Risk factors for renal injury in patients with meningomyelocele.

PATIENTS AND METHODS: Thirty operated patients of myelodysplasia were clinically evaluated for the age at presentation, the extent of lesion and neurological deficit. Urological assessment was done with urine cultures, serum creatinine, radiological (ultrasound of kidney, ureters and bladder, voiding cystourethrogram) and urodynamic (water cystometry) parameters. An objective scoring for bladder (Galloway, et al.) was applied. Dimercapto-succinic acid (DMSA) scan was done in all the patients for evidence of renal scars. The results of above investigations were correlated with presence or absence of renal scars (renal injury) on DMSA scan. None of the patients had received any prior bladder care. RESULTS: Twenty one patients had no renal scars and 9 patients had evidence of renal scarring. Patients with renal scars were older at presentation, they had greater degree of hydroureteronephrosis (P < or = 0.001) and vesicoureteric reflux (P < or = 0.005). The incidence of high leak pressures (>25 cm of water, P < or = 0.05), unacceptable bladder volumes (maximum cystometric capacity < 60% for age, P < or = 0.005) and high risk Galloway's score (> 5, P < or = 0.05) was high in patients with associated renal scarring as compared to their nonscarred counterparts. Three of these patients had serum creatinine >1 mg/dl (P < or = 0.005). The incidence of urinary complaints and positive urine cultures was also higher in these patients (NS). CONCLUSION: Increasing age, evidence of hydroureteronephrosis and vesicoureteric reflux, high leak pressures, low bladder volume and high combined Galloway score (>5) define a high risk bladder in our population and predispose to renal injury in patients of myelodysplasia. Early referral for bladder risk assessment and management of all myelodysplasia patients is recommended.

Anterior urethral valves.

Posterior urethral valves (PUV) are the most frequent cause of obstructive uropathy in boys. Rarer causes of obstructive uropathy include bladder diverticulae, meatal stenosis and urethral or bladder stones. Anterior urethral valves are rare causes of urinary obstruction in boys and are ten times less frequent than PUV in the literature(1-6). This paper highlights our experience with 5 patients with anterior urethral valves.

Association of angiotensin converting enzyme and angiotensin type 2 receptor gene polymorphisms with renal damage in posterior urethral valves.

OBJECTIVE: To examine the association with renal damage in patients with posterior urethral valves (PUV) of two renin-angiotensin system gene polymorphisms: angiotensin converting enzyme insertion/deletion (ACE I/D) and angiotensin type 2 receptor (AT2R A1332G), PATIENTS AND METHODS: In 120 patients with PUV, after stabilization, transurethral fulguration or a Blocksom vesicostomy was performed. Records were reviewed for age at diagnosis, biochemical renal function at diagnosis, results of urine cultures, voiding cystourethrograms, radiologic, sonographic and nuclear medicine scan findings, and follow-up data. ACE I/D genotypes were determined by the polymerase chain reaction using allele specific primers. RESULTS: The frequency of the ACE DD genotype was significantly higher in patients with chronic kidney disease (P=0.02) and renal scarring (P=0.05). These genotypes were also associated with a statistically higher incidence of vesicoureteral reflux, diurnal incontinence, proteinuria and hypertension. A significantly higher frequency of the AT2R GG genotype was found in PUV patients as compared to healthy unrelated control subjects (P=0.001), and in PUV patients with scarring (P=0.02). CONCLUSION: The ACE DD and AT2R GG genotypes are associated with chronic kidney disease and scarring in PUV patients. The GG genotype incidence is higher among PUV patients compared to the control population, and further studies in this area may help understanding of the genetic basis of PUV.

Comparative efficacy and safety of extended-release and instant-release tolterodine in children with neural tube defects having cystometric abnormalities.

AIM: To evaluate the comparative efficacy and safety of extended-release (ER) and instant-release (IR) tolterodine preparations in a pediatric population with neural tube defects having cystometric abnormalities. MATERIALS AND METHODS: Twenty-five patients with neural tube defects and a similar demographic profile underwent a routine hemogram, liver function tests, renal function tests, urine culture, X-ray lumbo-sacral spine, and renal and bladder ultrasound. Vesicoureteric reflux was diagnosed by micturating cystourethrogram under fluoroscopy. Dimercaptosuccinic acid renal scintigraphy was performed to study the presence or absence of renal scars. Patients were treated with tolterodine ER (Group I: 2mg once daily for 21 days) and tolterodine IR (Group II: 2mg twice daily for 21 day) in a cross-over study with a 10-day washout period between administrations. Evaluation was by subjective assessment, visual analog scale, urodynamic assessment and adverse drug reaction monitoring. RESULTS: There was ultrasound evidence of hydroureteronephrosis in 20% of the patients. One patient out of 25 had impaired renal function and eight patients had renal scarring on dimercaptosuccinic acid scans. Both forms of the drug increased the maximum cystometric bladder capacity, decreased detrusor leak pressures and increased compliance compared to pre-therapy levels (P=0.0001). Visual analog scale showed a significant clinical improvement with both ER and IR tolterodine. A significant increase in maximum bladder capacity in the group receiving IR tolterodine as compared to the ER preparation was noted (P=0.0001). The decrease in detrusor leak pressures and improvement in compliance were not significantly different between the groups. No adverse effects of hyperpyrexia, flushing or intolerance to outdoor temperatures, or dryness of mouth were observed in either group. No patient suffered from constipation. CONCLUSION: ER tolterodine 2mg once daily is as effective and well tolerated in children with neurogenic bladder as IR tolterodine 2mg twice a day. The latter was found to be more effective in terms of urodynamic parameters. ER formulation of tolterodine is less expensive and has the advantage of single dosage.

