Clinical Presentation, Etiological Factors and Outcome in Children Diagnosed With Urolithiasis in Ghaziabad, Uttar Pradesh

INTRODUCTION

Urolithiasis (UL) is often encountered in general paediatrics practice affecting children of all age groups Prevalence quoted for Asian countries like India, Pakistan, Thailand & Myanmar which lie on Afro-Asian stone belt is 1-5%.[1] Universal rise of UL cases in last two decades2 has been referred as stone wave. UL lead to high morbidity and accounts for 4-8% cases of end stage renal disease during childhood.[4-7] The etiology of pediatric urolithiasis still remains largely unknown in the developing world.[8,9] although western studies show anatomical abnormalities, infection and metabolic causes in up metabolic disorders,[11-20] obesity, diabetes etc contribute to the pathogenesis of the different types of stones.[2-4] High prevalence, rising incidence, troublesome symptoms and serious long term consequences along with relative paucity of data in childhood UL were the reason to conduct present research work.

to 90% of the cases.[10] Variousdietary factors,

Duration -September 2016- June 2018 (22 months) Sample size -All consecutive subjects of urolithiasis attending pediatrics OPD of hospital were enrolled prospectively. Inclusion Criteria-: Children (till 18 yrs of age) diagnosed with urolithiasis Exclusion Criteria-: Nephrocalcinosis. Ethical clearance was obtained from institute ethics committee.

information on clinical presentation ,positive family history of UL, 24 hr diet recall was recorded & used to analyze daily average intake of liquids, protein ,calcium & salt . Dietary calcium was considered normal if it was between 800-1000mg/dl per day. High salt intake was considered if it was more than 5gms/day. High protein was considered if it was more than 2.25gms/kg/day.

Idiopathic hypercalciuria- if child 24 h urine calcium was >4mg/kg/d with serum calcium levels of 9-11 mg/dl OR if spot urinary calcium to creatinine ratio was > 0.2 Idiopahic Hyperoxaluria - if child 24 h urine oxalate was >40mg/1.73 m2/d Idiopathic Hyperuricosuria - if child 24 h urine uric acid was >815/1.73 m2/d & his S.Uric acid is between 2-6 mg/dl Urine routine microscopy, complete blood count, blood urea &serum creatinine were done in all participants. Metabolic evaluation advised was serum calcium & magnesium, 24 hr urinary calcium, oxalate & uric acid, spot urinary calcium to creatinine ratio. Attempt was made to get these investigation done in all patients but even if these investigation couldn‘t be done due to any reason the patient was still included in the study. USG abdomen was done in all children. The dietary advice given to all participants consisted of -Increase daily fluid intake to 1-2 liters, to ensure adequate daily intake of calcium providing age specific RDA and to keep daily salt intake restricted to 3-5gms. In follow up parents were contacted telephonically at 6 months and 1year & information related to the persistence of symptoms, recurrence of stones & spontaneous passage of stones was recorded. During study period 48 children were enrolled. Median age of participants was 8.5 years; Age range was 1.3 years to 17 years. Majority (31, 64.5%) were male. The common presenting complaints were - localised abdominal pain/renal colic, dysuria and increased frequency of micturation reported by 40 (83.33%), 22 (45.83%) and 22 (45.83%) subjects respectively (Table I) .Two children (4.16%) presented with secondary enuresis while vomiting associated with abdominal pain was reported by 16 (33.33%) children.

Pyuria was found in 30 (62.7%) children while hematuria and granular casts were present in 29 (60.41%) & 1 (2.08%) children respectively. Urine culture was positive in 5 (10.41%) children. None of the participants had macroscopic hematuria. Majority (30, 62.5%) had unilateral stones. The kidney stones were commoner found in 33 (68.75%) participants than stones elsewhere in urinary tract. Bladder stones were found in 5 (10.41%) children only. Ureteric stones were found in 10 (20.83%) children of which only 2 (4.16%) had hydronephrosis requiring surgical intervention. Stones were smaller than 5 mm in 26 (54.16%) children. Metabolic Risk Factors: The metabolic abnormalities detected in study participants were idiopathic hyper-calciuria, hyperoxaluria & hyperuricosuria found in 9 (18.7%),12 (25%) & 2(4.2%)children respectively.

most significant association was found was hot and dry weather conditions and nearly half (45.83%, 22)participants presented in summer months (May & June). The next most important association was history of recurrent diarrhea present in 10 (20.83) children. Anatomical genito-urinary tract defects found was hydronephrosis .Only 2 participants were taking predisposing drug- magnesium trisilicate for few weeks due to gastritis out of the list of culprit drugs (like loop diuretics, acetazolamide, topiramate, laxatives, ciprofloxacin, magnesium trisilicate, indinavir, ephedrine ).Nutritional status of nearly 90% (43) children was normal and only 5(10.41%) children were overweight. None was immobilized for long duration. Outcome of study participants Out of total 48 children enrolled in study 46 were being managed with conservative medical treatment & 2 children underwent surgery for stone removal. History of recurrent renal calculi was found in 7 children (14.58%) while 18 (37.5%) children reported spontaneous passage of calculi and remained symptoms free till last contact at the end of 1 year. 28 (58.3%) children continue to suffer from mild to moderate attacks of renal colicky pain requiring intermittent symptomatic treatment.

