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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 2  |  Page : 269-275
IgA nephropathy: A clinicopathologic study from two centers in Saudi Arabia


1 Department of Pathology, College of Medicine, King Abdul Aziz University Hospital; Jeddah, Saudi Arabia
2 Department of Pathology, College of Medicine, King Abdul Aziz University Hospital; Jeddah; Department of Histopathology, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
3 Department of Medicine (Nephrology), King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
4 Department of Medicine (Nephrology), King Faisal Specialist Hospital and Research Centre, Saudi Arabia

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Date of Web Publication9-Mar-2010
 

   Abstract 

A total of 42 patients, who were diagnosed to have primary Immunoglobulin A neph­ropathy (IgAN) at the King Abdul Aziz University Hospital and King Faisal Hospital, Jeddah over the last seven years, were studied. The objective was to analyze their clinical and pathological fea­tures and to classify them according to Hass Classification by using light, immunofluorescence and electron microscopy. Majority of the study cases were males in the second, third and fourth decades of life. Hematuria was the most common clinical complaint followed by proteinuria. There were varying degrees of mesangial proliferation. Majority of the cases presented with class-2 followed by class-3. Immunofluorescence demonstrated diffuse granular deposition of IgA in the glomerular mesangium in majority of the cases. Ultrastructural analysis showed electron dense deposits within the matrix of the mesangium and paramesangium in majority of the cases. Sub-endothelial deposits and mesangial interposition were demonstrated in few cases. Extensive effacement with fusion of the visceral epithelial foot processes was detected in only few patients while focal effacement was demonstrated in many cases. Irregularities of the glomerular basement membrane were seen in some cases. We conclude that IgA nephropathy is an immune-complex glomerular disease, which occurs at all ages and with higher frequency in males and presents mostly with hematuria and proteinuria. Public health awareness is seriously needed to perform the investigations at an early stage.

How to cite this article:
Khawajah AQ, Al-Maghrabi J, Kanaan HD, Al-Ghamdi S. IgA nephropathy: A clinicopathologic study from two centers in Saudi Arabia. Saudi J Kidney Dis Transpl 2010;21:269-75

How to cite this URL:
Khawajah AQ, Al-Maghrabi J, Kanaan HD, Al-Ghamdi S. IgA nephropathy: A clinicopathologic study from two centers in Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 May 21];21:269-75. Available from: http://www.sjkdt.org/text.asp?2010/21/2/269/60193

   Introduction Top


Immunoglobulin A nephropathy (IgAN) is the most frequent primary glomerulonephritis that occurs globally and is recognized as a major cause of end-stage renal disease (ESRD) world­wide. [1],[2],[3] It tends to progress slowly, with prog­ression to ESRD within 25 years in about half of the affected patients. [4],[5],[6],[7],[8] Since 1968, when IgA nephropathy was first described, [9] great strides have been made in clarifying this disease as it poses many challenges to investigators and phy­sicians in its etiology, pathogenesis, prevention, and treatment. [10] The disease presents mainly with hematuria and often proteinuria. [11],[12] Mor­phologically, it is characterized by diffuse de­posits of IgA in the glomerular mesangium and by varying degrees of damage to the glomerular capillary network. [13] Renal biopsy and immu­nochemical analysis of renal tissue remain the gold standard for diagnosing IgA nephropa­thy. [14],[15] In the present study, we analyzed the cases of Ig-AN who presented in the last seven years in two hospitals of Jeddah region, with regard to their clinical, light microscopic, im­munofluorescence (IF) and electron micros­copic features and compared our findings with already published researches. Both these hospi­tals are tertiary referral centers in the Jeddah re­gion in the western part of Saudi Arabia. Al­though this study gives reasonable idea about the frequency of IgAN cases in our community, it cannot give an exact prevalence rate, for which we suggest a comprehensive multi-center study.


   Material and Methods Top


In the last seven years, a total of 42 patients were diagnosed to have primary IgAN on the basis of kidney biopsies performed at the King Abdul Aziz University Hospital and King Fai­sal Hospital, Jeddah, Saudi Arabia. The diagno­sis of IgAN was based on IF microscopy sho­wing mesangial deposits of IgA as the predo­minant or co-dominant immunoglobulin. Henoch­Schonlein purpura, systemic lupus erythemato­sus and liver cirrhosis were excluded by de­tailed clinical history, physical examination and laboratory findings. Blood and urinary labora­tory tests were performed in all patients' in­cluding serum creatinine, blood urea nitrogen, urine protein, and urinalysis. Main clinical pre­sentation(s) at the time of performing the renal biopsies were also noted.

