RENAL DATA FROM THE ARAB WORLD
|Year : 2014 | Volume
| Issue : 6 | Page : 1321-1327
|Fifteen years of kidney biopsies in children: A single center in Egypt
Ashraf Bakr1, Riham Eid1, Amr Sarhan1, Ayman Hammad1, Ahmed Mahmoud El-Refaey1, Atef El-Mougy1, Mohammed Magdy Zedan1, Fatma ElHusseini2, Ashraf Abd El-Rahman3
1 Pediatric Nephrology and Dialysis Unit, Mansoura University Children's Hospital, Mansoura University, Mansoura, Egypt
2 Pathology Department, Mansoura University Children's Hospital, Mansoura University, Mansoura, Egypt
3 Radiology Department, Mansoura University Children's Hospital, Mansoura University, Mansoura, Egypt
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|Date of Web Publication||10-Nov-2014|
| Abstract|| |
This study retrospectively investigates the indications and results of renal biopsy in children to determine the patterns of childhood kidney disease in a single tertiary children's hospital in Egypt. We included all the patients who underwent ultrasound-guided renal biopsy from 1998 to 2012. All the kidney biopsies were studied under light microscopy, while immunofluorescence and electron microscopy were performed when indicated. A total of 1246 renal biopsies were performed over 15 years, on 1096 patients. The mean age of the patients at the time of biopsy was 9.2 ± 3.7 years. The main indication for a biopsy was the steroid-resistant nephrotic syndrome (n = 354, 28.4%), followed by the atypical nephrotic syndrome (n = 250, 20.1%), and renal abnormalities in the systemic diseases (n = 228, 18.3 %). In the 1226 pathologically diagnosed specimens, primary glomerulonephritis was the most common finding (n = 826, 67.4%), followed by secondary glomerulonephritis (n = 238, 19.4%). The most common causes of primary glomerulonephritis were Minimal Change Disease (MCD) (n = 267, 21.8%), diffuse proliferative glomerulonephritis (n = 188, 15. 3%), and focal proliferative glomerulonephritis (n = 164, 13.3%). Lupus nephritis (n = 209, 17%) was the most common cause of secondary glomerulonephritis. We conclude that the steroid-resistant nephrotic syndrome was the most frequent indication for biopsy and minimal change disease was the most common histopathological finding in our population.
|How to cite this article:|
Bakr A, Eid R, Sarhan A, Hammad A, El-Refaey AM, El-Mougy A, Zedan MM, ElHusseini F, El-Rahman AA. Fifteen years of kidney biopsies in children: A single center in Egypt. Saudi J Kidney Dis Transpl 2014;25:1321-7
|How to cite this URL:|
Bakr A, Eid R, Sarhan A, Hammad A, El-Refaey AM, El-Mougy A, Zedan MM, ElHusseini F, El-Rahman AA. Fifteen years of kidney biopsies in children: A single center in Egypt. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2019 Nov 14];25:1321-7. Available from: http://www.sjkdt.org/text.asp?2014/25/6/1321/144307
| Introduction|| |
The first renal biopsy was an open surgical procedure.  Percutaneous renal biopsy was first described in 1934.  Data from the reports of renal biopsy provided an insight into the epidemiology of renal disease in children, which is an important basis for nephrologists to improve treatment.  Data on biopsy-based childhood renal diseases are available in studies from different countries. , There are few studies, with a small number of patients, on the patterns of kidney diseases in children from Arab countries. , However, there is no published data on the pattern of renal diseases in Egyptian children.
The aim of this study is to assess the indications for kidney biopsy in children and the pattern of glomerulonephritis (GN) and tubulo-interstitial disease among Egyptian children based on the histopathological results of the kidney biopsies.
| Subjects and methods|| |
We retrospectively analyzed the records of 1096 patients (591 males and 505 females) who underwent 1246 renal biopsies at the Pediatric Nephrology Unit, Mansoura University Children's Hospital, Mansoura, Egypt, from 1998 to 2012. Data regarding age, sex, indications for renal biopsy, and histopathological diagnoses were retrieved from the medical records. Kidney biopsies were performed after providing information to the families and obtaining written consents. Investigations performed before the biopsies included: hemoglobin blood levels, prothrombin time, activated partial thromboplastin time, platelet counts, renal function tests, and serological screening for viral hepatitis (B and C) and human immune deficiency virus. Biopsy was performed under sedation with midazolam and ketamine. The kidney specimens were considered adequate if >10 glomeruli were obtained or the pathologist was able to make a diagnosis based on the available number of glomeruli. All specimens were examined by light microscopy, while immunofluorescence and electron microscopy were performed when indicated. All the biopsies were reported by the same pathologist, in the same laboratory, for all the records over a period of 15 years.
