Overview of Common Obstructive Uropathy in Childhood DR RM AKUSE Consultant Paediatric Nephrologist, Ahmadu Bello University Teaching Hospital Zaria

DEFINITION Obstructive uropathy(OU) is a condition in which the flow of urine is blocked along the urinary tract. The hindrance may be structural or functional. if left untreated can lead to injury to kidney(s) and renal failure.  

WHY WORRY? Cause of morbidity and mortality in children – CKD, HYPERTENSION, UTI UPTH (1997-2002), 20 CHILDREN HYPERTENSION- 50% RENAL FAILURE- 30% DEATH - 35% Accounted for 16.5% of all pediatric renal transplants in 1997

Potential killer

RENAL FAILURE DUE TO OU 30-70% of all End stage renal disease (ESRD) NIGERIA UPTH- 30% UBTH - (9.6%) CALABAR – 6.7% OAUTH- 8%

Types Can occur in any part of the urinary system, In children often congenital Associated congenital abnormalites CLASSIFICATION Congenital/Acquired Acute/Chronic Anatomical- level of obstruction Unilateral/Bilateral

Types KIDNEY Ureteropelvic junction (UPJ) obstruction URETER Intraluminal = kidney stones, blood clots, papillae sloughing, scarring Extraluminal - enlarged lymph nodes, enlarged uterus (haematocolpos) cancer/tumors, strictures, trauma

Types BLADDER Neurogenic Stones Tumors or masses around the bladder neck or urethra Scarring Retroperitoneal fibrosis URETHRA Posterior and anterior urethral valve Atresia Tumors or masses Phimosis Meatal Stenosis – post circumcision

Common causes Congenital Posterior Urethral Valve (PUV) obstruction Pelvi-Ureteric junction Acquired Calculi Post traumatic Post inflammatory strictures Meatal stenosis Associated anomalies Dysplastic kidneys Imperforate anus Vertebral malformations Prune belly syndrome

Ardissino et al (2003) OU cause of ESRD in 27.1% of pediatric patients COMMONEST TYPES Posterior urethral valves (23.8%). Ureteropelvic junction (UPJ) obstruction= 3.6%, Obstructive megaureter 3.5%, some form of urethral hypoplasia/atresia 2.3%, ureterocele 1.7%, Other complex uropathies accounted for 5.9%.

UPTH – CAUSES OF OU (1997-2002) (n=20) Post urethral Valve -16 (80%), bladder calculi -2 (10%), bladder rhabdomyosarcoma - 1 (5%) urethral stenosis - 1 (5%)

PATHOPHYSIOLOGY MECHANICAL DAMAGE RELEASE OF BIOCHEMICAL MEDIATORS CELLULAR INFILTRATES FOETAL URINE FLOW IMPAIRMENT

MECHANICAL DAMAGE INCREASED INTRATUBULAR PRESSURE LOCAL ISCHEMIA SIGNIFICANT LOSS OF FUNCTIONAL RENAL PARENCHYMA SECONDARY REFLUX SUPERIMPOSED UTI.

RELEASE OF BIOCHEMICAL MEDIATORS prostaglandins, thromboxane [A.sub.2]), angiotensin II, atrial natriuretic peptide, nitric oxide, endothelin, platelet activating factor, nuclear factor kappa B (NF-[kappa]B), transforming growth factor-beta (TGF-[beta]

CELLULAR INFILTRATES Macrophages, T-lymphocytes, and fibroblasts glomerular damage,= albuminuria tubular damage= elevated microglobulin alpha-1. tubulointerstitium, - Most damage - Fiborsis

FOETAL URINE FLOW IMPAIRMENT Causes deregulation of renal precursor cell turnover and expression of growth factor/survival and transcription factor genes. Renal dysplasia

END RESULT HYDRONEPHROSIS, HYDROURETERS, HYPERTROPHIC BLADDER BIOCHEMICAL ABNORMALITIES sometimes type 1 renal tubular acidosis (reduced distal hydrogen secretion) RENAL DYSPLASIA -undifferentiated and metaplastic tissues. OBSTRUCTIVE NEPHROPATHY – bilateral, unilateral

