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ORIGINAL ARTICLE
Ahead of print publication  

A snapshot of children with congenital anomalies of the kidneys and urinary tract at three tertiary care centers of the armed forces


1 Senior Resident Pediatrics, Apollo Cradle Hospital, New Delhi, India
2 Cl Spl Pediatrics and Pediatric Nephrology, Associate Professor Pediatrics, Command Hospital (Central Command), Lucknow, India
3 Intern Medical Officer, Air Force Hospital, Bengaluru, Karnataka, India
4 Resident Pediatrics, Command Hospital (Central Command), Lucknow, India
5 Cl Spl Pediatrics and Pediatric Nephrology, Associate Professor Pediatrics, Army Hospital (R&R), New Delhi, India

Date of Submission10-Jun-2020
Date of Decision10-Jul-2020
Date of Acceptance12-Aug-2020
Date of Web Publication09-Oct-2020

Correspondence Address:
Suprita Kalra,
Army Hospital (R&R), Delhi - 110 010
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmms.jmms_74_20

  Abstract 


Introduction: Congenital anomalies of Kidney and Urinary Tract (CAKUT) are the most common reason for Chronic Kidney Disease in children. The spectrum of CAKUT includes a wide range of anomalies from mild unilateral hydronephrosis to bilateral hypoplastic /dysplastic kidneys. We designed this study with an aim to determine the clinical profile of children with CAKUT, any associated anomalies and the factors associated with poor outcomes. Methods: We reviewed the records of all children aged 0-14 years presenting with CAKUT at the pediatric nephrology OPD at three tertiary care centers of the Armed Forces. Antenatal findings, clinical features at presentation, course after birth, need and timing for surgery, serum creatinine, presence of acidosis, mineral bone disease and anemia and growth parameters were recorded. All patients were evaluated and managed as per standard guidelines. Results: 154 children were seen during the study. Unilateral Hydronephrosis with mild to moderate PUJO was the commonest lesion, (n=35). Conclusions: Children with CAKUT have variable clinical presentations and outcomes depending on the severity of the underlying anomalies. Timely detection, evaluation and long term follow up is therefore essential for improving long term outcomes.

Keywords: Chronic kidney disease, congenital anomalies of the kidneys and urinary tract, end-stage renal disease



How to cite this URL:
Biswas A, Bose T, Mandal RR, Kapoor T, Kalra S. A snapshot of children with congenital anomalies of the kidneys and urinary tract at three tertiary care centers of the armed forces. J Mar Med Soc [Epub ahead of print] [cited 2020 Nov 28]. Available from: https://www.marinemedicalsociety.in/preprintarticle.asp?id=297614




  Introduction Top


Congenital anomalies of the kidneys and urinary tract (CAKUT) are one of the most common congenital malformations detected on antenatal screening and after birth. They include a huge gamut of structural and functional malformations that may be seen at the level of the kidney (e.g., hypoplasia and dysplasia), the collecting system (e.g., hydronephrosis and megaureter), bladder (e.g., ureterocele and vesicoureteral reflux), or urethra (e.g., posterior urethral valves [PUV]).

The incidence of CAKUT is about 1 in 500 live born fetuses and cause neonatal death in 1 in 2000 births.[1],[2],[3] CAKUT is the leading cause of progressive chronic kidney disease (CKD) in children and young adults (47%–62%) and constitute the most frequent cause of end-stage renal disease (ESRD) and requirement of renal replacement therapy (RRT) in childhood.[4],[5] While most CAKUT cases are sporadic, familial clustering is common with renal abnormalities seen in close relatives of almost 10% of all CAKUT patients, suggesting strongly an underlying genetic basis.[1],[2],[3],[4],[5],[6]

With improved prenatal screening, most cases of CAKUT are detected during the antenatal ultrasounds though this is not uniform in developing countries and may depend on factors such as access to health care and socioeconomic status.[7],[8],[9]

While most cases are initially asymptomatic, effects of CKD such as growth retardation, anemia, mineral bone disease, hypertension, and proteinuria are seen in the long run. Reduced nephron mass can predispose to hypertension and accelerated heart disease, resulting in cardiovascular morbidity in later life.[10],[11],[12] Early identification of these congenital anomalies and their optimal management and close follow-up is essential, in order to prevent further renal damage.

