Kidney Disease in Bahrain: A Biopsy-Based Epidemiological Study A.A. Arrayed, S. Shariff, and M.M.A. Maamari ABSTRACT The aim of this study was to establish the incidence of renal diseases in Bahrain during January 2003 through October 2006, based on biopsy results. This study continued a previous biopsy-based survey covering 13 years from January 1990 through December 2002. Comparisons were made with the previous study to ascertain whether the disease pattern continued in the same trend. The current study included 145 biopsies on 130 patients, of whom glomerular diseases constituted 64.8%; transplant biopsies, 23.4%; chronic glomerulosclerosis, 8.9%; and other etiologies, 4.1%. There were comparable numbers of primary and secondary glomerular diseases in the present series. The incidence of renal biopsies per 100,000 population per year did not significantly change over the last 15 years: 5.4/100,000 per year in the present series versus 5.8/100,000 per year in the previous study. The pattern of primary glomerular diseases showed the minimal change disease—focal segmental glomerulosclerosis (MCD-FSGS) complex—remained the most common of all primary glomerular diseases, although decreased in absolute numbers compared with the previous study. A significant increase in the number of patients with immunoglobulin A nephropathy was observed over the years. Secondary glomerular diseases showed an increased incidence with lupus nephritis the number one diagnosis. Also we observed a steady increase in the number of allograft biopsies.
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PIDEMIOLOGICAL STUDIES on renal biopsies are necessary to establish the pattern and trends of renal diseases in a particular geographic area. This is important for monitoring disease trends and to establish policies for early detection and institution of appropriate measures for control of existing diseases. A report on the epidemiological pattern of renal diseases in the Kingdom of Bahrain was published in 2004.1 It covered the 13-year period from January 1990 to December 2002. The current study continues of the previous one, covering the period from January 2003 to October 2006. Specifically, it was undertaken to (1) establish the incidence of medical renal disease during this period; (2) provide an extension of the previous biopsy epidemiological study; (3) see whether the disease patterns continued in the same trend; and (4) compare the results with those available in the literature.
The indications for renal biopsy were proteinuria, macro/microscopic hematuria, nephrotic syndrome, or impaired renal function in nontransplant and renal transplant patients. All biopsies were obtained by a percutaneous Truecut needle. Three samples were embedded for light microscopy, immunoflurescence, and electron microscopy. Light microscopy examined 3- to 4-m-thick sections including a minimum of three hematoxylin and eosin-stained sections, one periodic acid Schiff, one Masson trichrome, and one Jones silver stain. Specimens were sent for electron microscopy abroad whenever necessary. The total number of cases and biopsies were recorded for patient demographic features: age, sex, nationality, and percentage incidence of disease. With regard to nationality patients were divided into Arab versus non-Arab. We determined incidence for each type of glomerular disease. Comparisons were made with the corresponding information obtained from the previous study and similar information from other countries.
MATERIALS AND METHODS All renal biopsies, nephrectomy specimens, and referral slides pertaining to renal parenchymal disease were reviewed for January 2003 through October 2006. Cases were categorized into the following groups: (1) glomerular diseases—primary and secondary; (2) tubulointerstitial disease; (3) transplant pathology; and (4) miscellaneous. © 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 39, 875– 878 (2007)
From the Departments of Nephrology (A.A.A.) and Pathology (S.S., M.M.A.M.), Salmaniya Medical Complex, Kingdom of Bahrain. Reprint requests to Dr Ahmed Al Arrayad, Chairman, Department of Nephrology, Salmaniya Medical Complex, Kingdom of Bahrain. 0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.03.079 875
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ARRAYED, SHARIFF, AND MAAMARI Table 1. Diseases Affecting 130 Patients Disease
No. of Patients
No. of Biopsies
Age Range
Male
Female
Arabs
Non-Arabs
Primary glomerular disease Secondary glomerular disease Acute allergic drug-induced tubulointerstitial nephritis Chronic tubulointerstitial/ESRD Transplant pathology Miscellaneous (segmental hypoplasia) No significant pathology
47 46 3 8 23 1 2
47 47 3 8 37 1 2
10 mo to 77 y 1–71 y 21–55 y 3–67 y
31 20 1 5 15 0 2
16 26 2 3 8 1 0
40 42 2 7 21 0 2
7 4 1 1 2 1 0
51 y 23–27 y
ESRD, end-stage renal disease.
In diabetic patients, kidney biopsy was only done if the history and urinalysis were not consistent with a diagnosis of diabetic nephropathy.
