In a biopsy series of 244 patients with IgAN, Haas found fewer African Americans (in a major urban setting), similar to that noted in other U.S.-based studies of IgAN [9
]. While limited by the size of certain ethnic groups in the study population, Haas found no significant difference in renal survival associated with "white race, black race or Hispanic origin" [8
]. The reason for a lower prevalence of IgAN in African Americans relative to other kidney diseases remains unclear. The frequency of IgAN in African Americans does not appear to be influenced by the higher prevalence of the IgA2 allotype among this group [12
In our study, the fraction of biopsies in subclasses I and II (18%) was similar to that observed by Haas (23%). However, we observed a higher proportion of biopsies in subclasses IV and V (64% vs. 31%), and a lower proportion of biopsies in subclass III (19% vs. 45%) compared with Haas, possibly reflecting a temporal trend towards a higher biopsy threshold along with intergrader measurement bias.
In a study reviewing the pattern of glomerulonephritis in Singapore over the past two decades, Woo and colleagues reported that IgAN was the most common primary GN occurring in Singapore (42% of all primary GNs in the first decade and 45% in the second decade) [13
]. In our biopsy population during the same period that we studied, IgAN represented 12.8% of all biopsies with primary glomerular diseases and 8.4% of all biopsies (excluding transplant biopsies for non-glomerular diseases). In China, Li reported that IgAN was the leading cause of ESRD, accounting for approximately 18% of patients [6
]. In a national survey of Japanese patients with ESRD, Koyama et al. reported that 28% of new dialysis patients had IgAN listed as their primary cause of ESRD. Moreover, due to the number of additional biopsies showing chronic glomerulonephritis without immunofluorescent microscopic descriptions in the survey, the authors estimated that possibly 40% of newly registered dialysis patients in Japan might have had CKD from IgAN. In contrast, only 0.8% of incident ESRD patients in the U.S. have documented or suspected IgAN [14
]. Katznelson and Cecka, using data from the United Network for Organ Sharing (UNOS), have also reported a higher incidence of IgAN and chronic glomerulonephritis causing ESRD in Asian/Pacific Islander American recipients of renal allografts between 1991 and 1996 [15
In contrast, based on smaller biopsy series, a striking variation in prevalence rates of IgAN has been reported from Europe and South America. In the UK, for example, Ballardie and colleagues noted comparatively low prevalence rates of IgAN in a predominantly white population (Manchester, England) in the early 1970's. In the subsequent 15-year period, however, these investigators reported a phenomenal rise in the observed incidence of IgAN (accounting for 31% of all glomerulopathies in 1986), which the investigators felt more likely reflected a higher frequency of detection rather than true rise in disease incidence. Similar prevalence rates have also been documented from isolated white populations in Finland and southern Italy [16
]. In contrast, few studies have addressed the epidemiology of IgAN in Latin America. In a small Brazilian single-center cohort (N = 205) of primary glomerular diseases, Mazzarolo et al. reported relatively modest prevalence rates (10.2%) of IgAN [18
]. A larger series (N = 1,263) of renal biopsies from Peru noted much lower prevalence rates of IgAN, which accounted for only 0.9% of all glomerular lesions over a 10-year period at a central reference renal pathology laboratory in Lima [19
These differences may be partially attributed to increased screening and disparities in the indication for kidney biopsy. In Japan and South Korea, for example, school-aged children undergo annual screening for urinary abnormalities; kidney biopsy is subsequently recommended for children with evidence of proteinuria or hematuria [20
]. More comprehensive yearly health exams are further performed on full-time salaried employees throughout Japan, Singapore, and Hong Kong, making detection more likely in these ethnic groups. Furthermore, a significant reporting bias may also contribute to the higher reported prevalence rates of IgAN in Asian/Pacific Islanders, e.g., in the study by Koyama et al., only 502 (7%) of the approximate 6800 patients diagnosed with IgAN had undergone a confirmatory kidney biopsy [7
Although the etiology of IgAN remains unknown, there exists a strong suspicion for an environmental antigen trigger combined with a genetic susceptibility factor. Along these lines, several hypotheses have been proposed to account for the reportedly higher prevalence of IgAN in Asian/Pacific Islanders. With respect to potential dietary antigens, Wakai et al. found that high intake of rice and n-6 polyunsaturated fatty acids (PUFA) were associated with an increased risk of IgAN [21
]. Recent reports from Japan have also suggested a potential role of H. parainfluenzae
as a causative agent of IgAN in Japanese children and adults. Such claims are supported by studies showing the glomerular deposition of outer membrane H. parainfluenzae
antigens and greater levels of plasma IgA1 antibody against OMHP in Japanese patients with IgAN (compared to Japanese patients with other renal diseases) [22
]. Whether Japanese, or Asian/Pacific Islanders in general, have higher rates of H. parainfluenzae
colonization and/or infection has yet to be established.
