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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2017  |  Volume : 28  |  Issue : 5  |  Page : 1064-1068
Nephrocalcinosis among children at king hussein medical center: Causes and outcome


1 Department of Pediatric Nephrology, Queen Rania Children Hospital, King Hussein Medical Center, Amman, Jordan
2 Department of Nephrology, King Hussein Medical Center, Amman, Jordan

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Date of Web Publication21-Sep-2017
 

   Abstract 


Nephrocalcinosis (NC) is defined as deposition of calcium crystals in the renal parenchyma and tubules. This is a retrospective review of all the data of 63 children presented to Pediatric Nephrology Clinic at King Hussein Medical Center (KHMC) over a 15-year period with bilateral NC. We determine their causes, clinical presentation and evaluate their growth and renal function during their follow-up. Thirty-five (55.5%) cases were males and 28 (44.5%) were females. The median (range) age at presentation was four (2–192) months. The most common leading cause to NC was hereditary tubulopathy in 48% followed by hyperoxaluria in 35%. The cause of NC remained unknown in 3% and Vitamin D excess accounts for 5% of the cases. The most presenting symptom was a failure to thrive (68%) and the second most common symptom was abdominal pain and recurrent urinary tract infection was found in 40%, polyuria and polydipsia were found in 32% of cases, and 16% of cases were diagnosed incidentally. At a median follow-up of 38 (14–200) months, estimated glomerular filtration rate had decreased from 84.0 (42–110) mL/min per 1.73 m2 body surface area to 68.2 (10–110) mL/min/1.73 m2 body surface (P = 0.001). This study illustrated the need for a national registry of rare renal diseases to help understand the causes of these conditions in our populations and provide support to affected patients and their families.

How to cite this article:
Al-Bderat JT, Mardinie RI, Salaita GM, Al-Bderat AT, Farrah MK. Nephrocalcinosis among children at king hussein medical center: Causes and outcome. Saudi J Kidney Dis Transpl 2017;28:1064-8

How to cite this URL:
Al-Bderat JT, Mardinie RI, Salaita GM, Al-Bderat AT, Farrah MK. Nephrocalcinosis among children at king hussein medical center: Causes and outcome. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Sep 20];28:1064-8. Available from: http://www.sjkdt.org/text.asp?2017/28/5/1064/215138



   Introduction Top


Nephrocalcinosis (NC) is defined as the deposition of both calcium oxalate and calcium phosphate in the kidney parenchyma and tubules.[1],[2] It occurs due to various metabolic or renal tubular disorders, Vitamin D excess, medication, and prematurity.[3] The condition can progress to chronic kidney disease (CKD), and the renal prognosis is determined by its underlying cause, so a diagnostic evaluation in all children with NC to determine its causes and preserve kidney function is mandatory. Since the use of kidney ultrasound (US) as a routine diagnostic procedure, NC is detected in growing numbers of adults and children. Different incidence rates and etiologies factors are reported in children with urolithiasis or NC, reflecting the difference in geographic, genetic, and socioeconomic back ground as well as the source of the series and the study design.[4] While the exact rates for NC are unknown, the incidence of childhood urolithiasis is believed to be approximately 10% of that in adults, which is around 5% in industrialized countries.[5] In view of the lack of data on NC in children in our region, we analyzed our data all patients who presented with NC and reviewed their clinical presentation, laboratory result and to evaluate their linear growth and renal function during their follow-up at the Pediatric Nephrology Clinic at KHMC, Amman, Jordan.


   Materials and Methods Top


Sixty-three children with US diagnosis of bilateral NC between January 2000 to January 2015 in Pediatric Nephrology division at King Hussein Medical Center (KHMC) were studied retrospectively. Neonates treated with furose-mide and premature infants with NC diagnosis were excluded from this study. The records of those children were evaluated regarding their age, sex, etiology of NC, clinical presentation, and their laboratory findings. The growth assessment was done by serial record of height and weight, and corresponding standard deviation scores were recorded.[6] Renal function and glomerular function was also described and compared at presentation and for the last follow-up visit.

