Renal Data from the Arab World

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1 Saudi J Kidney Dis Transpl 2013;24(2): Saudi Center for Organ Transplantation Saudi Journal of Kidney Diseases and Transplantation Renal Data from the Arab World Pattern of Glomerular Diseases in Oman: A Study Based on Light Microscopy and Immunofluorescence Nasar Yousuf Alwahaibi, Taiseer Ahmed Alhabsi, Samira Abdullah Alrawahi Department of Pathology, Sultan Qaboos University, Muscat, Oman ABSTRACT. Light microscopy and immunofluorescence play an important part in the final diagnosis of renal biopsy. The aim of this study was to analyze the pattern of various glomerular diseases in Oman. A total of 424 renal biopsies were retrospectively analyzed at the Sultan Qaboos University Hospital between 1999 and Focal and segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulopathy (MGN) and IgA nephropathy were the most common primary glomerular diseases encountered, accounting for 21.2%, 17%, 12.3% and 8.3%, respectively, of all cases. Lupus nephritis was the most common secondary glomerular disease and was the most prevalent among all biopsies, accounting for 30.4% of all biopsies. Amyloidosis was seen in only two cases. The presence of fluorescein isothiocyanate-fibrin in all renal cases was low when compared with IgG, IgA, IgM, C3 and C1q markers. In conclusion, based on the findings of this study, lupus nephritis was the most common of all glomerular diseases and FSGS was the most common primary glomerular disease. The importance of fluorescein isothiocyanate-fibrin in the diagnosis of renal biopsy needs to be further investigated. Introduction In Oman, recent data has shown that death caused by renal diseases constituted 3.32% of total deaths and was considered to be ranked 41 st in the world. 1 Despite the advanced technology and modern instrumentation in the diag- Correspondence to: Dr. Nasar Alwahaibi, Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box 35, Postal Code 123, Muscat, Oman nasarsidab@yahoo.com nosis of renal diseases, renal biopsy is still the method of choice for most nephrologists. Unlike other diseases in which histological examination by light microscopy is adequate, renal diseases are complex, and a combination of light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM) is needed. For LM, hematoxylin and eosin, periodic acid- Schiff, Jones methanamine silver and elastic Van-Gieson methods are used to demonstrate morphological details, which contribute greatly to the final diagnosis. However, histological picture alone is usually not enough to fully classify the pattern of renal diseases. IgG, IgA, IgM, C3, C1q and fibrin markers are routinely

2 388 Alwahaibi NY, Alhabsi TA, Alrawahi SA Figure 1. The distribution of glomerular diseases among five different age groups. LN: lupus nephritis, FSGS: focal and segmental glomerulosclerosis, MGN: membranous glomerulopathy, MCD: minimal change disease, IgAN: IgA nephropathy, FPGN: focal proliferative glomerulonephritis, APGN: acute proliferative glomerulonephritis, MesGN: mesangioproliferative glomerulonephritis, MPGN: membranoproliferative glomerulonephritis. demonstrated on frozen sections to evaluate the presence of immune deposits relevant to the investigated renal disease. IF constitutes the most widely used technique of immunohistochemistry. It is considered to be easier, faster, clearer and more sensitive than the immune-peroxidase method performed on formalin-fixed tissue. 2 Ultra-structural details are required to complete the picture of renal biopsy, especially with those diseases showing no immune deposits in the kidney. Unfortunately, and according to the best of our knowledge, there are no data on the pattern of renal diseases in Oman as there is no national renal biopsy registry. Thus, the aim of this study was to analyze the pattern of various glomerular diseases at the Sultan Qaboos University Hospital between 1999 and Materials and Methods This retrospective study was approved by the Medical Research Committee and Ethics Committee (MREC# 411) of the College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman. During the period from 1999 to 2010, data on 549 renal biopsies were available, of which 125 cases were excluded as they had an insufficient number of glomeruli. Thus, 424 cases were analyzed. The following procedure explains the routine handling of renal biopsies. Using a dissecting microscope, fresh biopsy was usually dissected into three pieces: one portion containing a good number of glomeruli was used for LM, the second portion containing a lesser number of glomeruli was used for IF and the third portion was processed for EM. For LM, the portion of renal biopsy was fixed in 10% neutral buffered formalin, histo-processed, cut at 3 µm thickness and stained with hematoxylin and eosin, periodic acid-schiff, Jone s methenamine silver and elastic Van- Gieson methods. For IF, the portion of renal biopsy was snap-frozen in liquid nitrogen, cut at 5 µm thickness, fixed in cold acetone and stained against fluorescence isothiocyanide conjugated IgG, IgA, IgM, C3, C1q and fibrin markers. Results A total of 424 renal biopsies were analyzed. In general, there were more males than females affected with primary glomerular diseases (60%

