Pediatric renal diseases in the Kingdom of Saudi Arabia
Jameela Abdulaziz Kari
Jeddah, Kingdom of Saudi Arabia
Author Affiliations: Department of Pediatrics, Faculty of Medicine, Department of King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia (Kari JA)
Corresponding Author: Jameela Abdulaziz Kari, Consultant Pediatric Nephrologist, King Abdulaziz University, PO Box 80215, Jeddah 21589, Kingdom of Saudi Arabia (Tel: +996 55677904; Fax: +996 (2) 6684603; Email: jkari@ doctors.org.uk)
Background: Pediatric nephrology is a growing subspecialty in the Kingdom of Saudi Arabia (KSA). Pediatric nephrologists are challenged with a different spectrum of renal diseases. Moreover, there is a lack of epidemiological studies for most of these diseases. In this article, we discuss the spectrum of renal diseases in KSA and highlight the differences that exist between reports from KSA and those from other countries.
Data sources: PubMed and MEDLINE databases were searched for articles on pediatric renal diseases.
Results: Genetically mediated renal diseases are considerably high in KSA. Congenital and infantile nephrotic syndrome is higher in KSA than in other countries. Post-infectious glomerular pathology is rather common but is declining, while tropical infections such as schistosomiasis have been controlled. Neurogenic bladder caused by spinal lesion is an important cause of chronic kidney disease among pediatric patients. Renal stones are also more frequent in KSA than in other countries.
Conclusions: The spectrum of pediatric renal diseases in KSA is rather different from that reported from Western countries. More epidemiological studies are required to understand the actual incidence and nature of these diseases.
Key words: children; kidney anomalies; renal diseases
World J Pediatr 2012;8(3):217-221
The Kingdom of Saudi Arabia (KSA) is a large country with a high percentage of child population. Children aged 0-14 years represent 29.4% of the population, and the child population growth rate is 1.54%. The rate of consanguinity is high (52%-56% of marriages) in the Saudi population, and it is associated with a high percentage of genetically mediated renal diseases.[2-4] Other factors such as infection are still considerably high, leading to a higher incidence of post-infectious glomerular pathology, which was reported to affect 4% of pediatric patients with glomerulonephritis (GN). The lack of awareness among general pediatricians about the importance of early diagnosis of neurogenic bladder both in patients with spinal cord lesion or non-neurogenic neurogenic bladder contributed to the increased incidence of chronic kidney disease (CKD) in affected children at an early age of the disease as it was reported that they could have end-stage kidney disease (ESKD) before they finished their first decade of life. In this article, we review the pattern of kidney diseases in Saudi children and compare it with reports from other countries.
We searched the medical databases PubMed and MEDLINE to identify studies that were related to kidney diseases in pediatric patients. We used the search words kidney, renal, children, Saudi and pediatrics. We retrieved 534 articles and reviewed the abstracts of articles that were potentially relevant. We selected the abstracts of 54 articles that were relevant, and obtained the full text of the studies.