Glomerular function was assessed by estimated glomerular filtration rate (eGFR) calculated using Schwartz formula, and level more than 90 mL/min/1.73m2 were considered normal. Those children <1 year of age, age specific limits for serum creatinine were used to evaluate renal function.[7] Initial investigations included blood pH and blood levels of creatinine, electrolytes, calcium, magnesium, urea, phosphorus, alkaline phosphatase and uric acid. Urine specimens were examined for spot and 24 h excretion of calcium, creatinine, uric acid, and oxalate level. Blood levels of parathyroid hormone and thyroid function test were also done. Vitamin D metabolites requested individually according to the case if there is high Ca level on two or more occasions.

The diagnosis of the underlying cause of NC was made as follows: Bartter syndrome in those with hypokalemia, metabolic alkalosis and normal blood pressure, with evidence of urinary potassium and chloride wasting. Familial hypomagnesemia with hypercalciuria and NC (FHHNC) in those with low serum magnesium (<1.5 mg/dL), and urinary magnesium wasting (fractional excretion >6%) and hypercalciuria and NC by US. Distal renal tubular acidosis (dRTA) in those with normal anion gap hyperchloremic, hypokalemic metabolic acidosis, high urine pH >5.5, and positive urinary anion gap. Primary hyperoxaluria in patients with elevated urinary oxalate excretion (>45 mg/1.73 m2/day) with no history of malabsorption, some cases were diagnosed by molecular analysis. Idiopathic hypercalciuria (IH) in patients with elevated urinary calcium >4 mg/kg/day or spot urinary Ca/creatinine ratio >0.8, >0.6, >0.4, and >0.2 mg/mg in children aged <6 months, 6–12 months, 1–2 years, and >2 years of age, respectively, on two or more occasions), with the absence of other tubular defects and normal Ca levels. Vitamin D excess diagnosed in patients with hypercalcemia (Ca level >11 mg/dL), high blood levels of 25 (OH) Vitamin D (>90 ng/mL), with hypercalciuria and history of excess Vitamin D intake.

All data were expressed as median (range) values and were analyzed using Excel spreadsheet. Wilcoxon rank sum was applied and P <0.05 was considered statistically significant.


   Results Top


A total of 63 children enrolled in this study. Thirty-five (55.5%) cases were males and 28 (44.5%) were females. The median (range) age at presentation was 42 (2–192) months. A positive family history of calculi or NC or renal failure was present in 25 (40%) patients. The most common leading cause to NC was hereditary tubulopathy in (48%) followed by hyperoxaluria in 35%. The cause of NC remained unknown in 3%. Vitamin D excess account for 5% of the causes, while congenital adrenal hypoplasia CAH and AME account for 3% and 1%, respectively [Table 1] demonstrate detailed causes of NC.
Table 1: Causes of nephrocalcinosis in 63 children; values represent numbers (percentage).

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Most patients showed significant retarded growth [Table 2]. The most presenting symptoms and sign was a failure to thrive and was found in 42 (68%), abdominal pain and recurrent urinary tract infection was found in 25 (40%), polyuria and polydipsia found in 20 (32%) of cases. Ten patients (16%) were diagnosed incidentally during US screening. Two patients (3%) presented with recurrent convulsion secondary to hypomagnesemia. The median systolic and diastolic pressures were 105 (80–132) mm Hg and 65 (50–85) mm Hg, respectively. At initial presentation, the median blood levels of creatinine were 0.60 (0.3–2.6) mg/dL. Calcium 9.0 (6.2–12.2) mg/dL, phosphorus 4.8 (3.4–6.8), and alkaline phosphatase 544 (146–2114) IU/L. Urinary oxalate excretion was increased in 22 patients where it was ranged from 100 to 260 mg/1.73 m2/day, three of them diagnosed as Type 1 Primary oxaluria based on genetic study that was requested by other center outside. Hypercalciuria was present in 48 (76%) patients, with a median Ca excretion of 4.6 (2.8–12.8) mg/kg/day, and spot Ca/creatinine ratio of 0.6 (0.04–2.2). Fractional excretion of magnesium was >6% in eight patients. Estimated GFR was 84.0 (42–110) mL/min/1.73 m2 that was declined to 68.2 (10–110) mL/min/1.73 m2 over the median duration of follow-up of 38 (14–200) months: (P = 0.001), [Table 2]. At their follow-up, 10 patients with primary hyperoxaluria, and eight patients with FHHNC had (CKD stage 3–5), and another two sisters with Bartter syndrome, one died with ESRD, and the other had living related kidney transplant. All the other patients had eGFR >90 mL/min/1.73 m2. During the median duration of follow-up of 38 (14–200) months, most patients continue to have a marked stunted growth, despite medical therapy, and correction of metabolic acidosis and relief symptoms of polyurea and polydipsia in most patients [Table 2] demonstrate parameters at presentation and after follow-up.
Table 2: Represent growth parameter, laboratory results at presentation and after follow-up.

