Accepted Article
Primary IgA Nephropathy in Elderly Patients1
Authors: Wisit Cheungpasitporn, MD1; Samih H. Nasr, MD2; Charat Thongprayoon, MD1; Michael A. Mao, MD1; Qi Qian, MD1
Institutional affiliations: 1 Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN. 2Division of Laboratory Medicine and Pathology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN
Running Title: IgA Nephropathy in Elderly
Corresponding author: Qi Qian, MD Department of Medicine, Division of Nephrology and Hypertension Mayo Clinic College of Medicine 200 First Street SW, Rochester, MN 55905 Tel: (507) 266-7960, Fax: (507) 266-7891 Email: [email protected]
Financial support: None Conflicts of interest: None
Abstract word count: 198 words Manuscript word count: 3,209 words
Keywords: Primary IgA nephropathy; elderly patients; chronic kidney disease; kidney disease progression; end stage renal failure; mortality
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nep.12440
1 This article is protected by copyright. All rights reserved.
Accepted Article Abstract
Background: Data on clinicopathological features, treatment and outcomes of IgA nephropathy (IgAN) in elderly patients are limited. Methods: Native kidney biopsies with a pathological diagnosis of IgAN (n=1084) from Mayo Clinic Rochester in the years 1994-2013 were examined. After exclusion of the secondary IgAN, 45 elderly IgAN patients (age ≥65 years) were identified. 162 younger adults (age 18-64 years) with IgAN were randomly selected for comparison. Results: Compared to younger adults, elderly patients showed a higher rate of chronic hypertension (62.2 vs. 27.2%), higher pulse pressures (65±17 vs. 51±15 mmHg), requiring greater number of antihypertensive medications (2.5±1.2 vs. 1.7±0.7) and lower blood hemoglobin (11.1±2.3 vs. 12.7±2.1 g/dL) at time of kidney biopsy, all P65 years old) have not been adequately evaluated. In a recent meta-analysis gathering all searchable data, from 1980 to 2010, only 9 studies1-9 of reasonable quality included
elderly patients (4 from Japan, 1 from France, 1 from Iran, 1 from Italy, 1 from Spain, and 1 from China).10 Among the 9 studies, only a minority (50 or >65 years). Despite the heterogeneity of these 9 studies, the meta-analysis was able to summarize that elderly patients had a higher incidence of glomerulosclerosis and tubulointerstitial fibrosis and a higher rate of progression to end-stage renal disease (ESRD), associated with poor outcomes. The pathological and clinical correlation was not evaluated. Only one of the 9 studies from Europe4 was specifically designed for evaluation of elderly patients with IgAN. The study involved 33 IgAN patients age >50 years, in which 16 had pathological evaluation (not by the Oxford classification). The meta-analysis also confirmed a lower incidence of IgAN in Europe compared to that in Asia and subgroup analysis also showed a lower relative risk (RR) for worsening kidney function in patients from European countries (RR: 1.11) than patients from Asian countries (RR: 2.56).
To date, there has been no published study from the United States designed to examine the clinicopathological features and outcomes of IgAN in elderly patients. The aim of the current study is to determine the clinical presentation, pathological features, treatment and outcomes of IgAN in elderly patients (age >65 years) and compare the findings to younger counterparts (age 18-64 years).
3 This article is protected by copyright. All rights reserved.
Accepted Article
Methods
The Mayo Clinic Institutional Review Board approved the study. Kidney biopsy specimens were processed according to institutional protocol for light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM) using standard techniques. IF was performed on cryosections of the biopsy tissues using specific fluorescein-conjugated antibodies.
Native kidney biopsies with a pathological diagnosis of IgAN (n=1084) from researchauthorized patients at Mayo Clinic Rochester in the years 1994-2013 were screened. We included all elderly patients aged ≥65 years (n=60) and randomly selected younger adults aged 18-64 years (n=180) with IgAN with 1:3 ratio. Comprehensive review of the medical records
revealed that 15 of the 60 elderly and 18 of the 180 younger adults had secondary IgAN, including the Henoch-Schönlein purpura (IgA vasculitis); these secondary IgAN patients were excluded as secondary IgAN etiologically and clinically differs from the primary IgAN, 11 . After the exclusion, 45 elderly and 162 younger adults were included in the study.
Two researchers (WC and CT) were trained to independently review kidney biopsy report of IgAN and score biopsies for all study participants according to Oxford Classification (Table 1).12 In cases of disagreement between two reviewers, a nephropathologist (SHN) reviewed the biopsy slides and reconciled the differences. The percentages of segmental and global sclerosis per the total number of glomeruli were also obtained. Cellular, fibrocellular crescents (global or segmental) and fibrinoid necrosis were categorized as present/absent and calculated in percentage of the total glomeruli.