Patterns of renal diseases
Nephrotic syndrome (NS) is reported to be more common in Asian children than in Caucasian children. Similarly, it is thought to be more common in Arab children. However, no epidemiological data are available to confirm this observation. Mattoo et al reported that Saudi children with primary NS showed no differences in age of onset, male predominance and response to initial prednisolone therapy when compared with published data from other countries. However, they reported a higher incidence (6%) of familial occurrence. Congenital and infantile nephrotic syndrome was also reported to be higher in KSA than in other countries, a finding that has also been observed by pediatric nephrologists practicing in KSA. Abdurrahman et al reported an incidence of 17.0% for infantile nephrotic syndrome and 4.3% for congenital nephrotic syndrome in a cohort of 92 children with nephrotic syndrome. Histopathological reports of Saudi children with glomerular diseases have shown the predominance of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative glomerulonephritis (MesGNS) to be in the range of 24%-39% and 24%-35%, respectively.[5,7,10] On the other hand, IgA nephropathy was reported in 3%-4% of children with GN, which is less common than in Western countries.[9,10] Membranoproliferative glomerulonephritis (MPGN) seems to present at an earlier age in Arab children and tends to have a severe course with rapid progression to end-stage renal disease (ESKD). We reported 8 children with MPGN who presented with steroid-resistant nephrotic syndrome at a mean age of 1.1 years and progressed very quickly to ESKD. Similar to other parts of the world, it was observed that there was a shift toward an increasing prevalence of FSGS over the recent years in KSA. Post-infectious GN as a cause of nephrotic syndrome is not common. In a study conducted in 100 patients with nephrotic syndrome, Mattoo et al found that post-infectious GN was the cause of the condition in only 2% of their study population. Post-streptococcal GN is declining as it was reported as the underlying cause of GN in only 2.7%-2.9% of adult patients and 4% of pediatric patients.  However, it could present as early as 14 months. Lupus nephritis (LN) is a cause of glomerular disease in a significant number of children, and the familial form has been reported in 25 patients from 7 families with the mean age at presentation of 90.6 months (range: 24-144 months). The authors suggested the mode of inheritance to be autosomal recessive assuming Mendelian inheritance of single gene disorder. Early onset (<5 years) LN was also reported, and it was associated with poor outcome.
Structural abnormalities of the renal tract
Similar to reports from other parts of the world, congenital renal anomalies were reported in 45%-64.5% of children as the main underlying cause of CKD and ESKD in KSA.[19-21] Prenatal (antenatal) ultrasound (US) screening is the routine recommendation in KSA, and this has led to the detection of renal anomalies in 0.7% of screened babies, similar to the rate (0.76%) reported in a British cohort study. However, the availability and accuracy of US screening are varied as this examination is more available and done by more experienced staff in the big cities. This is, unfortunately, not the case in rural areas and small cities where availability and accuracy are limited. A study from Riyadh reported that the antenatal detection rate of posterior urethral valves (PUV) was only 27%, less than the international rate of 70%, despite the fact that most antenatal follow-ups were done in referral centers in the capital. This was reflected in the delay of the diagnosis in many of those children.
Neurogenic bladder caused by spinal lesion or non-neurogenic neurogenic bladder is an important cause of ESKD in KSA.[5,19,25] A study from the western province revealed that neurogenic bladder was the underlying cause of ESKD in 19.6% of children with CKD, and in 13.6% of the cases, it was associated with neural tube defects. The limited awareness of the importance of bladder management in children with spina bifida among pediatricians led to a considerable delay in commencing clean intermittent catheterization (CIC) in the affected children[5-25] and therefore to early CKD and ESKD. Neel et al[26,27] reported that although there were many complaints from children and their families, even from patients with sensate urethra, CIC was generally accepted by Saudis. However, most pediatric nephrologists and urologists observe a considerable degree of denial and non-acceptance of CIC in their patients. The Mitrofanoff principle, which involves the creation of a continent abdominal stoma, provides a satisfactory alternative to children who need CIC. Unfortunately, this principle is not widely available and in the absence of a clear referral system it is not done for all children who could benefit from it. Reports of other structural abnormalities of the renal tract such as multicystic dysplastic kidney (MCDK) with a natural history of involution are not different from those reported from other countries.[30,31] Al-Ghwery et al reported that 86% of children with MCDK in their study had a complete or partial involution at a mean age of 43.6 months. Cultural issues could influence the decision to go for some urological operations such as the repair of anterior hypospadias, which might not be necessary since urination is normally done in a sitting or squatting position in KSA.
