Permanent Renal Damage Research Articles

ELECTROLYTE IMBALANCE FOLLOWING ILEAL URINARY DIVERSION

SUMMARY Measurements of serum electrolytes were made in 38 patients in whom ileum was used in the urinary tract. A high incidence (61 per cent.) of transient early hyperchlorzmic acidosis due to reabsorption was found but most patients were able to compensate for it. However, 27 per cent. of patients were unable to compensate because of permanent renal damage and they developed chronic hyperchlorzmic acidosis. Normal levels of serum uric acid, calcium and inorganic phosphorus were found in all of the patients. For monitoring renal function in patients with ileal urinary diversion measurements of serum creatinine were found to be more useful than estimation of blood urea.

Concurrent urinary tract infection and stone disease: pathogenesis, diagnosis and management

Urinary tract stones and urinary tract infection are strongly associated. Infection is implicated as the cause of stones in about 15% of stone formers, and the development of infection can complicate the management of pre-existing stones. Left untreated, both situations can result in loss of kidney function, and can, on occasion, be life threatening. The underlying pathophysiology of infection stones is generally well understood, but factors dictating why a particular individual should be affected are less clear, although obstruction is a uniformly recognized risk factor. Surgery is the mainstay of treatment for infection calculi: stone clearance is the goal and a range of minimally invasive treatments is available. Systemic sepsis remains the most serious complication of treatment, and, although rare, still occurs despite antibiotic prophylaxis. Once the stone and the causative infection have been removed, various strategies can be employed to minimize the risk of recurrence. When infection complicates pre-existing stone disease, the primary aim of management is to treat the infective episode and delay definitive stone management until the infection has cleared. In such cases where obstruction is also present, prompt drainage of the affected kidney is likely to prevent permanent renal damage, and may be life saving.

Impact of micturating cystourethrography and DMSA renal scintigraphy on the investigation scheme in children with urinary tract infection

The relationships among urinary tract infection (UTI), vesicoureteral reflux (VUR), and permanent renal damage in children are not fully understood. The aim of this study was to evaluate the incidence of renal scarring in children with a history of UTI and to determine the change in the probability of permanent renal damage owing to the presence of VUR documented on micturating cystourethrography (MCU). We analyzed 201 children (400 renal units, two children with solitary kidney). Seventy-four boys and 127 girls (aged 7 months to 7 years, median 2.5 years) with culture verified UTI were referred for technetium-labeled dimercaptosuccinic (DMSA) renal scintigraphy 4-6 months after acute UTI. MCU was also performed mostly 1 month prior to DMSA. Statistical analysis was performed using chi2 test or Fisher's exact test. Likelihood ratio (LR) positive and negative, diagnostic odds ratio (DOR), and post-test probability of (no) disease were calculated for VUR on MCU versus scarring on DMSA. Vesicoureteral reflux was found in 158 (39.5%) kidneys, and evaluated as grades I, II, III, IV, and V in 3, 70, 43, 25, and 17 refluxing renal units (RRU), respectively. Permanent renal damage according to DMSA was seen in 15.2% (61/400) kidneys. Scarring was shown in 29.7% (47/158) of kidneys with VUR and in 5.8% (14/242) kidneys without VUR (P<0.0001). LR positive was 2.353 (95% CI 1.889, 2.865), LR negative 0.341 (95% CI 0.209, 0.523), and DOR 6.895 (95% CI 3.533, 14.093). Rate of scarring significantly increased with VUR of grades III, IV, and V. There was no significant difference in the incidence of scarring in kidneys without VUR and RRU with low-grade (I and II) VUR (P=0.306). The presence of VUR on MCU increased the chance of renal damage on DMSA by about 15%, whereas negative MCU increased the chance of no-renal involvement by 9%. Micturating cystourethrography should not be used as a first-line test to rule out the permanent renal damage owing to UTI. The priority of imaging strategy should be focused on early identification of renal lesions to prevent further deterioration.