4 This article is protected by copyright. All rights reserved.
Accepted Article
Clinical records of all enrolled patients were reviewed. The Charlson Comorbidities Index (CCI), 13
including 19 comorbidities for each participant, was computed based on the comorbid
conditions at the time of kidney biopsy. Proteinuria was quantified by 24-hour urine protein measurement. When appropriate, spot urine protein-to-osmolality ratio was also used to determine proteinuria.14 Nephrotic proteinuria was defined as urine protein excretion ≥3.5 g/day. Partial remission was defined as a reduction of 24-hour proteinuria to
Primary IgA Nephropathy in Elderly Patients1
Authors: Wisit Cheungpasitporn, MD1; Samih H. Nasr, MD2; Charat Thongprayoon, MD1; Michael A. Mao, MD1; Qi Qian, MD1
Institutional affiliations: 1 Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN. 2Division of Laboratory Medicine and Pathology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN
Running Title: IgA Nephropathy in Elderly
Corresponding author: Qi Qian, MD Department of Medicine, Division of Nephrology and Hypertension Mayo Clinic College of Medicine 200 First Street SW, Rochester, MN 55905 Tel: (507) 266-7960, Fax: (507) 266-7891 Email: [email protected]
Financial support: None Conflicts of interest: None
Abstract word count: 198 words Manuscript word count: 3,209 words
Keywords: Primary IgA nephropathy; elderly patients; chronic kidney disease; kidney disease progression; end stage renal failure; mortality
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nep.12440
1 This article is protected by copyright. All rights reserved.
Accepted Article Abstract
Background: Data on clinicopathological features, treatment and outcomes of IgA nephropathy (IgAN) in elderly patients are limited. Methods: Native kidney biopsies with a pathological diagnosis of IgAN (n=1084) from Mayo Clinic Rochester in the years 1994-2013 were examined. After exclusion of the secondary IgAN, 45 elderly IgAN patients (age ≥65 years) were identified. 162 younger adults (age 18-64 years) with IgAN were randomly selected for comparison. Results: Compared to younger adults, elderly patients showed a higher rate of chronic hypertension (62.2 vs. 27.2%), higher pulse pressures (65±17 vs. 51±15 mmHg), requiring greater number of antihypertensive medications (2.5±1.2 vs. 1.7±0.7) and lower blood hemoglobin (11.1±2.3 vs. 12.7±2.1 g/dL) at time of kidney biopsy, all P65 years old) have not been adequately evaluated. In a recent meta-analysis gathering all searchable data, from 1980 to 2010, only 9 studies1-9 of reasonable quality included
elderly patients (4 from Japan, 1 from France, 1 from Iran, 1 from Italy, 1 from Spain, and 1 from China).10 Among the 9 studies, only a minority (50 or >65 years). Despite the heterogeneity of these 9 studies, the meta-analysis was able to summarize that elderly patients had a higher incidence of glomerulosclerosis and tubulointerstitial fibrosis and a higher rate of progression to end-stage renal disease (ESRD), associated with poor outcomes. The pathological and clinical correlation was not evaluated. Only one of the 9 studies from Europe4 was specifically designed for evaluation of elderly patients with IgAN. The study involved 33 IgAN patients age >50 years, in which 16 had pathological evaluation (not by the Oxford classification). The meta-analysis also confirmed a lower incidence of IgAN in Europe compared to that in Asia and subgroup analysis also showed a lower relative risk (RR) for worsening kidney function in patients from European countries (RR: 1.11) than patients from Asian countries (RR: 2.56).
To date, there has been no published study from the United States designed to examine the clinicopathological features and outcomes of IgAN in elderly patients. The aim of the current study is to determine the clinical presentation, pathological features, treatment and outcomes of IgAN in elderly patients (age >65 years) and compare the findings to younger counterparts (age 18-64 years).
3 This article is protected by copyright. All rights reserved.
Accepted Article
Methods
The Mayo Clinic Institutional Review Board approved the study. Kidney biopsy specimens were processed according to institutional protocol for light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM) using standard techniques. IF was performed on cryosections of the biopsy tissues using specific fluorescein-conjugated antibodies.
Native kidney biopsies with a pathological diagnosis of IgAN (n=1084) from researchauthorized patients at Mayo Clinic Rochester in the years 1994-2013 were screened. We included all elderly patients aged ≥65 years (n=60) and randomly selected younger adults aged 18-64 years (n=180) with IgAN with 1:3 ratio. Comprehensive review of the medical records
revealed that 15 of the 60 elderly and 18 of the 180 younger adults had secondary IgAN, including the Henoch-Schönlein purpura (IgA vasculitis); these secondary IgAN patients were excluded as secondary IgAN etiologically and clinically differs from the primary IgAN, 11 . After the exclusion, 45 elderly and 162 younger adults were included in the study.
Two researchers (WC and CT) were trained to independently review kidney biopsy report of IgAN and score biopsies for all study participants according to Oxford Classification (Table 1).12 In cases of disagreement between two reviewers, a nephropathologist (SHN) reviewed the biopsy slides and reconciled the differences. The percentages of segmental and global sclerosis per the total number of glomeruli were also obtained. Cellular, fibrocellular crescents (global or segmental) and fibrinoid necrosis were categorized as present/absent and calculated in percentage of the total glomeruli.
4 This article is protected by copyright. All rights reserved.
Accepted Article
Clinical records of all enrolled patients were reviewed. The Charlson Comorbidities Index (CCI), 13
including 19 comorbidities for each participant, was computed based on the comorbid
conditions at the time of kidney biopsy. Proteinuria was quantified by 24-hour urine protein measurement. When appropriate, spot urine protein-to-osmolality ratio was also used to determine proteinuria.14 Nephrotic proteinuria was defined as urine protein excretion ≥3.5 g/day. Partial remission was defined as a reduction of 24-hour proteinuria to
