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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2012  |  Volume : 23  |  Issue : 3  |  Page : 532-537
Predisposing factors for renal scarring in children with urinary tract infection


1 Nephrology and Urology Research Center, Baqiyatallah Medical Sciences University, Tehran, Islamic Republic of Iran
2 Chemical Injury Research Center, Baqiyatallah Medical Sciences University, Tehran, Islamic Republic of Iran
3 Department of Pediatrics, Baqiyatallah Medical Sciences University, Tehran, Islamic Republic of Iran

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Date of Web Publication7-May-2012
 

   Abstract 

This study was undertaken to determine the predisposing factors for renal scarring in children with urinary tract infection. In this prospective cohort study, 176 children with documented urinary tract infection were categorized into four groups: ≤1 year old, 1-2 years old, 2-7 years and 7-14 years old. Ultrasonography and Technetium-99 m-DMSA scan were used to detect the possible abnormalities. Infants under 12 months old presented as the most common group for renal scarring (27 cases, 52.9%), and vesicoureteral reflux (VUR) was diagnosed in 29 cases (56.8%). Fifteen (41.67%) children between the ages of one and two years had renal scar, and VUR was detected in half of the patients. In the third group, 36.3%, and in fourth group, 41.6% of the patients had renal scar. Also, 38.6% in group three and 50% in the final group had VUR. A co-incidental finding that was observed in this study was the high incidence of pseudohypoaldesteronism (PHA) in our patients: in 39.2% of the children in group one, 22.2% in group two and 4% in group three. In group four however, none of the patients had PHA. Risk of scar formation with urinary tract infection (UTI) was higher in the younger age group and in those with recurrent UTIs.

How to cite this article:
Beiraghdar F, Panahi Y, Einollahi B, Moharamzad Y, Nemati E, Amirsalari S. Predisposing factors for renal scarring in children with urinary tract infection. Saudi J Kidney Dis Transpl 2012;23:532-7

How to cite this URL:
Beiraghdar F, Panahi Y, Einollahi B, Moharamzad Y, Nemati E, Amirsalari S. Predisposing factors for renal scarring in children with urinary tract infection. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2019 Jul 23];23:532-7. Available from: http://www.sjkdt.org/text.asp?2012/23/3/532/95793

   Introduction Top


Urinary tract infection (UTI) is one of the most common infections in children, which can cause fever of unknown origin (FUO). In 5% of the children with a primary diagnosis of fever, UTI leads to pyelonephritis, renal scar­ring, hypertension and end-stage renal dysfunction. [1]

At the beginning of the 20 th century, the mor­tality rate of UTI in children was approxi­mately 20%. Nowadays, with the introduction of new antibiotics, modern diagnostic and good treatment, the mortality rate of children with UTI has decreased significantly. [2] However, unfavorable sequelae of pyelonephritis, such as recurrent UTI, hypertension, renal scarring, progressive renal deterioration to uremia and renal transplantation, still remain. [2],[3] Unfortu­nately, renal scarring following pyelonephritis is more common in children than in adults. [4] Early diagnosis, appropriate treatment along with recognition of risk factors of renal scar­ring and close and continuous follow-up of patients with UTI are the most important fac­tors in the prevention of severe complications. [2],[3]

At present, the best method for detection of renal scarring is the Technetium-99-DMSA (Dimercaptosuccinic acid) scan, which can detect scar in the renal cortex as focal or global areas of diminished uptake. [5],[6] This study was carried out to evaluate the predisposing factors for renal parenchymal scarring in children and to determine scar extension in the kidney by DMSA scan.


   Methods and Materials Top


This prospective cohort study was performed in the Pediatric Nephrology Unit of our hos­pital. All the children aged 14 years or less who were referred to our department following their first UTI or significant bacteriuria (pure bacteria colony count of ≥105/mL likely uropathogens) during 2004-2007 were entered into the study. Patients were categorized into four age groups:

  1. First group consisted of 51 patients under the age of one year (N = 51). UTI was confirmed based on the results of supra-pubic urine specimen cultures. Any bacte­rial growth was considered diagnostic. [7]
  2. Second group had 36 cases who were aged 1 to 2 years (N = 36). Urine culture was done on urine samples that were collected by sterile urine bags after disinfecting the perineum. In this group, urine culture showing ≥10 5 pure colony-forming units (cfu)/mL in two separate samples, both in girls and in boys, was considered diagnos­tic of UTI. [8]
  3. Third group included children who were aged 2 to 7 years (N = 77).
  4. Fourth group consisted of children in the age group of 7 to14 years (N = 12). In the latter two groups, Urine culture was done on mid-stream urine specimens.
All patients were checked for hypertension by appropriate cuff for their age and weight. The blood pressure recorded at more than 95 th percentile for age-gender and height measured on at least three separate occasions was consi­dered hypertension. [9]

