1. OBSTRUCTIVE UROPATHY: ROLE OF NEPHROPREVENTION
DR. ADANZE O. ASINOBI
PAEDIATRIC NEPHROLOGY UNIT
UNIVERSITY COLLEGE HOSPITAL
IBADAN

2. OUTLINE
DEFINITIONS INTRODUCTION LEVELS OF PREVENTION & MEASURES. RECOMMENDATIONS.

3. DEFINITIONS
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.

4. 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.

5. INTRODUCTION
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.

6. Introduction cont.
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.

7. 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.)

8. Causes of ESRD – UK Register

9. Data on CRF in Nigerian Children
Anochie I. and Eke F. (2005) PH: Prevalence > per million children (45 in 15 years)
Olowu W. et al – 6 new/ year
Ibadin (Benin) 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Ibadan (unpublished) requiring Dialysis – 16 in 3 years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.

10. Data on Obstructive Uropathy in Nigerian Children
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.

11. Causes of ARF in UPTH

12. Congenital malformations 10 (4.7) 5 (%) PUV) HUS 7 (3.3) 2 (1.6)
Aetiology
Anochie&Eke No./% 18yr Review-211 total
Olowu&AdelusolaNo./% A 9-yr Prospective study- 123 total (mortality 46.2%)
Seriki No./% 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
37 (23)
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
HIV related
3 (1.4)
Others
(4.2)
(4.9)
10(43.5)

13. Kidney disease Prevention in childhood – 3 Levels:
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

14. Levels of Prevention 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.

15. 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.

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

17. Findings from Experimental Animals
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.

18. 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.

19. Secondary Prevention of Obstructive Uropathy
Antenatal diagnosis
Early treatment of bladder outlet obstruction

20. Foetal Diagnosis and Intervention
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) 

21. Normal Foetal Renal Lengths
Gestational age, weeks Mean kidney length, cm % CI, cm
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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Licensed to: AO Asinobi

22. Foetal Diagnosis and Intervention
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

23. 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.

24. 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.

25. Grades of antenatal hydronephrosis

27. 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)
/- 27.0
13-21yrs ( males)
/- 30.0
13-21 yrs (females)
/- 22.0

28. Tertiary Prevention contd.
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.

30. 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).

31. ACEI’s & ARB’s

32. Diet and Statins

33. Citrate and bicarbonate

34. ? Erythropoietin

35. Practical Steps of Prevention
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.

36. Practical Steps of Prevention contd.
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.

37. 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.

38. RECOMMENDATIONS 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 ;
- Dipsticks
Equipping a centres for tertiary/quartenary care.
Advocacy at the 3levels of governance.
More research – Basic & clinical to be encouraged.

39. 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)

41. Thank you for your attention