There is dearth of data on CAKUT in Indian children[8],[9] and none available for children of armed forces personnel. We therefore, designed this cross-sectional study across three tertiary care hospitals of the armed forces medical services (AFMS) with an aim to present a snapshot of the clinical and radiological profile and the associated anomalies in children with CAKUT presenting to the pediatric nephrology outpatient department (OPD) during the study.


  Materials and Methods Top


All consecutive children, <14 years (as 14 years is the upper age limit for registration in pediatric OPD and for admission to pediatric ward), with any one or more CAKUT with or without associated anomalies in other systems were enrolled in this cross-sectional observational study. The study was conducted from January 2019 to June 2019 after written obtaining clearance from the institutional ethical committee and informed consent was taken from the parents/caregivers of all children included in the study.

The exclusion criterion was death at <48 h of life or discharge at <48 h of life with no follow-up visit thereafter.

The sample size was not calculated and all consecutive children presenting with CAKUT meeting the criterion during the study were enrolled to determine the burden of the same among our dependent population.

The study was conducted at three tertiary care AFMS Hospitals at Pune, Lucknow, and Kolkata with well-established pediatric nephrology OPD s and facilities for in-patient care and RRT. The centers have been referred here after as center A, B, and C, respectively.

Antenatal findings, if available, clinical features, associated anomalies, serum creatinine measured by modified Jaffe's reaction, and estimated glomerular filtration rate (eGFR) as per modified Schwartz formula were recorded.[13] Weight was recorded by an electronic weighing scale accurate to 0.05 g and height was measured using a portable stadiometer and recorded in all enrolled children. Percentage of children having weight or height or both < 3SD as per WHO charts in children 0-60 months[14] and Indian Academy of Pediatrics charts in older children[15] was noted. We also calculated and compared, the proportion of these children among those having CKD I–III and those with CKD IV–V. Blood pressure was checked in all children using the auscultatory method using nonmercury sphygmomanometers and the proportion of children having hypertension for age and gender was compared between those having CKD I–III and those with CKD IV–V.

All patients were evaluated and managed as per standard guidelines.[16],[17] Ultrasound of the kidneys, ureters, and bladder (USG KUB) was done as the first investigation in all children suspected to have CAKUT based on their antenatal investigations and clinical symptoms or examination findings. Diuretic renogram was done for children with hydronephrosis with no ureteric dilatation to confirm pelvi-ureteric junction obstruction (PUJO) and differential function of kidneys recorded. Children with PUJO with differential function of the affected kidney <40% or obstructive pattern on diuretic renography with T1/2 >20 min or decline in differential function by >10% on follow-up were taken up for pyeloplasty.[18],[19] Voiding cystourethrogram (VCUG) was done for all children with hydroureteronephrosis (HDUN) on USG KUB or history of culture positive urinary tract infection (UTI) in children <1 year of age and in older children with history of culture positive UTI with scarring on dimercaptosuccinic acid (DMSA) scan. VCUG was done within 48 h of life in male neonates antenatally detected to have bilateral HDUN with oligohydramnios with poor stream of urine or inability to pass urine after birth to rule out bladder outlet obstruction (BOO) due to PUVs.

DMSA scan was done for all children with culture positive UTI <5 years of age and in older children with abnormal USG. It was also done for all children with high grade reflux and in children with renal agenesis, crossed fused ectopia, Horse Shoe Kidney, and MCDK to rule out renal scarring as per standard guidelines.[15],[16],[20] Vesicoureteric reflux (VUR) was graded as I–V as per International Reflux Scale.[21] Prophylactic antibiotics were started with cotrimoxazole in all children with antenatally detected unilateral or bilateral HDUN with high grade reflux till definitive surgical interventions were done or up to 5 years of age whichever was earlier. Infants were continued on prophylactic antibiotics till 1 year of age even if they had low grade reflux. Infants <3 months or those with allergy to cotrimoxazole, were given cephalexin prophylaxis as per standard guidelines.[16] Ureteric reimplantation for VUR was done only in children with high grade reflux with recurrent febrile UTI or in those who had a single functioning kidney with high grade reflux.

