1. DR SAMPSON ANTWI SMS/KNUST/GHANA AUDIT OF POSTERIOR URETHRAL VALVE AT RED CROSS CHILDREN’S HOSPITAL, SOUTH AFRICA 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

2. Introduction Worldwide, the number of patients with chronic kidney disease (CKD) is rising markedly. 1 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

3. Introduction cont. Given the high cost of treatment for patients with end-stage-renal-failure (ESRF) which may be beyond the reach of most people in resource-constraint countries and where the expertise for chronic RRT may be lacking, the approach to CKD must emphasise on early detection and aggressive management aimed at slowing disease progression. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

4. Introduction cont. In children, congenital anomalies of the kidney and urinary tract (CAKUT) together with hereditary nephropathies are the main causes of ESRF. 2,3 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

5. Introduction cont. Posterior urethral valve (PUV) is the most common cause of bladder outlet obstruction in male children and is an important cause of ESRF. 4 Early diagnosis and intervention to decrease bladder pressure and stabilise the upper tract are important to delay or prevent the progression of renal insufficiency. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

6. Study Objectives & Methods A retrospective folder review of children with PUV at Red Cross Children’s Hospital (RXCH), South Africa, from January 2002 to January 2009 to determine the clinical presentation, timing of diagnosis, timing and method of surgical intervention, and disease progression. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

7. Results Forty-eight patients were reviewed. Median duration of follow-up was 52 months (IQR 24-107 months). 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

8. Results cont. Age at diagnosis Nineteen (39.6%) of the 48 patients were diagnosed prenatally. Of the remaining 29 patients diagnosed postnatally, age at diagnosis ranged from 1day to 2,950 days (median 17 days, IQR 1.0-90.5 days). Seventeen (58.6%) of the postnatally diagnosed patients were diagnosed within first 3 months of age. Figure 1 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

9. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

10. Results cont. Clinical presentation Ten (34.5%) of the 29 patients diagnosed postnatally were diagnosed following evaluation for UTI. Four (13.8%) patients presented with abdominal mass, 3 (10.3%) with voiding difficulties, and 2 (6.9%) with enuresis. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

11. Clinical presentation cont. Ten (34.5%) patients presented with symptoms unrelated to the urinary system such as gastroenteritis and failure to thrive. It is significant to note that dribbling of urine on micturition as a presenting complaint was identified in only 2 (6.9%) out of the 29 postnatally-diagnosed patients. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

12. Surgical methods employed Twenty-nine (60.4%) of the 48 patients had primary valve ablation as the sole surgical intervention employed Six ((12.5%) patients had valve ablation plus secondary urinary diversion (vesicostomy or ureterostomy). 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

13. Surgical methods cont. Twelve (25.0%) patients had vesicostomy alone. One (1.0%) patient had vesicostomy plus secondary ureterostomy. Two children had their valves ablated incidentally during passage of urethral catheter. Figure 2. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

14. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

15. Results cont. Time from confirmation of diagnosis to primary surgery The median time interval from confirmation of PUV to primary surgical intervention was 8.5 days (IQR 6 - 15days). Except for 2 cases whose surgery were delayed beyond 30 days at 40 and 120 days respectively, all cases (95.8%) had primary surgical intervention within the first 30 days of confirmation of PUV. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

16. Results cont. Disease progression and outcome of study subjects Stages of CKD based on K/DOQI guideline at end of follow-up is represented in Figure 3. Only one patient had reached CKD stage V (ESRF) over 5 years 3 months. He had since undergone successful renal transplant with functioning graft after 4 years 2 months (serum creatinine at last visit 48 μmol/l). 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

17. Figure 3: Stages of CKD at end of follow-up 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

18. Results cont. Mortality outcomes No death was recorded but significant numbers 14 (29.1%) were lost to follow-up. Prognostic factors identified were: Serum creatinine at presentation (p-value 0.008) Serum creatinine at 1 year of age (p-value 0.002) Nadir serum creatinine 1-year post surgery (p-value 0.003) 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

19. Discussion Age at diagnosis For all forms of obstructive uropathies including PUV, the goal of therapy is to relieve the obstruction in the earliest possible time. Such a goal can only be met if the condition is diagnosed early. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

20. Age at diagnosis cont. Urinary tract dilatation is generally regarded as one of the foetal abnormalities that could easily be identified by prenatal ultrasound scan. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

21. Age at diagnosis cont. The tendency in the present decade, therefore, is towards a 100% prenatal diagnosis. 5 In this study, about 40% of cases were detected prenatally whilst 58.6% of the postnatally diagnosed cases were identified within the first 3 months of life. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

22. Age at diagnosis cont. The findings from this study parallels that of a series in the British Isles. 6 Given the often poor maternal health care services in Africa with its attendant lack of prenatal ultrasound scan, the findings from this African study is commendable. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

23. Discussion Modes of clinical presentation Outside prenatal detection, the modes of presentation of PUV identified in this audit is consistent with reports in the literature. 6 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

24. Clinical presentation cont. The findings stress the importance of routine examination of the newborn for palpable kidneys or bladder and the need for universal radiological investigation in all boys with UTI particularly in Africa where a prior antenatal scan might have lacked contrary to NICE recommendations for advanced economies. 7 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

