letter to the editor
kidney disease and socioeconomic deprivation.2 Based on the hygiene hypothesis,3 it would appear that IgA nephropathy, being a mesangial proliferative glomerulonephritis (GN), would appear to be more prevalent among the socioeconomically deprived and this would be one explanation for the increased incidence of IgA nephropathy in Scotland. We have studied the changing pattern of primary GN in Singapore and other Asian countries over the past three decades.4 In Singapore the prevalence of mesangial proliferative GN has decreased from 32% in the first decade to 7% in the third decade, but IgA nephropathy has remained the most common cause of primary GN, with 42% in the first decade and 40% in the third decade. A similar trend is observed in the surrounding Asian countries.4 IgA nephropathy still remains the most common GN worldwide. We believe that the pathogenesis of IgA nephropathy is multifactorial and socioeconomic deprivation is only one aspect of the disease. Initially it may be associated with socioeconomic deprivation in some populations, but later, with urbanization, changing lifestyle, and exposure to other dietary antigens and environmental allergens, its pathogenesis may evolve. Geographical and racial or genetic factors would also play a role.5 1.
2. 3. 4.
5.
McQuarrie EP, Mackinnon B, McNeice V et al. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation. Kidney Int 2014; 86: 198–203. Hossain MP, Goyder EC, Rigby JE et al. CKD and poverty: a growing global challenge. Am J Kidney Dis 2009; 53: 166–174. Hurtado A, Johnson RJ. Hygiene hypothesis and prevalence of glomerulonephritis. Kidney Int 2005; 68: S62–S67. Woo KT, Chan CM, Chin YM et al. The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades. Clin Nephrol 2010; 7: 372–383. Gharavi A, Kiryluk Krzysztof, Choi M et al. Genome- wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 2011; 43: 321–327.
Keng-Thye Woo1, Marjorie Foo1, Hui-Lin Choong1, Han-Kim Tan1, Kok-Seng Wong1 and Choong-Meng Chan1 1 Department of Renal Medicine, Singapore General Hospital, Singapore Correspondence: Keng-Thye Woo, Department of Renal Medicine, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. E-mail: [email protected]
Kidney International (2014) 86, 651–652; doi:10.1038/ki.2014.169
The Authors Reply: We thank Dr Woo and colleagues for their response to our article describing the increased incidence of biopsy-proven immunoglobulin A (IgA) nephropathy in patients living in areas of multiple socioeconomic deprivation.1,2 Dr Woo proposes that the hygiene hypothesis may partially explain our findings. The hygiene hypothesis suggests that in developed nations the lack of exposure to significant infection in childhood predisposes to allergy and a predominantly T-helper 2 (Th2)-driven immune response. With IgA nephropathy being a predominantly a Th2-driven disease, the 652
hypothesis is that immune conditioning may be partially responsible for the increased incidence of IgA nephropathy seen in developed nations.3 This may explain some of the difference in incidence of the disease between Scotland, as a developed nation, and other less-developed nations. However, if significant infections would be expected to be more common in areas of multiple socioeconomic deprivation, then perhaps the incidence of IgA nephropathy would be expected to be lower in these areas if this were the main explanation. If our finding of an association with socioeconomic deprivation is confirmed, then this may go some way toward explaining the variation in incidence of disease worldwide and apparent changes in incidence over time. However, we agree that further work needs to be done to explore which aspects of socioeconomic deprivation influence the pathogenesis of disease, including infection, diet, smoking, hydrocarbons, and genetics. Other factors are also certainly involved in the apparent disparity in incidence of IgA nephropathy and other biopsy-proven renal diseases, not least the threshold for biopsy. 1. 2.
3.
Woo K-T, Foo M, Choong H-L et al. The incidence of IgA nephropathy is associated with socioeconomic deprivation. Kidney Int 2014; 86: 651–652. McQuarrie EP, Mackinnon B, McNeice V et al. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation. Kidney Int 2014; 86: 198–203. Hurtado A, Johnson RJ. Hygiene hypothesis and prevalence of glomerulonephritis. Kidney Int 2005; 68: S62–S67.
