DR. ADANZE O. ASINOBIPAEDIATRIC NEPHROLOGY UNITUNIVERSITY COLLEGE HOSPITAL

IBADAN

OBSTRUCTIVE UROPATHY: ROLE OF NEPHROPREVENTION

DEFINITIONS INTRODUCTION LEVELS OF PREVENTION & MEASURES. RECOMMENDATIONS.

OUTLINE

Obstructive Uropathy refers to the structural or functional changes in the urinary tract that impede the normal flow of urine.

Obstructive Nephropathy refers to the renal disease caused by impaired flow of urine or tubular fluid.

Hydronephrosis refers to the dilatation of the urinary tract. It can occur without functional obstruction to the urinary tract and can be absent in established obstruction.

DEFINITIONS

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-Components: Renal maldevelopment (Aplastic, Dysplastic or Hypoplastic

kidneys), Urinary tract obstruction &

Vesicoureteral reflux.

Children with CAKUT often have fewer nephrons at birth than normal.

Kidneys with significantly fewer nephrons (< 50% the normal number) show marked compensatory changes in the residual nephrons through up-regulation of a number of cytokines and vasoactive compounds.

Obstructive Uropathy is a major cause of renal impairment in infants and children. 

In the early stages of foetal development, chronic UT Obstruction impairs renal growth and development.

If obstruction occurs late in gestation and is low grade or unilateral, hydronephrosis and nephron loss will still occur, but renal function may be sufficient to allow survival and such pts may present later in childhood.

INTRODUCTION

In acute urinary tract obstruction, changes are mainly functional.

These changes may recover after effective relief of the obstruction but any sructural changes will be permanent →Chronic impairment of renal function.

Introduction cont.

In most of the developed countries of the world CAKUT is the leading cause of ESRF in children with Renal Dysplasia being topmost and Obstructive Uropathy being the 2nd most common cause (See Table 1.)

Causes of ESRD – UK Register

Diagnostic Group Patients < 15 yrs Proportion of total Patients 15 - 40 yrs Proportion of total

Renal dysplasia ± reflux 187 34.3% 104 34.8%

Obstructive uropathy 95 17.4% 58 19.4%

Glomerular diseases 77 14.1% 73 24.4%

Tubulo-interstitial disease 31 5.7% 23 7.7%

Metabolic diseases 16 2.9% 24 8.0%

Congenital nephrosis 52 9.5% 4 1.3%

Polycystic kidney disease 24 4.4% 4 1.3%

Renovascular disease 33 6.1% 2 0.7%

Malignancy 14 2.6% 2 0.7%

Drug nephrotoxicity 3 0.6% 1 0.3%

Unknown aetiology 13 2.4% 4 1.3%

Diagnostic Group Patients < 15 yrs Proportion of total Patients 15 - 40 yrs Proportion of total

Renal dysplasia ± reflux 187 34.3% 104 34.8%

Obstructive uropathy 95 17.4% 58 19.4%

Glomerular diseases 77 14.1% 73 24.4%

Tubulo-interstitial disease 31 5.7% 23 7.7%

Metabolic diseases 16 2.9% 24 8.0%

Congenital nephrosis 52 9.5% 4 1.3%

Polycystic kidney disease 24 4.4% 4 1.3%

Renovascular disease 33 6.1% 2 0.7%

Malignancy 14 2.6% 2 0.7%

Drug nephrotoxicity 3 0.6% 1 0.3%

Unknown aetiology 13 2.4% 4 1.3%

Data on CRF in Nigerian Children Anochie I. and Eke F. (2005) PH: Prevalence

>1995 -15per million children (45 in 15 years) Olowu W. et al – 6 new/ year Ibadin (Benin) - 24 in 5yrs. Estimated

Prevalence – 4 pmp Ibadan (unpublished) requiring Dialysis – 16

in 3 years Aetiology mainly – Chronic G/N - CAKUT with PUV being the

most common.

Anochie & Eke 2004 – PUV the commonest seen.

Reviews of Pattern of Renal Disorders from other parts of the country corroborate the above.

Paucity of data. Antenatal Diagnosis poor.

Data on Obstructive Uropathy in Nigerian Children

Causes of ARF in UPTH

0

10

20

30

40

50

60

70

1

Causes of ARF

Nu

mb

er

of

cases

Gastro/e

Septicae

Tetanus

AGN

Malaria

B/asphyx

HUS

Leukemia

B/Lymph

HIV related

PUV

R/agenesis

RVT

Aetiology Anochie&Eke No./% 18yr Review-211 total

Olowu&AdelusolaNo./% A 9-yr Prospective study- 123 total (mortality 46.2%)

Seriki No./% 1968-1970-23 total

Gastroenteritis 61 (28.9) 9 (7.3) 3 (13)

Septicaemia 32 (15.2) 25 (20.3) -

AGN 29 (13.7) 9 ( 7.3) 6 (26.1)