Genetically transmitted renal diseases in children
An estimated 70% of cases of kidney diseases in childhood are congenital with a likely genetic basis. In KSA, due to the high rate of consanguineous marriages, this percentage is presumably even higher particularly for diseases with an autosomal recessive transmission. There are few published epidemiological studies on the actual incidence of various genetically transmitted renal diseases in KSA. Preliminary observations indicate that children in KSA probably have a higher incidence of polycystic kidney disease, familial juvenile nephronophthisis, congenital urological anomalies, familial nephrotic syndrome and tubular diseases such as familial hypomagnesemia hypercalciuria nephrocalcinosis syndrome (FHHNC) and renal tubular acidosis (RTA). There are few published descriptive and observational studies on various genetically transmitted renal diseases.[35-37] Collaborative research with researchers from developed countries led to Saudi contribution to a better understanding of some of these diseases, such as FHHNC, congenital nephrotic syndrome, and RTA.[38,39]
Some renal diseases with a familial predisposition have been reported for the first time from KSA. Ohlsson et al reported a syndrome of osteopetrosis, renal tubular acidosis and cerebral calcification. The disease, known as "marble brain disease", is associated with stunted growth and mental retardation, and has been linked to carbonic anhydrase II enzyme deficiency. In a study conducted in KSA, the authors reported that children with a deficiency of this enzyme required a long-term follow-up. Furthermore, new associations were reported as a possibility of new syndromes.[43,44] Recently, the availability of new high-throughput genotyping and sequencing technologies have provided help for genetic diagnosis of individuals with an inherited form of kidney disease. Genetic studies revealed novel mutations of cystinosis and nephrogenic diabetes insipidus. Aldahmesh et al studied the mutation spectrum of CTNS of cystinosis in 21 children from 13 families. Eight mutations were identified, four of which were novel (c.530A>G, c.681G>A, 1013T>G, and c.1018_1041del) with the conclusion that those alleles will provide the basis for routine molecular diagnosis of cystinosis in the region. Two novel mutations were identified in each of AVPR2 and AQP2 underlying nephrogenic diabetes insipidus in Arab families.
Infections and renal diseases
Urinary tract infections (UTIs) are common in Saudi children, but the exact incidence is unknown. There are cultural issues, which reduce the incidence of UTI in children such as circumcision done to all children based on Islamic religious instruction, and the standard practice of washing the genital or anal area with water after urination or defecation. However, it is believed that structural renal abnormalities are more common in Saudi children. It was reported that vesico-uretral reflux is higher (41%) in Saudi children after their first UTI compared with other reports of 25%-30%. The commonest causing organism is Escherichia coli followed by Klebsiella. Tropical infections such as schistosomiasis have been controlled more than two decades ago in most parts of KSA and recently even in endemic areas such as Jazan in the south, near Yemen. The success of the interventions, which were based on case finding, treatment of infected individuals, and the chemical and environmental control of freshwater snails, led, in mid-2002, to a strategy to eliminate human infection with Schistosoma haematobium from Jazan.
Renal stones are more common, and they affect up to 20% of the Saudi adult population. This could be attributed to the hot weather and other environmental factors as well as nutritional and genetic factors. Similarly, it was reported that nephrolithiasis was not uncommon in children and adolescents. Calcium oxalate stones are the most common in adults and children.[54,55] Shock wave lithotripsy is widely used for management, and it is known to have a high rate of success.[56,57] Vesical calculosis due to malnutrition in the very early years of life is currently very rare in KSA. This could be explained by the recent affluence, which has spread to all social classes and with it the tendency to eat "rich" food in large quantities. Primary metabolic defect as the underlying cause was reported as well in about 11% of the patients in a study conducted at a tertiary hospital in Jeddah, but the actual percentage could be higher as the sophisticated facilities to diagnose rare inborn errors of metabolism are available in few referral centers only.
The spectrum of pediatric renal diseases in KSA is rather different from that reported from Western countries. More epidemiological studies are required to understand the actual incidence and nature of these diseases.
Ethical approval: Not needed.
Competing interest: The author declares no conflict of interest.
Contributors: Kari J is the sole author of the paper.
1 Saudi Arabia Demographics Profile 2012. Index Mundi Website. http://www.indexmundi.com/saudi_arabia/demographics_profile.html (accessed February 11, 2012).
