POSTERIOR URETHRAL VALVES: PRELIMINARY OBSERVATIONS ON THE SIGNIFICANCE OF PLASMA RENIN ACTIVITY AS A PROGNOSTIC MARKER MINU BAJPAI,* AKSHAY PRATAP, MADHAVI TRIPATHI AND C. S. BAL From the Departments of Pediatric Surgery (MB, AP) and Nuclear Medicine (MT, CSB), All India Institute of Medical Sciences, New Delhi-110029, India ABSTRACT Purpose: A significant number of children with posterior urethral valves (PUVs) have chronic renal failure due to tubulointerstitial damage. Activation of the renin-angiotensin system is known to inflict this injury. We investigated the role of plasma renin activity (PRA) in patients with PUVs and sought to establish a relationship between renal damage and PRA. Materials and Methods: The records of patients with PUVs were reviewed regarding the time of valve ablation, serum creatinine, scars, grade of reflux and glomerular filtration rate (GFR). PRA was measured before and after valve ablation. Results: A total of 25 patients had PUVs (mean age 3.2  2.4 years, mean period of observation 4.5  1.2 years). Mean PRA was increased before valve ablation in all patients irrespective of age, and decreased after ablation. Of 25 patients 14 (56%) had renal damage, with a mean PRA of 36  4.5 ng/ml per hour compared to 26  8.2 ng/ml per hour in patients with normal renal function (chi-square 4.2 p = 0.01). Of the 14 patients with renal damage 9 (64%) had normal GFR at age 1 year but increased PRA. Of these 14 patients the accepted criteria for renal damage of increased serum creatinine, high grade reflux, scars and decreasing GFR were present in only 6 (43%), 3 (21%), 2 (14%) and 4 (29%), respectively. PRA was increased in all 14 cases. Conclusions: PRA was increased before valve ablation and decreased after ablation. It is increased in patients with early renal damage. Our preliminary observations indicate that PRA may be helpful in identifying patients with early renal damage. KEY WORDS: renin, urethral, cicatrix, urologic diseases, polymorphism (genetics) Posterior urethral valves (PUVs) are a heterogeneous dis- order with an incidence of 1 in 4,000 to 7,500 male infants. 1 Although the short-term outcome for boys with PUVs is pres- ently good, the long-term prognosis is still far from satisfac- tory. Chronic renal failure occurs in a significant number of children with PUVs and accounts for 16.8% of the population of children with end stage renal disease. 2,3 Since long-term renal deterioration is common in patients with PUVs, early identification of detrimental factors can help in guiding ther- apy. Emerging evidence has highlighted the pivotal role of the renin-angiotensin system (RAS) as a mediator of renal injury and interstitial fibrosis in other renal diseases. 4 Plasma renin activity (PRA) as an indicator of activation of RAS has not been studied in patients with posterior urethral valves. In this prospective study we serially measured PRA and sought to establish a relationship between accepted cri- teria of renal damage and PRA through a post hoc analysis. To our knowledge we report the first documented activation of RAS, using PRA, in patients with posterior urethral valves. MATERIALS AND METHODS Study patients were males 2 months to 6 years old with the diagnosis of posterior urethral valves followed at our clinic. Exclusion criteria were diversion surgery (vesicostomy or uret- erostomy) before valve ablation, since such patients usually have advanced disease, and bladder dysfunction on urodynam- ics, since high pressures within abnormal bladders may be transmitted to the pelvicaliceal system and are known to cause disturbances in the renin-angiotensin system. 5 All patients included in the study had 4.5  1.2 years of followup and bladder behavior had been evaluated in at least 2 urodynamic studies. Of 60 boys with PUVs 25 had normal bladder dynamics and were included in the study. The records of these patients were reviewed regarding the time of valve ablation, adequacy of ablation on voiding cystourethro- gram and serum creatinine. Renal scars were studied using 99m techetium dimercaptosuccinic acid scans. Grade of reflux was recorded by voiding cystourethrogram according to the international classification. Split renal function and glomer- ular filtration rate (GFR) were measured by diethylenetetra- minepentaacetic acid scans. Glomerular filtration rate was calculated each time using venous blood samples obtained at 60, 90, 150 and 180 minutes after 99m technetium diethyl- enetetraminepentaacetic acid injection. 6 Percentage change in GFR was calculated by the formula adopted by Smellie et al. 7 Plasma renin activity was meas- ured before and after ablation. The latter was measured 1 month after ablation and then every 6 months. PRA was measured by radioimmunoassay using a commercially avail- able kit (DiaSorin, Stillwater, Minnesota). Normal labora- tory PRA was 4 to 8 ng/ml per hour at 1 to 12 months, 1 to 9 ng/ml per hour at 1 to 3 years, 1 to 5 ng/ml per hour at 3 to 6 years, 1.4 to 2.6 ng/ml per hour at 6 to 15 years and less than 4.3 ng/ml per hour at 15 to 18 years. Data are reported as mean  standard deviation. Statisti- cal comparisons between group means were done by the unpaired Student t test, while proportions were compared by means of the Yates corrected chi-square test. Multiple linear Submitted for publication October 24, 2003. * Correspondence and requests for reprints: Department of Pedi- atric Surgery, All India Institute of Medical Sciences, New Delhi- 110029, India (telephone: 91-11-26593555, FAX: 91-11-26588663 or 91-11-26588641; e-mail: bajpai2@hotmail.com). 0022-5347/05/1732-0592/0 Vol. 173, 592–594, February 2005 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000150573.26650.70 592