Nephrotic syndrome

- 6 (4.9) -

P. Falciparum malaria

29 (13.7) 37 (23) 3 (13)

Birth asphyxia 27 (12.8) 37 (30) -

Congenital malformations

10 (4.7) 5 (%) PUV) -

HUS 7 (3.3) 2 (1.6) 1(4.3)

Malignancies 6 (2.8) 17 (13.8)Burkitt

Intravascular haemolysis

- 6 (4.9) -

HIV related 3 (1.4) -

Others (4.2) (4.9) 10(43.5)

Primary Prevention –

Aims at preventing kidney disease from occurring at all Calls for knowledge of

risk factors that predispose to renal disease risk factors that initiate renal damage. modification, removal, or avoidance of factors. development of a positive health seeking attitude and

behaviour

Kidney disease Prevention in childhood – 3 Levels:

Secondary Prevention – Is used after the disease has occurred, but before the

person notices that anything is wrong. In many cases, the disease can be cured.

It aims at making a correct and early diagnosis and instituting prompt and appropriate treatment of the kidney disease.

Levels of Prevention

Tertiary: Tertiary prevention targets the person who already

has symptoms of the disease.

The goals of tertiary prevention are: -To prevent damage and pain from the disease -To slow down the disease -To prevent the disease from causing complications -To give better care to people with the disease

make people with the disease healthy again and able to do what they used to do.

Developing better treatments is an example of tertiary prevention.

Levels of Prevention

Development of Congenital anomalies of the kidney and urinary tract (CAKUT) is likely to be polygenic as with congenital anomalies.

Genetics of Obstructive Uropathy

Mice lacking a functional gene for a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) -1 develop fibrotic changes at the UPJ/PUJ with a renal phenotype of obstructive uropathy.

Mice lacking lysosomal membrane protein LIMP-2/LGP85 develop unilateral or bilateral UPJ obstruction 2° to disturbed uroplakin expression.

Deletion of most of the components of the renin-angiotensin system or calcineurin results in defective pyeloureteral peristalsis, functional UPJO and obstructive uropathy.

Findings from Experimental Animals

A mutant mouse has been developed which develops megabladder (mgb) due to a primary defect in the development of smooth bladder muscles. They develop progressive hydroureteronephrosis and renal failure similar to patientss with PUV.

`Although the primary morphogenetic mechanisms responsible for clinical congenital OU have not yet been revealed, the present studies underscore the importance of a functional urinary tract in assuring normal renal development.

Findings from Experimental Animals

◦ Antenatal diagnosis◦ Early treatment of bladder outlet obstruction

Secondary Prevention of Obstructive Uropathy

N/B Between the 12th and 15th week of gestation, the fetal kidney can be detected by transabdominal ultrasonography.

The renal cortex and medulla are distinctly demonstrated by ultrasound by the 20th to 25th week of gestation.

Fetal renal length based upon gestational age is a marker of renal growth and is illustrated in the table (table 1) 

Foetal Diagnosis and Intervention

Gestational age, weeks Mean kidney length, cm 95% CI, cm 18 2.2 1.6 - 2.8 19 2.3 1.5 - 3.1 20 2.6 1.8 - 3.4 21 2.7 2.1 - 3.2 22 2.7 2.0 - 3.4 23 3.0 2.2 - 3.7 24 3.1 1.9 - 4.4 25 3.3 2.5 - 4.2 26 3.4 2.4 - 4.4 27 3.5 2.7 - 4.4 28 3.4 2.6 - 4.2 29 3.6 2.3 - 4.8 30 3.8 2.9 - 4.6 31 3.7 2.8 - 4.6 32 4. 1 3.1- 5.1 33 4.0 3.3 - 4.7 34 4.2 3.3 - 5.0 35 4.2 3.2 - 5.2 36 4.2 3.3 - 5.0 37 4.2 3.3 - 5.1 38 4.4 3.2 - 5.6 39 4.2 3.5 - 4.8 40 4.3 3.2 - 5.3 41 4.5 3.9 - 5.1 Reproduced with permission from Cohen, HL, Cooper, J, Eisenberg, P, et al. Normal length of fetal

kidneys: sonographoc study in 397 obstetric patients. AJR Am J Roentgenol 1991; 157:545. Copyright © 1991 The American Journal of Roentgenology.

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Normal Foetal Renal Lengths

Normally, the fetal ureters are not seen on ultrasonography. However, if they are visualized, it may be indicative of ureteric or bladder obstruction, or vesicoureteral reflux (VUR).

The urine-filled bladder is normally identified at 13 to 15 weeks gestation.

Urine in the bladder suggests at least one functioning kidney. The normal bladder wall is normally thin. If the bladder wall is thick, urethral obstruction such as posterior urethral valves in a male fetus may be present..

The sensitivity of detecting renal malformations by antenatal ultrasonography depends upon the gestational age and the skill of the ultrasonographer.

