| Abstract|| |
The study reviews causes of urolithiasis and its manifestations in North-West (NW) Libya. Libyan childhood urolithiasis accounted for 3.6% of nephrology out-patient work load. There were 59 children with urolithiasis, including 34 boys and 25 girls with a mean age of 2.8 ± 2.42 years. Urolithiasis was more common among younger age groups (P = 0.001) and in boys with primary oxaluria and infective etiology. The causes of urolithiasis included metabolic stones in 64%, infective in 26%, and it was idiopathic in 10%. Overall, family history of renal stone disease was elicited in 59%; it was 92% in patients with primary oxaluria. The main presenting features were abdominal pain (27%), gross hematuria (22%), associated urinary tract infection (UTI; 24%), and stone release in 19%. Stone location was bilateral in 64%, multiple in 68%, and in the upper tract in 93% (P = 0.05). Important complications encountered included chronic renal failure (13%), hydronephrosis (34%), systemic hypertension (8%), and rickets in 17%. Calcium oxalate was the most prominent constituent, seen in 41% of the calculi, followed by struvite (21%), uric acid (10%), carbapatite (7%), and cystine (3.5%). Diagnostically helpful findings were family history, age at presentation, UTI by urease producing organisms, rickets, imaging and chemical analysis of calculi. Early detection and prompt treatment helps in preventing long-term sequelae in patients with urolithiasis.
|How to cite this article:|
Halim M B, Bash-Agha I, Elfituri O, Turki M, Hawas A. Childhood urolithiasis in North-Western Libya. Saudi J Kidney Dis Transpl 2012;23:162-70
|How to cite this URL:|
Halim M B, Bash-Agha I, Elfituri O, Turki M, Hawas A. Childhood urolithiasis in North-Western Libya. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2020 Aug 4];23:162-70. Available from: http://www.sjkdt.org/text.asp?2012/23/1/162/91414
| Introduction|| |
Urolithiasis is a well-known disease as evidence of bladder calculi has been found in Egyptian mummies preserved over 7000 years,  while surgical treatment of urinary calculi dates back to the time of Hippocrates in the fourth century BC. ,, Urolithiasis has wide geographical variations, and different factors contribute to its occurrence, such as inherited metabolic disorders, local kidney abnormalities, and urinary tract infection (UTI) in children, while nutritional and environmental factors play a role in adults. 
Despite its rarity  when compared with other renal disorders, urolithiasis carries a high morbidity which is a cause for concern.  The patho-physiological process of calculus formation depends on two major mechanisms: either super-saturation of urinary solutes or urinary stasis, and many factors account for the occurrence of both. ,, This study is a review of the causes of urolithiasis and their clinical, biochemical, and imaging manifestations in Libyan children. It is aimed at revealing the etiological factors involved and to relate clinical and laboratory findings to the diagnoses reached by chemical analysis of the calculi.
| Patients and Methods|| |
A total of 59 out of 1056 files, which satisfied the study criteria of abdominal imaging evidence of nephrolithiasis and/or nephrocalcinosis, were obtained from the pediatric nephrology department follow-up clinic at Tripoli Children Hospital (TCH), spanning the period from June 1984 to July 2000 (16 years). Clinical features recorded included age at presentation, presenting symptoms and signs at onset, family history of renal stone disease and other renal disorders, parental consanguinity and the clinical findings. Laboratory records included urinalysis for pH, red blood cells (RBCs), white blood cells (WBCs), bacterial culture, calcium/creatinine ratio, and nitroprusside test. Blood analysis for kidney function tests included: urea/creatinine, electrolytes (Na sup>+, K+, Cl─), serum calcium, phosphorous, alkaline phosphatase, uric acid, and arterial acid-base status (ABS). Imaging records were in the form of plain X-ray and sonography of abdomen at the time of diagnosis. Calculus analysis consisted of describing physical characteristics of 29 collected calculi and their chemical analysis, which was carried out at TCH Laboratory Department. Nephrolithiasis is defined as presence of one or more stones in kidney or urinary tract, while nephrocalcinosis is urolithic deposits in kidney parenchyma. Urolithiasis comprises both.
