OBSTRUCTIVE UROPATHY

Obstructive uropathy, the commonest cause of chronic renal failure in children, is characterized by urinary obstruction at any level from calyceal infundibula to urethral meatus, and its pathophysiological effects on renal functions.

Etiology: Although obstructive uropathy is a consequence of many congenital or acquired lesions of urinary tree (Table 21.24), posterior urethral valve is the commonest cause in boys, while In girls, PUJ obstruction is most common.

Pathophysiological effects of obstruction depend on its site, cause, severity and age of onset. While urethral or bladder obstruction present with acute urinary retention, obstructions above the level of bladder cause unilateral hydronephrosis, which manifests after many years or remains undetected throughout life.

Obstruction of urinary tract at any site ultimately affects renal functions by—(a) back pressure and dilatation of proximal tract, (b) urinary stasis with increased risk of UTI and stones. While early changes are reversible, prolonged obstruction may lead to progressive and irreversible damage to renal architecture and function.

TABLE 21.24: Causes of obstructive uropathy

1. Congenital anomalies:

- Posterior urethral valves

- Pelviureteric junction obstruction

- Vesicoureteric reflux

- Others: aberrant vessels

2. Calculi

3. Neurogenic bladder

4. Retroperitoneal fibrosis

5. Post-inflammatory: UTI, TB

6. Surgical/traumatic injury

Clinical presentation: Urinary tract obstruction may be silent or present with:

• Micturation problems, e.g. retention, weak stream, incontinence, etc.

• Recurrent UTI with fever, dysuria, etc.,

• Hydronephrosis with renal mass, hematuria, etc.

• Renal colic due to stones or Dietal's crisis,

• Signs of chronic renal failure, e.g. failure to thrive.

Diagnosis: USG is the baseline investigation to detect obstructive uropathy and hydronephrosis, including for prenatal diagnosis.

Postnatal assessment of hydronephrosis on USG needs detailed investigations to identify the cause of obstruction, status of renal functions and progression of the disease, by:

• Voiding cystourethrography in bilateral hydro­nephrosis to detect VUR and PU valves,

• Renal scintigraphy, i.e. DMSA scan and MAG-3 (with diuretic renogram) to assess renal functions.

• Urodynamic studies, e.g. Whitaker test in equivocal cases

• Other investigations, e.g. spinal X-ray/MRI to exclude neuropathic bladder and cystoscopy to visualize uretero-vesical abnormalities.

Management depends on the cause of obstruction and status of renal functions. Before any surgical intervention, it is mandatory to—(a) assess the functional status of other kidney and expected benefits from surgery, (b) exclude or treat co-existing UTI, and (c) manage other complications, e.g. hypertension or chronic renal failure.

Posterior urethral valves and pelviureteric junction obstruction are commonest causes of obstructive uropathy in males and female children respectively, discussed earlier in Ch 21.13. Some other important causes of obstructive uropathy are as follows:

Vesicoureteral reflux (VUR), i.e. retrograde flow of the urine from bladder to the ureter and renal pelvis, is the cause as well as effect of obstructive uropathy. It is seen in ~1% of normal children and gt;30-35% of those with febrile UTI.

Etiology: VUR may be primary or secondary.

• Primary VUR denotes a congenital anomaly at ureterovesical junction that allows urinary backflow, e.g. (a) shorter intravesical ureteric tunnel, (b) impaired flap-valve mechanism, or (c) ectopic ureter, etc. Primary VUR is a leading cause of prenatal hydronephrosis in males, which is frequently inheri­ted, seen in 35% siblings and 50% offsprings.

• Secondary VUR is a consequence of distal obstructive uropathy, e.g. in PU valves, bladder neck obstruction or neurogenic bladder. In later case, VUR may develop without urinary obstruction.

*up to pelvis and calyces.