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FHHNC was the most common hereditary tubulopathy and was found in 12 (18%) patients, positive family history in (50%) of patients, four patients belong to the same family, and another two brothers belong to another family. The median ages of the clinical presentation were 24 (6–48) months. Recurrent convulsion was the most common initial presentation. Failure to thrive was seen in all patients. Eight patients had eGFR <60 mL/min/1.73 m2 body surface area.


   Discussion Top


Nephrocalcinosis is uncommon findings that seem to be primarily appear in the 1st years of life because it is frequently attributed to hereditary tubulopathy or inborn error of metabolism that most likely discovered early in life. Heterogeneous group of diseases cause of NC that have a great impact on the patients prognosis and outcome. There is limited data on the etiology and outcome of NC in developing countries,[3],[8],[9],[10],[11] and most published data from the developed countries,[12],[13],[14],[15] and whether it has effect on the growth parameter and kidney function.[3],[8],[9],[10],[11],[12],[13] This retrospective study is up to our know-ledge the only study reporting data regarding NC in our country, and since our center is the only referral for such cases of NC, we expect that the spectrum of diagnosis, in our study may reflect the epidemiology of NC in our country.

Our results confirm that most children with NC have underlying hereditary and metabolic defects that can be detected based on clinical feature and laboratory results, in addition to the positive family history of such cases. In our study, hereditary tubulopathy was the most common cause of NC account for (48%), of which FHHNC was seen in 12 (18%) of them, and dRTA in eight (13%). In a multicenter series from Germany, Ronnefarth et al reported IH as the main cause of NC in 34% of 152 patients, in which primary oxaluria was excluded.[13] Growth retardation was the most common clinical manifestation in our study which show similarity to other studies.[3],[8],[10],[11],[12]

The long-term outcome in our patients was not promising as retardation of growth continued in most of our patients during their follow up. However, this was also reported by Mantan et al in their survey in North India.[8] In contrast, in multicenter German series,[13] those patients with IH had significant catch-up growth, while a patient with hereditary tubulopathy had less significant catch-up growth. The cause of growth retardation in those patients could include chronic hypokalemia and metabolic acidosis, rickets, and CKD.[8],[16],[17] However, Ammenti et al,[12] and Dogan et al[3] concluded that early and appropriate treatment may ensure growth improvement in patients with tubulopathy, the most common cause of NC in their studies.

In this study, at a median follow-up period of 38 months, there was a significant decline in GFR. In 29% patients had the renal impairment was significant with a GFR <60 mL/min. Of the two siblings with Bartter syndrome, one died with ESRD on HD, the other underwent renal transplantation. This reflects that primary etiology of NC was probably the most important factor to determine the outcome of NC to develop CKD in those patients. Actually, the high consanguineous marriage in our area accounts for this high proportion of patients with hereditary tubulopathy and metabolic defect that cause NC and in most of the cases ended with CKD. In a comparison to other studies,[3],[8],[9],[10],[11],[12],[13] primary hyperoxaluria and FHHNC were founded in a large number of our patients with NC.


