90 minutes and four hours after obstruction,
• elevated intratubular pressure is sustained but renal
• blood flow decreases secondary to afferent and efferent
• arteriolar vasoconstriction in response to vasoconstrictory
• substances including thromboxane A2
• and endothelin (20,21). GFR is thus reduced to
• approximately 20% of control levels (22). Phasic
• changes in glomerular haemodynamics in acute
• UUO are presented in Figure 2.
• After the initial 24 hours of obstruction, collecting
• system pressure is reduced, but remains around
• 50% elevated versus normal levels (23). The continued
• pooling of urine in the renal pelvis is likely to contribute
• to the sustained dilatation of particularly the distal
• tubular segments (24).

18. • As obstruction persists, adaptive dilatation of the
• efferent renal lymphatics occurs secondary to
• increased venous pressure (25). This limits the urinary
• pooling effect, helps to maintain glomerular filtration
• by reducing intratubular pressure and ultimately limits
• renal damage.
• Ureteric compliance also increases with sustained
• obstruction and the retrograde peristaltic effect is lessened
• as the ureter takes on a ‘‘baggy’’ appearance

19. • POSTOBSTRUCTIVE RENAL FUNCTION
• Predicting Functional Recovery
• Degree and duration of obstruction are clearly parameters
• that can affect recoverability of ipsilateral renal
• function in UUO, both of which are factors that are
• difficult to control for outwith the experimental field.
• Recuperation of GFR post obstruction has been noted
• Figure 4 Defective AVP-collecting duct axis in UUO. The figure illustrates the defect in transmission of the AVP signal in the collecting
• duct during/after obstructive injury. The failure of AVP to stimulate cAMP induced PKA activation prevents adaptive AQP2 membrane
• translocation and CREB mediated AQP2 upregulation. The net result is a failure to appropriately reabsorb water from the filtrate leading
• to dilution of the urine (AVP-arginine vasopressin, AQP2-aquaporin 2, cAMP-cyclic adenosine monophosphate, PKA-protein kinase A
• CREB-cyclic adenosine monophosphate responsive element binding protein).
• Chapter 7: Upper Urinary Tract Obstruction 109
• to bear an inverse relationship to the length of prior
• obstruction in rats (50).

20. • In an attempt to increase the ability to predict the
• outcome of obstruction in the clinical setting, a recent
• prospective study was made of 91 adult patients with
• UUO and a normally functioning contralateral kidney
• (51). This demonstrated that on multivariate analysis,
• only preoperative renographic clearance and perfusion
• of the obstructed kidney predicted recoverability
• of function. Kidneys with a renographic GFR of less
• than 10 mL/min/1.73 m2 were subsequently found to
• be irreversibly damaged.
• Postobstructive Tubular Function
• The postobstructed kidney initially produces hypotonic
• urine. However, this is generally insignificant in
• individuals with intact contralateral function and only
• becomes clinically relevant in cases of BUO or solitary
• kidney UUO.
• The recovery of a normal urinary osmolality and
• pH has been shown to take up to one month to stabilize
• in rats subjected to a reversible UUO of 24 hours
• duration reflecting the time required to reestablish
• correct epithelial polarity and vectorial transport (52).
• Recovery of renal tubular structure concomitant
• with reversal has been observed in adult mice following
• the release of UUO of 10 days duration (53).

21. • Effect of Nephrogenic Stage in Neonatal
• Obstruction
• Completion of nephrogenesis is delayed postnatally in
• the rat, it serves as a good model to compare recovery
• following transient complete neonatal obstruction at
• different time points versus temporary and complete
• obstruction in adult animals. Study of animals three
• months subsequent to unilateral obstruction during the
• early postnatal phase (days 1–5, 10% of nephrons
• formed) revealed a relatively attenuated injury versus
• the results obtained in animals obstructed at two weeks
• of age when nephron number has peaked (54). Such
• studies may offer important insights into debate regarding
• the best time to operate on the obstructed neonate.
• Evidence of Long-Term Renal Injury in UUO
• Despite acute recovery of renal function in terms of
• the measurable GFR and renal blood flow, recent
• studies in rats indicate that complete obstruction of
• three days duration causes a progressive histological
• renal injury following relief (55). The authors in this
• study equate this progression to the establishment of
• an irreversible fibrotic lesion in the kidney.

