Nephrology 1 Pathophysiology of upper tract obstruction Euan Green Mr Brough

Nephrology 1

Pathophysiology of upper tract obstruction

Euan Green

Mr Brough

• 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?”

• No!

• Hydronephrosis = dilatation of renal pelvis or calyces with or without obstruction

• Hydroureteronephrosis = above + dilated ureter

• Obstruction = obstruction to the flow of urine

•Does this mean my kidney is blocked?

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

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

• What do you do next?

• U&E?

• CT?

• Renogram?

Na+ 140

K+ 4.2

Urea 5.0

Creat 70

• What do you do next?

• U&E?

• CT?

• Renogram?

•What is the diagnosis?

•Extrarenal pelvis

• 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

•Followed by a renogram

• 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

Unilateral obstructionRenal blood

flowCollecting

system pressureComment

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

Unilateral obstruction

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

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

• What is the likely diagnosis?– 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

• 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

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

Macroscopic effects on kidney

• Dilatation of pelvis/calyxes – hydronephrosis

• Dilation of ureter

• Flattened papillae (42hrs)

• Parenchymal oedema (7 days)

• Cortical parenchymal thinning (21 days)

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

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

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

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

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

• 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

• She wants to know what the diagnosis is?– Left PUJ obstruction

• 1:500-1000• 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

• 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

Right – 18%Left – 82%

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

• 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

Treatment options in PUJO

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

Anderson-Hynes Pyeloplasty

• Excise PUJ• Spatulate the ureter• Narrow pelvis defect if

large• Anastomose

spatulated ureter to pelvis

• Usually over a stent

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

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

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

Treatment options in PUJO

• Most now managed with laparoscopic pyeloplasty

• Poorly functioning kidneys– <15-20%– Can consider nephrectomy

• 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?”

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

Imaging for obstruction

• IVU– Dynamic test– Functional information– Complete vs partial– Level of obstruction– Time consuming in

obstructed patients

Imaging for obstruction

• CT with or without contrast– Cheap– Quick– Good at identifying

causes both intrinsic and extrinsic

– Comparatively high radiation dose

Imaging for obstruction

• MRI– Can identify

hydronephrosis– Can’t detect stones– No radiation– Useful in the

pregnant patient

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

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

• O’Reilly Curves

• F+20 renogram

Back to the patient

• What does this show?

• What next?– F-15 Renogram

• What if it’s still equivocal?– Whittaker’s test

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

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

• 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

• 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

MCQ 2

• In post-obstructive diuresis which one is true?

1. All patients require IV fluids

2. The catheter should be clamped after each litre of urine output to discourage diuresis

3. It only occurs in those with bilateral obstruction

4. 10% will develop hyperkalaemia

5. 1% develop a long term diuresis

• 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

MCQ 3

• Which is the most common cause of upper tract obstruction?

1. Urolithiasis

2. Ureteric stricture

3. Retroperitoneal fibrosis

4. Iatrogenic

5. Bladder outflow obstruction

MCQ 4

• Regarding upper tract obstruction:

1. Whittaker’s test is the investigation of choice2. In association with sepsis it should always be

treated as an emergency3. Is always caused by urinary tract pathology4. Will result in a non-functioning kidney unless

relieved within 72 hours5. Is always present where there is hydronephrosis

• 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.

EMQA. urethral catheter E. Culp DeWeerd pyeloplastyB. Nephrostomy F. EndopyelotomyC. Nephrectomy G. ObservationD. Anderson-Hynes pyeloplasty H. Retrograde pyelogram

Which of the above would be the most appropriate management for:

1. 28 year old woman with a left PUJO, a history of recurrent pyelonephritis and 12% function in her left kidney

2. 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

3. 75 year old man with new renal failure and bilateral hydroureteronephrosis and a distended bladder on ultrasound

EMQA. urethral catheter E. Culp DeWeerd pyeloplastyB. Nephrostomy F. EndopyelotomyC. Nephrectomy G. ObservationD. Anderson-Hynes pyeloplasty H. Retrograde pyelogram

Which of the above would be the most appropriate management for:

1. 28 year old woman with a left PUJO, a history of recurrent pyelonephritis and a relative function of 12% in her left kidney C

2. 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

3. 75 year old man with new renal failure and bilateral hydroureteronephrosis and a distended bladder on ultrasound A

Suggested reading

• Comprehensive Urology

• Campbell-Walsh

• Scientific Basis of Urology

Any Questions?