Angiotensin-converting enzyme gene polymorphism in North-west Indian children with posterior urethral valves.

PURPOSE: To investigate the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and other risk factors with renal scarring in patients with posterior urethral valves (PUV). MATERIALS AND METHODS: Forty consecutive patients from North-west India were treated for PUV in 1997-2004. The patients were divided into group 1 (no renal scarring, n=12) and group 2 (renal scars present, n=28) based on dimercato-succinic acid scans. ACE I/D polymorphism was determined by polymerase chain reaction in PUV patients and unrelated healthy controls (n=100). RESULTS: Mean age at presentation was 23.7+/-37.2 months and mean follow up was 4.8+/-1.5 years. Preoperative mean serum creatinine levels for group 1 (non-scarred) and group 2 (scarred) were 1.1+/-1.6 mg/dl and 1.7+/-1.6 mg/dl, respectively. One year after treatment, the serum creatinine levels had decreased to 0.6+/-0.1 mg/dl and 0.8+/-0.3 mg/dl in group 1 and group 2, respectively. ACE genotype distribution in children with PUV was no different from that of controls. The occurrence of D allele was significantly (p=0.04) higher in patients of group 2. Multivariate logistic regression analysis showed that D allele had a significant impact on renal scar formation, introducing a 4.6-fold risk (odds ratio 4.6, 95% confidence interval 1.03-20.38, p=0.04). A highly significant correlation between the occurrence of renal scarring and presence of breakthrough urinary tract infection (odds ratio=7.5, 95% confidence interval 1.60-35.07, p=0.006) and serum creatinine at follow up (odds ratio=0.6, 95% confidence interval 0.47-0.81, p=0.03) was observed. The mean values for glomerular filtration rate (GFR) after 1 year of treatment (p=0.006) and at follow up (p=0.027) were significantly different between the patients with II genotype and ID/DD genotype. Hypertension was observed in 13 patients and proteinuria in nine patients with no significant difference between the patients having II/I D/DD genotypes. CONCLUSION: The presence of D allele is associated with progression of renal scarring and reduced GFR in PUV patients.

Factors affecting renal scarring in posterior urethral valves.

AIM: To retrospectively review the occurrence of renal scarring in patients with posterior urethral valves (PUV), and correlate it with various causative factors. METHODS: The records of 52 patients treated for PUV by the authors were reviewed. Patients with vesico-ureteric reflex (VUR) dysplasia syndrome were excluded from the study. The patients were divided into group I (no renal scarring, n=18) and group II (renal scars present, n=34) based on dimercapto-succinic acid scans. The mode of treatment, presence/absence of breakthrough urinary tract infections (UTI), presence/absence of history of nocturnal/diurnal incontinence, presence/absence of VUR, stable postoperative serum creatinine, rate of drainage of ureters on diethylene triamine penta acetic acid (DTPA) scans and management of bladder dysfunction, if any, were noted. The presence or absence of renal scarring was statistically correlated with occurrence of any of the above factors. RESULTS: Primary valve fulguration was performed in 41 patients and 11 patients had an initial vesicostomy. The median follow up was 3.5 years (range 1.5-15 years). Renal scarring was present in either kidney in 34 patients (bilateral 14, unilateral 20). The mode of initial treatment did not affect the incidence or rate of scarring. The preoperative and postoperative serum creatinine at the end of 1 year did not differ between the two groups. Presence/severity of VUR did not affect the pattern of renal scarring. A highly significant correlation between the occurrence of renal scarring and presence of diurnal incontinence (P< or =0.007, odds ratio=4.5) and breakthrough UTI (P< or =0.002, odds ratio=7.0) was observed. There was also correlation with slow drainage in the ureters on a DTPA scan (P< or =0.0005). Detrusor instability and low compliance on urodynamic assessment did not affect occurrence in the limited number of patients studied. The rate of somatic growth in both groups was retarded as compared to normal healthy counterparts. CONCLUSION: Breakthrough UTI, diurnal incontinence and poor drainage of ureters on DTPA are associated with a higher incidence of renal scarring. Mode of initial treatment, presence or absence of VUR, and bladder abnormalities do not affect renal scarring in the short term.