Cochrane review: Interventions for primary vesicoureteric reflux

AbstractBackgroundVesicoureteric reflux (VUR) results in urine passing, in a retrograde manner, up the ureter. Urinary tract infections (UTIs) have been considered the main cause of permanent renal parenchymal damage in children with reflux. Management of these children has been directed at preventing infection by antibiotic prophylaxis and/or surgical correction of reflux. Controversy remains as to the optimum strategies.ObjectivesTo evaluate the benefits and harms of different treatment options for primary VUR.Search strategyRandomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. Date of last search: June 2006Selection criteriaAny treatment of VUR including surgery, antibiotic prophylaxis of any duration, non‐invasive techniques and any combination of therapies.Data collection and analysisTwo authors independently searched the literature, determined study eligibility, assessed quality, extracted and entered data. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model.Main resultsEleven studies (1148 children) were identified. Seven compared correction of VUR (by surgery or endoscope) plus antibiotics for 1‐24 months with antibiotics alone, two compared antibiotics with no treatment and two compared different materials for endoscopic correction of VUR. Risk of UTI by 2, 5 and 10 years was not significantly different between surgical and medical groups (2 years RR 1.07, 95% CI 0.32 to 2.09; 5 years RR 0.99, 95% CI 0.79 to 1.26; 10 years RR 1.06, 95% CI 0.78 to 1.44). Combined treatment resulted in a 50% reduction in febrile UTI by 10 years (RR 0.54, 95% CI 0.55 to 0.92) but no concomitant reduction in risk of new or progressive renal damage by 10 years (RR 1.03, 95% CI 0.53 to 2.00). In two small studies no significant differences in risk for UTI (RR 0.75, 95% CI 0.15 to 3.84) or renal damage (RR 1.70, 95% CI 0.36 to 8.07) were found between antibiotic prophylaxis and no treatment.Authors' conclusionsIt is uncertain whether the treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.Plain language summaryIt is unclear whether the identification and treatment of children with vesicoureteric reflux has any clinically important benefitVesicoureteric reflux (VUR) is the backflow of urine from the bladder up the ureters to the kidney. People with VUR are thought to be more likely to get urinary tract infections (UTIs) involving the kidney tissue, which may cause permanent kidney damage. Current treatment options include surgery, surgery plus long‐term antibiotics, long‐term antibiotics alone and endoscopic (injection of a substance around the entry of the ureter into the bladder) correction using different materials. Surgery decreased the number of feverish UTIs, but did not change the number of children developing any UTI or kidney damage. In small studies, antibiotics did not change the number of children developing UTI compared with no treatment. More studies are needed.

Urinary tract infection caused by Haemophilus influenzae and Haemophilus parainfluenzae in children

There are few reports on urinary tract infections caused by Haemophilus influenzae or Haemophilus parainfluenzae in children. The true incidence is not known, since bacteria of Haemophilus species do not grow in standard urine culture media. With the objective of investigating the occurrence and character of urinary tract infections (UTIs) caused by Haemophilus bacteria in children, we searched the files of our UTI clinic. Over a 24-year period 36 children with Haemophilus spp. bacteriuria were identified out of a total of more than 5,000 UTI episodes. There was a significant gender difference in that Haemophilus influenzae dominated in girls and Haemophilus parainfluenzae in boys. With one exception, all children had important urinary tract abnormalities, such as malformation, gross reflux or bladder dysfunction. Permanent renal damage was seen in 25. We conclude that growth of Haemophilus bacteria in urine is associated with serious urinary tract abnormalities. The inability of bacteria of the Haemophilus species to grow in standard media commonly used for culture of uropathogens suggests that the true frequency of these strains as a cause of urinary tract infections is underestimated.