The presence of either hypertension or proteinuria ≥ 3.0 g/24 hrs at the time of diagnosis significantly correlated with worsened renal survival in IgAN, even when controlling for serum creatinine at the time of kidney biopsy [2
]. We found no difference in the distribution of Haas subclass, hypertension and nephrotic proteinuria among Caucasians, Asian/Pacific Islanders, and Hispanics.
Despite ongoing investigative efforts, scant data are available regarding genetic markers that may predispose individuals to progressive disease from IgAN. Recent immunogenetic studies have suggested a potential role for the T-cell receptor (TCR) in the development of immune-mediated diseases. Deenitchina and colleagues found that genetic polymorphism of the TCR constant alpha chain was associated with progression of CKD in a cohort of Japanese patients with IgAN. Although promising, such polymorphisms of the TCR gene have yet to be evaluated in large, prospective studies or by genetic analysis of familial IgAN [24
Our results contest the assertion that IgAN follows a more severe course in individuals of Asian/Pacific Islander descent. One reason for the similar disease severity of IgAN in our study population may stem in part from the large subpopulation of Filipino patients comprising our Asian/Pacific Islander cohort. It is unclear whether certain subpopulations of Asian/Pacific Islanders, including Filipinos, exhibit IgAN prevalence rates similar to those documented by Koyama and Woo. Anecdotal reports from Thailand and India documenting prevalence rates of 4–9% suggest that IgAN may not have the same epidemiology among all southeast Asians [1
]. Despite having higher incidence rates of ESRD than the U.S. white population, the Asian/Pacific Islanders remain a largely unstudied group, for whom more comprehensive data collection is warranted.
There are several important limitations to this report. As with any single-center biopsy series, we may have been underpowered to detect a clinically significant difference due to the limited sample size (type II error). In addition, racial admixture may have also confounded the results, as we were unable to subclassify patients in the Asian/Pacific Islander group or account for the growing population of bi- or multi-ethnic individuals in our population. Furthermore, due to the study's case control design, and breadth of our referral base (northern California and Hawaii), we were unable to control for the criteria for kidney biopsy. As a result, a biopsy bias may have confounded our results. In other words, Asian/Pacific Islander patients in our referral base with mild to moderate proteinuria and/or hematuria might have been given a presumptive diagnosis of IgAN without nephrology referral or confirmatory kidney biopsy. With regard to disease prevalence, these potential referral and biopsy biases based on race/ethnicity are largely conservative in nature, and would have biased our results towards the null. Finally, we have included data from a modest-sized IgAN transplant population (N = 25), the donor demographics of which were unavailable at the time of the study. However, the association of race/ethnicity and distribution of glomerular lesion persisted, even when stratified by kidney transplant, and thus our overall conclusions remained the same. In addition, a small European study of donor-recipient pairs (average follow-up 7 years) has shown that when a donor kidney with asymptomatic IgA deposits is transplanted into a recipient with ESRD secondary to a disease other than IgAN, the IgA immune deposits in the donor kidney are rapidly removed [25