Other laboratory data gathered included full blood count, erythrocyte sedimentation rate, blood urea nitrogen, creatinine, sodium, potas­sium, blood sugar, calcium, phosphorous and alkaline phosphatase. Hyponatremia was defined as serum sodium concentration <130 mmol/L, hyperkalemia as potassium concentration >5.5 mmol/L, hypoglycemia as serum glucose <50 mg/dL and leukocytosis was considered if the white blood cell count was more than 15,000/ μL. Clinical pseudohypoaldesteronism (PHA) was detected by hyponatremia and hyperkalemia, with or without hypoglycemia. [10] Because PHA was not our target, we did not perform specific tests for documenting this disease, but documented only evidence for clinical PHA.

One skilled pediatric radiologist performed urinary tract ultrasound in all patients for the evidence of urinary tract anomaly, such as upper urinary tract dilatation and renal scarring as well as determination of residual urine volume.

All patients had DMSA scan performed on them, for acute lesions in the first two weeks itself and, later, for chronic lesions. [11] Scars in the kidney were classified into four classes [Table 1]. [12] Antibiotic treatment was started empirically for all children with documented UTI as soon as possible based on epidemio­logy data of our center and then, if required, changed to appropriate antibiotics according to the results of the sensitivity tests. The most common organism found was E. coli. Because vesicoureteral reflux (VUR) is a significant risk factor for acute pyelonephritis and renal scarring, [13] we performed a voiding cystourethrography (VCUG) two weeks post-treatment or four weeks after acute infection to detect VUR for all patients with febrile UTI and acute pyelonephritis. [14] VUR was graded into five classes: Grade I; only fills the ureter but no dilation. Grade II; fills ureter, pelvis and calyces but without dilation and normal appearing calyces. Grade III; mild or moderate dila­tion of the ureter and pelvis, but no or only slight blunting of the fornices. Grade IV; moderate dilation or tortuosity of ureter with mild dilation of renal pelvis and calyces, with blunting calyces. Grade V; gross dilation and tortuosity of ureter, gross dilation of renal pelvis and calyces, papillary impressions are no longer visible in most calyces. [15]
Table 1: Grading of renal scar according to DMSA scan

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   Statistical Analysis Top


Data were analyzed using the SPSS, version 16.0. Variables were expressed as frequency and percentage. For relationships between age groups about VUR and renal scar, we used the Chi-square test. Correlation between age groups with regard to hyponatremia, hyperkalemia, sex and anomaly of kidney were also done by the Chi-square test. The relation between hypoglycemia and hypertension between all groups were tested by the Fisher exact test. A P-value of less than 0.05 was considered as statistically significant.


   Results Top


A total of 176 patients, 136 girls (77.2%) and 40 boys (22.7%) were entered into our study. The most common presentation of UTI in all groups was fever. Other symptoms were irri­tability, abdominal and flank pain, failure to thrive and urinary tract symptoms, such as uri­nary frequency, urgency and dysuria. UTI without high fever occurred predominantly du­ring the first few months of life.

Fifty-one infants (24 girls and 27 boys) were categorized into the first group (≤1 year). Renal scarring was observed in DMSA scan (types 1-3) in 27 patients (52.9%) [Table 2]. Twenty patients had hyponatremia and hyperkalemia (39.2%), and hypoglycemia was also detected in ten patients (19.6%). Overall, 29 patients (56.8%) had VUR (grades I-V) [Table 2]. Ultrasound findings consistent with kidney anomalies (like fullness and hydronephrosis) were detected in 15 patients (29.4%).
Table 2: Vesicoureteral reflux (VUR), renal scar, hyponatremia and hyperkalemia, hypoglycemia, anomaly of kidney, hypertension and sex among 166 children with urinary tract infection.

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Thirty-six patients (29 girls and seven boys) were in the second group (1-2 years). Fifteen patients (41.6%) had renal scarring (types 1- 3) [Table 2]. Hyponatremia and hyperkalemia were seen in eight infants (22.2%), but hypoglycemia was not detected. Eighteen patients had VUR (grades I-V), exactly 50% of the group [Table 2]. According to the ultrasound reports, 11 patients (30.5%) had anomaly in their kidneys.

In the third group (2-7 years old), there were 77 patients (72 girls and five boys). Types 1-4 of renal scaring were detected in 28 cases (36.3%) [Table 2]. Hyponatremia and hyperkalemia were found in 4%, but no cases of hypoglycemia were detected. Thirty patients from this group had VUR (38.9%), grades I- V. Thirty-one percent had urinary tract ano­malies in their sonography.