Urine interleukin‐1β in children with acute pyelonephritis and renal scarring

Acute pyelonephritis is a common infectious disease in children and can result in permanent renal damage. Interleukin (IL)-1beta is an important inflammatory mediator that appears early during bacterial infection. This prospective study examined urine IL-1beta levels in children with acute pyelonephritis documented by (99m)Tc-dimercaptosuccinic acid (DMSA) scan, and also evaluated whether this cytokine correlated with renal scarring. A total of 75 children aged 1-121 months with a diagnosis of first-time febrile urinary tract infection (UTI) were studied. The following inflammatory markers were assessed: fever, white blood cell (WBC), neutrophil, C-reactive protein (CRP) and urine IL-1beta. Urine samples were collected for IL-1beta measurement by enzyme-linked immunosorbent assay before and after antibiotic treatment of the infection. Follow-up DMSA scan was performed at 6-12 months after the acute pyelonephritis to detect renal scarring. Twenty children with other febrile illnesses served as non-renal febrile controls. The 75 children were divided into acute pyelonephritis (n = 41) and lower UTI (n = 34) groups according to the findings of DMSA scans. Fever, WBC count, neutrophil count and CRP were significantly higher in the children with acute pyelonephritis than in those with lower UTI (all P < 0.001). The initial urine IL-1beta levels of children with acute pyelonephritis were significantly higher when compared with lower UTI and non-renal febrile controls (P < 0.001). Urine IL-1beta in children with acute pyelonephritis was positively correlated with fever, CRP, WBC, neutrophil and leucocyturia. Renal scarring was found in 12 (29.3%) of the 41 children with acute pyelonephritis. The mean age was significantly lower in the children with renal scarring compared with those without (P < 0.05). These results have shown that urine IL-1beta level may serve as a useful marker for the early detection of acute pyelonephritis in febrile children. Young children are at a risk of the development of renal scarring following acute pyelonephritis.

Relationship Among Vesicoureteral Reflux, Urinary Tract Infection and Renal Damage in Children

We studied the relationship among vesicoureteral reflux, urinary tract infection and permanent renal damage in children. We retrospectively analyzed 303 children younger than 2 years with a first time, nonobstructive, culture verified urinary tract infection. The protocol included ultrasonography and voiding cystourethrography within 3 months after urinary tract infection, and (99m)technetium dimercapto-succinic acid scintigraphy after 1 to 2 years. Vesicoureteral reflux was found in 36 of 163 boys (22%) and in 44 of 140 girls (31%). Of the 303 patients 80 (26%) had permanent renal damage according to dimercapto-succinic acid scintigraphy. The rate of abnormality increased significantly with grade of vesicoureteral reflux in boys and girls. The relative risk of renal damage was significantly increased in patients with vesicoureteral reflux grade II and higher. Maximum C-reactive protein concentration, maximum temperature during urinary tract infection, presence of vesicoureteral reflux and febrile recurrences of urinary tract infection were significantly related to permanent renal damage. In stepwise logistic regression vesicoureteral reflux was the only independent variable for boys, while C-reactive protein and vesicoureteral reflux were independent factors for girls. There was a significant relationship between grade II vesicoureteral reflux and higher and permanent renal damage in boys and girls. However, while the association between renal damage and vesicoureteral reflux was evident in boys, the role of urinary tract infection and renal inflammation seemed to be equally or more important in girls. These findings support the concept that renal damage is associated with vesicoureteral reflux and is often congenital in boys, while in girls it is more related to urinary tract infection with vesicoureteral reflux as a reinforcing factor.

The nephrologist in the HAART era

The nephrologist in the HAART era

Serum and urine levels of interleukin-6 and interleukin-8 in children with acute pyelonephritis

Urinary tract infection (UTI) is a common clinical disorder in younger infants and children and may result in permanent renal damage. The inflammatory cytokines interleukin (IL)-6 and IL-8 play an important role in response to bacterial infection. This prospective study investigated the association between serum and urine IL-6 and IL-8 levels and acute pyelonephritis confirmed by 99mTc-dimercaptosuccinic acid (DMSA) scan. A total of 78 children aged 1–121 months with a diagnosis of first-time febrile UTI were included. The following inflammatory markers were assessed: fever; white blood cells count (WBC); C-reactive protein (CRP); and serum and urine IL-6 and IL-8. The patients were divided into the acute pyelonephritis group ( n = 42) and the lower UTI group ( n = 36) according to the results of DMSA scan. Fever, WBC and CRP levels were significantly higher in children with acute pyelonephritis than in those with lower UTI (all p < 0.001). Significantly, higher initial serum and urine IL-6 and IL-8 levels were found in children with acute pyelonephritis than in those with lower UTI (all p < 0.001). Serum and urine IL-6 in children with acute pyelonephritis were positively correlated with fever, CRP and leucocyturia. These results indicate that both serum and urine IL-6 and IL-8 levels, particularly IL-6, are useful diagnostic tools for early recognition of acute pyelonephritis in febrile children.

Letters to the Editor

Letters to the Editor

222: Urine Cultures in Emergency Department Patients with Renal Stones

A patient with an obstruction from a kidney stone can develop complications including pyelonephritis, sepsis, or permanent renal damage. The current recommended practice of emergency physicians is to limit antibiotics only to those with a documented infection. We investigated both the frequency and outcomes of urine cultures on renal stone patients.

