1. Nephrology 1 Pathophysiology of upper tract obstruction
Euan Green
Mr Brough

2. 40 yr old man Referred by GP Vague abdominal pain
USS shows solitary left kidney with hydronephrosis
Seen in clinic and asymptomatic
Wants to know “What’s up doc?”

3. Does this mean my kidney is blocked?
No!
Hydronephrosis = dilatation of renal pelvis or calyces with or without obstruction
Hydroureteronephrosis = above + dilated ureter
Obstruction = obstruction to the flow of urine

4. What’s the cause? Congenital or acquired
Intra-luminal, in the lumen wall or extraluminal
Complete or incomplete

5. Site Cause Kidney Ureter Lower urinary tract 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

6. What do you do next? U&E? CT? Renogram? Na+ 140 K+ 4.2 Urea 5.0
Creat 70

7. What do you do next?
U&E?
CT?
Renogram?

9. What is the diagnosis?
Extrarenal pelvis

10. 25 yr old woman Sudden onset severe right loin pain Colicky Vomiting
Dipstick haematuria
Comes to A&E
Seen by SHO who arranges a CT Urogram

11. Followed by a renogram

12. Your SHO asks you “what will happen
Your SHO asks you “what will happen? Will the kidney just fill up and then burst?”
Triphasic response to upper tract obstruction
Different for unilateral and bilateral obstruction

13. 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

14. Unilateral obstruction

16. 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

17. 75 yr old man Previously completely well
Nocturnal enuresis for the last 6 weeks
Tired
Pitting ankle oedema
BP 180/100
Large abdominal mass

18. What is the likely diagnosis? Initial management?
High pressure Chronic retention of urine
Initial management?
U&E
Creatinine 1500, Urea 43, K+ 6.8
Admit as an emergency
Catheterise
3.5 Litre residual
ECG & Treat K+
CaGluconate, insulin dextrose, fluids, salbutamol
If K+ still high with ECG changes?
Dialysis
USS urinary tract

19. The patient wants to know:
What has happened to his kidneys
What to expect over the next few days
Whether his kidney function will recover

20. 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

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

22. 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

23. 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

24. Post-obstructive diuresis
Rare after relief of unilateral obstruction
Typically a physiological response to retained solutes (urea, sodium) and water
Pathological component due to tubular defects as mentioned, in particular the downregulation of aquaporin channels resulting in reduced sensitivity to ADH and the obliteration of the concentration gradient around the loop of Henle
Can be due to excess fluid replacement
Some patients develop hyponatraemia and hyperkalaemia due to tubular resistance to aldosterone

25. Post-obstructive diuresis
Those at increased risk:
Hypertension
Oedema
CCF
Long standing obstruction
Clinical uraemia
20% have a urine output >4L in 24hrs
5-10% require IV fluids
~1% develop long term salt loss/diuresis

27. 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

29. 21 year old woman comes to the haematuria clinic
Left sided loin pain after nights out in the pub
Occasional haematuria
Otherwise fit and well
Flexible cystoscopy normal
Young so she gets an MRI rather than a CT

31. She wants to know what the diagnosis is?
Left PUJ obstruction 1:
50% present in adult life, 50% as a child
Male 2:1 Female, Left > Right
Associated with other abnormalities in 50%
10% bilateral
VUR
Horseshoe/renal duplication/ectopia
Due to crossing vessel/poor canalisation during formation/abnormal insertion into renal pelvis/ smooth muscle mal-development causing atonic segment

32. What are you going to do next?
Right – 18%
Left – 82%
What are you going to do next?
Confirm obstruction and assess function in that kidney. i.e. do a renogram
She wants to know: “how can this be treated?”
Conservative
Stent
Endopyelotomy
Pyeloplasty

33. Treatment options in PUJO
Conservative Mx
Suitable if asymptomatic and >40% relative function and unilateral
Need monitoring
Asymptomatic, non-functioning units
Stent
Palliation for the unfit
Management of the acute presentation
?Diagnostic role

34. Treatment options in PUJO
Endopyelotomy
Ureteroscopy + laser/knife (60-85% success)
Acucise Device (Retrograde balloon catheter + cutting wire) (65-80% success)
Percutaneous endopyelotomy (80% success)
See NICE guidance Dec 2009
Various definitions of success – all relatively short term success

35. Treatment options in PUJO
Pyeloplasty (>90% success)
Open
Laparoscopic
Robotic
Aim of surgery is to restore normal urine flow
Anastomosis has to be watertight and funnelled into the ureter