The final group (7-14 years) consisted of 12 patients (11 girls and one boy). Five patients (41.6%) had renal scarring (types 1-3) [Table 2]. No electrolyte imbalance was reported in this group. Six cases (50%) had VUR (grades I-IV, [Table 2]. Renal ultrasonography detec­ted anomalies in five cases (41.6%).

For documenting whether any permanent scar had developed, a DMSA scan was repeated after four to six months following UTI, and 85% of the patients who had initial renal scar­ring were found to have permanent scar. In our patients, a transient rise in blood urea nitrogen and serum creatinine was seen in groups I-IV (2%, 3.5%, 4% and 4.5%, respectively). A total of eight patients had hypertension. One patient was in the first group, two infants were in the second set, four children were in the third group and one patient in the final group.


   Discussion Top


In the current study, UTI was more common in girls in all groups, except in group I (P = 0.0001). Two former studies have pointed out to this gender distribution of UTI in various age groups, as boys were more commonly affected than girls only during the first months of life; however, after six months of age, girls formed the majority of patients. [16],[17]

Weinberg et al [18] showed that about 30% of girls with a first-time UTI were found to have repeated infections. In our study, 25% of the girls and 10% of the boys had recurrent UTI during the first year of life. After one year of age, boys had few recurrences, and repeated infections were uncommon.

It has been shown that both sensitivity and specificity of the DMSA scan (92% and 98%) are higher than that of intravenous pyelogram (80% and 92%) in the detection of renal scar. [5] This method is a valid diagnostic tool for documentation of acute pyelonephritis and presence of renal scarring. [5] In our experience, 52.9% of the patients with febrile UTI in the first group, 41.6% in the second set, 36.3% in the third group and 41.6% of the patients in the latest class have abnormal DMSA renal scan. Renal scar is related to age, and more scars are seen in those with early onset in life, as seen in our study. [2]

In groups I and II, electrolyte abnormalities, in particular hyponatremia, hyperkalemia and hypoglycemia, were seen most commonly than in other groups. These complications were ob­served most commonly in group I when com­pared with the other groups (P <0.0001). Fortunately, these changes were reversible.

It appears likely that abnormal function of adrenals, presenting as PHA, occurs in acute pylonephritis, with renal scar in the early-stage of life. [10] This was observed in our study as well.

The presence of hypertension in patients with renal scarring varies, based on the duration of follow-up and severity of the scarring. [19] Martin et al, [20] reported that approximately 6-13% of the children with renal scarring develop hyper­tension. The current results showed that the overall risk of hypertension was 4.5%. How­ever, in group IV, 8.3% of the patients de­veloped hypertension.

Clinical and experimental investigations using DMSA renal scintigraphy have provided new insights into the etiology, pathophysiology and clinical outcome of acute pyelonephritis in children. [21] VUR was seen most commonly in the first group in our study, and grading of VUR increases with increasing age (P = 0.02). Merguerian et al, [22] showed that 32.2% of the children younger than one year, 33.2% bet­ween one and five years and 62.5% older than six years with high-grade reflux had diffused scarring.

Our study suggests that risk of urinary tract infection and its recurrence are more common in girls. Renal scar and PHA are seen most commonly among children in the early stages of life.

In addition, UTI usually occurs without symp­toms in infants, and this means that below one year, diagnosis of UTI is hard to make in the first few months of life. Therefore, we must carefully observe the children and, if there is any doubt of UTI, urinanalysis and urine cul­ture needs to be done.

 
   References Top

1.P Panahi Y, Beiraghdar F, Moharamzad Y, Matinzadeh ZK, Einollahi B. The incidence of urinary tract infections in febrile children during a two-year period in Tehran, Iran. Trop Doct 2008;38247-9.  Back to cited text no. 1
    
2.Yadlu HS. Urinary tract in infection; In: Avnet ED, Harmon WE, Niaudet P (eds). Pediatric nephrology. 5th ed, Philadelphia: Lippincott Williams's and wilkins; 2004. pp 1007-27.  Back to cited text no. 2
    
3.Jose SS, Sharif ES. New NICE guidelines for UTI management: what will change? Arch Dis Child 2008;93:716-7.  Back to cited text no. 3
    
4.Newman TB, Bernzweig JA, Takayama JI, Finch SA, Wasserman RC, Pantell RH. Urine testing and urinary tract infections in febrile infants seen in office settings: the Pediatric Research in Office Settings' Febrile Infant Study. Arch Pediatr Adolesc Med 2002;156: 44-54.  Back to cited text no. 4
    