Emily P. McQuarrie1, Bruce Mackinnon1, Valerie McNeice2, Jonathan G. Fox1 and Colin C. Geddes1 1
Glasgow Renal and Transplant Unit, Glasgow, UK and 2Glasgow Centre for Population Health, Glasgow, UK Correspondence: Emily P. McQuarrie, Western Infirmary—Renal Unit, Dumbarton Road, Glasgow G11 6NT, Scotland, UK. E-mail: [email protected] Kidney International (2014) 86, 652; doi:10.1038/ki.2014.170
IgA nephritic patients of Pacific Asian origin with increased risk of progression to end-stage renal disease To the Editor: We read with great interest the above article1 in which the authors compared two groups of patients, a group of 202 Canadian patients of Pacific Asian origin and a group of 467 Canadian patients (mainly Caucasians), over a follow-up period of 46 months. These patients were recruited through the Toronto GN Registry and were registered from 1974 to 2012. The authors found that by univariate analysis the risk of end-stage renal disease (ESRD) was similar in the two groups, but that by multivariate analysis the risk of ESRD was significantly higher in the Pacific Asian group. This was supported by a significant 1.62 ml/min/year of faster estimated glomerular filtration rate (eGFR) decline in Kidney International (2014) 86, 649–653
letter to the editor
the Pacific Asian group. However, we note that in Table 1, 73.3% of Pacific Asian patients versus 45.3% of Caucasian patients were on angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers (ACEI/ARB) (Po0.001). Similarly, there were more Pacific Asian patients on steroids compared with Caucasians (23.8% versus 15.9%, Po0.02). Also, more Pacific Asian patients were on immunosuppressants compared with Caucasians (25.7% versus 19.3%, Po0.07). These two groups of patients in Canada would presumably have received standard medical care, and their medication would have been prescribed on the basis of clinical indications, such as proteinuria and eGFR. Considering the larger number of patients in the Pacific Asian group who required treatment, it would suggest that this group probably had more severe disease. Hence, it would not be surprising that the Pacific Asian group would have a more rapid decline of renal function and progression to ESRD. We believe that these two groups are not comparable on the basis of patient numbers and on the proportion of patients who are on treatment in the two groups. It may therefore be premature to attribute the more rapid decline in eGFR in the Asian patients to a ‘racial effect’. D’Amico,2 in a worldwide review of the actual renal survival at 10 years for patients with IgA nephritis, reported 87% patient survival in Australia, 85% in Europe, 81% in Germany, 85% in Italy, 80% in Japan, 83% in the United Kingdom, 78% in the United States of America, and 82% in Singapore. Li et al.3 reported a 10-year survival of 82% among the Chinese in Hong Kong. There was not much variation in renal survival for IgA nephritics worldwide. With regard to the rate of eGFR decline, Prakesh et al.4 compared two cohorts of Asian patients with IgA nephritis from two continents in a retrospective study. A cohort of 76
Kidney International (2014) 86, 649–653
patients from Thailand (1994–2005) was compared with a cohort of 152 Asian Canadian patients (1975–2006) who were also from the Toronto GN Registry. The adjusted rate of eGFR decline in the Thai patients was 0.8 ml/min/year compared with 3.35 ml/min/year in the Asian Canadian patients. The Asian Canadian patients were not treated with ACEI/ARB as their study period predated the introduction of ACEI/ARB in Canada. However, the Thai patients received ACEI/ARB and steroids, which may explain the slower rate of eGFR decline, although the authors attribute this difference to what they consider the ‘continental effect’ causing the variation in the rate of eGFR decline in these two groups of Asian patients. This study demonstrates that not all Asians with IgA nephritis have an increased risk of progression to ESRD. It may be a ‘continental effect’, as suggested by the authors, but the ‘racial effect’ appears nonexistent. 1.
2. 3.
4.
Barbour SJ, Cattran DC, Kim SJ et al. Individuals of Pacific Asian origin with IgA nephropathy have an increased risk of progression to end-stage renal disease. Kidney Int 2013; 84: 1017–1024. D’Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Seminars Nephrol 2004; 24: 179–196. Li PKT, Kai KLH, Szeto CC et al. Prognostic indicators of IgA nephropathy in the Chinese—clinical and pathological perspectives. Nephrol Dialysis Transpl 2001; 17: 64–67. Prakash S, Kanjanabuch T, Austin PC et al. Continental vatiations in IgA nephropathy among Asians. Clin Nephrol 2008; 70: 377–384.