3 Pattern of glomerular diseases in Oman 389 Table 1. Patterns and frequencies of glomerular diseases in the study cases. Renal disease Frequency Percentage Lupus glomerulonephritis Focal and segmental glomerulosclerosis Minimal change disease Membranous glomerulopathy IgA nephropathy Acute proliferative glomerulonephritis Focal proliferative glomerulonephritis Mesangial proliferative glomerulonephritis Membranoproliferative glomerulonephritis Amyloidosis vs. 42%). When assessed individually, the male preponderance was evident for focal and segmental glomerulosclerosis (FSGS, 53.3% vs. 46.7%), membranous glomerulopathy (MGN, 53.8% vs. 46.2%) and IgA nephropathy (IgAN, 77.1% vs. 22.9%). Age of the patients with primary glomerular diseases ranged from few weeks to 60 years. Females were more frequently affected with secondary glomerular disease than males (80.9% vs. 19.1%). This was particularly evident with lupus nephritis (LN, 82.2% vs. 17.8%). The age of the patients with secondary glomerular diseases ranged from 8 to 45 years. LN and minimal change disease (MCD) were the most common glomerular diseases in children below the age of 14 years. Also, LN was the dominant lesion in adults aged between 15 and 25 years. At older age, MGN was more common (Figure 1). Of the study patients, 69.1% showed primary glomerular disease while 30.9% showed secondary glomerular disease (Table 1). LN was the most common of all glomerular diseases and accounted for 30.4% of the cases. FSGS and MCD were the common primary glomerular diseases and accounted for 21.2% and 17%, respectively. Mesangial proliferative glomerulonephritis (MesGN) and membranoproliferative glomerulonephritis (MPGN) were the least frequently encountered primary glomerular diseases and accounted for 1.9% and 1.4%, respectively. Amyloidosis was seen in only two cases (Table 1). The dominant deposit on IF in LN was C3 (96%), followed by IgG (87%), IgM (85%) and IgA (80%). IgG (98%) was dominant in MGN. High deposits of IgM (91%) were seen in MGN and focal proliferative glomerulonephritis. C3 (100%) was dominant in IgAN, MPGN, acute proliferative glomerulonephritis and MesGN. Fibrin was low in LN, focal segmental glomerulonephritis, MCD and IgAN and absent in MGN, MPGN, focal proliferative glomerulonephritis, acute proliferative glomerulonephritis and amyloidosis (Table 2). Table 2. Distribution of immunofluorescence markers in different glomerular diseases. Renal disease IgG IgM IgA C1q C3 Fibrin (%) (%) (%) (%) (%) (%) Lupus glomerulonephritis Focal segmental glomerulosclerosis Minimal change disease Membranous glomerulopathy IgA nephropathy Acute proliferative glomerulonephritis Focal proliferative glomerulonephritis Mesangial proliferative glomerulonephritis Membranoproliferative glomerulonephritis Amyloidosis

4 390 Alwahaibi NY, Alhabsi TA, Alrawahi SA Discussion The most common primary glomerular disease in our study was FSGS, followed by MCD, accounting for 21.2% and 17.0%, respectively. This finding is in line with reports from other Arab countries. In the Kingdom of Saudi Arabia and Sudan, FSGS and MCD were the first and second top listed primary glomerular diseases, respectively. 3,4 However, a similar study conducted in Bahrain showed that MCD was the most common primary glomerular disease, accounting for 30% of all cases, while FSGS was second, seen in 23.8% of the cases. 5 Surprisingly, in the United Arab Emirates, MGN was the most common primary glomerular disease, accounting for 21.8%, followed FSGS and MCD. 6 Reports from some non-arab Asian countries such as India, Pakistan and Bangladesh indicate that FSGS was the most common primary glomerular disease in India and Pakistan. 2,7 MCD was the second most common in India, while in Pakistan MGN was the second and MCD was the third most common primary glomerular disease. MesGN (34.3%) was the most common glomerular disease in Bangladesh, followed by MPGN (20.2%). The prevalence of FSGS and MCD was low in these countries, accounting for 2.8% and 2.1% of all cases, respectively. 8 Globally, IgAN remains the most common primary glomerular disease as reported in Italy and in the Czech republic. 9,10 LN was the most common cause of secondary glomerular disease. In fact, it was the dominant pattern of all types, accounting for 30.4%. This finding is consistent with previous findings Not surprisingly, LN was more common in females than in males, with a ratio of 4.6:1. This finding is in line with other studies In fact, other studies found a much higher ratio. 12,15 Amyloidosis is a rare cause of secondary glomerular disease in Oman. Other studies have also found similar results One of the important findings of the present study was the fibrin marker. It was found that fluorescein isothiocyanate-fibrin marker was low in the frequently encountered glomerular diseases, including LN, MCD, FSGS and IgAN, accounting for 9%, 6%, 3% and 3% of all cases, respectively. Other glomerular diseases showed even less or negative findings. This finding is in line with other similar studies, which showed low or negative findings of fibrin. 3,8 These two studies did not highlight the importance of reduction or absence of fibrin. The question that arises is the importance of fibrin marker in renal IF. It is known that fluorescein isothiocyanate-fibrin is expensive, time consuming and requires extra sections. In addition, the demonstration of fibrin can be performed on paraffin-embedded sections using Martius, Scarlet, Blue (MSB) method, which stains fibrin a red color. 16 The present study indicated that 22.8% of all cases were excluded as no glomeruli were seen in the biopsy core. This finding is consistent with other studies, which showed that analysis of renal biopsies could not be performed in 17.4%, % 17 and 23.9% 18 of all cases. As a limitation of this study, we should point out the absence of EM findings. However, as shown in other studies, LM and IF give adequate diagnosis of renal biopsies. In conclusion, based on the findings of this study, LN was the most common glomerular disease encountered and FSGS was the most common primary glomerular disease in Oman. The importance of fluorescein isothiocyanatefibrin in the diagnosis of renal biopsy needs to be further investigated. References 1. World Health Organization. Available from: [Last accessed on 2011 Dec]. 2. Narasimhan B, Chacko B, John GT, Korula A, Kirubakaran MG, Jacob CK. Characterization of kidney lesions in Indian adults: Towards a renal biopsy registry. J Nephrol 2006;19: Huraib SO, Abu-Aisha H, Mitwalli A, Mahmood K, Memon NA, Sulimani F. The spectrum of renal disease found by kidney biopsies at King Khalid University Hospital. Saudi Kidney Dis Transpl Bull 1990;1: Khalifa EH, Kaballo BG, Suleiman SM, Khalil EA, El-Hassan AM. Pattern of glomeruloneph-

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