   Conclusion Top


The most common cause of NC in this study is similar to the other studies. The high percentage of our patients with low GFR at the end of follow-up necessitate that national registry educate our population about the hereditary and metabolic disease causes of renal diseases and support further scientific studies.

Conflict of interest: None declared



 
   References Top

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Wrong O. Nephrocalcinosis. In: Davison AM, Cameron JS, Grunfeld J, et al., editors. Oxford Texbook of Clinical Nephrology. Oxford: Oxford University Press; 2005. p. 1375.  Back to cited text no. 1
    
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Dogan CS, Uslu-Gökçeoglu A, Comak E, Alimoglu E, Koyun M, Akman S. Renal function and linear growth of children with nephrocalcinosis: A retrospective single-center study. Turk J Pediatr 2013;55:58-62.  Back to cited text no. 3
    
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López M, Hoppe B. History, epidemiology and regional diversities of urolithiasis. Pediatr Nephrol 2010;25:49-59.  Back to cited text no. 4
    
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Hesse A. Reliable data from diverse regions of the world exist to show that there has been a steady increase in the prevalence of urolithiasis. World J Urol 2005;23:302-3.  Back to cited text no. 5
    
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National Center for Health Statistics, Centers for Disease Control. NCHS Growth Curves for Children: Birth-18 Years. DHEW Puplication (PHS) 78 1650. Ser. 11, 165. Washington, DC: US Government Printing Office; 1978.  Back to cited text no. 6
    
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Boer DP, de Rijke YB, Hop WC, Cransberg K, Dorresteijn EM. Reference values for serum creatinine in children younger than 1 year of age. Pediatr Nephrol 2010;25:2107-13.  Back to cited text no. 7
    
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Mantan M, Bagga A, Virdi VS, Menon S, Hari P. Etiology of nephrocalcinosis in northern Indian children. Pediatr Nephrol 2007;22:829-33.  Back to cited text no. 8
    
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Neyzi O, Ertugrul T. Cocuk ve Hastaliklari. Cilt 1. Istanbul: Nobel Kitabevi; 1989. p. 57-88.  Back to cited text no. 9
    
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Kiran BV, Barman H, Iyengar A. Clinical profile and outcome of renal tubular disorders in children: A single center experience. Indian J Nephrol 2014;24:362-6.  Back to cited text no. 10
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Mortazavi F, Ghergherehchi R. Causes of nephrocalcinosis in children referring to children hospital of Tabriz. Urmia Med J 2012; 23:172-7.  Back to cited text no. 11
    
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Ammenti A, Pelizzoni A, Cecconi M, Molinari PP, Montini G. Nephrocalcinosis in children: A retrospective multi-centre study. Acta Paediatr 2009;98:1628-31.  Back to cited text no. 12
    
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Rönnefarth G, Misselwitz J. Nephrocalcinosis in children: A retrospective survey. Members of the Arbeitsgemeinschaft für pädiatrische Nephrologie. Pediatr Nephrol 2000;14:1016-21.  Back to cited text no. 13
    
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Lin MT, Tsau YK, Tsai WY, Tsai WS, Lu FL, Hsiao PH, et al. Nephrocalcinosis in childhood. Acta Paediatr Taiwan 1999;40:27-30.  Back to cited text no. 14
    
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Cremin B, Wiggelinkhuizen J, Bonnici F. Nephrocalcinosis in children. Br J Radiol 1982;55:413-8.  Back to cited text no. 15
    
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Caldas A, Broyer M, Dechaux M, Kleinknecht C. Primary distal tubular acidosis in childhood: Clinical study and long-term follow-up of 28 patients. J Pediatr 1992;121:233-41.  Back to cited text no. 16
    
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Gil-Peña H, Mejia N, Alvarez-Garcia O, Loredo V, Santos F. Longitudinal growth in chronic hypokalemic disorders. Pediatr Nephrol 2010;25:733-7.  Back to cited text no. 17
    

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Correspondence Address:
Jwaher T Al-Bderat
Department of Pediatric Nephrology, Queen Rania Children Hospital, Amman
Jordan
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PMID: 28937064

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