22. • EMERGING THERAPIES IN OBSTRUCTIVE
• NEPHROPATHY
• The model of UUO in rodents is extensively used by
• those with a broader interest in the prevention of renal
• injury both in terms of the acute tubular apoptosis and
• chronic fibrotic progression. Administration and/or
• neutralization of a number of growth factors and
• cytokines show a beneficial effect in reducing renal
• injury intraobstructively (13). Chief among the growth
• factors which have been shown to have a positive
• effect intraobstructively in vivo are the administration
• of bone-morphogenic protein-7 (BMP-7), an epithelial
• growth factor downregulated in renal injury, epidermal
• growth factor (EGF) therapy, which provides an
• antiapoptotic proproliferatory stimulus to the renal
• epithelium, and hepatocyte growth factor (HGF)

23. • administration, which has been shown to work chiefly
• through the inhibition of TGF-b1 signaling (56–58).
• Separately, neutralizing anti-TGF-b1 antibody has
• been demonstrated to ameliorate tubular apoptosis
• following UUO in rats (59).
• While the results of these studies are both interesting
• and useful, they are limited by two factors.
• Firstly, many of the demonstrations of efficacy are
• based on prophylactic deployment at the initiation of
• obstruction, a scenario irreplicable clinically and secondly,
• the use of recombinant proteins may in many
• cases prove economically unviable.
• A number of studies have centered on the effectiveness
• of established pharmaceutical agents on injury

24. • in UUO. Angiotensin type 1 receptor antagonists
• and angiotensin converting enzyme inhibitors are
• particularly attractive agents given the involvement
• of the RAS in all aspects of renal injury following
• obstruction (13). These have been shown to particularly
• effective in preventing the glomerular vasoconstriction
• in UUO. Enalapril and Losartan have also been shown
• to prevent fibrosis following UUO in rats (60). This
• effect has been related to preservation of renal nitric
• oxide synthesis (61). In the same article, provision of
• the nitric oxide substrate L-arginine had a similar
• protective effect.
• One recent study used the generic, tested and
• inexpensive anti-inflammatory sulfasalazine as an
• anti-inflammatory strategy implemented three days

25. • after induction of UUO in rats (62). Treated animals
• showed much reduced indices of renal injury in terms
• of inflammation and fibrosis. Results with this
• delayed approach to therapy have been replicated in
• the case of HGF in adult obstruction in rats and EGF
• in neonatal obstruction in mice (63,64).
• The HMG-CoA reductase inhibitors simvastatin,
• fluvastatin and pravastatin have also shown promising
• antioxidative, anti-inflammatory and antifibrotic
• effects in UUO in rodents (65–67).
• However, particular clinical relevance should
• be attached to studies in which therapies have been
• initiated in the postobstructive phase. A good example
• is a study in which provision of the nitric oxide
• synthase substrate L-arginine ad libitum to rats after
• the relief of a three-day UUO, significantly reduced
• tubular apoptosis, macrophage infiltration and interstitial
• fibrosis in the absence of any beneficial effect
• on GFR and renal plasma flow (68).

26. Site Cause
Kidney Stone TCC
RCC Renal cysts
PUJO Extrinsic mass
Ureter
Stone Tumour
Retroperitoneal fibrosis Stricture
Extrinsic compression Blood clot
Sloughed papilla Ureterocoele
Retrocaval ureter Endometriosis
Ureteric atresia Surgical ligation
Pregnancy Trauma
Lower urinary tract
BPH (HPCR) Stones
Urethral stricture Procidentia
Posterior urethral valves Hydrocolpos
Meatal stenosis Phimosis
Tumour

28. Unilateral obstruction
Renal blood
flow
Collecting system
pressure
Comment
1 0 – 90 min
 
(6.5 to 70 mmHg)
Afferent arteriolar
vasodilation
2 90 min – 5h

(by 40 – 70%)

(remains elevated)
Afferent and
Efferent arteriolar
vasoconstriction
3 5 – 18h

(continued
decrease)

(towards resting)
✴Collecting system
dilatation
✴Pyelotubular
reflux
✴Pyelovenous reflux
✴Pyelolymphatic
reflux