The primary objective of present research was to identify the clinical profile of pediatric urolithiasis (UL), its associated etiological factors & outcome after one year follow-up. Since it was a hospital based study so the data collected gave a rough idea of disease (symptomatic cases) burden in served locality. Forty eight USG confirmed cases of UL were enrolled The important feature of abdominal pain in most children was it being quite severe, non-localized & without associated gastro-intestinal symptoms like constipation or diarrhea unlike in adults where presentation is typical colicky loin pain & its characteristic radiation of groin. The important clue for getting detailed investigations done in study subjects was either recurrent abdominal pain or UTI and symptoms refractory to routine treatment. Almost similar results have been reported from different parts of India by few researchers& according to them the top three presentations of pediatric UL were urinary tract infection (UTI), abdominal pain and flank pain found in 29.3%, 24.1% and 17.2% children respectively.[3,7,17-19] While Rajma et al reported that 90% children with UL presented with abdominal pain & symptomatic UTI was present in 33% children.[3] According to Bhatt et al 54% children presenting with UTI had UL.[1] None of the participants in present study had gross hematuria although microscopic hematuria was percentages of various presenting symptoms could be the difference in the site of affection or size, shape, type of stones & duration of disease. Another significant finding in present study was confirmation of the preponderance of kidney stones over bladder stones. This shift from bladder stones to kidney stones is recent & has been documented by many researchers worldwide including India.[1,7] In present research the stones were located in kidneys, upper urinary tract & urinary bladder in 68.7%, 20.8% & 10.4 % children respectively. The observations of present research are in concordance with Bhatt et. al.[1] who found kidney stones in 82.6% children and bladder stones in 3.4% children. Second objective of present study was to identify various etiological associations in enrolled study participants. Different etiological factors implicated in pediatric UL are metabolic[16-19], genitourinary defects, genetic[1,2], infective and dietary factors which may often co-exist.[16] Important associations found in present study were UTI, positive family history of urolithiasis, history of frequent diarrhea & obesity found in 62.7%(30), 45.83%(22), 20.83%(10) & 10.4%(5) participants respectively . Some researchers[2] found UTI in 54% & metabolic abnormality like idiopathic hypercalciuria in 2(6.6%) children.[16] In a retrospective study hyperoxaluria, hypercalciuria ,hypocitruria & hyperuricosuria were found in 79.3%, 25.9%,22.4% & 24% pediatric urolithiasis patients respectively.[10] The major limitation of present research work was that basic metabolic evaluation could be done in only 13(27%) children and hypercalciuria, hypercalcemia & hypocalcaemia was present in 6.25%, 4.16% & 8.33% children respectively. Various reasons for this inability to get basic metabolic workup done in present study ranged were financial constraints, parental reluctance & their firm faith in alternative treatment forms (other than allopathy). Petrarulo et. al.[6] reported UTI in 25% subjects and according to them majority of such children had uro-genital anomalies in contrast to our observations where hydronephrosis was found in 4.16% subjects only. In present research only 5(10.4%) children were obese and none was malnourished, this may be because of small sample size & the enrolled patients belonged to middle or lower middle class families. Third objective in present study was to identify the dietary factors associated with UL. Among dietary risk factors for UL in present work inadequate water intake topped the list & was found in staggering 79% children, which directly explained