2 El-Mouzan MI, Al-Salloum AA, Al-Herbish AS, Qurachi MM, Al-Omar AA. Regional variations in the prevalence of consanguinity in Saudi Arabia. Saudi Med J 2007;28:1881-1884.
3 El Mouzan MI, Al Salloum AA, Al Herbish AS, Qurachi MM, Al Omar AA. Consanguinity and major genetic disorders in Saudi children: a community-based cross-sectional study. Ann Saudi Med 2008;28:169-173.
4 Al-Abdulkareem AA, Ballal SG. Consanguineous marriage in an urban area of Saudi Arabia: rates and adverse health effects on the offspring. J Community Health 1998;23:75-83.
5 Al-Sabban E. Spectrum of glomerular disease among children in Saudi Arabia. Saudi J Kidney Dis Transpl 1997;8:285-288.
6 Kari JA. Neuropathic bladder as a cause of chronic renal failure in children in developing countries. Pediatr Nephrol 2006;21:517-520.
7 Sharples PM, Poulton J, White RH. Steroid responsive nephrotic syndrome is more common in Asians. Arch Dis Child 1985;60:1014-1017.
8 Mattoo TK, Mahmood MA, Al-Harbi MS. Nephrotic syndrome in Saudi children clinicopathological study of 150 cases. Pediatr Nephrol 1990;4:517-519.
9 Abdurrahman MB, Shipkey FH, Elidrissy AT, Al-Kahtani W. Nephrotic syndrome in Saudi infants in the first year of life. Ann Trop Paediatr 1989;9:140-146.
10 Al-Rasheed SA, Al-Mugeiren MM, Al-Salloum AA, Al-Sohaibani MO. Childhood renal diseases in Saudi Arabia. A clinicopathological study of 167 cases. Int Urol Nephrol 1996;28:607-613.
11 Kari JA. Early presentation of membranoproliferative glomerulonephritis in Arab children. Saudi Med J 2003;24:157-160.
12 Kari JA. Changing trends of histopathology in childhood nephrotic syndrome in western Saudi Arabia. Saudi Med J 2002;23:317-321.
13 Mattoo TK, Al-Sowailem AM. Spectrum of renal pathology in 100 selected children with nephrotic syndrome. Ann Saudi Med 1993;13:420-422.
14 Mitwalli AH. Glomerulonephritis in saudi arabia: a review. Saudi J Kidney Dis Transpl 2000;11:567-576.
15 Kari JA, Bamagi A, Jalalah SM. Severe acute post-streptococcal glomerulonephritis in a 14 month-old-girl. Saudi J Kidney Dis Transpl. In press 2012.
16 Al Arfaj AS, Khalil N, Al SS. Lupus nephritis among 624 cases of systemic lupus erythematosus in Riyadh, Saudi Arabia. Rheumatol Int 2009;29:1057-1067.
17 Qari A, Al-Mayouf S, Al-Owain M. Mode of inheritance in systemic lupus erythematosus in Saudi multiplex families. Genet Couns 2009;20:215-223.
18 Al-Mayouf SM, Al SA. Influence of gender and age of onset on the outcome in children with systemic lupus erythematosus. Clin Rheumatol 2008;27:1159-1162.
19 Kari JA. Chronic renal failure in children in the western area of Saudi Arabia. Saudi J Kidney Dis Transpl 2006;17:19-24.
20 Al HN. Chronic renal failure in children in Asir region of Saudi Arabia. Saudi J Kidney Dis Transpl 1997;8:294-297.
21 Al-Ghwery S, Al-Asmari A. Chronic renal failure among children in Riyadh Military Hospital, Riyadh, Saudi Arabia. Saudi J Kidney Dis Transpl 2004;15:75-78.
22 Raboei E, Abou-Seoud M, Abou-Nassef N, Mehboob F, Saggaf A, Luoma R. Prenatal ultrasound screening of the urinary tract is useful. Pediatr Surg Int 2002;18:432-434.