29. Unilateral obstruction

31. The contralateral kidney
• Compensatory Growth
• Response proportional to degree of injury
• Initial vasoconstriction, subsequent vasodilation
• Hypertrophy
• Increased blood flow and GFR
• Compensatory growth is age dependent
• The number of nephrons remains constant
• Increase in proximal tubular length due to increase
in cell size

32. Bilateral obstruction
• Similar to unilateral upper tract obstruction
• Less pronounced rise in blood flow initially
• Less afferent vasodilation
• Lasts 90 mins
• More substantial decline in blood flow after
• Greater vasoconstriction (thought to be due to no renal
clearance of vasoconstricters from other kidney)
• Renal pelvic and ureteric pressures remain raised
for longer, approaching pre-obstruction pressure
at 24 hrs
• No other side to compensate

33. Macroscopic effects on kidney
• Dilatation of pelvis/calyxes – hydronephrosis
• Dilation of ureter
• Flattened papillae (42hrs)
• Parenchymal oedema (7 days)
• Cortical parenchymal thinning (21 days)

34. Microscopic effects
• 42 hrs – lymphatic dilatation, interstitial oedema
• 7 days – collecting duct, tubular dilation, widening of
Bowman’s space, tubular basement membrane thickening
• 9 days – papillary tip necrosis and inflammatory cell
infiltrate
• 16 days – interstitial fibrosis
• 3 weeks – tubular loss, fibroblast growth, collagen
deposition
• 6 weeks – Widespread tubular atrophy and fibrosis
• Apoptosis is the principle mechanism of cell loss

35. Effect on tubular function
• Down-regulation of aquaporin channels impairs concentrating
ability
• Some down-regulation of active sodium transporters. In
addition fluid overload stimulates ANP secretion encouraging
natriuresis
• Reduction in GFR and down-regulation of Na+/K+ ATPase
transporters reduces K+ excretion
• Down-regulation of active H+ transporters results in a relative
failure of H+ ion excretion
• In unilateral obstruction the other kidney can compensate

36. • Pathology
• Macroscopically
• Renal Pelvis Dilates. No studies in humans but hydronephrosis in rabbits occurs after 24 hours. Generally assumed to occur in the first few days after ureteral obstruction.
Extrarenal pelvis dilatation>>intrarenal dilatation. Increased intrarenal pelvic pressure results in papillary compression and thinning, with eventual septation and production of a
‘rim’ of functioning cortex.
• Initial Increase in Mean Kidney Weight. Oedema > atrophy in first three months. Animal studies in rabbits have shown a decrease in mean kidney weight after 90 days.
• Pigmentation, Focal Ischaemia and Necrosis. Focal necrosis and haemorrhage of papilla and fornix in particular.
• Microscopically
• Tubular damage and interstitial fibrosis
• Tubular Apoptosis. Delicate tubules bear brunt. Initial dilatation and thinning of epithelium. Apoptosis within 30 mins in animal models . Dysregulation of proliferation and
apoptosis, evidenced by increased p53 and p21 levels. Disappearance of recognisable tubular subunits within 21 days.
• Glomerular Sparing. Slight thickening of GBM with loss of filtration slits. Hyalinisation reported but not until ~ 6-9 months following obstruction, and then only in a relatively small
number of glomeruli.
• Inflammatory Infiltrate. Influx of predominantly macrophages but a few T-cells after 3-4 hours. Associated conversion of fibroblasts to
• Pathophysiology of UUT obstruction Tom Walton January 2011 2
• myofibroblasts. Production of mediators (TXA2, PAF and TGFB), leading to tubuloinsterstitial fibrosis (TGF beta major is determinant)
• Tubulointerstitial fibrosis. Thought to be major determinant of deranged renal function and failed recovery following release of obstruction

37. • Physiology
• Unlilateral Ureteric Obstruction (UUO)
• A. Renal Blood Flow, Glomerular Filtration Rate, and Ureteral Pressure
• Characterisation by Moody and Gillenwater (Investig Urol
1975;13:246–251). Acute UUO in five awake dogs.
• Desribed a triphasic response of RBF in relation to ureteral pressure