Antibiotics for acute pyelonephritis in children

AbstractBackgroundUrinary tract infection (UTI) is one of the most common bacterial infection in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent renal damage. Published guidelines recommend treatment of acute pyelonephritis initially with intravenous (IV) therapy followed by oral therapy for seven to 14 days though there is no consensus on the duration of either IV or oral therapy.ObjectivesTo determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children.Search strategyWe searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings without language restriction.Date of most recent search: June 2004.Selection criteriaRandomised and quasi‐randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected.Data collection and analysisTwo reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI).Main resultsEighteen trials (2612 children) were eligible for inclusion. No significant differences were found in persistent renal damage at six months (one trial, 306 infants: RR 1.45, 95% CI 0.69 to 3.03) or in duration of fever (WMD 0.80, 95% CI ‐4.41 to ‐ 6.01) between oral cefixime therapy (14 days) and IV therapy (three days) followed by oral therapy (10 days). Similarly no significant differences in persistent renal damage (three trials, 315 children: RR 0.99, 95% CI 0.72 to 1.37) were found between IV therapy (3‐4 days) followed by oral therapy and IV therapy for 7‐14 days. In addition no significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (one trial, 179 children, persistent symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53).Authors' conclusionsThese results suggest that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2‐4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Trials are required to determine the optimal total duration of therapy and if other oral antibiotics can be used in the initial treatment of acute pyelonephritis.Plain language summaryOral antibiotics may be as effective as the combination of injection and oral antibiotics for kidney infections in childrenAcute pyelonephritis refers to infection of the kidneys and is the most severe form of urinary tract infection (UTI). It causes high fever, vomiting, stomach pain, irritability and poor feeding in infants. Usual treatment is antibiotics given first by injection (IV) and then orally for 7‐14 days to clear the infection and prevent kidney damage. These results suggest that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2‐4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Copyright © 2006 The Cochrane Collaboration. Published by John Wiley &amp; Sons, Ltd.

Role of positional instillation of contrast cystography in the algorithm for evaluating children with confirmed pyelonephritis

Objectives To assess the utility of positional instillation of contrast (PIC) cystography in detecting vesicoureteral reflux (VUR) in patients with renal scarring from recurrent febrile urinary tract infections that standard voiding cystourethrography and nuclear cystogram imaging failed to reveal. Methods Between June 2004 and November 2004, a total of 5 pediatric patients with recurrent febrile urinary tract infections and radiologic evidence of upper tract involvement were examined with PIC cystography. All patients had at least one previous negative standard reflux study (voiding cystourethrography or nuclear cystography). Results All 5 patients showed VUR on PIC cystography. Unilateral reflux was detected in 3 patients, and 2 patients had bilateral VUR. Conclusions The PIC cystogram should be integrated into the algorithm for diagnosing patients with recurrent febrile urinary tract infection, who do not exhibit VUR on standard imaging modalities. The morbidity associated with undiagnosed VUR, as demonstrated by this group of patients, suggests that permanent renal damage may be prevented by early diagnosis and treatment.

May we go on with antibacterial prophylaxis for urinary tract infections?

Recurrent urinary tract infections (UTIs), with or without vesicoureteric reflux (VUR), are by far the most frequent reason for long-term antibacterial prophylaxis in infants and children today. However, the strategies of antibacterial prophylaxis for the prevention of recurrent urinary tract infection are no longer universally accepted. In infants and children at risk, the benefits of antibacterial prophylaxis definitively are not yet proven by evident data. To put antibacterial prophylaxis in its place, risk groups for recurrent symptomatic infections, ascending UTI and permanent renal damage have to be defined and the efficacy of prophylaxis in these groups has to be proved by prospective randomised studies. Nevertheless, until the results of these studies are available, antibacterial prophylaxis will remain one of the most frequently practised methods to protect risk patients from pyelonephritic damage and UTI recurrences.

Laparoscopic partial nephrectomy: Is it advantageous and safe to clamp the renal artery?