Clinical course: VUR is often discovered as an under­lying abnormality during investigations for obstructive uropathy, recurrent UTI, hypertension, chronic renal disease or prenatal hydronephrosis. Further course depends on it severity (Table 21.25) and age of presentation.

Primary VUR may resolve spontaneously if-mild (lt;Grade II), unilateral or diagnosed at younger age. Spontaneous resolution is unlikely beyond 5 years.

Severe/persistent VUR may lead to recurrent or persistent pyelonephritis due to ascending infection, consequent renal scarring with progressive renal insufficiency. Reflux nephropathy is characterized by renal cortical scarring, predominantly at the poles, leading to hypertension and renal failure.

Diagnosis of VUR includes—(a) detection and grading of severity, (b) identification of etiology, and (c) assessment of secondary renal damage, e.g. obstructive uropathy and renal scarring.

USG is the baseline investigation to detect pre-/ postnatal VUR that reveals—(a) dilatation of urinary tract, (b) actual ureteral reflux during voiding phase on flow-Doppler study, (c) renal scarring.

Confirmation of diagnosis usually rests on—

(a) voiding cystourethrography (MCU) for direct visualization of reflux, or (b) radionuclide cystography to detect renal scarring and pyelonephritis. Urodynamic studies and uroflowmetry are indicated in suspected neuropathic bladder. Cystoscopy helps to directly visualize ureteric or bladder abnormalities.

Management depends on the severity of reflux, age of the patient and presence of bladder bowel dysfunction (BBD).

• Low-grade VUR (I and II) without bladder-bowel dys­function (BBD) do not need any intervention, while others should receive antibiotic prophylaxis till resolution of BBD.

• High-grade VUR (#8805; III) need antibiotic prophylaxis for

(a) 1 year after last UTI attack or till 2 years of age in absence of BBD, or (b) till resolution of BBD. Repeat imaging is indicated in these cases after 24-36 months, preferably with radionuclide cystogram.

Early surgical correction is indicated in—(a) severe VUR gt;grade III, (b) recurrent UTI despite prophylactic antibiotics, (c) progressive renal insufficiency. Apart from treatment of primary cause, VUR surgery involves lengthening of intramural ureter or creating a flap-like mechanism to establish an effective valvular mechanism (uretero-neocystostomy). Open surgical repair is effective in 80-95%. Endoscopic repair by subtrigonal injection of a bulking agent under ureteric orifice to create artificial flap-valve, is an alternative but less effective (60-80%) option.

Urinary prophylaxis: Single bed-time dose of oral cotrimoxazole (1-2 mg/kg), nitrofurantoin (1-2 mg/ kg), cephalaxin (10 mg/kg) or cephadroxil (5 mg/kg) may be used for prophylaxis, though first two drugs are contraindicated in infants lt; 3 months or G6PD deficiency.

All siblings should also be screening for VUR by USG, in view of the strong hereditary risk.

Outcome: Primary VUR usually resolves by 6-10 years in 70-90% cases with grade I or II severity and 10-35% in higher grade VURs.

Neuropathic bladder: Urinary bladder function is regulated by three neural mechanisms—(a) excitatory parasympathetic flow (S2-3), (b) inhibitory sympathetic flow (L1-2), and (c) Voluntary corticospinal flow.

Clinically, according to the site of lesion, neuropathic bladder may present as:

• Urinary retention due to predominant loss of excita­tory parasympathetic flow, e.g. in sacral injury.

• Urinary incontinence, due to predominant loss of sympathetic outflow, e.g. in lumbar or cauda equine lesions.

• Reflex bladder in cortical or high spinal lesions with intermittent involuntary evacuation without volun­tary control.

Etiology: Neuropathic bladder denotes voiding abnor­malities due to spinal cord lesions like: (a) congenital defects, e.g. meningomyelocele, sacral agenesis, etc. (b) traumatic spinal injuries, and (c) spinal tumors.

Important consequences of neuropathic bladder are urinary incontinence, recurrent UTI, obstructive uropathy and vesicoureteral reflux.