5.Ruhton HG, Majd M. Dimercaptosuccinic acid renal scintigraphy for the evaluation of pyelo­nephritis and scarring: a review of experimental and clinical studies. J Urol 1992;148:1726-32.  Back to cited text no. 5
    
6.Szlyk GR, Williams SB, Majd M, Belman AB, Rushton HG. Incidence of new renal parenchymal inflammatory changes following break­through urinary tract infection in patients with vesicoureteral reflux treated with anti-biotic prophylaxis: evaluation by 99MTechnetium dimercapto-succinic acid renal scan. J Urol 2003;170:1566-8.  Back to cited text no. 6
    
7.Jadal U. Suprapubic aspiration of urine in the diagnosis of urinary tract infection. Acta Pediatric 2002;91:497-8.  Back to cited text no. 7
    
8.Hoberman A, Wald R, Reynolds EA, Penchansky L, Charron M. Pyuria and bacteriuria in urine specimens obtained by catheter from young children with fever. J Pediatric 1994;128:513-9.  Back to cited text no. 8
    
9.Medscape [Internet]. Brookes L. More guide­lines, CCBs, ACE, and ARBs, and Novel pre­dictors: Latest US government guidelines for hypertension in children [cited 2012 April 11]. Available from: http://www.medscape.com/ viewarticle/4884232.  Back to cited text no. 9
    
10.Joubert G, Lim R. Pseudohypoaldosteronism secondary to urinary tract infection. Paediatr Child Health 2008;13:387-90.  Back to cited text no. 10
    
11.Rushton HG. The evaluation of acute pyelo­nephritis and renal scarring with 99Tc-dimercaptosuccinic acid renal scintigraphy, evolving concepts and future directions. Pediatr Nephrol 1997;11;108-20.  Back to cited text no. 11
    
12.Goldraich NP, Rames OL, Goldraich IH. Urography versus-DMSA scan in children with vesicoureteral reflux. pediatr Nephrol 1989;3:1.  Back to cited text no. 12
    
13.Cascio S, Chertin B, Colhoun E, Puri P. Renal parenchymal damage in male infants with high grade vesicoureteral reflux diagnosed after the first urinary tract infection. J Urol 2002;168: 1708-10.  Back to cited text no. 13
    
14.Gross GW, Lebowitz RK. Infection does not cause reflux. AJR Am J Roentogenol 1987; 148;483.  Back to cited text no. 14
    
15.International classification of vesicoureteral reflux modified from international Reflux committee.medical versus surgical treatment of primary vesicoureteral reflux. Pediatrics 1981; 67;392.  Back to cited text no. 15
    
16.Hansson S, Bollgren I, Esbjorner E, Jakobsson B, Mårild S. Urinary tract infections in chil­dren below two years of age: a quality assu­rance project in Sweden. The Swedish Pediatric Nephrology Association. Acta Paediatr 1999;88:270-4.  Back to cited text no. 16
    
17.Jacobson B, Esbjorner E, Hansson S. Mini­mum incidence and diagnostic rate of first urinary tract infection. Pediatrics 1999;104: 222-6.  Back to cited text no. 17
    
18.Winberg J, Andersen HJ, Bergstrom T, Jacobsson B, Larson H, Lincoln K. Epidemiology of symptomatic urinary tract infection in child­hood. Acta Paediatr Scand Suppl 1974; 252:1-20.  Back to cited text no. 18
    
19.Goonasekera CD, Shah V, Wade AM, Barratt TM, Dillon MJ. 15-year follow-up of renin and blood pressure in reflux nephropathy. Lancet 1996;347:640-3.  Back to cited text no. 19
    
20.Martinell Y, Lidin-Janson G, Jagenburg R, Sivertsson R, Claesson I, Jodal U. Girls prone to urinary infections followed into adulthood. Indices of renal disease. Pediatr Nephrol 1996; 90:139-42.  Back to cited text no. 20
    
21.Rushton HG. The evaluation of acute pyelo­nephritis and renal scarring with technetium 99m-dimercaptosuccinic acid renal scintigraphy: evolving concepts and future directions. Pediatr Nephrol 1997;11:108-20.  Back to cited text no. 21
    
22.Merguerian DA, Jamal MA, Agarwal SK, et al. Utility of SPECT DMSA renal scanning in the evaluation of children with primary vesicoureteral reflux. Urology 1999;53:1024-8.  Back to cited text no. 22
    

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Correspondence Address:
Yunes Panahi
Chemical Injury Research Center, Baqiyatallah Medical Sciences University, Vanak, Sq., Molla-Sadra Ave., Tehran
Islamic Republic of Iran
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