Following the biopsy procedure, the patients were instructed to remain in bed for 24 hours. Vital signs were assessed at 15-minute intervals for the first two hours and hourly for a day thereafter. Each urine sample voided was examined for gross hematuria, for a day. Follow-up measurements of hemoglobin levels were performed 2-4 and 6-12 hours after the biopsy. The patients were discharged after 24 hours if there were no complications.
Indications for renal biopsy included the nephrotic syndrome (NS), renal manifestations of systemic diseases, chronic kidney diseases (CKD), with no definite etiology (defined as estimated glomerular filtration rate (eGFR) <75 mL/minute, calculated and normalized to the body surface area, according to Schwartz's formula),  acute renal failure (ARF) of unclear cause (diagnosed by rapidly reduced renal function), hematuria (recurrent gross or persistent microscopic, with or without proteinuria), and rapidly progressive glomerulonephritis (RPGN) (rapid deterioration of renal function, >50% decrease in GFR). No transplant biopsies were included.
All NS patients fulfilled the criteria for the International Study for Kidney Disease in Childhood, for the diagnosis of NS.  Systemic lupus erythematosus (SLE) was diagnosed according to the criteria of the American College of Rheumatology (ACR).  The indications of biopsy in NS were, (1) steroid-resistant nephrotic syndrome (SRNS) (2) atypical presentation: (Age: <12 months or >10 years, gross hematuria, low C3, sustained hypertension or renal impairment), and (3) steroid-dependent nephrotic syndrome (SDNS) and frequent relapsing nephrotic syndrome (FRNS), before starting the immunosuppressive therapy. The SDNS was defined as any relapse of the disease during maintenance therapy (any dose) or within two weeks of the end of the maintenance therapy. The FRNS was defined as a relapse two or more times in six months. These patients, according to our protocol, received re-induction till remission, followed by maintenance therapy for six months, with steroid therapy 0.5 mg/kg/every other day (EOD). The next relapse was treated with six months of steroid (1 mg/kg/EOD), and the following third relapse was treated with six months of steroids with levamizole (2.5 mg/ kg/EOD) and the fourth relapse treated with mycophenolate. A kidney biopsy would be considered, before starting, calcineurin inhibitors, or cyclophosphamide.
Primary glomerulonephritis (GN) included minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), focal proliferative glomerulonephritis (FPGN), diffuse proliferative glomerulonephritis (DPGN), membranoproliferative glomerulonephritis (MPGN), crescentric glomerulonephritis, IgA nephropathy, membranous GN, and chronic GN. Secondary GN included lupus nephritis (LN), hemolytic uremic syndrome (HUS), amyloidosis, and Henoch Schonlin Purpura (HSP). Kidney biopsy was indicated in the HUS, in cases of: All atypical HUS, typical HUS, who needed dialysis, and cases with suspicion of HUS as a cause of ARF.
Tubulointerstitial diseases included acute tubular necrosis and chronic tubulointerstitial nephritis. Hereditary glomerular diseases included congenital nephrotic syndrome (nephrotic syndrome presenting in the first three months of life, after exclusion of congenital infections), Alport's syndrome, and medullary sponge kidney.
| Statistical Analysis|| |
Data were described as frequencies and percentages for categorical variables. Continuous variables were reported as medians and ranges or as means and standard deviations. All data were analyzed using the Statistical Package for the Social Sciences (SPSS) software (Version 16, Chicago, USA).
| Results|| |
We studied the records of 1096 patients (591 males and 505 females), who had 1246 ultrasound-guided closed kidney biopsies. The mean age of the patients at the time of the biopsies was 9.2 ± 3.7 years (0.2-18 years). Age and sex distribution are summarized in [Table 1]. A single kidney biopsy was performed on 976 patients, two biopsies in 90, and three biopsies in 30 patients. The median number of glomeruli in the biopsy specimens was 12, while insufficient specimens were encountered in 20 specimens only.
|Table 1: Age and gender distribution of children who have undergone renal biopsy.|
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The most frequent indications for renal biopsy [Figure 1] were, the SRNS (n = 354, 28.4%), atypical NS (n = 250, 20.1%), and renal manifestations of systemic diseases (n = 228, 18.3%). [Table 2] shows that among the 1226 biopsies with determined pathological diagnosis, 826 (67.4%) biopsies revealed primary GN and 238 (19.4%) revealed secondary GN. The most common cause of primary GN was MCD (n = 267, 21.8%) followed by DPGN (n = 188, 15.3%). Lupus nephritis was the leading cause of secondary GN (n = 209, 17%) followed by HUS 1.3%. Hereditary glomerular diseases were present in 32 specimens (2.56%); 21 of them showed congenital NS. The frequencies of LN pathological classes are presented in [Figure 2].
|Figure 1: Frequency of indications of renal biopsy. NS: nephrotic syndrome. SRNS: steroid-resistant nephrotic syndrome. FRNS: frequent relapsing nephrotic syndrome. SDNS: steroid-dependent nephrotic syndrome.|
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| Discussion|| |
The histopathological findings in kidney diseases in children are of great importance in determining the accurate diagnosis and long-term prognosis, especially with the availability of a wide range of effective therapies. ,
The mean age at the time of biopsy in our study was 9.2 ± 3.7 years, which is comparable to studies from Jordan (7.56 years),  Sudan (8.71 years),  and Saudi Arabia (10.6 years). 