In one study, the sensitivity of antenatal screening for renal malformations was reported as 82 percent at a mean gestational age of 23 weeks

Foetal Diagnosis and Intervention

Amniotic fluid — Assessment of amniotic fluid volume and analysis of biochemical markers are used to evaluate fetal renal function.

Volume — Although fetal urine production begins at nine weeks of gestation, its contribution to amniotic fluid volume becomes significant at the start of the second trimester.

By 20 weeks gestation, fetal urine accounts for more than 90 percent of the amniotic fluid volume.

Thus, a decrease in amniotic fluid volume (oligohydramnios) at or beyond the 20th week of gestation is an excellent predictor of abnormal fetal renal function.

Foetal Diagnosis and Intervention

Intervention may allow preservation of renal mass prior to completion of nephrogenesis as well as improved pulmonary development.

The Primary limiting factor at present in identifying early who would benefit from intervention is the difficulty in visualising the developing kidneys by USS prior to 18weeks’ gestation.

Successful Vesicoamniotic shunt placement has been found to aid pulmonary development but often did notprevent renal insufficiency.

At Children’s Hospital of Philadelphia, 1/3rd required dialysis & transplantation while the majority reported satisfactory quality of life.

Foetal Diagnosis and Intervention

Grades of antenatal hydronephrosis

GFR Estimation on a Regular Basis -Normal GFR in children and Young adults

Age (Sex) Mean GFR +/-SD (ml/min/1.73m2)

1 week (Males & Females) 40.6 +/- 14.8

2-8 wks (males & females) 65.8 +/- 24.8

>8 wks (males & females) 95.7 +/- 21.7

2-12yrs (males & females) 133.0 +/- 27.0

13-21yrs ( males) 140.0 +/- 30.0

13-21 yrs (females) 126.0 +/- 22.0

Avoid/Control factors that could accelerate CKD Progression – HTN, Proteinuria, Nephrotoxic drugs, Dietary control etc.

Early commencement of RRT – Acute or Chronic.

Pre-emptive renal transplantation.

Tertiary Prevention contd.

CKD PROGRESSION: The initial reduction in nephron number from

whatever injury to the kidneys progressively damages the remaining ones, which suffer the consequences of adaptive increases in glomerular pressure and flow.

Several workers have shown that hypertension and proteinuria are among some of the factors that contribute to progressive renal function deterioration in chronic kidney disease( Klag et al 1996, Bakis 1998, Ruggenenti et al 1998, Peterson JC 1995).

ACEI’s & ARB’s

Diet and Statins

Citrate and bicarbonate

? Erythropoietin

From in utero - Routine Antenatal USS - Suspected Oligohydramnios - Foetal Surgery ANC & Post-natal – Teaching parents, nurses & doctors to observe

the urinary stream of their male infants/pts b/4 discharge & other features of Obstructive uropathy

-Straining at micturition -Failure to thrive – a feature of Obstructive Uropathy - Abdominal mass

- Abdominal pains -Features of UTI -Identifying pts at risk – Chromosomal abnormality, Pre-

aurical tag, Positive family Hx.

Practical Steps of Prevention

Early referral to appropriate place for definitive Rx – Paed. Nephrologist/Urologist.

Follow-up using – Sonographic renal pelvic diameter Quantitative diuretic renogram Markers of glomerular & tubular function TGFβ etc

If CKD develops, appropriate follow-up with appropriate measures to retard progression.

If ESRD sets in early institution of RRT and Pre-emptive Tx.

Practical Steps of Prevention contd.

CAKUT It is now standard practice in Paediatrics to have a

high index of suspicion for UTI, detect the predisposing factors such as vesico-ureteric reflux and obstructive uropathy early and institute appropriate management.

A lot of benefits have accrued from the use of prenatal ultrasonography and subsequent scintigraphy in this regard.

Workers are now advocating for routine screening for congenital anomalies of the kidney and urinary tract (CAKUT) by ultrasonography in healthy neonates and infants since they are presently the most common cause of CRF in some countries.

Encourage prevention at all levels. Public Health Education – through the Media - Community outreaches - World Kidney Day Activities

Strengthening our Primary Health Care Centres – Training and retraining of Staff and provision of Basic equipment –

-BP apparatus - Infantometer - Stadiometer - Weighing Scale ; - DipsticksEquipping a centres for tertiary/quartenary care.Advocacy at the 3levels of governance.More research – Basic & clinical to be encouraged.

RECOMMENDATIONS

Reference Books Pediatric Nephrology 6th Ed Avner, Harmon,

Niaudet & Yoshikiwa

Paediatric Nephrology by Postlethwaite

Comprehensive Clinical Nephrology- John Feehally, Jurgen Floege & Richard J. Johnson 3rd Ed.

Up To Date

Pediatric Nephrology (Journal of the IPNA)

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