For light microscopy, the specimens were fixed in 10% buffered formalin, later dehydrated in ascending grades of series of ethanol, cleared in xylene and embedded in paraffin. Sections were cut at a thickness of three microns, with a stan­dard microtome, mounted on glass slides and stained with hematoxylin and eosin (H& E), periodic acid schiff (PAS), Masson's trichrome (MT) and Jones Methenamine Silver (JMS) stains. Only biopsies containing five or more glomeruli were considered adequate. The lesions were classified according to Hass Classification as follows: [13],[16]

Class-1: Minimal or no mesangial hypercellu­larity

Class-2: Focal and segmental glomerulosclero­sis without cellular proliferation

Class-3: Focal proliferative glomerulonephritis

Class-4: Diffuse proliferative glomerulonephritis

Class-5: ≥ 40% global glomerulosclerosis, and/ or ≥ 40% cortical tubular atrophy

For IF, the fresh tissue in transport media was frozen and cryostat sections were cut at 5µ and incubated with antibodies specific for IgA, IgG, IgM, C3, C1q and fibrinogen. The intensity of immunofluorescence was graded as 0, 1+, 2+, and 3+.

For electron microscopy, small tissue sections (2 × 3 mm) from biopsy cores were fixed in phosphate-buffered 1% gluteraldehyde plus 4% formaldehyde (or 2.5% gluteraldehyde), post­fixed in osmium and embedded in plastic. Sur­vey sections were stained with toludine blue and examined to advantage by light microsco­py. Thin sections were stained with uranyl ace­tate and lead citrate for electron microscopic evaluation.


   Results Top


Of the 42 patients studied, there were 31 males and 11 females with age ranging from six to 72 years [Table 1]. Among males, most of the pa­tients (16.7%) presented in the age-group between 11 and 20 years. The second most com­mon group was between 21 and 30 years and 31 to 40 years, each occurring in 14.3% of the patients. Among females, most of the cases pre­sented in two age-groups, one between 11 and 20 years and the other between 31 and 40 years (7.1% each). Only one female patient presented at 72 years of age.

The clinical characteristics at the time of per­forming the renal biopsies are shown in [Table 2]. Hematuria was the most common presentation followed by proteinuria. Most of the patients pre­sented with macroscopic hematuria. One patient had severe loin pain along with gross hema­turia. A total of 16.7% of the patients had the nephrotic-nephritic syndrome (NNiS) and 21.4% patients had the nephritic syndrome (NiS), indi­cating that hematuria is a common finding in IgA nephropathy. No case of microscopic he­maturia without the NiS was noted. Majority of the patients presented with generalized edema. Twelve cases of the nephrotic syndrome were seen, two of whom were steroid resistant. Three cases presented with acute renal failure; one of them had a lymphoproliferative disorder. Non­specific presentation was seen in four patients (9.6%) who presented with hepatosplenomegaly, sore throat and/or hypertension.

There were varying degrees of mesangial proli­feration and abnormality. The distribution of the glomerular classes of the 42 patients is shown in [Table 3]. The majority of cases had class-2 (45.2%) followed by class-3 (21.4%). Only one case of minimal change disease was seen. Immu­nofluorescence findings are described in [Table 4]. Two cases could not be processed for IF study. In all cases, IF demonstrated diffuse granular deposits of IgA in the glomerular mesangium. Out of the 40 cases, 24 showed very strong positivity for IgA while only four cases showed a weak positivity for IgA. A total of 22.5% of the biopsies showed IgA and C3 positivity. Two cases with full-house IF and two cases (5%) with C1q, C3 and IgM showed IgA predomi­nance. Electron microscopic (EM) findings of the renal biopsy are shown in [Table 5]. There were electron dense deposits within the matrix of the mesangium and paramesangium in majo­rity of the cases. Sub-endothelial deposits and mesangial interposition were demonstrated in few cases. Only one case showed mesangial, paramesangial, intra-membranous and sub-epithelial deposits. Extensive effacement with fusion of the visceral epithelial foot processes was detected in two patients while focal effacement of the foot processes was demonstrated in 14 patients.


   Discussion Top


The male preponderance (male to female ratio of 2.8:1) shown in our study is also borne in international literature. [17],[18],[19] In Saudi Arabia, due to cultural reasons women tend to avoid such investigations. But in this context, even in other countries, it has to be remembered that usually more men undergo renal biopsies than women. [14] In one study the research showed the male to female ratio as 58:22. [15]