Objectives To compare the outcomes of laparoscopic partial nephrectomy (LPN) performed with and without vascular clamping and to evaluate the impact of clamping on postoperative renal function. Methods A total of 45 patients underwent LPN, 29 with and 16 without vascular occlusion. The two groups were compared regarding complication rates, blood loss, conversion rates, operative time, mean tumor size, and incidence of positive margins. Renal function was evaluated by postoperative dimethyl mercaptosuccinic acid scans. Results The mean blood loss was lower when vascular clamping was applied (320 versus 510 mL, P <0.05) than when it was not. The conversion rates were similar (10.3% versus 12.5%), and the mean operative time was shorter in the nonclamped group (115 versus 126 minutes). Urinary leakage occurred in 2 patients, 1 from each group. The mean tumor diameter was 3.2 cm in the clamped and 1.9 cm in the nonclamped group ( P <0.05). In 2 patients (12.5%) in the nonclamped and 1 patient (3.4%) in the clamped group, the surgical margins were focally positive for tumor. The mean warm ischemia time was 28 minutes, and dimercaptosuccinic acid scans performed in 18 patients showed normal ipsilateral renal function (mean relative function 48%). Conclusions LPN without vascular clamping is feasible in selected cases. However, clamping of the artery seems to be associated with reduced blood loss and a lower incidence of positive margins. Moreover, according to the postoperative dimercaptosuccinic acid scan findings, limited warm ischemia does not seem to result in permanent renal damage. We suggest that clamping of the renal artery should be considered during LPN, even for very small, superficial tumors.

Mechanisms of renal damage owing to infection

Urinary tract infection (UTI) is a common bacterial illness in children. It is known to be associated with an increased risk of permanent renal cell damage and scarring which may lead to generation of pathological conditions such as hypertension, pre-eclampsia during pregnancy, renal insufficiency, and end-stage kidney disease. The pathophysiology of renal scarring is still obscure, which makes the prevention of renal damage difficult. During acute infection, there are numerous factors that may contribute to tissue damage. Inflammatory responses are activated by host defense mechanisms as well as by specific bacterial virulence factors. Understanding of these complex mechanisms would be helpful to better identify children at high risk of developing renal scarring following UTI.

Response to Letters to the Editor from Lugassy and Balla Regarding “Safety and Convenience of a 15-Minute Infusion of Zoledronic Acid”

The Oncologist 2005;10:311–312 www.TheOncologist.com I appreciate the interest of Prof. Lugassy [1] and Dr. Balla [2] in the potential complications from intravenously administered bisphosphonate therapy. Regarding the impairment of renal function from intravenously administered bisphosphonates, this has been known since the early reports with clodronate. It is important to recognize that the presence of a rise in creatinine in cancer patients receiving these agents does not necessarily implicate the bisphosphonate since these patients have a myriad of other possible causes for their deterioration in renal function including progression of the cancer itself. In large placebocontrolled as well as pamidronate-controlled trials involving patients with all types of cancers, it is clear that this risk is extremely low as long as zoledronic acid is infused over 15 minutes every 3–4 weeks. In addition, among the patients in these studies (baseline creatinine <3 mg/dl), there was no clear cut higher risk of renal deterioration among patients enrolled with higher baseline serum creatinine levels. Although Dr. Balla suggests that the risk of renal impairment is likely to be higher with the more frequent dosing of zoledronic acid used in cancer patients compared to those patients with osteoporosis not associated with cancer, it is important to recognize that these less intense infrequent dosing schedules have not been shown to be effective in reducing the risk of skeletal complications in the setting of the profound bone loss that occurs in cancer patients with metastatic bone disease. Monitoring of renal function with monthly serum creatinine has become a necessary part of the treatment ritual for these patients, and has been shown to help reduce the risk of any significant permanent renal damage from these agents. There have also been several very recent reports of a potential association of these agents with the development of an otherwise rare complication of the jaw known as osteonecrosis of the jaw (ONJ). These reports involve a series of anecdotal reports documenting jaw abnormalities among cancer patients receiving either zoledronic acid or pamidronate. After the acceptance of our paper, a recent web-based survey was reported in abstract form at the December, 2004 American Society of Hematology meeting, and showed a high incidence of jaw problems among myeloma and breast cancer patients answering the survey who received these drugs [3]. Because of the anonymous nature of the web-based survey which was entered through a site that asked patients with these cancers if they had jaw problems, the patient's cancer diagnosis, exact nature of the jaw problem, or any other responses could not be confirmed. Although the anecdotal reports also are interesting and suggest a possible link, this has not been firmly established by any of the reports published to date. Recently, I have observed ONJ confirmed by an expert oral surgeon regarding this condition in six myeloma patients receiving pamidronate or zoledronic acid. It is also important to be aware that this condition can vary greatly in severity. Many patients including my own improve with better oral hygiene and intermittent antibiotic therapy, and continue long-term intravenous bisphosphonate treatment without significant sequelae from their jaw problem. With the recent recognition that aggressive surgery may worsen this condition, it is hoped that the clinical manifestations of this problem will be greatly reduced for most patients. As a result of this potential complication, an ODAC panel was convened to The Oncologist Letter to the Editor