38. • Phase I (0-90 mins).
• Pre-glomerular vasodilatation
• Increased RBF in response to increased ureteral pressure. Due to pre-glomerular vasodilatation, a
compensatory response intended to increase capillary hydrostatic pressure and thus GFR. Vascular
mediators thought to play major role
• Eicosanoids. Implicated for years. Pre-treatment with indomethacin abolishes RBF response in dogs (Allen,
1978). PGE2 probably responsible (Frokiaer, 1995). PGE2 excretion from contralateral kidney markedly
increased in UUO, and inhibition with indomethacin significantly attenuates response.
• o Nitric Oxide. Nitric oxide synthase inhibition attenuates RBF increase in acute UUO (Lanzone 1995).
Furthermore L-arginine infusion reverses indomethacin-mediated abolition of RBF increase. (Schulsinger
1997). Micropuncture studies show an increase in glomerular capillary hydrostatic pressure after UUO - ?
release of NO in response to endothelial stretching.
• WARNING: Most of the studies in dogs or rats, which have unicalyceal kidneys. Studies in pigs, baboons
and lambs (which have multicalyceal kidneys) fail to demonstrate an increase in RBF with acute UUO.

39. • Phases II and III
• Post-glomerular vasoconstriction, then pre- and post-glomerular vasoconstriction
• Phase II (90 mins – 4/5 hours) characterised by a fall in RBF with a continued rise in ureteral pressure. Due to post-glomerular
vasoconstriction. Further attempt by kidney to maintain GFR.
• Phase III (5 hours+) associated with concomitant falls in RBF and ureteral pressure. Further fall in RBF due to pre-glomerular
vasoconstriction. By 24 hours tubular pressure and ureteral pressure fall to 30% and 50% of control values respectively.
• Vaso-constrictive mediators in Phase II and III:
• o Eicosanoids. Potent vasoconstrictors TXA2 and TXB2 implicated in decline of RBF (and ureteral pressure) following UUO.
Thromboxanes thought to be derived from inflammatory infiltrate, and specifically released by platelet activating factor.
Irradiation of the obstructed kidney, significantly reducing the cellular infiltrate, markedly reduces urinary TXB2 and improves RBF
and GFR (Schreiner 1988). However treatment with TXA2 synthesis inhibitors/ receptor blockers leads to improved RBF and GFR in
some animal studies but not in others.
• o Renin/ Angiotensin II. Elevated renin and AII levels in obstructed dogs and rats. Intrarenal generation of AII in obstructed pigs.
ACE inhibitors and AT blockers shown to improved RBF and GFR in
• Pathophysiology of UUT obstruction Tom Walton January 2011 4

40. • some studies (dog and rat), but results not confirmed in other studies (including those in pigs).
• o Endothelin. Vascular derived mediator. Released in response to endothelial stretch. Causes marked
vasoconstriction by allowing calcium influx into smooth muscle cells. Elevated endothelin levels documented
in obstructed dogs (Kahn 1995). Same group significantly improved RBF and GFR in post-obstructed kidney
by verapamil infusion.
• Decreased GFR due to (i) reduced single-nephron renal blood flow and (ii) shunting of blood from outer to
inner cortex, decreasing the total number of perfused glomeruli. ? Mechanism of shunting. Increased
production of renin witnessed in outer vs. inner cortex.
• Fall in ureteral pressure due to;
• o Reduced GFR
• o Pelvicalyceal dilatation
• o Pyelolymphatic and pyelovenous backflow
• B

42. • GFR markedly reduced following release of obstruction, but total excretion from post-obstructed kidney normal/ slightly elevated, due to ineffective
• Pathophysiology of UUT obstruction Tom Walton January 2011 5
• Na reabsorption and water retention in the tubules, leading to impaired concentrating ability
• Active transport markedly impaired. Selective down-regulation of both transporter activity and transporter protein synthesis after 24 hours of obstruction [ NB. PGE2 known to
inhibit Na/K ATPase and aquaporins]
• Proximal tubule relatively spared, but marked failure of active transport mechanisms from loop of Henle to collecting duct. Reduced reabsorption of sodium in ascending limb,
leads to a reduction in interstitial hypertonicity. Combined with insensitivity to ADH in collecting duct, results in impaired concentrating ability.
• Potassium excretion falls proportionate to fall in GFR, due to defective distal tubular secretion. Failed active transport also leads to an inability to acidify urine.
• Urine
• o Normal/ mildly elevated excretion of filtered load
• o Low osmolality
• o Normal/ high pH
• o High sodium content (increased filtered fraction)
• o Low potassium content
• o Low phosphate content