Keng-Thye Woo1, Marjorie W.Y. Foo1, H. Lina Choong1, Han Khim Tan1, Kok-Seng Wong1 and Choong-Meng Chan1 1 Department of Renal Medicine, Singapore General Hospital, Singapore Correspondence: Keng-Thye Woo, Department of Renal Medicine, Singapore General Hospital, Singapore 16960, Singapore. E-mail: [email protected]
Kidney International (2014) 86, 652–653; doi:10.1038/ki.2014.8
653
kidney disease and socioeconomic deprivation.2 Based on the hygiene hypothesis,3 it would appear that IgA nephropathy, being a mesangial proliferative glomerulonephritis (GN), would appear to be more prevalent among the socioeconomically deprived and this would be one explanation for the increased incidence of IgA nephropathy in Scotland. We have studied the changing pattern of primary GN in Singapore and other Asian countries over the past three decades.4 In Singapore the prevalence of mesangial proliferative GN has decreased from 32% in the first decade to 7% in the third decade, but IgA nephropathy has remained the most common cause of primary GN, with 42% in the first decade and 40% in the third decade. A similar trend is observed in the surrounding Asian countries.4 IgA nephropathy still remains the most common GN worldwide. We believe that the pathogenesis of IgA nephropathy is multifactorial and socioeconomic deprivation is only one aspect of the disease. Initially it may be associated with socioeconomic deprivation in some populations, but later, with urbanization, changing lifestyle, and exposure to other dietary antigens and environmental allergens, its pathogenesis may evolve. Geographical and racial or genetic factors would also play a role.5 1.
2. 3. 4.
5.
McQuarrie EP, Mackinnon B, McNeice V et al. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation. Kidney Int 2014; 86: 198–203. Hossain MP, Goyder EC, Rigby JE et al. CKD and poverty: a growing global challenge. Am J Kidney Dis 2009; 53: 166–174. Hurtado A, Johnson RJ. Hygiene hypothesis and prevalence of glomerulonephritis. Kidney Int 2005; 68: S62–S67. Woo KT, Chan CM, Chin YM et al. The changing pattern of primary glomerulonephritis in Singapore and other countries over the past 3 decades. Clin Nephrol 2010; 7: 372–383. Gharavi A, Kiryluk Krzysztof, Choi M et al. Genome- wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet 2011; 43: 321–327.
Keng-Thye Woo1, Marjorie Foo1, Hui-Lin Choong1, Han-Kim Tan1, Kok-Seng Wong1 and Choong-Meng Chan1 1 Department of Renal Medicine, Singapore General Hospital, Singapore Correspondence: Keng-Thye Woo, Department of Renal Medicine, Singapore General Hospital, Outram Road, Singapore 169608, Singapore. E-mail: [email protected]
Kidney International (2014) 86, 651–652; doi:10.1038/ki.2014.169
The Authors Reply: We thank Dr Woo and colleagues for their response to our article describing the increased incidence of biopsy-proven immunoglobulin A (IgA) nephropathy in patients living in areas of multiple socioeconomic deprivation.1,2 Dr Woo proposes that the hygiene hypothesis may partially explain our findings. The hygiene hypothesis suggests that in developed nations the lack of exposure to significant infection in childhood predisposes to allergy and a predominantly T-helper 2 (Th2)-driven immune response. With IgA nephropathy being a predominantly a Th2-driven disease, the 652
hypothesis is that immune conditioning may be partially responsible for the increased incidence of IgA nephropathy seen in developed nations.3 This may explain some of the difference in incidence of the disease between Scotland, as a developed nation, and other less-developed nations. However, if significant infections would be expected to be more common in areas of multiple socioeconomic deprivation, then perhaps the incidence of IgA nephropathy would be expected to be lower in these areas if this were the main explanation. If our finding of an association with socioeconomic deprivation is confirmed, then this may go some way toward explaining the variation in incidence of disease worldwide and apparent changes in incidence over time. However, we agree that further work needs to be done to explore which aspects of socioeconomic deprivation influence the pathogenesis of disease, including infection, diet, smoking, hydrocarbons, and genetics. Other factors are also certainly involved in the apparent disparity in incidence of IgA nephropathy and other biopsy-proven renal diseases, not least the threshold for biopsy. 1. 2.
3.
Woo K-T, Foo M, Choong H-L et al. The incidence of IgA nephropathy is associated with socioeconomic deprivation. Kidney Int 2014; 86: 651–652. McQuarrie EP, Mackinnon B, McNeice V et al. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation. Kidney Int 2014; 86: 198–203. Hurtado A, Johnson RJ. Hygiene hypothesis and prevalence of glomerulonephritis. Kidney Int 2005; 68: S62–S67.