Ureterocele With Duplicated Collecting System

A ureterocele is a congenital disorder of the terminal ureter. Although ureteroceles may be asymptomatic, there is an associated sequela of hydronephrosis and reflux that can lead to permanent renal damage. This case study involves the sonographic diagnosis of a ureterocele in utero and associated urinary tract abnormalities. These findings are then correlated with postnatal imaging studies.

Albuminuria and tubular markers in juvenile idiopathic arthritis

This study investigates whether renal damage occurs in children with juvenile idiopathic arthritis (JIA) either secondary to the disease per se or due to the side effects of non-steroidal anti-inflammatory drugs (NSAIDs) and slow-acting anti-rheumatic drugs (SAARDs) used in treatment. In this cross-sectional study, albuminuria, N -acetyl glucosaminidase (NAG), beta(2)-microglobulin (beta(2)M), and creatinine (Cr) levels were measured in urine samples of 45 patients (23 female, 22 male, 9.4+/-3.9 years) with JIA and a sex- and age-matched control group of 33 healthy children. The urinary albumin/Cr, NAG/Cr, and beta(2)M/Cr ratios of children with JIA and of the control group did not differ statistically. No difference was noted between patient groups with different types of JIA (12 systemic, 18 polyarticular, and 15 oligoarticular JIA). JIA patients with active disease (n=16) had higher NAG/Cr values than patients with inactive disease (P=0.002). NAG/Cr levels correlated with erythrocyte sedimentation rate (r=0.66, P<0.001) and platelet count (r=0.61, P<0.001) and showed a slight correlation with the number of joints with active arthritis in children with polyarticular JIA (r=0.45, P=0.055). Neither beta(2)M/Cr nor albumin/Cr ratios were associated with disease activity. No difference was noted between patient groups treated with different NSAIDs and SAARDs. In children with JIA tubular enzymuria increases during the active phase of the disease; however, it seems that permanent renal damage does not occur.

Interventions for primary vesicoureteric reflux.

Vesicoureteric reflux (VUR) results in urine passing, in a retrograde manner, up the ureter. Urinary tract infections (UTIs) have been considered to be the main cause of permanent renal parenchymal damage in children with reflux. Therefore management of these children has been directed at preventing infection by antibiotic prophylaxis and/or surgical correction of reflux. However controversy remains as to the optimum strategies for management of children with primary VUR. To evaluate the benefits and harms of the different treatment options for primary VUR. Published and unpublished randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. RCTs were included if they compared any treatments of VUR including surgery (open and closed techniques), antibiotic prophylaxis of any duration, non-invasive techniques such as bladder training and any combination of therapies. Two reviewers independently searched the literature, determined trial eligibility, assessed quality, extracted and entered data. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. Ten trials involving 964 evaluable children comparing long-term antibiotics and surgical correction of VUR with antibiotics (seven trials), antibiotics with no treatment (one trial) and different materials for endoscopic correction of VUR (two trials) were identified. Risk of UTI by 1-2 and 5 years was not significantly different between surgical and medical groups (by 2 years RR 1.07, 95% CI 0.55 to 2.09; by 5 years RR 0.99; 95% CI 0.79 to 1.26). Combined treatment resulted in a 60% reduction in febrile UTI by 5 years (RR 0.43, 95% CI 0.27 to 0.70) but no concomitant significant reduction in risk of new or progressive renal damage at 5 years (RR 1.05, 95% CI 0.85 to 1.29). In one small study no significant differences in risk for UTI or renal damage were found between antibiotic prophylaxis and no treatment. It is uncertain whether the identification and treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.