Clinical features Consider OU in patients with any of the following: Diminished or absent urine output Unexplained renal insufficiency Pain that suggests distension in the urinary tract oliguria or anuria alternating with polyuria

Clinical features Fever Dysuria Problems with passing urine – incontinence, hesitancy, increased frequency Poor urinary stream Dribbling Symptoms associated with primary disease

INVESTIGATIONS URINALYSIS may be normal Abnormal - casts, WBCs, RBCs, albuminuria Urine MCS Urea, electrolytes, creatinine FBC and differential. IMAGING

Abdominal ultrasonography Detection of hydronephrosis. Follow up of hydronephrosis false-negative results- if obstruction is early, if obstruction is mild if retroperitoneal fibrosis or tumour encases the collecting system preventing dilation of the ureter.

Voiding cystourethrography (VCUG) Displays anatomy of BLADDER NECK and URETHRA Volume of urine left in the bladder after voiding Vesicoureteral reflux,

Voiding cystourethrogram posterior urethral valves associated reflux (Grade V).

IVU USEFUL when CT cannot identify the level of obstructive uropathy when acute obstructive uropathy is thought to be caused by calculi, sloughed papilla, or a blood clot  Must have some renal function Allergic reactions may occur ANTEGRADE OR RETROGRADE PYELOGRAPHY

Antegrade pyelogram. stricture of distal ureter in patient with moderate hydroureteronephrosis.  

CT SCAN/MRI CT SCAN- Used when obstruction cannot be shown by ultrasonography or IVU. NOTE ultrasonography and CT may not be able to differentiate hydronephrosis from multiple renal or parapelvic cysts. MRI (with or without contrast). used when avoiding ionizing radiation is important (eg, in young children). as accurate as ultrasonography or CT.

Radionuclide scans Don’t use contrast agents Can determine perfusion Identifies functional renal parenchyma BUT cannot detect specific areas of obstruction mainly used TOGETHER WITH diuresis renography to evaluate hydronephrosis without apparent obstruction.

Diuretic renography Frusemide given before i.v injection of radiopharmaceutical (Tc 99m DPTA or MAG 3) or IVU). Note- Must have enough renal function to respond to the diuretic. Rate of washout of radionuclide (or contrast agent) is measured Rapid washout - dilated non-obstructed system. Delayed washout - obstructed pattern Indeterminate - Washout between 1.5 and 20 minutes False-positive and false-negative are common

LEFT: complete obstruction of one kidney (upper graph) partial obstruction of other kidney. RIGHT: Discrepancy in function but no evidence of obstruction

Foetal urinary electrolytes normal foetal kidney makes hypotonic urine foetal urinary biochemical markers most useful after 20 weeks' gestation Reliability varies foetal urinary sodium <100 mEq/L and β-2 microglobulin -more appropriate predictor of postnatal serum creatinine in the foetus

INTERPRETATION A dilated renal collecting system may not mean a true obstruction. HYDRONEPHROSIS must distinguish whether it secondary to an ongoing obstruction or secondary to a prior obstructive event that occurred and resolved antenatally. THIS AFFECTS MANAGEMENT

MANAGEMENT A challenge for paediatricians and urologists is to diagnose and intervene appropriately for problems without overreacting to variants of normal.

MANAGEMENT GOALS Relieve obstruction – antenatal/Postnatal Maximize renal function Maintain normal bladder function Minimize morbidity Prevent iatrogenic problems

COMPLICATIONS CHRONIC KIDNEY DISEASE, ESRF UTI – Chronic or recurrent BLADDER PROBLEMS- incontinence, retention CALCULI – Renal or uretal Complications due to long-term catheter use

PROGNOSIS Duration Specific nature of the blockage, Other factors -Financial constraints - Availability of diagnostic facilities equipment drugs  

Posterior urethral valve (PUV) Commonest cause OU in children Occurs sporadically but familial cases have been reported Cause -obstructing membrane in lumen of the posterior (prostatic) urethra.

