340 CHAPTER 7 Miscellaneous urological diseases of kidney

Autosomal dominant (adult) polycystic kidney disease (ADPKD)

Definition

ADPKD is an autosomal dominant inherited disorder leading to the development of multiple expanding renal parenchymal cysts.

Epidemiology

Incidence is 0.1%; 95% of cases are bilateral. Symptoms manifest in the fourth decade. ADPKD accounts for 10% of all cases of renal failure.

Pathology

The kidneys reach an enormous size due to multiple fluid-filled cysts and can easily be palpated on abdominal examination. Expansion of the cysts results in ischemic atrophy of the surrounding renal parenchyma and obstruction of normal renal tubules.

End-stage renal failure is inevitable and occurs around the age of 50 years.

Associated disorders

These include a 10–30% incidence of Circle of Willis berry aneurysms (associated with subarachnoid hemorrhage); cysts of the liver (33%), pancreas (10%), and spleen (<5%); renal adenoma; cardiac valve abnormalities; aortic aneurysms; and diverticular disease.

Etiology

PKD-1 gene defects (chromosome 16) account for 90% of cases; PKD-2 gene defects (chromosome 4) cause 10%, and now a third gene, PKD-3 is also implicated.

Pathogenesis theories include intrinsic basement membrane abnormalities; tubular epithelial hyperplasia (causing tubular obstruction and basement membrane weakness); and alterations in the supportive extracellular matrix due to defective proteins, all of which may cause cyst formation.

Presentation

Patients have a positive family history (50% inheritance); palpable abdominal masses; flank pain (due to mass effect, infection, stones, or following acute cystic distension due to hemorrhage or obstruction); macroscopic (and microscopic) hematuria; UTI; and hypertension (75%).

Renal failure may present with lethargy, nausea, vomiting, anemia, confusion, and seizures.

Differential diagnosis

This includes renal tumors; simple cysts; von Hippel–Landau syndrome (cerebellar and retinal hemangioblastomas; renal, adrenal, and pancreatic cysts); and tuberous sclerosis (adenoma sebaceum, epilepsy, learning difficulties, with polycystic kidneys and renal tumors).

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Investigation

This depends on the presenting symptoms.

-For suspected UTI—culture urine

-For hematuria—urine cytology, flexible cystoscopy, and renal ultrasound. On ultrasound the kidneys are small and hyperechoic, with multiple cysts of varying size, many of which show calcification. If the nature of the cysts cannot be determined with certainty on ultrasound, arrange for a renal CT.

-Renal failure will be managed by a nephrologist. Anemia may occur, though ADPKD may cause increased erythropoietin production and polycythemia.

-Renal imaging (ultrasound and CT are useful for investigation of complications)

Treatment

The aim is to preserve renal function as long as possible (control hypertension and UTI). Infected cysts (abscesses) should be drained.

Persistent, heavy hematuria can be controlled by embolization or nephrectomy.

Progressive renal failure requires dialysis and, ultimately, renal transplantation.

342 CHAPTER 7 Miscellaneous urological diseases of kidney

Vesicoureteric reflux (VUR) in adults

VUR is the retrograde flow of urine from the bladder into the upper urinary tract with or without dilatation of the ureter, renal pelvis, and calyces. It can cause symptoms and may lead to renal failure (reflux nephropathy). In adults 10–15% of patients requiring hemodialysis or transplantation do so because of reflux nephropathy.

Pathophysiology

Reflux is normally prevented by low bladder pressures, efficient ureteric peristalsis, and the ability of the vesicoureteric junction (VUJ) to occlude the distal ureter during bladder contraction. This is assisted by the ureter passing obliquely through the bladder wall (the “intramural” ureter), which is 1–2 cm long. Normal intramural ureteric length to ureteric diameter ratio is 5:1.

VUR of childhood tends to resolve spontaneously with increasing age because as the bladder grows, the intramural ureter lengthens.

Classification

Primary

A primary anatomical (and therefore functional) defect is where the intramural length of the ureter is too short (ratio <5:1).

Secondary

A secondary defect is secondary to some other anatomical or functional problem:

-Bladder outlet obstruction (BPO, DSD due to neuropathic disorders,1 posterior urethral valves, urethral stricture) that leads to elevated bladder pressures

-Poor bladder compliance or the intermittently elevated pressures of detrusor hyperreflexia (due to neuropathic disorders1—e.g., spinal cord injury, spina bifida)

-Iatrogenic reflux following TURP or TURBT (a tumor overlying the ureteric orifice)—this is rare; ureteric meatotomy (incision of the ureteric orifice) for removal of ureteric stones at the VUJ; following incision of a ureterocele; ureteroneocystostomy; after pelvic radiotherapy

-Inflammatory conditions affecting function of the VUJ: TB, schistosomiasis, UTI

Associated disorders

VUR is commonly seen in duplex ureters (the Meyer–Weigert law).2 Cystitis can cause VUR through bladder inflammation, reduced bladder compliance, increased pressures, and distortion of the VUJ. Coexistence of UTI with VUR is a potent cause of pyelonephritis—reflux of infected urine under high pressure causes reflux nephropathy, resulting in renal scarring, hypertension, and renal impairment.