[Figure 1] summarizes the schemata for evaluation and management followed in our institution for children reporting with CAKUT. MedCalc was used for statistical analysis.
Figure 1: Summary of schemata for evaluation and management in children congenital anomalies of the kidneys and urinary tract

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  Results Top


Sixty-two children of CAKUT in center A, 50 in center B, and 42 in center C (total of 154) were seen during the study period with lesions ranging from unilateral hydronephrosis to PUVs with severe oligohydramnios were studied. The average monthly pediatric OPD at these three centers during this period was 1884 per month and children with CAKUT formed 3.02% of the total pediatric OPD. Their baseline characteristics along with the particular CAKUT seen are summarized in [Table 1]. The mean age of the patients at enrolment was 26 completed months ± 8.6 months with a range of 0 days–132 months. Eighty-six (55.84%) were male. Ninety children presented within 1st year of life. Eighty-seven (56.49%) were detected on antenatal USG, however, only 59 (38.31%) were detected before 20 weeks.
Table 1: Baseline characteristics of children diagnosed with congenital anomalies of the kidneys and urinary tract

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Unilateral hydronephrosis was the most common lesion (n = 60, 38.96%). Forty-six of these children had no or only partial obstruction on diuretic renogram with differential function of the affected kidney >40% and were advised follow-up.

VUR was seen in 33 (21.2%) children on VCUG. Of these 21 had high grade reflux (Grade III–V) and the reflux was bilateral in 18. DMSA scan revealed scars in 22 children and the scarring was bilateral in 13 children.

Twenty-five male neonates were diagnosed to have PUV. Of these, 14 were detected antenatally to have bilateral HDUN with oligohydramnios. The remaining 11 children were diagnosed at 5 months–53 months when evaluated for UTI and/or poor urinary stream. USG and DMSA scan 3 months' postfulgration of PUV revealed that 10 children had one-sided (6 right side and 4 left side) small shrunken kidney which had a split function <15% and 13 children had bilateral and 9 had unilateral photenic areas suggestive of scars.

Our study also included 7 children with crossed fused ectopia, 5 with Horse Shoe Kidney, 3 with Ureterocele, 5 with MCDK, 6 with single kidney, and 2 with duplex system with reflux.

Fourteen (9.09%) children had associated anomalies in other systems which included patent ductus arteriosus in one child, one each with ventricular septal defect and atrial septal defect, anorectal malformation (ARM) in four children, facial dysmorphism in three children, one child had Prune belly syndrome, one child with down syndrome with atrioventricular canal defect, and two with vertebral, anal, cardiac, tracheoesophagus, renal, and limbs anomalies. Five (3.24%) children had another sibling also affected by CAKUT.

One hundred and forty-four children had CKD I–III and 10 (6.49%) children had CKD IV–V as per eGFR calculated according to the modified Schwartz formula. Among the children with CKD IV–V, 6 had PUV with BOO and 1 child had horseshoe shaped kidney with single functioning kidney with Grade IV VUR with scarring on DMSA, the remaining 3 children had bilateral high grade VUR.

Forty-eight children had weight <3 SD with 41 of them also having short stature defined by height <3 SD. This included all the 10 children with CKD IV–V. The difference between proportion of children having weight <3 SD and height <3 SD among those with CKD Stage I–III and CKD IV–V was highly significant (P < 0.0001). The children with CKD I–III with weight and height <3 SD included 17 with PUV and 14 with bilateral high grade VUR.

Eighteen children had hypertension. Of these 12 were in CKD Stage I–III and 6 in Stage IV–V. The difference between proportion of children having hypertension among those with CKD Stage I–III and CKD IV–V was highly significant (P < 0.0001). The underlying diagnosis in these children was PUV in 7 children and VUR in 11 children including 7 with bilateral high grade reflux and 4 with single kidney with high grade reflux.

[Table 2] gives a summary of children with CAKUT in various stages of CKD with failure to thrive, short stature and hypertension. Significantly higher percentage of children with CKD IV-V were found to have failure to thrive, short stature and hypertension.
Table 2: Stages of chronic kidney disease in children with congenital anomalies of the kidneys and urinary tract children with weight or height or both <3 standard deviation and stages of chronic kidney disease and associated complications

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  Discussion Top


CAKUT occur in 3%–6% of all live births and account for at least 30% of ESRD in Indian children.[8],[9] There are very few studies in India discussing the prevalence, spectrum, presentation, and outcome of children with CAKUT and none in the children dependent on AFMS hospitals.

The aim of our study therefore was to present a snapshot of the clinical and radiological profile of children with CAKUT presenting to the pediatric nephrology OPD in three tertiary care AFMS hospitals.