coupled with decrease fluid intake leading to super saturation of calcium and other metabolites followed by stone formation. Low dietary calcium intake was found in 72.9% children in present study which is higher than 59% reported by Gajengi et. al.,[7]. Low calcium intake causes UL by two mechanisms; first it increases intestinal oxalate availability and rising super saturation of calcium oxalate. Second mechanism could be via stimulation of calcitriol production leading to hypercalcemia, inhibiting PTH production and hyper-calciuria. In their large cohort study Curhan et. al.[8] stressed on the need of high oral fluid intake and optimum (to meet RDA) calcium supplementation. Another important observation related to diet consumed in present study participants was that their daily consumption of salt & protein was much higher than recommendations. The high dietary protein (animal source) is associated with calcium oxalate stones which are usually located in upper urinary tract.[1] High dietary salt intake expands intravascular volume, increases urinary calcium level most probably by decreasing renal tubular calcium re-absorption and is associated with increased urinary stones.[16] The last objective was to know the outcome at the end of study period in the participants. In present research recurrent calculi were reported by 7 (14.5 %), spontaneous passage of calculi was reported by 18 (37.5%) while 28 (58.3 %) children continued to suffer from persistence of symptoms of variable severity. Only 2 children in our study underwent surgery for stone removal & rest all were being managed conservatively. Stone recurrence was found in 31 % children by Bhatt et. al.[1]. Sternberg et. al.[4] reported that pediatric UL patients have 65 % lifelong recurrence of stone. This recurrence could be prevented or at least it could be decreased by taking sufficient amount of liquids, dietary calcium should be adequate to provide RDA along with reduced consumption of amounts of salt, animal protein, and oxalate rich foods. ―At risk children‖ like those with positive family history of UL or those with urogenital malformations may also be benefitted by these dietary modifications. One of the major limitations of present work was inability to get stone for its chemical analysis so that specific dietary manipulations could be advocated to the children. There is still strong need of multi-centric studies having larger sample size, longer follow up period with more detailed metabolic workup in maximum number of participants to obtain answers to lots of poorly answered queries related to pediatric UL. Pediatric urolithiasis: What role does metabolic evaluation has to play? Int J Res Med Sci.; 4: pp. 3509-12. 2. Shah AM, Kalmunkar S, Punekar S.V. et. al. (1991). Spectrum of pediatric urolithiasis in western India.Indian J Pediatr; 58: pp. 543. 3. Rajma J, Arun AC, Ganesapillai M. (2017). Clinical profile of urolithiasis among hospitalized children- a single center study. Pediatric Review: International Journal of Pediatric Research; Vol. 4(5): pp. 343-349. 4. Sternberg K, Greenfield SP, Williot P, et. al. (2005). Pediatric stone disease: an evolving experience. J Urol.; 174: pp. 1711-4. 5. Sharma AP, Filler G. (2010). Epidemology of pediatric urolithiasis. Indian J Urol.; 26: pp. 516-22. 6. Petrarulo M, Vitale C, Facchini P, Marangella M. (1998). Biochemical approach to diagnosis and differentiation of primary hyperoxalurias: An update. J Nephrol.; 11: pp. 23-8. 7. Gajenji AKR, Wagaskar VG, Tanwar H, Mhaske S, Patwardhan SK (2016). Metabolic Evaluation in Paediatric Urolithiasis: A 4- Year Open Prospective Study. J Clin Diagn Res.: 10(2) pp. PC04–PC06. 8. Curhan GC (1997). Dietary calcium, dietary protein, and kidney stone formation. Miner Electrolyte Metab.; 23: pp. 261-4 9. Kit LC, Filler G, Pike J, Leonard MP (2008). Pediatric urolithiasis: Experience at a tertiary care pediatric hospital. Can Urol Assoc J.; 2: pp. 381-6. 10. Syed A.H. Rizvi, Sajid Sultan, Mirza N. Zafar, Bashir Ahmed, Syed M. Faiq, Kehkashan Z. Hossain, Syed A.A. Naqvi. Evaluation of children with urolithiasis.Indian J Urol. 2007 Oct-Dec; 23(4): pp. 420–427. 11. Alpay H, Ozen A, Gokce I, Biyikli N. (2009). Clinical and metabolic features of urolithiasis and microlithiasis in children. Pediatr Nephrol.; 24(11): pp. 2203-9. 12. Durgawale P, Shariff A, Hendre A, Patil S, Sontakke A. (2010). Chemical analysis of 13. Hess B. (2003). Pathophysiology, diagnosis and conservative therapy in calcium kidney calculi. Ther Umsch; 60: pp. 79-87. 14. Lewandowski S and Rodgers AL (2004). Idiopathic calcium oxalate Urolithiasis: Risk factors and conservative treatment. Science Direct-Chimica Acta.; 345: pp. 17-34. 15. Rizvi SA, Naqvi SA, Hussain Z, Hashmi A, Hussain M, Zafar MN, et. al. (2002). Pediatric urolithiasis: Developing nation perspectives. J. Urol.; 168: pp. 1522-5. 16. Rizvi SA, Sultan S, Zafar MN, Ahmed B, Aba Umer S, Naqvi SA (2016). Paediatric urolithiasis in emerging economies. Int J Surg.; 36: pp. 705–12. 17. Abhishek, Kumar J, Mandhani A, et. al. (2013). Pediatrics urplithiasis: experience from a tertiary referral center. J. Pediatr Urol.; 9: pp. 825-30. 18. Gouru VR, Pogula VR, Vaddi SP, Manne V, Byram R, Kadiyala LS (2018). Metabolic evaluation of children with urolithiasis. Urol Ann.; 10: pp. 94-99. 19. Joshi A, Gupta SK, Srivastava A (2013). Metabolic evaluation in first-time renal stone formers in North India: a single center study. Saudi J. Kidney Dis Transpl.; 24: pp. 838–43. 20. Mantan M, Bagga A, Virdi VS, Menon S, Hari P. (2007). Etiology of nephrocalcinosis in northern Indian children. Pediatr Nephrol.; 22: pp. 829-33.

MD Pediatrics, Professor Pediatrics, Santosh Deemed to be University, Ghaziabad, U.P., India veenu2908@gmail.com