43. • Bilateral Ureteric Obstruction (Obstructed Solitary Kidney)
• A. Changes in RBF, GFR and Ureteric Pressure
• Moody and Gillenwater (Investig Urol 1975;13:246–251).
• No triphasic pattern
• Biphasic pattern
• o Initial short-lived rise in RBF as in UUO, due to pre-glomerular vasodilatation
• o Marked fall in RBF, associated with a persistently elevated ureteric pressure > 24 hours. Associated with
post-glomerular vasoconstriction.
• o NO pre-glomerular vasoconstriction seen in late-stage BUO. ? accumulation of a ‘substance’ which
prevents pre-glomerular vasoconstriction. Confirmed by Harris (1975): GFR preservation, diuresis and
natriuresis in UUO with contralateral nephrectomy, and with contralateral urine perfusion of obstructed
kidney, but not in UUO with normal contrateral kidney. Substance believed to be Atrial Natriuretic Peptide

44. • Atrial Natriuretic Peptide
• Characterised by Cogan (Annu Rev Physiol 1990;52:699–708)
• Released by cardiac atrium in response to increased intravascular volume
• Effects designed to maximise diuresis and natriuresis
• o Increased GFR thro’ pre-glomerular vasodilatation and post-glomerular vasoconstriction
• o Increased glomerular capillary ultrafiltration co-efficient (leakier membrane)
• o Direct inhibition of tubuloglomerular feedback mechanism (renin/ AII)
• Pathophysiology of UUT obstruction Tom Walton January 2011 7
• o Specific inhibition of NaCl co-transport in ascending limb of loop of Henle
• o Blocks vasopressin-mediated osmotic water permeability
• Elevated in BUO but not in UUO in rats (Fried 1987)

45. • B. Tubular Function in Bilateral Ureteric Obstruction
• Similar tubular defects as seen in UUO, but exacerbated due to activity of ANP
• Marked post-obstructive diuresis and natriuresis may be seen. Multiple investigators in animal and human
studies have shown that degree and duration of diuresis proportional to intravascular volume status as
reflected by circulating ANP levels. NB. Diuresis not thought to be related to circulating urea as an osmotic
load. (Jaenike 1972) as a urea infusion fails to produce a diuresis in UUO.
• A marked increase in Na delivery to the distal nephron, combined with elevated serum potassium, results in
an increased filtration fraction of potassium
• Urine
• o Significantly increased total excretion of filtered load
• o Low osmolality (lower cf. UUO)
• o Normal/ High pH
• o High sodium content
• o High potassium content

46. • Renal Function after Release of Ureteric Obstruction
• A. Unilateral Ureteric Obstruction
• Seminal work by Vaughan and Gillenwater (Investigative Urology 1971a; 9:109-118). Subsequently confimed by Fink 1980.
• o 15 dogs: different durations of acute UUO
• o If reversed within 2 weeks = full recovery of function
• o After 14 days ~ up to 70% return of function
• o No functional recovery after 6 weeks
• o Continued improvement up to 6 months following obstruction
• Very few other studies of functional return
• Situation appears to be different in humans
• o Anecdotal reports of total return to function after as long as 6 months (Better 1973;Shapiro 1976; Dhabuwala 1982; Okubo 1998;)
• o ? due to multi-calyceal kidney or pyelolymphatic ‘escape’.
• Pathophysiology of UUT obstruction Tom Walton January 2011 8
• B. Bilateral Ureteric Obstruction
• No clear relationship between the duration of obstruction and recoverability of function. Furthermore no pre-release chemistry which can predict recoverability.
• Best human study by Jones et al. Examined 21 patients prospectively and following release of 3 months obstruction. Described 2 phases of recovery of function: An initial ‘tubular’
phase associated with improvements in creatinine clearance and fractional excretion of sodium; a further ‘glomerular’ phase associated with a gradual improvement in GFR over
approximately 3 months