25. Clinical presentation cont. Interestingly, only 2 (4.17%) patients presented with dribbling of urine similar to the 5.5% identified by Atwell. 6 Thus, the widely held belief of “no urine dribbling in a boy, no PUV” should be discarded. Instead, any symptom referable to the urinary tract in a boy including enuresis should warrant some investigation to rule out PUV. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

26. Discussion cont. Timeliness of surgical intervention The timeliness in surgical intervention following diagnosis (median 8.5 days, IQR 6-15 days) is highly commendable given the general lack of personnel and equipments in Africa. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

27. Discussion cont. Modalities of surgery used The variety of surgical treatment of PUV described in the literature were employed in this study; preliminary urinary diversion, valve ablation, etc. 8 In this audit, both lower and upper tract diversionary procedures were employed as has been the practice elsewhere. 8 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

28. Modalities of surgical cont. It is significant to note that majority (60.4%) of the study patients had the definitive surgical treatment of valve ablation as the primary and sole surgical treatment. This audit identified surgical bladder augmentation for patients with failed medical treatment of bladder dysfunction, similar to what has been the practiced elsewhere. 9 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

29. Modalities of surgery cont. Obsolete valve ablation procedures like disruption of valve by blind passage of a valve hook 9, perineal urethrostomy 6, and transvesical approach to valve ablation 6 were not identified in this audit. Instead, Bugbee electrocauterisation was the main method used which is in keeping with modern methods. 9 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

30. Discussion cont. Disease progression At the end of follow-up, only one (2.7%) patient had reached ESRF (i.e. stage 5) and had been successfully transplanted. The rest (97.3%) were in early stages of CKD (stage I- IV) with 54.1% being in stage I. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

31. Disease progression cont. This slow progression of CKD towards ESRF identified in this audit could be attributed to observation that congenital anomalies generally progress slower to ESRF. 8 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

32. Disease progression cont. The contribution of the promptness in diagnosis and comprehensiveness of therapeutic interventions employed in case management could, however, not be ignored. It may be argued, though, that the duration of follow up in this audit (median 52 months) was not long enough for full assessment of disease progression. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

33. Discussion cont. Prognostic factors The three prognostic factors identified in this study - serum creatinine at diagnosis, nadir serum creatinine in first year following relief of obstruction, and serum creatinine at oneyear of age - have all been reported in the literature and reflect the functional reserve of the kidney following relief of obstruction. 10,11 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

34. Prognostic factors cont. Other factors such as age at diagnosis (outside prenatal), age at surgery, and presence of VUR could not be confirmed in this study. Thus several prognostic factors in PUV seem to vary among different studies. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

35. Discussion cont. Conclusion This audit highlights the point that with the right priorities given to the health sector by African governments, coupled with a well determined and motivated team of health professionals, congenital kidney anomalies like PUV could be successfully managed in Africa to decrease disease progression to ESRF. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

36. Conclusion cont. Such an approach will not only improve the quality of life of the African child with chronic kidney disease, but could save our national budgets substantial amount of money in averting the expensive treatment cost of ESRF. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

37. Acknowledgement The support of all staff of the records department of RXCH is hereby acknowledged so is the contribution of Dr Samuel Blay Nguah of Komfo Anokye Teaching Hospital in the data analysis. 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

38. List of References 1. Lysaght MJ. Maintenance dialysis population dynamics: current trends and long-term implications. J Am Soc Nephrol. 2002; 13:37-40 2. Antwi S, Gajjar P, Burger H, Sinclair P, Nourse P, Savage I, Ocheke I, McCulloch M, Wiggelinkhuizen J, Maythem D,Van Dauteren G, Morrison C. Epidemiology/Aetiology of ESRF among renal transplant recipients at Red Cross Children’s Hospital. Pediatr Nephrol (2009). 24:1879 (Abstract). 3. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). 2001 Annual Report. Available from: URL: http://www.naprtcs.orghttp://www.naprtcs.org 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

39. List of References 4. Wiener JS. Posterior urethral valves. 2007. [Online]. Available: http://emedicine.medscape.com/article/412226 5. Roth SK, Carter WH Jr, Chan JCM. Obstructive uropathy in children: Long-term progression after relief of posterior urethral valve. Pediatrics. 2001;107:1004- 1010 6. Atwell JD. Posterior urethral valves in the British Isles: A multicenter B.A.P.S. Review. J Pediatr Surg. 1983;18:70-74 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

40. List of References 7. NICE guidelines on UTI. [Online]. Available: http:/www.nice.org.uk 8. Warshaw BL, Edelbrock HH, Ettenger RB, Malekzadeh MH, Pennsi AJ, Uittenbogaart CH, et al. Progression to end-stage renal disease in children with obstructive uropathy. J Pediatr. 1982;100:183-187 9. Bomalaski DM. Posterior urethral valves. [Online]. Available: http://emedicine.medscape.com/article/1016086 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

41. List of References 10. Warshaw BL, Hymes LC, Trulock TS, and Woodard JR. Prognostic features in infants with obstructive uropathy due to posterior urethral valves. J Urology. 1985; 133:240-243 11. Nickavar A, Otoukesh H, and Sotoudeh K. Validation of initial serum creatinine as a predictive factor for development of end stage renal disease in posterior urethral valves. Indian J Pediatr. 2008;75:695-697 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana

42. THANK YOU 9/1/2010 Dr S Antwi/SMS/KNUST/Ghana