The kidney biopsies were done more frequently in males, the same as that reported elsewhere. ,,
The pattern of kidney diseases in children is quite different among different countries. ,,,,, These differences are related to racial and geographical factors, number of patients in the different studies, differences in biopsy indications, referral bias, and the non-availability of the necessary facilities (e.g., electron microscopy) in some of the reporting centers.
In our study, almost two-thirds of the children were biopsied due to indications related to NS. The SRNS was the most frequent indication (28.4%) followed by atypical NS (18.3%). These results are consistent with results from some countries and quiet different from the others. For example, the NS was the most frequent indication for renal biopsy in a study from Serbia (32%), of which SDNS was the most frequent.  Moreover, in a study from Turkey, NS was the most frequent indication (47%), of which SRNS was the most frequent.  On the other hand, Yuen et al reviewed 209 kidney biopsies obtained from 171 children with different renal diseases in Hong Kong and reported that NS was the second most common indication for renal biopsy (28%), of which SRNS was the most frequent (12%). 
In the current study, MCD was the most frequent histological pattern (21.8%) in children with NS, despite the empiric steroid therapy for patients with a high probability of having MCD, without confirmation of the diagnosis by renal biopsy. This could be explained by the non-selectivity of the cases, as our center received both new cases and others, referred by general hospitals and general practitioners. These results were consistent with some reports where MCD was the most frequent pathology result of renal biopsies from Saudi Arabia  and Sudan.  However, a report from Namibia found MCD in only 7.4% of the biopsy results.  In our study, FSGS prevalence was 10.5% (the fifth common pathological finding) close to the other reports from Sudan (13.7%)  and Turkey (7.3%).  Although, FSGS was the most common histopathological finding in Serbia (20.9%). 
In our study, IgA nephropathy (cases with confirmed diagnosis by immunofluorescence) was reported only in 0.36% of the patients. The low prevalence in the current study is in contrast to the findings in about 8.9% of the studies in Serbia  and 12% of the studies in Hong Kong.  This difference may be due to early screening of school children in Japan and Australia, apart from the racial, genetic and environmental factors,  and lack of immune studies and electron microscopy in many cases. 
In our study, the renal manifestations of systemic diseases accounted for 18.3% of the biopsy indications and LN was the most common secondary GN. Our results were quite different from the results from other Arab countries, where, LN represented only 5.5% in Saudi Arabia,  4.9% in Sudan,  and 3.4% in Jordan.  The high prevalence of LN in this study may be due to referral bias, as we are running a specialized lupus clinic, which receives SLE cases from different parts of the country. In our study, class IV LN was the most frequent one (30.1%) followed by class III (24.4%), which were both consistent with the results from a previous study conducted in our center in 2005, on 52 SLE children. 
In our study, HSP was the fourth cause of secondary GN and represented only 0.24% of all biopsy results; however, HSP was the most common cause of secondary GN in some studies as in Jordan,  Korea,  and England. 
Despite the high incidence of consanguineous marriages in our country, hereditary glomerular diseases represented only 2.6% of all cases, of which congenital NS represented only 21 cases of all the biopsied children, because clinically typical cases of Finnish-type congenital NS were not biopsied. The Alport syndrome was present only in eight cases because of lack of early urinalysis screening in school children. Cho and Im (2007)  and Hogg (2009),  highlighted the importance of urinalysis screening for the early detection of different glomerular diseases, including the Alport syndrome.
The most important limitations to this study include its retrospective design, thus missing data were encountered, as also irregular use of electron microscopy. As this is not a national survey, but a single-center study, indications to renal biopsy may have affected the percentage of frequency of the various glomerular diseases.
This study is the first single-center pediatric report of renal histopathological findings in Egypt; where SRNS was the most frequent indication, while MCD was the most common renal biopsy diagnosis. Data collected in this study should be a basis for a future Egyptian Registry of renal biopsy in children. This study enables the comparison of indications for renal biopsy and a spectrum of renal disease in children, with earlier published reports.
Financial support : No financial support.
Disclosure: All the authors have declared no competing interest.
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Dr. Riham Eid
Pediatric Nephrology and Dialysis Unit, Mansoura University Children's Hospital, Mansoura University, Mansoura
[Figure 1], [Figure 2]
[Table 1], [Table 2]
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