47. • Post-obstructive diuresis
• After release of bilateral urinary obstruction or obstructed solitary kidney
• Typically normal physiological response to accumulated fluid and electrolytes. Once free water
and solute excess resolves, diuresis resolves
• Most patients only require access to oral fluid and regular monitoring (vital signs, hourly urine
output, daily weight and daily U+E and Mg)
• ~10% of patients demonstrate pathological diuresis due to impaired concentrating ability
(downregulation of sodium and aquaporin channels) Diuresis may be isotonic or hypotonic. In
general sodium chloride should be given initially, but hypotonic fluid may be given if serum
osmolality high and/or urine osmolality low.Studies from North West have shown that a UO >
20mml/h for >= 6 hours increases the likelihood of a pathological diuresis.IV fluids should be
administered if there are signs of hypotension or impaired cognition
• General rule of thumb
• If UO >= 200 ml/h for more than 6 hrs institute IV fluid replacement at input = output - 50ml/h
[Allowing for insensible losses (~800ml) removes 2L/day if patient NBM; 1L oral fluid restriction
therefore leads to losses of 1L/day]

48. Return of renal function
• Degree function return difficult to predict, relates to
degree of obstruction, duration and prior function
• Dog experiments have been carried out:
• 7 days: full functional recovery
• 14 days: 70% recovery
• 28days: 30% recovery
• 6 weeks: no functional recovery
• In humans return of function has been noted after 150
days
• Difficult to predict
• 2 phases of recovery:
• First 2 weeks – recovery in tubular function
• Next 10 weeks – recovery in GFR

50. Imaging for obstruction
• USS
• Can show dilatation (ie hydronephrosis)
• False +ve
• Excess flow eg Diuresis
• Anatomy eg Extrarenal pelvis, Cysts
• False –ve
• Too little flow eg dehydration
• Operator dependant
• Can use doppler renal resistive index
• >0.7 suggests obstruction, ~0.6 normal
• (Peak systolic velocity-peak diastolic velocity) / Peak systolic velocity

51. Imaging for obstruction
• IVU
• Dynamic test
• Functional information
• Complete vs partial
• Level of obstruction
• Time consuming in
obstructed patients

52. Imaging for obstruction
• CT with or without
contrast
• Cheap
• Quick
• Good at identifying
causes both intrinsic and
extrinsic
• Comparatively high
radiation dose

53. Imaging for obstruction
• MRI
• Can identify
hydronephrosis
• Can’t detect stones
• No radiation
• Useful in the pregnant
patient

54. Imaging for obstruction
• Renogram
• A study of the uptake, transit and elimination by the
kidney of an intravenous dose of a radionucleotide
• Gives drainage and relative function
• Limited anatomical information
• Use of diuretic improves discrimination between
obstructed and non-obstructed

55. Renography
• 3 phases
• Vascular phase,
represents uptake
• Transit phase, represents
transit through kidney
• Elimination phase,
excretion from the
kidney and expulsion
down the ureter
1 2 3
TIME (minutes)
DOSE %
0
4
8
12
10 20 30
Bladder
Renal

56. • O’Reilly Curves
• F+20 renogram

57. Back to the patient
• What does this show?
• What next?
• F-15 Renogram
• What if it’s still equivocal?
• Whittaker’s test

58. Whittaker’s test
• A test to help differentiate in those
with equivocal obstruction or poor
function where renogram unhelpful
• Quite invasive
• Nephrostomy in affected kidney
• Catheterise
• Patient prone in fluoroscopy
• Infuse contrast/saline via
nephrostomy at 10mls/min
• Measure pressure in kidney and
bladder and subtract to get the
difference
• <15 cm H20 – unobstructed
• 15-22 cm H20 – equivocal
• >22 cm H20 - obstructed

59. MCQ 1
• Which is not an agent that has been used in renography
1. 99mTc-MAG-3
2. 123I-Hippuran
3. 99mTc- DTPA
4. 99mTc-DMSA
5. 131I-Hippuran

60. • 131I-Hippuran
• Used in the 1960s
• Hippuran is an excellent renography agent very
rapidly cleared by tubular secretion and some
filtration
• 131I emits around 90% of its radiation as beta decay,
which damages local tissue but doesn’t penetrate far
enough to be detected
• 123I-Hippuran
• All gamma decay
• Half life of 13 hrs and needs a cyclotron to produce
• Very expensive

61. • 99mTc- DTPA
• Cleared by filtration
• Slow rate of clearance
• High background signal
• 99mTc produced from a Mo-99 generator
• 99mTc-MAG-3
• Rapidly cleared by tubular secretion and some filtration
(although 60% slower than Hippuran)
• Low background signal
• 99mTc-DMSA
• Used for renal scans for scars
• Fixes in tubules – function, not drainage