Evaluation of these cases must include: (a) urodynamic studies to assess bladder volume and voiding pressure,

(b) uroimaging to assess the secondary hydronephrosis, VUR, etc., (c) urine cultures to exclude UTI, and (d) evaluation of primary cause.

Treatment includes: (a) reduction of bladder pressure with anticholinergics, e.g. oxybutynin and intermittent catheterization, (b) long-term antimicrobial prophylaxis, and (c) surgical correction, i.e. augumentation entero- cystoplasty in severe cases.

Nephrolithiasis (renal calculi), is relatively less common in children than in adults, contributing ~5% of obstructive uropathy. Calcium phosphates or oxalates stones account for gt;70% of urinary stones in childhood, followed by struvite stones of magnesium ammonium phosphate (~20%), uric acid stones (lt;5%) and rarely, cystine stones (lt;1%). Underlying metabolic abnormality is present in ~50% cases.

Nephrocalcinosis refers formation of crystalline deposits within renal parenchyma, usually detected on ultrasonography.

Etiologically, important contributory factors for urolithiasis are:

• Increased urinary excretion of solutes, e.g. calcium, oxalates, cystine, uric acid etc,

• Impaired stability of solutes due to abnormal urine pH (cystine in acidic pH, phosphates in alkaline pH),

• Decreased excretion of solute-binders, e.g. magnesium, citrate, etc.

• Urinary stasis with solute concentration, and

• Urinary infection, specially with proteus infection.

While important causes of urinary calculi are given in Table 21.26, idiopathic hypercalciuria is the commonest cause of calcium stones in children (Ch 21.11.2).

Clinically, these cases may be entirely asymptomatic or present at any age with—(a) recurrent painful hematuria,

(b) abdominal flank pain or typical renal colic, (c) intermittent/acute urinary retention, (d) passage of stone/gravel in urine, and (e) signs of causative disease. Diagnosis involves visualization of stone and etiological evaluation by:

• Radioimaging: While gt;90% stones are radio-opaque (except pure uric acid and cystine stones) visible on X-rays, USG is the preferred choice to detect small or radiolucent stones, as well as to exclude co-existing obstructive uropathy.

• Metabolic screening, e.g. estimation of 24-hour urinary excretion for calcium, phosphate, oxalate, uric acid,

TABLE 21.27: Prevention of metabolic urinary stones

For calcium stones

• Restricted dietary intake

• Thiazide diuretics to decrease Ca++ excretion

• Inhibitors - citrates, e.g. lemonades, K+ citrate For uric acid stones

• Urinary alkalinization (NaHCO3/Na citrate)

• Allopurinol therapy

For cystine stones

• Urinary alkalinization

• Chelators - D-penicillamine, N-acetylcystine

For oxalic acid stones

• Restricted dietary intake

• Inhibitor: K+citrate, pyridoxine

along with simultaneous serum levels. Serum vitamin D and parathormone levels should also be assessed.

• Microbial evaluation for associated UTI.

• Examination of stone passed in urine.

Management depends on the location, size and composition of stone as well as presence of obstruction and infection. Medical management includes use of high volume fluid therapy with use of diuretic flush therapy.

While very small stones (5-7 mm) may pass spon­taneously, percutaneous or laparoscopic surgical removal or extracorporeal shock wave lithotripsy (ESWL) is indicated in—(a) large or impacted stones,

(b) recurrent ureteric colic/hematuria, or (c) progressive hydronephrosis. #945;-adrenergic blockers, e.g. tamsulosin, may facilitate passage of small stones by relaxing the ureter below the stone. In some cases, a ureteral stent may be passed endoscopically to dilate the ureter and allow the calculus to pass.

Preventive measures include—(a) ensuring high fluid intake, (b) treatment of underlying metabolic problem (Table 21.27) and (c) prophylactic long-term antimicrobial therapy in selected cases.

21.15