The vesicoureteral reflux dysplasia syndrome in patients with posterior urethral valves.

PURPOSE: We retrospectively reviewed outcomes in children followed for posterior urethral valves and the vesicoureteral reflux dysplasia (VURD) syndrome. MATERIALS AND METHODS: Of 65 patients with posterior urethral valves 13 fulfilled the criteria for the VURD syndrome. Patients were assessed with diethylenetriamine pentaacetic acid and dimercapto-succinic acid scans at followup to evaluate stability of renal function, presence of renal scarring and drainage of the contralateral kidney. Student's t test and the chi-square test were used for statistical analysis, with p < or = 0.05 considered significant. RESULTS: Based on the dimercapto-succinic acid scan reports, patients were classified into group 1 (6 patients), in which the contralateral kidney had no evidence of scarring, and group 2 (7 patients), in which the contralateral kidney had evidence of scars. Patients in group 1 had no breakthrough urinary tract infections or history of urinary incontinence. There was no dilatation of the contralateral upper urinary tract, and 5 of 6 patients had prompt ureteral drainage on scans. They also attained a long-term serum creatinine of 0.6 +/- 0.0 mg/dl. Patients in group 2 had a significant incidence of breakthrough urinary tract infections (p < or = 0.03) and diurnal incontinence (p < or = 0.01). Hydroureteronephrosis and slow drainage were seen in 6 of 7 patients on scans. The long-term mean serum creatinine attained in this group was 0.9 +/- 0.3 mg/dl. CONCLUSIONS: About half of the patients with the VURD syndrome had renal scarring in the contralateral kidney. These patients had evidence of hydroureteronephrosis, slow drainage of the ureter in association with breakthrough urinary tract infections and diurnal incontinence. Although serum creatinine in patients with the VURD syndrome and renal scarring in the contralateral kidney was not statistically different from that in children with a normal contralateral kidney in the short term, in the long term the deleterious effects of renal scarring, viz hypertension, proteinuria and renal failure, are likely to manifest. The presence of the VURD syndrome may not always be as good a prognostic indicator as believed previously.

Does mode of treatment affect the outcome of neonatal posterior urethral valves?

PURPOSE: A prospective study on the outcome of posterior urethral valves (PUV) was performed. The data analyzed were whether the modality of treatment (fulguration vs vesicostomy) affected renal function and somatic growth, and whether the presence of vesicoureteral reflux (VUR) and abnormal serum creatinine levels affected somatic growth. MATERIALS AND METHODS: A total of 45 consecutive neonates were diagnosed and treated for PUV with fulguration (24) or vesicostomy (21) between 1997 and 2003. Postoperative stable creatinine values, renal function and somatic growth were recorded. Well tempered renal scans using diethylenetetraminepentaacetic acid were performed during the first and second years of life at followup. Standard anthropometric techniques and statistical methods were used to compute distance statistics for body weight and crown-heel length at age intervals of 3 months for year 1 and 6 months for year 2. RESULTS: Of the patients 9 were lost to followup and 6 died in the first year of life due to renal failure. Preoperative and postoperative mean serum creatinine was 1.6 +/- 1.5 and 0.7 +/- 0.2 mg/dl, for the fulguration group and 1.7 +/- 1.5 and 0.9 +/- 0.7 mg/dl, respectively, for the vesicostomy group. In 10 patients renal function deteriorated or there was no improvement after treatment. With the advancement of age neonates with PUV showed normal increase in body weight and crown-heel length. Those with VUR were significantly shorter compared to neonates with no VUR at the end of year 2 of life (p <0.05). Patients with creatinine less than 1 mg/dl had significantly greater increase in body weight (at 3 and 6 months) as well as crown-heel length (at 3 and 9 months), respectively (p <0.05). Physical growth of the fulguration and vesicostomy groups remained substantially lower than that of their normal healthy counterparts. Newborns treated with vesicostomy did not have any breakthrough urinary tract infections. Although patients treated with vesicostomy were lighter and smaller initially (p <0.05), they were comparable to those treated with fulguration at the end of 2 years, thus demonstrating catch-up growth. CONCLUSIONS: Our prospective study demonstrated that transurethral fulguration and vesicostomy are equally effective for neonatal valves and achieve similar renal function. Both groups showed retarded growth compared to healthy counterparts. Somatic growth was delayed by serum creatinine greater than 1.0 mg/dl and the presence of VUR. Vesicostomy seemed to help neonates catch-up the growth deficit in the first 2 years of life.