Antenatal USG imaging is able to detect anomalies of the kidney and urinary tract as early as 11–12 weeks. The presence of CAKUT warns the obstetrician or the fetomaternal specialist of possible syndromic affliction in the fetus or serious renal conditions such as obstructive uropathy or bilateral hypoplasia which have poor renal outcome.[22] In our study, 90 children presented within 1st year of life. Eighty-seven (56.79%) were detected on antenatal USG, however, only 59 were detected before 20 weeks. The relatively low percentage of the detection of CAKUT in second trimester in our study may be due to delay in initiating the routine antenatal care despite it being easily available to the dependent clientele of armed forces due to various factors including families continuing to stay in villages and remote areas during posting of the soldiers in field stations.

Unilateral hydronephrosis was the most commonly seen lesion in all the three centers accounting for 60 (38.96%) cases. Majority of them had no or only partial obstruction at the pelviureteric junction as seen on diuretic renography and were advised follow-up as per standard guidelines. This has been reported in previous studies also.[23],[24]

Thirty-three children had VUR with 21 having high grade reflux (Grade IV or V) and 18 children had bilateral reflux. VCUG is the only test that provides reliable grading of VUR and is recommended for its diagnosis and grading. Recent guidelines recommend that decision to manage these children medically with antibiotic prophylaxis and follow-up or early surgery should be based on grade of VUR along with their clinical course.[15],[16] Studies have shown that the grade of VUR is strongly associated with clinical outcomes including its spontaneous resolution, UTIs, renal scarring, hypertension, proteinuria, and progression of CKD and is a well-recognized cause of hypertension, proteinuria, and ESRD in children and young adults.[25],[26],[27] In our study also, we found that children with bilateral high grade reflux or those with single kidney with high grade reflux formed a considerable proportion of children with CKD IV–V (4/10, 40%), short stature and failure to thrive (18/41, 43.9%), and hypertension (11/18, 61.11%).

Our study included 25 male neonates with BOO due to PUV on VCUG. While 14 were detected on antenatal USG, 11 were detected later between 5 months and 53 months, when they presented with features of poor urinary stream and recurrent UTI. Neglected PUV in male neonates is unfortunately still common and is known to cause rapid deterioration of renal functions and poor renal outcomes despite surgical correction. Nadir serum creatinine has been defined as an important predictor of functional outcome in these children.[28] In our study also, we found that 6 children had CKD IV–V (6/25, 24%) despite relieving the anatomical obstruction by cystoscopic fulguration of valves. Furthermore, 10 children had one-sided (6 right side and 4 left side) small shrunken kidney which had a split function <15% and 13 children had bilateral and 9 had unilateral scars on follow-up USG and DMSA scan. A large proportion of these children had weight and height <3 SD (21/41, 51.21%) and hypertension (7/18, 38.88%).

Almost a third of the children with CKD included in our study had growth retardation with significant (P < 0.0001) difference between proportion of children having weight <3 SD and height <3 SD among those with CAKUT with CKD Stage I–III and CKD IV–V. This has been reported in earlier studies also.[27],[29]

Hypertension is a common complication in children with CKD and strict blood pressure control has been shown to retard the progression of CKD.[30] Our study, similar to previous studies,[27],[30] showed that there was a significant difference between proportion of children having hypertension among those with CAKUT with CKD Stage I–III and CKD IV–V.

Our study therefore brings forth the clinical complications in children with CAKUT including poor renal outcomes defined by low eGFR, failure to thrive, short stature and hypertension, increasing the overall morbidity in these children. Also, in our study, we demonstrated that a large proportion of children with PUV, bilateral reflux, or single kidney with reflux have poor growth and hypertension despite normal or near normal eGFR and serum creatinine. This has been documented in previous studies also in children with CAKUT[29] and adequate control of blood pressure has been shown to retard the progression of CKD.[30]

In addition, almost one-tenth (9.09%) of the children in our study had extrarenal manifestations ranging from mild facial dysmorphism to cardiac anomalies and ARM. Previous studies have also shown the presence of other nonrenal congenital anomalies in children with CAKUT.[31]

Through this cross-sectional study conducted at three tertiary care centers of the Armed Forces, we aimed to present a snapshot of CAKUT in our dependent pediatric population and the clinical profile of these children. It highlights the importance of their systematic evaluation, close monitoring and cohesive interdisciplinary management and follow-up by pediatric surgeons and/or urologists along with pediatricians and pediatric nephrologists.


  Conclusions Top


Children with CAKUT form a significant proportion of the patients coming to the pediatric OPD in tertiary care AFMS hospitals and the management of these children entails careful systematic evaluation and management by pediatric surgeons and the pediatric nephrologist.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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