RESULTS
In the 3-year and 10-month period, 145 renal biopsies were obtained from 130 patients in the Department of Pathology, Salmaniya Medical Complex, included more than one biopsy each for patients with transplants and two biopsies from one case of lupus nephritis. Of the 130 patients, 114 were Arab, constituting 87.6% of the total. Seventy-four patients were male and 56 female with a male-to-female ratio of 1.3:1. Table 1 shows the diseases affecting these 130 patients in relation to age, sex, and ethnic origin. Table 2 shows the distribution of the various types of primary glomerular diseases during this period of time in relation to age, sex, and ethnic origin; Table 3 shows the distribution of various types of secondary glomerular diseases in relation to the same characteristics. Thirty-four biopsies (23.4% of total) were allograft cases belonged to 23 patients (Table 4). Electron microscopy was performed on 20 of the 145 biopsies. It helped to confirm the diagnosis in cases of MPGN, thin membrane disease, congenital nephrotic syndrome, FSGS, and lupus nephritis. It ruled out MPGN in two cases. DISCUSSION
The present population of Bahrain is 698,585.2 Based on this, the incidence rate of renal biopsy in the present series
is 5.4/100,000 per year. This is similar to the biopsy rate of 5.8/100,000 per year observed in the previous study,1 namely, an average of 38 biopsies per year. While this rate of renal biopsies in the Kingdom of Bahrain is higher than that reported in other Middle Eastern countries like the United Arab Emirates,3 and the eastern European country of Romania4 (1 per 100,000/yr), it is equal to the incidences in Spain5 and Macedonia,6 and much lower than Australia7 (21.5 per 100,000 population), Korea,8 Hong Kong,9 or India.10 Though biopsy rates may indirectly reflect the prevalence of renal disease in a particular geographic region, they are influenced by several factors: population status, biopsy policies, and type of institution. Glomerular diseases constituted 64.1% of the total biopsies in the present study. In the previous series,1 they constituted 67.5% of the total biopsies. In the Chan et al series,9 (primary and secondary) glomerular diseases constituted 73% of total biopsies, while in the Narasimhan et al series from India,10 71% of all biopsies were a primary glomerular disease alone. Primary and secondary glomerular diseases were observed in almost equal numbers in the present series, whereas in the previous study primary glomerular diseases outnumbered secondary ones, namely, 66.4% primary versus 33.6% secondary.1 Of the primary glomerular diseases the spectrum of MCD- FSGS constituted the highest frequency in the present study (12/47; 25.5%) closely followed by MPGN (10/47; 21.3%). Immunoglobulin A (IgA) nephropathy and membranous glomerulonephritis were next in frequency (14.9% and 12.8%, respectively). The percent-
Table 2. Types of Primary Glomerular Diseases Disease
No. of Patients
No. of Biopsies
Age Range
Male
Female
Arabs
Non-Arabs
MCD FSGS Membranous GN Postinfectious GN IgA nephropathy IgM nephropathy MPGN* Cresentic GN Thin membrane disease Congenital nephrotic syndrome Sickle cell nephropathy
4 8 6 3 7 1 10 1 1 3 3
4 8 6 3 7 1 10 1 1 3 3
19–29 y 14–44 y 21–74 y 5–35 y 7–54 y 51 y 9–77 y 13 y 12 y 10 mo–3 y 20–38 y
1 6 3 3 4 1 8 0 1 1 3
3 2 3 0 3 0 2 1 0 2 0
3 7 5 1 7 0 9 1 1 3 3
1 1 1 2 0 1 1 0 0 0 0
*One of the 10 cases also showed end-stage renal disease.
KIDNEY DISEASE IN BAHRAIN
877 Table 3. Types of Secondary Glomerular Diseases
Disease
No. of Patients
No. of Biopsies
Age Range (y)
Male
Female
Arabs
Non-Arabs
Lupus nephritis Diabetic nephropathy Hypertension HUS Henoch Schonlein purpura
21 13* 7* 4 1
22 13 7 4 1
11–57 30–71 38–62 1–47 6
2 10 5 2 1
19 3 2 2 0
20 12 6 3 1
1 1 1 1 0
*Three of 13 and one of eight cases also showed end-stage renal disease.