23 Mallik M, Watson AR. Antenatally detected urinary tract abnormalities: more detection but less action. Pediatr Nephrol 2008;23:897-904.
24 Neel KF, El-Faqih SR, De CR, Abu Daia JM, Al-Shammari AM, Al-Jasser A, et al. Presentation of posterior urethral valves in Saudi Arabia in the 90's. Saudi J Kidney Dis Transpl 2001;12:516-519.
25 Kari JA, Safdar O, Jamjoom R, Anshasi W. Renal involvement in children with spina bifida. Saudi J Kidney Dis Transpl 2009;20:102-105.
26 Neel KF, Salem MA, Soliman SM, Al-Hazmi H, Gomha AB, Khatab AA. Acceptance and compliance of clean intermittent catheterization among Saudi patients. Saudi Med J 2008;29:1014-1017.
27 Neel KF. Feasibility and outcome of clean intermittent catheterization for children with sensate urethra. Can Urol Assoc J 2010;4:403-405.
28 De Castro R, Fouda Neel KA, Alshammari AM, Abu Daia JM, Abd Al-Aaly MA. Clean intermittent catheterization in Saudi children. Suggestion for a common protocol. Saudi Med J 2000;21:1016-1023.
29 Ahmed S, Sen S. The Mitrofanoff procedure in paediatric urinary tract reconstruction. Aust N Z J Surg 1998;68:199-202.
30 Al-Ghwery S, Al-Asmari A. Multicystic dysplastic kidney: conservative management and follow-up. Ren Fail 2005;27:189-192.
31 Aslam M, Watson AR. Unilateral multicystic dysplastic kidney: long term outcomes. Arch Dis Child 2006;91:820-823.
32 Anikwe RM, Kamal BA, Hegazi MM, Hashish M, El-Darawani H, Taha SA. Anterior hypospadias. Is repair necessary with urination in a sitting or squatting position? Saudi Med J 2000;21:364-367.
33 Bockenhauer D, Medlar AJ, Ashton E, Kleta R, Lench N. Genetic testing in renal disease. Pediatr Nephrol 2012;27:873-883.
34 Mattoo TK. Genetically transmitted renal diseases in children: a saudi perspective. Saudi J Kidney Dis Transpl 1998;9:105-109.
35 Mattoo TK, Khatani Y, Ashraf B. Autosomal recessive polycystic kidney disease in 15 Arab children. Pediatr Nephrol 1994;8:85-87.
36 Kari JA, Farouq M, Alshaya HO. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Pediatr Nephrol 2003;18:506-510.
37 Zakzouk SM, Sobki SH, Mansour F, Al Anazy FH. Hearing impairment in association with distal renal tubular acidosis among Saudi children. J Laryngol Otol 1995;109:930-934.
38 Schoeb DS, Chernin G, Heeringa SF, Matejas V, Held S, Vega-Warner V, et al. Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS). Nephrol Dial Transplant 2010;25:2970-2976.
39 Konrad M, Hou J, Weber S, Dotsch J, Kari JA, Seeman T, et al. CLDN16 genotype predicts renal decline in familial hypomagnesemia with hypercalciuria and nephrocalcinosis. J Am Soc Nephrol 2008;19:171-181.
40 Ohlsson A, Stark G, Sakati N. Marble brain disease: recessive osteopetrosis, renal tubular acidosis and cerebral calcification in three Saudi Arabian families. Dev Med Child Neurol 1980;22:72-84.
41 Ohlsson A, Cumming WA, Paul A, Sly WS. Carbonic anhydrase II deficiency syndrome: recessive osteopetrosis with renal tubular acidosis and cerebral calcification. Pediatrics 1986;77:371-381.
42 Awad M, Al-Ashwal AA, Sakati N, Al-Abbad AA, Bin-Abbas BS. Long-term follow up of carbonic anhydrase II deficiency syndrome. Saudi Med J 2002;23:25-29.