1 Neuropathic disorders therefore cause VUR because they lead to intermittently or chronically raised bladder pressure (due to BOO, poor compliance, and/or detrusor hyperreflexia).

2 The lower pole ureter inserts into the bladder in a proximal location to the upper pole ureter, which inserts distally—i.e., nearer the bladder neck. The lower pole ureter has a shorter intramural length and therefore refluxes. The upper pole ureter has a longer intramural length and tends to be obstructed.

VESICOURETERIC REFLUX (VUR) IN ADULTS 343

Presentation

-VUR may be symptomless, being identified during VCUG, IVP, or renal ultrasound (which shows ureteric and renal pelvis dilatation) done for some other cause.

-UTI symptoms

-Flank pain associated with a full bladder or immediately after micturition

Symptoms of recurrent UTI or of flank pain may have been present for many years before the patient seeks medical advice. Even then it may take some time for a diagnosis of VUR to be made because a high index of suspicion is required and the definitive test for making a diagnosis of VUR (VCUG—see below) is invasive (although VUR may be diagnosed by the less invasive use of IVP).

Investigation

The definitive test for the diagnosis of VUR is cystography. VUR may be apparent during bladder filling or during voiding (voiding cystourethrography [VCUG]—also known as micturating cystourethrography [MCUG]).

Urodynamics establishes the presence of voiding dysfunction (e.g., DSD) if this is suspected from the clinical picture. If there is radiographic evidence of reflux nephropathy, check blood pressure, check the urine for proteinuria, measure serum creatinine, and arrange for a 99mTc-DMSA isotope study to assess renal cortical scarring and determine split renal function.

Management

VUR is harmful to the kidney:

-In the presence of infected urine

-Where bladder pressures are markedly elevated (due to severe BOO, poor compliance, or high-pressure hyperreflexic bladder contractions)

In the absence of urinary infection or severe outflow obstruction/ raised bladder pressures, VUR is not harmful, at least in the short term (months).

Subsequent management depends on the following:

-The presence and severity of symptoms

-The presence of recurrent, bacteriologically proven urinary infection

-The presence of already established renal damage (radiological evidence of reflux nephropathy, hypertension, proteinuria— proteinuria is a poor prognostic factor in patients with VUR, indicating the likelihood of impending end-stage renal failure)

For the patient with primary VUR, recurrent UTIs with no symptoms between infections, no hypertension, and good renal function, treat the UTIs when they occur and consider low-dose antibiotic prophylaxis if UTIs occur frequently (say >3 per year). If the UTIs are regularly associated with constitutional disturbance (acute pyelonephritis rather than simple cystitis), then ureteric reimplantation is indicated.

344 CHAPTER 7 Miscellaneous urological diseases of kidney

For the patient with primary VUR and objective evidence of deterioration in the affected kidney (i.e., progressive radiological signs of reflux nephropathy or reduction in renal function), use ureteric reimplantation.

Reflux into a nonfunctioning kidney (<10% function on DMSA scan) with recurrent UTIs and/or hypertension requires nephroureterectomy.

Primary reflux with severe recurrent flank pain requires ureteric reimplantation.

Secondary reflux

For secondary reflux into a transplanted kidney, no treatment is needed. For VUR in association with the neuropathic bladder, treat the underlying cause—relieve BOO and improve bladder compliance (options: intravesical Botox injections, augmentation cystoplasty, sacral

deafferentation).

For VUR with no symptoms, no UTI, no high bladder pressures and no BOO, the management of these patients is controversial because it is not known whether low-pressure, sterile reflux causes deterioration in renal function over many years without treatment.

Grade I and II reflux (reflux of contrast into nondilated ureter) probably does not require surgery, and many urologists would not recommend surgery but would monitor the patient for infection, hypertension, and evidence of deterioration in the appearance and function of the kidneys.

Grade III or more may require surgical intervention, and many urologists would recommend ureteric reimplantation or a STING procedure (see Fig. 7.1 for grading system for reflux).

VESICOURETERIC REFLUX (VUR) IN ADULTS 345

Grade I Contrast into non-dilated ureter

Grade II Contrast into renal pelvis and calyces; no dilatation Grade III Mild dilatation of ureter; pelvis, and calyces

Grade IV Dilated ureter becomes slightly tortuous; moderate dilatation of pelvis and blunting of calyces

Grade V Severe ureteric dilatation and tortuosity; gross dilatation of pelvis and calyces

Figure 7.1 International reflux classification