The worldwide frequency of IgA nephropathy varies widely from 2% to 52% of all renal biop­sies. [16] The frequency of 4.7%, noted in our study comes in the lower range, may be due to the lesser number of patients coming for their medical check up. As the awareness and oppor­tunity of medical facilities increase, the frequency of such diseases usually rises. For example, the available evidence shows an increasing inci­dence in India. In 1987, a frequency of 4.2% was reported from Tamil Nadu, a South Indian state. [20] In 1992, a frequency of 7.24% was reported from New Delhi in North India, [21] and in 1995, a fre­quency of 10.37% was reported from the North Indian Union Territory of Chandigarh. [22] Saudi Arabia is a rapidly developing country, not only in materialistic terms but also in medical aware­ness. Thus, with time we expect that in new re­searches we may see more number of cases of IgA nephropathy. This argument gets more im­petus from the other papers published before from Saudi Arabia. In a study carried out in the King Fahad Hospital, [23] IgA nephropathy was seen in 2.8% of their cases while in the King Khalid University Hospital, Riyadh, 3.0% of the cases had IgA nephropathy. [24] The low prevalence in Saudi Arabia, in contrast to the findings of about 40% prevalence in Japan, [25],[26] is quite striking. This difference may be also due to early scree­ning of school children in Japan apart from racial, genetic and environmental factors. One accepted fact is that there is a definite geogra­phic variation. In Europe, the highest frequency was reported from Italy (35.9%). [27] Among Asian countries, it ranged from 25% to 52%, [28] with the highest reported prevalence being from Singapore (52%). [29]

In a study from South Africa, the authors re­ported a very low prevalence in the black population (0.7%) as compared with Indian resi­dents (13.3%) supporting the conclusion from Yoshino's study that race and ethnicity are im­portant factors affecting the distribution of Ig­AN. [30] The low frequency of IgAN seen in our study may be due to avoidance of biopsy pro­cedure by the patients. Biopsy policy is certainly an important factor affecting the reported fre­quency of IgA nephropathy as has been poin­ted out in a study from the UK in which the fre­quency varied from 7.1% (1972-78) to 21.1% (1979-86). [31] The biopsy policy varied depending on the nephrologists and the availability of IF facility.

In our study, mesangial proliferation (class-2) was the most common class of IgA nephropa­thy. Class-3 was the second most common. How­ever, reports from different parts of the world indicate differences in the pattern of disease class. In a recent review, Tumlin et al reported that proliferative and crescentic forms (class-4) were responsible for up to 30% of reported IgA nephropathy. [32]

Since the features of IgA nephropathy identi­fied by light microscopy are nonspecific, IF or immunoperoxidase studies demonstrating a pre­dominant deposition of IgA are essential to es­tablish a definitive diagnosis of IgA nephropa­thy. The immune-complex deposits are found pre­dominantly within mesangial regions of glome­ruli with focal paramesangial or sub-endothelial extension. In our study, IgA was found to be the dominant immunoglobulin in 60% of the cases which is in concordance with the other resear­ches. [26],[28] As reported in literature, [17],[18] a variety of other immunoglobulins and complement are frequently co-distributed with IgA. In our study also, IgA was found to be positive in some ca­ses with other immunoglobulins including IgM and IgG.

In addition to the glomerular alterations, a va­riety of tubulointerstitial and vascular changes may be identified in patients with IgA nephro­pathy, including interstitial fibrosis, tubular atro­phy, interstitial inflammation, vascular sclerosis, or red-cell casts and proteinaceous casts within the tubules. [33],[34] Also, in our study, we found tu­bular atrophy in 14.3% of the cases along with interstitial inflammation and fibrosis.

Clinically, in the early stages of the disease, many patients have no obvious symptoms and are unaware of any problems. In these patients, IgA nephropathy may be suspected only during routine screening or investigation of another condition. In our study, only one such case was reported. Most of our patients presented in later stages. Clinical experience tells us that this is not only specific for IgA nephropathy but it is one of the general trends of our society.

Patients with IgA nephropathy usually present with one of the following: [11],[20] episodes of mac­roscopic hematuria (tea-colored urine) that may coincide with an infection of the upper respi­ratory tract or abnormal sediment in the urine and proteinuria in patients without symptoms. In our study, hematuria and proteinuria were the most common presentations as mentioned in other studies. [20],[25]

We conclude that IgA nephropathy, the most common form of primary glomerular disease, is an immune-complex-mediated glomeruloneph­ritis defined immunohistologically by the pre­sence of glomerular IgA deposits accompanied by a variety of lesions identified histopatholo­gically. A definitive diagnosis of IgA nephropa­thy can be made only by renal biopsy and im­munohistologic examination. It occurs at all ages, particularly in the second, third and fourth de­cades and more frequently in males. The disease may show regional variations in frequency which may be explained by genetic differences, differen­ces in renal-biopsy practices or differences in public awareness. The two most common clini­cal presentations are episodic hematuria and pro­teinuria. We advise that health authorities should actively participate in public health awareness programs so that the patients may be able to undergo special investigations at an early stage.

 
   References Top

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Correspondence Address:
Azhar Qayyum Khawajah
Department of Pathology, College of Medicine, King Abdul Aziz University Hospital, P.O. Box 80205, Jeddah 21589
Saudi Arabia
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