Emily P. McQuarrie1, Bruce Mackinnon1, Valerie McNeice2, Jonathan G. Fox1 and Colin C. Geddes1 1
Glasgow Renal and Transplant Unit, Glasgow, UK and 2Glasgow Centre for Population Health, Glasgow, UK Correspondence: Emily P. McQuarrie, Western Infirmary—Renal Unit, Dumbarton Road, Glasgow G11 6NT, Scotland, UK. E-mail: [email protected] Kidney International (2014) 86, 652; doi:10.1038/ki.2014.170
IgA nephritic patients of Pacific Asian origin with increased risk of progression to end-stage renal disease To the Editor: We read with great interest the above article1 in which the authors compared two groups of patients, a group of 202 Canadian patients of Pacific Asian origin and a group of 467 Canadian patients (mainly Caucasians), over a follow-up period of 46 months. These patients were recruited through the Toronto GN Registry and were registered from 1974 to 2012. The authors found that by univariate analysis the risk of end-stage renal disease (ESRD) was similar in the two groups, but that by multivariate analysis the risk of ESRD was significantly higher in the Pacific Asian group. This was supported by a significant 1.62 ml/min/year of faster estimated glomerular filtration rate (eGFR) decline in Kidney International (2014) 86, 649–653
letter to the editor
the Pacific Asian group. However, we note that in Table 1, 73.3% of Pacific Asian patients versus 45.3% of Caucasian patients were on angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers (ACEI/ARB) (Po0.001). Similarly, there were more Pacific Asian patients on steroids compared with Caucasians (23.8% versus 15.9%, Po0.02). Also, more Pacific Asian patients were on immunosuppressants compared with Caucasians (25.7% versus 19.3%, Po0.07). These two groups of patients in Canada would presumably have received standard medical care, and their medication would have been prescribed on the basis of clinical indications, such as proteinuria and eGFR. Considering the larger number of patients in the Pacific Asian group who required treatment, it would suggest that this group probably had more severe disease. Hence, it would not be surprising that the Pacific Asian group would have a more rapid decline of renal function and progression to ESRD. We believe that these two groups are not comparable on the basis of patient numbers and on the proportion of patients who are on treatment in the two groups. It may therefore be premature to attribute the more rapid decline in eGFR in the Asian patients to a ‘racial effect’. D’Amico,2 in a worldwide review of the actual renal survival at 10 years for patients with IgA nephritis, reported 87% patient survival in Australia, 85% in Europe, 81% in Germany, 85% in Italy, 80% in Japan, 83% in the United Kingdom, 78% in the United States of America, and 82% in Singapore. Li et al.3 reported a 10-year survival of 82% among the Chinese in Hong Kong. There was not much variation in renal survival for IgA nephritics worldwide. With regard to the rate of eGFR decline, Prakesh et al.4 compared two cohorts of Asian patients with IgA nephritis from two continents in a retrospective study. A cohort of 76
Kidney International (2014) 86, 649–653
patients from Thailand (1994–2005) was compared with a cohort of 152 Asian Canadian patients (1975–2006) who were also from the Toronto GN Registry. The adjusted rate of eGFR decline in the Thai patients was 0.8 ml/min/year compared with 3.35 ml/min/year in the Asian Canadian patients. The Asian Canadian patients were not treated with ACEI/ARB as their study period predated the introduction of ACEI/ARB in Canada. However, the Thai patients received ACEI/ARB and steroids, which may explain the slower rate of eGFR decline, although the authors attribute this difference to what they consider the ‘continental effect’ causing the variation in the rate of eGFR decline in these two groups of Asian patients. This study demonstrates that not all Asians with IgA nephritis have an increased risk of progression to ESRD. It may be a ‘continental effect’, as suggested by the authors, but the ‘racial effect’ appears nonexistent. 1.
2. 3.
4.
Barbour SJ, Cattran DC, Kim SJ et al. Individuals of Pacific Asian origin with IgA nephropathy have an increased risk of progression to end-stage renal disease. Kidney Int 2013; 84: 1017–1024. D’Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Seminars Nephrol 2004; 24: 179–196. Li PKT, Kai KLH, Szeto CC et al. Prognostic indicators of IgA nephropathy in the Chinese—clinical and pathological perspectives. Nephrol Dialysis Transpl 2001; 17: 64–67. Prakash S, Kanjanabuch T, Austin PC et al. Continental vatiations in IgA nephropathy among Asians. Clin Nephrol 2008; 70: 377–384.
Keng-Thye Woo1, Marjorie W.Y. Foo1, H. Lina Choong1, Han Khim Tan1, Kok-Seng Wong1 and Choong-Meng Chan1 1 Department of Renal Medicine, Singapore General Hospital, Singapore Correspondence: Keng-Thye Woo, Department of Renal Medicine, Singapore General Hospital, Singapore 16960, Singapore. E-mail: [email protected]
Kidney International (2014) 86, 652–653; doi:10.1038/ki.2014.8
653