The statistical package of social sciences (SPSS, version 10, SPSS Inc., Chicago, IL, USA) was applied for analysis of the data.
| Results|| |
Urolithiasis accounted for 3.6% of nephrology out-patient follow-up clinic work load. There were 59 patients, 34 boys and 25 girls, a gender ratio of 1.4:1. The patients' age ranged between two months and 16 years, with a mean age of 2.8 ± 2.42 years (2.68 ± 2.54 for boys and 2.87 ± 2.31 years for girls). The classification of causes of urolithiasis is shown in [Figure 1]. The 19 patients with distal renal tubular acidosis (DRTA) who had no significant gender difference had a combined mean age of 2 ± 1.93 years (1.67 ± 1.18 years for boys and 3.05 ± 2.92 years for girls). The most common complaints/findings were failure to thrive (FTT) followed by deafness, which is a notable peculiarity in patients with autosomal recessive DRTA [Table 1]. A family history of consanguineous marriage and/or urolithiasis was seen in 12 patients (63%). [Table 2] shows the patients' laboratory investigative results. All patients with DRTA had ultrasonography findings of medullary nephrocalcinosis, while three of them (16%) had nephrolithiasis as well and were of older age at presentation (≥6 years).
|Figure 1: Etiology and frequency of urolithiasis in NW Libyan children (n = 59).|
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|Table 2: Laboratory results in Libyan children with urolithiasis (n = 59).|
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There were 13 patients with primary oxaluria and their age ranged from two months to 14 years, with a mean age of 2.43 ± 2.05 years. Associated UTI was the commonest presenting complaint. Presence of chronic renal failure (CRF) was a striking finding in five of these patients (38%). Three patients (23%) presented with positive family history without other complaints, while a family history of consanguineous marriage and urolithiasis was elicited in 12 patients (92%). Three patients (23%) each had nephrocalcinosis or nephrolithiasis and seven patients (54%) had both.
Uric acid stone formation was seen in two boys and one girl. Their mean age was 1.56 ± 1.09 years. The two boys presented with UTI, and the girl presented with gastroenteritis and the stone in the right kidney was an incidental finding on abdominal sonography. All the biochemical investigations of these patients were normal, and chemical analysis of the stone showed uric acid and calcium.
Cystinuria was seen in two brothers, aged seven and 12 years, respectively, with a mean age of 9.5 ± 3.54 years. They had a positive family history of consanguineous marriage and presented with abdominal pain and dysuria. The diagnosis was established by the presence of cystine crystals in urine and by positive nitroprusside test. Chemical analysis of the stone confirmed the diagnosis.
Idiopathic hypercalciuria was seen in one girl aged 1.8 years. The stone was detected incidentally on abdominal X-ray and ultrasonography which showed features of medullary nephrocalcinosis. The blood investigations were normal, but urinalysis showed presence of UTI as well as high calcium/creatinine ratio.
UTI was seen in 15 patients (26%), including 12 boys (80%) and three girls (20%). Their age ranged from six months to 12 years, with a mean age of 5.18 ± 3.20 years. The age at presentation of these patients was four years or older. All patients presented with recurrent UTI, one patient (7%) had systemic hypertension and nine (60%) had hydronephrosis. Urease producing organisms were isolated in 11 patients (73%) (6 Proteus, 3 Klebsiella, and 2 Pseudomonas).
Two boys and four girls had idiopathic stones; their age ranged from five months to 15 years, with a mean of 4.32 ± 6.07 years. Two patients presented with UTI and one with stone release. All patients underwent complete biochemical investigations, but no diagnosis could be established.
Most metabolic stones (64%) were located in the upper urinary tract and were multiple and bilateral [Figure 2], [Figure 3]. Forty-one percent of the analyzed stones were calcium oxalate stones; their color ranged from light to dark brown, with smooth or rough surfaces. Stones associated with UTI varied in shape and included one stag-horn calculus. All stones were fragile. The single cystine stone was small in size and dark in color with a smooth surface.
|Figure 2: Clinical and imaging manifestations scoring system for Libyan children with urolithiasis (n = 59).|
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|Figure 3: A large (4 × 3.5 × 2 cm) urinary bladder stone in an 8-year-old Libyan child who presented with acute on chronic renal failure due to four years of chronic obstructive uropathy.|
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The complications encountered in the study patients included UTI in 24%, FTT in 26%, rickets and hearing loss in 17% each, hydronephrosis in 34%, CRF in 13%, and systemic hypertension in 6% of the patients.
| Discussion|| |
Little is known about the epidemiology of childhood urolithiasis locally, ,,, and its diagnosis is difficult as presentation in pediatric age can frequently be atypical, and in one of five patients, the stone may be detected incidentally. ,,, Urolithiasis in children is uncommon, but still remains one of the major causes of morbidity in developing countries. ,,,, It was reported from the UK as unusual, and detected in probably less than one in a 1000 admissions although present in about 1% at autopsy. ,,, The data in the present study represent a very small percentage of nephrology unit OPD workload over a 16-year study period.