36. Anderson-Hynes Pyeloplasty
Excise PUJ
Spatulate the ureter
Narrow pelvis defect if large
Anastomose spatulated ureter to pelvis
Usually over a stent

37. Culp-DeWeerd Spiral flap
Suited to those with a long stricture
Open a spiral flap of renal pelvis
Rotate down and use flap to augment the width of the stenosed ureter

38. Foley V-Y Pyeloplasty Useful for high ureteric insertion into pelvis
V-shaped flap from renal pelvis
Inserted into Y-shaped defect opened over stricture

39. Ureterocalicostomy
Suitable for revision surgery or renal abnormalities that prevent other options
Anastomose ureter to a lower pole calyx
Requires lower pole partial nephrectomy to reduce risk of stenosis

40. Treatment options in PUJO
Most now managed with laparoscopic pyeloplasty
Poorly functioning kidneys
<15-20%
Can consider nephrectomy

41. 50 yr old man
Presents with loin pain
Intermittent
Can be severe
GP arranges USS which shows hydronephrosis
A medical student in clinic asks “What types of imaging can be used to demonstrate obstruction?”

42. 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

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

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

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

46. 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

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

48. O’Reilly Curves
F+20 renogram

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

50. 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

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

52. 131I-Hippuran 123I-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

53. 99mTc- DTPA 99mTc-MAG-3 99mTc-DMSA 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

54. MCQ 2 In post-obstructive diuresis which one is true?
All patients require IV fluids
The catheter should be clamped after each litre of urine output to discourage diuresis
It only occurs in those with bilateral obstruction
10% will develop hyperkalaemia
1% develop a long term diuresis

55. Only those with symptomatic hypovolaemia should be given IV fluids
Clamping catheters has no effect on diuresis
Although much less likely to occur diuresis can occur following relief of unilateral obstruction – typically due to pathological changes rather than solute load
<1% develop hyperkalaemia due to aldosterone insensitivity

56. MCQ 3 Which is the most common cause of upper tract obstruction?
Urolithiasis
Ureteric stricture
Retroperitoneal fibrosis
Iatrogenic
Bladder outflow obstruction

57. MCQ 4 Regarding upper tract obstruction:
Whittaker’s test is the investigation of choice
In association with sepsis it should always be treated as an emergency
Is always caused by urinary tract pathology
Will result in a non-functioning kidney unless relieved within 72 hours
Is always present where there is hydronephrosis

58. Extrinsic, non-urological causes can easily result in obstruction
Whilst the Whittaker’s test is good at identifying obstructed from non-obstructed it is an invasive test and should be used in cases of ambiguity
Obstruction and sepsis should always be regarded as a urological emergency
Extrinsic, non-urological causes can easily result in obstruction
The return in function is proportional to the degree of obstruction and the duration.
7 days: full functional recovery
14 days: 70% recovery
28days: 30% recovery
6 weeks: no functional recovery
Data from dogs however.
Not all patients with hydronephrosis are obstructed.

59. EMQ A. urethral catheter E. Culp DeWeerd pyeloplasty
B. Nephrostomy F. Endopyelotomy
C. Nephrectomy G. Observation
D. Anderson-Hynes pyeloplasty H. Retrograde pyelogram
Which of the above would be the most appropriate management for:
28 year old woman with a left PUJO, a history of recurrent pyelonephritis and 12% function in her left kidney
28 year old woman with a left PUJO, a history of recurrent pyelonephritis and 32% function in her left kidney with a crossing vessel on CT
75 year old man with new renal failure and bilateral hydroureteronephrosis and a distended bladder on ultrasound

60. EMQ A. urethral catheter E. Culp DeWeerd pyeloplasty
B. Nephrostomy F. Endopyelotomy
C. Nephrectomy G. Observation
D. Anderson-Hynes pyeloplasty H. Retrograde pyelogram
Which of the above would be the most appropriate management for:
28 year old woman with a left PUJO, a history of recurrent pyelonephritis and a relative function of 12% in her left kidney C
28 year old woman with a left PUJO, a history of recurrent pyelonephritis and a relative function of 32% in her left kidney with a crossing vessel on CT D
75 year old man with new renal failure and bilateral hydroureteronephrosis and a distended bladder on ultrasound A

61. Suggested reading Comprehensive Urology Campbell-Walsh
Scientific Basis of Urology

62. Any Questions?