CLINCAL FEATURES broad spectrum of clinical severity The most severe forms do not survive in utero, Mildest forms may go undetected. Antenatally detected on routine foetal ultrasonography, – hydronephrosis, renal parenchymal echogenicity, renal cysts

PRENATAL ULTRASOUND OF FETUS WITH PUV renal dysplasia Severe hydronephrosis, parenchymal thinning, increased echogenecity of parenchyma. Sagittal view of upper pole of kidney with renal cyst.

Ultrasound of bladder of patient with PUV Full bladder with thickened wall and dilated ureters posterior to the bladder (black arrows). Prenatal ultrasound with dilated posterior urethra and dilated bladder (“keyhole” sign).

POSTNATAL age at presentation- BIRTH -13 YEARS, Poor urinary stream. incontinence recurrent UTIs. Urinoma Urinary ascites

MANAGEMENT - POSTNATALLY ASSESS PATIENT Treat Acute illness Surgery - Ablation of valve Urinary diversion -vesicostomy, cutaneous ureterostomy, augmentation cystoplasty with later reconstruction. Manage CKD RENAL TRANSPLANT FOLLOW UP - Check for persisting or increasing upper urinary tract dilatation, increasing serum creatinine, bladder problems

PRENATAL INTERVENTION Uncertain whether antenatal diagnosis or treatment improves long-term renal outcome Identify those who intervention may benefit using gestational age, amniotic volume, Renal dysplasia - cortical cysts, increased echogenicity. renal function - -urinary electrolytes, β-microglobulin levels Karyotype

Foetal surgery continues to remain controversial. normal outcomes can occur without intervention. Indications ? for the carefully selected patient who has normal-appearing kidneys and normal urinary electrolytes with severe oligohydramnios Surgery - vesicoamniotic shunts, valve ablation , bladder marsupialization  

COMPLICATIONS of interventions Shunt failure and declining appearance of fetal lungs kidney. Chorioamnionitis, Spontaneous ruptures of membrane, amniotic fluid leak. Premature labor with respiratory failure. Fetal mortality rate – 33-43%.

POSTNATALLY intervention may not change the prognosis of renal function We must not give families unrealistic expectations that fetal surgery is the cure for obstructive uropathy or that the child will not need extensive follow-up after delivery.

Outcome BLADDER DYSFUNCTION hyperreflexia, hypertonic, small capacity bladder, sphincter incompetence and/or myogenic failure. End-stage renal disease – Renal failure - in 19% to 64% diagnosed prenatally in 25% to 40% diagnosed postnatally  

CONCLUSION: Advances in postnatal surgery and medical management have reduced the mortality in PUV Earlier diagnosis by ultrasound, Developments in surgical technique Meticulous attention to neonatal care.

UPJ obstruction Intrinsic obstruction hypoplastic adynamic ureteral segment at the UPJ Extrinsic causes - aberrant vessels, kinks, PAIN - abdominal or flank -worse with diuresis hematuria following mild trauma, chronic nausea, UTI. DIURETIC RENOGRAPHY – may be delayed washout Rx – Nil, surgery, Antibiotics

Uretervesical junction (UVJ) OBSTRUCTION hydroureter + HYDRONEPHROSIS NORMAL BLADDER megaureter. - not necessarily obstructed. mainly found incidentally on prenatal sonography, Usually normal physical exam UTI, hematuria, abdominal pain or mass, uremia.

Management Depends on presence of obstruction presence of reflux, Continued surveillance Patients with nonobstructed system often resolve spontaneously antibiotic prophylaxis is recommended until a proper diagnosis can be made. Surgery -

SURGERY increasing hydronephrosis on ultrasound, decreasing renal function, Recurrent infections Persistent symptoms Calculi Careful follow up  

The Future ? Development of molecular markers for diagnosis and progression ? Improve criteria to select patients for treatment ? improve prenatal treatment to improve bladder function, ? Better imaging techniques ???fetal magnetic resonance imaging to assist in differentiating PUV from other causes of severe hydronephrosis, eg, prune belly syndrome, vesicoureteral reflux

Prevention need to improve the country's socioeconomic conditions Need to improve health facilities make medical facilities more available to children prevent renal diseases that may lead to ESRF Education at the community level