43 Faqeih E, Al-Akash SI, Sakati N, Teebi PA. Four siblings with distal renal tubular acidosis and nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial appearance: a possible new autosomal recessive syndrome. Am J Med Genet A 2007;143A:1951-1957.
44 Kari JA, Bamashmous H, Lingawi S, Al-Sabban E, Akhtar M. Infantile nephrotic syndrome and congenital glaucoma. Pediatr Nephrol 2001;16:894-897.
45 Al-Romaih KI, Genovese G, Al-Mojalli H, Al-Othman S, Al-Manea H, Al-Suleiman M, et al. Genetic diagnosis in consanguineous families with kidney disease by homozygosity mapping coupled with whole-exome sequencing. Am J Kidney Dis 2011;58:186-195.
46 Aldahmesh MA, Humeidan A, Almojalli HA, Khan AO, Rajab M, Al-Abbad AA, et al. Characterization of CTNS mutations in Arab patients with cystinosis. Ophthalmic Genet 2009;30:185-189.
47 Carroll P, Al-Mojalli H, Al-Abbad A, Al-Hassoun I, Al-Hamed M, Al-Amr R, et al. Novel mutations underlying nephrogenic diabetes insipidus in Arab families. Genet Med 2006;8:443-447.
48 Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J 2008;27:302-308.
49 Al-Ibrahim AA, Girdharilal RD, Jalal MA, Alghamdy AH, Ghazal YK. Urinary tract infection and vesicoureteral reflux in saudi children. Saudi J Kidney Dis Transpl 2002;13:24-28.
50 Al-Harthi AA, Al-Fifi SH. Antibiotic resistance pattern and empirical therapy for urinary tract infections in children. Saudi Med J 2008;29:854-858.
51 Ashi J, Arfaa F, Jeffri M, Suwairy M. Progress achieved in the control of schistosomiasis in Saudi Arabia. J Trop Med Hyg 1989;92:27-31.
52 Al Ghahtani AG, Amin MA. Progress achieved in the elimination of schistosomiasis from the Jazan region of Saudi Arabia. Ann Trop Med Parasitol 2005;99:483-490.
53 Ramello A, Vitale C, Marangella M. Epidemiology of nephrolithiasis. J Nephrol 2000;13 Suppl 3:S45-S50.
54 Khan AS, Rai ME, Gandapur, Pervaiz A, Shah AH, Hussain AA, et al. Epidemiological risk factors and composition of urinary stones in Riyadh Saudi Arabia. J Ayub Med Coll Abbottabad 2004;16:56-58.
55 Al-Rasheed S, Al Jurayyan NA, Al Nasser MN, Al-Mugeiren MM, Al-Salloum AA, Petterson BA. Nephrolithiasis in children and adolescents in the South Western region of Saudi Arabia. Saudi J Kidney Dis Transpl 1995;6:396-399.
56 Tayib AM, Mosli HA, Farsi HM, Atwa MA, Saada HA. Shock wave lithotripsy in patients with renal calculi. Saudi Med J 2008;29:1180-1183.
57 Farsi HM, Mosli HA, Alzemaity M, Bahnesy AA, Ibrahim MA. In situ extracorporeal shock wave lithotripsy (ESWL) for the management of primary ureteric calculi in children. J Pediatr Surg 1994;29:1315-1316.
58 Trinchieri A. Epidemiology of urolithiasis. Arch Ital Urol Androl 1996;68:203-249.
59 Al-Rasheed SA, El-Faqih SR, Husain I, Abdurrahman M, Al-Mugeirin MM. The aetiological and clinical pattern of childhood urolithiasis in Saudi Arabia. Int Urol Nephrol 1995;27:349-355.
60 Cochat P, Pichault V, Bacchetta J, Dubourg L, Sabot JF, Saban C, et al. Nephrolithiasis related to inborn metabolic diseases. Pediatr Nephrol 2010;25:415-424.
Received February 14, 2012 Accepted after revision April 3, 2012