age distribution of primary glomerular disease in the previous Bahrain study was: MCD (30%), FSGS (23.8%), MPGN (14.3%), membranous GN (13.5%), mesangioproliferative glomerulonephritis (5.8%). The incidence of IgA nephropathy in the current series was significantly higher: 14.9% in the present versus 0.4% in the previous study. IgA nephropathy is the most common primary nephropathy seen in many series.7,9,11,12 Better standardization of the detection techniques for immunoglobulin on biopsy material may have contributed to the increased incidence. Secondly, it is possible that in the former series some cases of IgA nephropathy were categorized as mesangioproliferative glomerulonephritis (the most common morphological form of IgA nephropathy). Ten cases of MPGN were observed in the present study (21.3%), which was greater than the 14.3% in the former study. In other studies IgA among primary glomerulopathies have varied from 29.4%4 to 5.9%8 and 3.7%.10 The percentage of postinfectious glomerulonephritis, congenital nephrotic syndrome, and sickle cell nephropathy was each 6.4% in the present study. In the previous study, lupus nephritis was the most common cause of secondary glomerular diseases (38.9%) followed by diabetic nephropathy (31.9%) and hypertension (20.4%.). This order has also been evident in the present study: 45.6%, 28.2%, and 17.3%, respectively. A significantly increased incidence of performing transplant biopsies has been reported in the present study (23.5% of the total biopsies) compared with the previous one (12.2%). This may be due to various factors: increased number of transplants and awareness with regard to patient welfare and management leading to enthusiastic monitoring by the clinician. The percentage of allograft biopsies as a percentage of the total number in the series of Chan et al was 15.3%.9 Chronic tubulointerstitial disease leading to end-stage renal disease (ESRD) was seen in eight patients. In addi-
tion, advanced glomerulosclerosis was observed in five other patients (Table 2 and 3), totaling 13 patients out of 111 when allograft biopsies were excluded (ie, 11.7%). Varying percentages of ESRD have been observed, and ESRD is a growing problem worldwide. In most cases the cause in not known.13,14 Male patients dominated primary glomerular diseases in the former as well as the current study with male-to-female ratios being 1.3:11 and 1.9:1, respectively. This is contrary to the marked predominance of female patients with lupus nephritis, which has shifted the ratio in favor of females among secondary glomerular diseases in the present series (ie, 1:1.3 as compared to 1:1.05 in the past).1 The numbers in the various categories are few for conclusions to be drawn with regard to age. In conclusion, the incidence of renal biopsies per 100,000 population per year in the Kingdom of Bahrain has remained the same over the last 15 years. The pattern of primary glomerular diseases demonstrated the MCD-FSGS complex to be the number one etiology for primary glomerular disease in the last 15 years, although decreased in absolute numbers. We observed a significant rise in the occurence of IgA nephropathy. Secondary glomerular diseases showed an increased incidence, with lupus nephritis continuing to be the most common secondary glomerulopathy. We observed steady increase in allograft biopsies. REFERENCES 1. Al Arrayed A, George SM, Malik AK et al: The spectrum of glomerular diseases in the Kingdom of Bahrain: an epidemiological study based on renal biopsy interpretation. Transplant Proc 36:xxx, 2004 2. Available at wwwcountryreports.org/country.aspx?countryID⫽ 20&countryName⫽Bahrain-76k 3. Yahya TM, Pingle A, Boobes Y, et al: Analysis of 490 kidney biopsies: data from the United Arab Emirates Renal Diseases Registry. J Nephrol 11:148, 1998
Table 4. Transplant Pathology Disease
No. of Patients
No. of Biopsies
Age Range (y)
Male
Female
Arabs
Non-Arabs
Acute cellular rejection Chronic allograft nephropathy Cyclosporine toxicity alone Glomerular disease ATN alone Vascular thrombosis/infarction
8* 6 4 4 1 2†
15 9 4 4 2
28–64 37–65 44–52 44–65 37
6 3 3 1 1
2 3 1 3 0
7 5 3 4 1
1 1 0 0 0
*Four of these patients went on to subsequently show acute cyclosporine toxicity. † Lesions occurred as an end result in patients shown in other categories.
878 4. Covic A, Schiller A, Volovat C, et al: Epidemiology of renal disease in Romania: a 10 year review of two regional renal biopsy data bases. Nephrol Dial Transplant 21:419, 2006 5. Riveria F, Lopez-Gomez JM, Perez-Garcia R: Frequency of renal pathology in Spain 1994 –1999. Nephrol Dial Transplant 17:1594, 2002 6. Polenakovic MH, Grcevska L, Dzikova S: The incidence of biopsy proven primary glomerulonephritis in the republic of Macedonia-long term follow up. Nephrol Dial Transplant 18(suppl5):v26, 2003 7. Briganti EM, Dowling J, Finlay M, et al: The incidence of biopsy proven glomerulonephritis in Australia. Nephrol Dial Transplant 16:1364, 2001 8. Choi IJ, Jeong HJ, Hans DS, et al: An Analysis of 4,514 cases of renal biopsy in Korea. 42:247, 2001 9. Chan KW, Chan TM, Cheng IKP: Clinical and pathological characteristics of patients with glomerular diseases at a university
ARRAYED, SHARIFF, AND MAAMARI teaching hospital: 5 year prospective review. Hong Kong Med J 5:240, 1999 10. Narasimhan B, Chacko B, John GT, et al: Characterisation of kidney lesions in Indian adults: towards a renal biopsy registry. J Nephrol 19:205, 2006 11. Maisonneuve P, Agodoa L, Gellert R, et al: Distribution of primary renal diseases leading to end stage renal failure in the United States, Europe and Australia and New Zealand: results from an international comparative study. Am J Kidney Dis 35:157, 2000 12. Schena FP, Cerullo G, Torres DD, et al: The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait. BMC Nephrology 6:14, 2005. Available at: http://www.biomedcentral.com/1471-2369/6/14 13. Reikes ST: Trends in end stage renal disease-epidemiology, morbidity and mortality. Postgrad Med 108:124, 2000 14. Santa Cruz F, Cabrera W, Barreto S, et al: Kidney disease in Paraguay. Kidney Int 68(suppl 97):120, 2005