CONCLUSION OU – IMPORTANT CAUSE OF RENAL IMPAIRMENT ADEQUATE MEASURES NEEDED TO PREVENT OR TREAT ESRF RESOURCE CONSTRAINED COUNTRIES – SEVERAL CHALLENGES  

REFERENCES Anochie I, Eke F.Obstructive uropathy in childhood, as seen in University of Port Harcourt Teaching Hospital, Nigeria. Niger J Med. 2004 Apr-Jun;13(2):136 Michael IO, Gabriel OE. Pattern of renal diseases in children in midwestern zone of Nigeria. Saudi J Kidney Dis Transpl. 2003 Oct-Dec;14(4):539-44. Nasir AA, Ameh EA, Abdur-Rahman LO, Adeniran JO, Abraham MK. Posterior urethral valve. World J Pediatr. 2011 Aug;7(3):205-16. Epub 2011 Aug 7. Etuk IS, Anah MU, Ochighs SO, Eyong M..Pattern of paediatric renal disease in inpatients in Calabar, Nigeria. TropDoct. 2006 Oct;36(4):256. Eke FU, Eke NN Renal disorders in children: a Nigerian study. PediatrNephrol. 1994 Jun;8(3):383 Woolf AS; Thiruchelvam . Congenital obstructive uropathy: its origin and contribution to end-stage renal disease in children.Adv Ren Replace Ther.  2001; 8(3):157-63  Obstetric uropathy . Considerations for the nephrology nurse. Nephrology Nursing Journal . March 2004 Ardissino et al 2003). Nicholas Holmes, Michael R. Harrison, Laurence S. Baskin, Fetal Surgery for Posterior Urethral Valves: Long-Term Postnatal Outcomes Obstructive uropathy - Overview http://www.umm.edu/ency/article/000507.htm#ixzz1jdfjZGzr ROTH Karl S) ; KOO Harry P. ; SPOTTSWOOD Stephanie E. ; CHAN James C. M.Obstructive uropathy: An important cause of chronic renal failure in children Congenital obstructive uropathy: its origin and contribution to end-stage renal disease in children. Adv Ren Replace Ther.  2001; 8(3):157-63  N Eke, SN Elenwo. Obstructiveuropathy in childhood: A review Port Harcourt Medical Journal>Vol 1, No 3 (2007) Casale AJ Early ureteral surgery for posterior urethral valves. . Urol Clin North Am. 1990 May;17(2):361-72.

Anochie I, Eke F.Obstructive uropathy in childhood, as seen in University of Port Harcourt Teaching Hospital, Nigeria. Niger J Med. 2004 Apr-Jun;13(2):136   Michael IO, Gabriel OE. Pattern of renal diseases in children in midwestern zone of Nigeria. Saudi J Kidney Dis Transpl. 2003 Oct-Dec;14(4):539-44. Nasir AA, Ameh EA, Abdur-Rahman LO, Adeniran JO, Abraham MK. Posterior urethral valve. World J Pediatr. 2011 Aug;7(3):205-16. Epub 2011 Aug 7. Etuk IS, Anah MU, Ochighs SO, Eyong M..Pattern of paediatric renal disease in inpatients in Calabar, Nigeria. TropDoct. 2006 Oct;36(4):256. Eke FU, Eke NN Renal disorders in children: a Nigerian study. PediatrNephrol. 1994 Jun;8(3):383 . Woolf AS; Thiruchelvam . Congenital obstructive uropathy: its origin and contribution to end-stage renal disease in children.Adv Ren Replace Ther.  2001; 8(3):157-63 ( Obstructive uropathy: considerations for the nephrology nurse. : Nephrology Nursing Journal Publication Date: 01-MAR-04 Ardissino et al 2003). Nicholas Holmes, Michael R. Harrison, Laurence S. Baskin, Fetal Surgery for Posterior Urethral Valves: Long-Term Postnatal Outcomes Obstructive uropathy - Overview http://www.umm.edu/ency/article/000507.htm#ixzz1jdfjZGzr

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