Females appear to be at higher risk than males because they are anatomically more susceptible to UTI, a predominance that was confirmed and reported in Icelandic girls. , An unexpected significant gender difference, however, was found among primary oxaluria and infection groups where 80% of Libyan patients were boys (P = 0.05). Males continue to suffer more renal stones than females, a predominance that is in keeping with some reports, ,,,, but not all. , Elsewhere in the world, renal stone disease appears to be three to four times more common in the male gender ,,, [Table 3]. A large number of Libyan patients (n = 45; 76.3%) were below the age of five years and the youngest was two months old. Of the 38 patients (52%) with underlying metabolic etiology, 31 (82%) were three years of age or younger (P = 0.0001). The mean age of the two brothers with cystinuria was 9.5 ± 3.54 years. Most patients (67%) classified with infective etiology were older, with mean age of 5.18 ± 3.2 years at onset of symptoms. Icelandic children with urolithiasis and others of different nationalities also presented at an older mean age of 6.9-9.4 years. ,,,,, Among the Arab countries reviewed, a similar tendency was found in Tunisian children (mean age 8 years). 
|Table 3: Comparison of various studies on urolithiasis in some European countries, USA, and NW Libya.|
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Our findings suggest that an underlying disorder is present in a large proportion of children with urolithiasis where appropriate treatment may be beneficial. In 53 children (90%), a cause was found which could be responsible for calculus formation. Similar findings were reported from Johns Hopkins Hospital and Children Center  (P = 0.05). A metabolic abnormality was found in 38 children (64%) (P = 0.05), 15 (26%) were classified as infective, and in only six patients (10%) no apparent cause could be established [Figure 1]. A much higher proportion of metabolically classified stones and a correspondingly very low proportion of infection-related stones were reported from Iceland  and Kuwait.  The Kuwaiti study reported a high proportion (70%) of calcium oxalate and struvite stones which are related to infective etiology! ,, The reduced proportion of children with infective stones may be related, at least in Iceland, to increased awareness, early diagnosis, and treatment of UTI. 
A strong epidemiological factor, such as a family history of urolithiasis, ,, seems to characterize this disease in Libyan children, particularly those with genetic disorders,  where the overall incidence was 64%. The incidence is also known to vary among ethnic groups with predisposition to inherited biochemical abnormalities. , Most patients with primary oxaluria (54%) and a strong family history of the disease originated from the Berber region in the western mountainous areas of NW Libya (P = 0.009).
The most striking features were the initial presentation of seven children (13%) after the development of CRF: two (29%) had DRTA and five (71%) had primary oxaluria, similar to those reported locally previously,  rather than infection-related stones as reported from Turkey,  Tunisia,  and Saudi Arabia  [Table 4].
|Table 4: Comparison of various studies on urolithiasis in some Arab countries.|
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Some of the children might have had preexisting anatomical defects such as hydronephrosis and other causes of partial obstructtion of the urinary tract. , Hydronephrosis was found in 20 patients (34%), most of whom had infection-related stone formation.
Three other findings are worth noting: rickets (17%), severe wasting (74%), and neurosensory deafness (47%) in autosomal recessive DTRA. All are well-recognized features, although the latter has not been recorded in the literature reviewed for the present study. ,, This may be due to scarcity of patients with DRTA in their societies. There was otherwise no other remarkable finding which differed from already reported modes of presentation. Spontaneous stone release (19%) was a less frequent occurrence than those reported from Kuwait  (65%), USA  (39%), and Croatia  (32%).
In 93% of patients, 80% of whom were boys, the stones were located in the upper urinary tract (P = 0.05). They were bilateral in 64% and multiple in 68% [Figure 2]. The upper location also predominated in reports from other nations. , In Tunisian  and Pakistani  patients, a higher proportion of stones found in the lower urinary tract may reflect transition from an agrarian to an urbanized society. , Our data suggest that bilateral nephrocalcinosis may indicate DRTA in 84% of cases; nephrocalcinosis and one or more stones is more likely to be primary oxaluria in 75% of patients, whereas a single stone in the right kidney, especially in a boy, is more likely to be infective in 87% or idiopathic in 67% of cases.
Chemical analysis of recovered stones showed that most (67%) of their composition was not dissimilar to those reported by others, , namely, a variable mixture of calcium oxalate, struvite, and carbapatite [Table 5]. Other stones were composed of uric acid and cystine. Stones composed of either calcium oxalate or struvite are the most frequently found in patients with UTI. , Eleven (60%) infection-related patients and five (39%) primary oxaluria patients had UTI by urease producing organisms.
Our study suggests that Libyan children in NW Libya with renal stone disease are more likely to have an underlying metabolic abnormality which may predict severe bilateral disease. The disease is of diverse etiology and requires carefully planned individualized management and follow-up protocols. Diagnosing the underlying disorder permits siblings at risk of prolithogenic metabolic abnormalities to be detected before they develop overt stones. This should allow not only initiating preventive treatment early, but also siblings to be infectively and metabolically screened if necessary.
|Table 5: Comparative results of chemical analysis of renal stones in different studies.|
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| Acknowledgment|| |
The authors are grateful to Dr. Khalid Shembesh, MBChB, MSc, PhD, for the statistical analysis of the data.
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M Ben Halim
Department of Pediatrics, Medical School, Tripoli University, Tripoli
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]