IgA nephropathy study in Indians
| ISRCTN | ISRCTN36834159 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN36834159 |
| Secondary identifying numbers | IA/CPHE/14/1/501501 |
- Submission date
- 05/10/2017
- Registration date
- 11/10/2017
- Last edited
- 21/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English Summary
Background and study aims
According to the World Health Organization (WHO) Global Status Report 2010, non-communicable disease (NCD) deaths are projected to increase by 15% globally and by 20% in South Asia between 2010 and 2020. Chronic kidney disease (CKD) is associated with an eight- to tenfold increase in cardiovascular (heart disease) mortality (death) and is a risk multiplier in patients with diabetes and hypertension (high blood pressure). A nationwide study conducted by the Indian Council of Medical Research found NCDs were responsible for 42% of all deaths. An Indian population-based study calculated the age-adjusted incidence of end stage kidney disease (ESKD) at 232 per million population. The Indian government has included care for kidney disease in its 12th 5-year plan cycle. IgA nephropathy (IgAN) is one of the leading causes of ESKD in India and worldwide. In IgA nephropathy (IgAN), Indians seem to develop disease early and of greater severity. There is an urgent need to understand the differences in disease progression and provide a prognosis to Indian patients with IgAN. The plan is to assess the differences in clinical presentation and outcomes, and apply newly developed methods for the assessment of kidney damage.
Who can participate?
Patients age 18 and over with primary IgA nephropathy
What does the study involve?
Patients are divided into low and high risk categories based on clinical and kidney tissue findings. These patients are followed up and based on the findings, they are divided into those who get worse faster (rapid progressors) and those who remain stable or worsen slowly (slow/non-progressors). Blood and kidney tissue samples are taken.
What are the possible benefits and risks of participating?
This study will help to understand the differences in the behaviour of this disease in an Indian population and allow better prediction of disease progression. The results will help with decision-making regarding the need for immunosuppression for aggressive IgA nephropathy. This study may also help define the role of targeted screening in at-risk communities, as whole-population based screening programs for kidney disease are not cost effective, especially in a developing country like India. There are no risks for participants as it is an observational study and only involves blood sampling.
Where is the study run from?
Christian Medical College (India)
When is the study starting and how long is it expected to run for?
May 2014 to December 2021
Who is funding the study?
1. Christian Medical College (India)
2. DBT India Alliance (India)
Who is the main contact?
Prof. Suceena Alexander
Contact information
Scientific
Department of Nephrology
Christian Medical College
Ida Scudder Road
Vellore, Tamil Nadu
632004
India
 ORCID ID |
0000-0001-7692-606X |
|---|
Study information
| Study design | Observational prospective longitudinal cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Why is IgA nephropathy aggressive in Indians? Study of the effect of galactose deficient IgA1, anti-glycan antibodies including immune complexes and complement components on the rate of progression of renal disease. |
| Study acronym | GRACE- IgANI (Glomerular Research And Clinical Experiments- IgA Nephropathy study in Indians) |
| Study hypothesis | IgA nephropathy (IgAN) is the most common glomerular disease, and a frequent cause of end stage kidney disease. In India, IgAN is characterized by marked severity in a younger population. IgAN in India occurs mostly in 20-30 year olds, which is in sharp contrast to the older age (35-40 years) of Caucasian and East Asian patients. Thirty to 40% of Indian patients have nephrotic syndrome and renal dysfunction at presentation, as compared to a slowly progressive disease with an actuarial survival of 80-85% over 10 yrs among Caucasians. A study showed a 10 year renal survival of 35% and a >20% decline of renal function over a mean follow up of 27 months in a cohort of IgAN patients. There is an urgent need to understand the differences in disease progression and provide a prognosis to Indian patients with IgAN. The plan is to characterize the differences in clinical presentation and outcomes, and apply newly developed methods for assessment of mechanisms of renal damage to patients. The trialists hypothesise that differential galactosylation and levels of serum Gd-IgA1 and/or AGlyIgA and activation of the lectin pathway of complement contribute to the progressive IgAN seen in Indians. |
| Ethics approval(s) | 1. Pilot study: The Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College Vellore, 23/07/2014, Ref. No. IRB Min. No. 8962 2. Full study: The Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College Vellore, 24/06/2015, Ref. No. IRB Min. No. 9481 |
| Condition | Chronic kidney disease and IgA nephropathy (IgAN) |
| Intervention | 200 IgAN patients will be recruited and classified into low and high risk groups based on a validated risk score. High risk IgAN group are IgAN patients with an Absolute Renal Risk (ARR) score of ≥23 points. Low risk IgAN group are IgAN patients with an ARR score of <23 points. Equivalent number of healthy people and patients with other glomerulonephritis will serve as controls for standardisation methods in sera. Based on the rate of decline in estimated glomerular filtration rate (eGFR) during the average five-year follow-up, the primary clinical outcome in IgAN patients will be either rapid-progressors or slow/non-progressors. Antigen, antibody and complement staining in renal tissue at baseline will be correlated with clinical outcomes at follow-up. Molecular characterization of biomarkers in sera collected annually will be compared between the two groups. The trialists hope to incorporate these biomarkers into a risk score equation for better determination of disease prognosis in our population. They will also be bio-banking biological fluids for future biomarker analysis. |
| Intervention type | Other |
| Primary outcome measure | 1. Levels of serum Gd-IgA1 and AGlyIgA including immune complexes, measured using ELISA at baseline and annually 2. Rate of progression of IgAN, measured by the rate of fall in estimated glomerular filtration rate (eGFR) estimated by the CKD-EPI creatinine equation measured annually till composite end-point or end of follow-up (average of five years) |
| Secondary outcome measures | 1. Composite end-point of 50% decline in eGFR, ESKD or death, whichever occurs earlier, measured using CKD-EPI creatinine equation and ESKD defined as eGFR by CKD-EPI creatinine equation <15ml/min/1.73m2 and/or requiring renal replacement therapy 2. Co-deposition of components of the lectin and alternative pathway of complement activation in renal biopsies, measured by immunofluorescence and immunohistochemistry at baseline 3. Proteinuria, measured using 24 hour urine protein (g/day) at baseline and annually till composite end-point or end of follow-up (average of five years) |
| Overall study start date | 01/05/2014 |
| Overall study end date | 31/12/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 500 |
| Total final enrolment | 201 |
| Participant inclusion criteria | 1. Age ≥18 years 2. Primary IgA nephropathy diagnosed by renal biopsy 3. Written informed consent 4. Willing to come for follow-up visits 5. Immunosuppression naive for three months prior to recruitment |
| Participant exclusion criteria | 1. Secondary IgA nephropathy: e.g. due to lupus, liver cirrhosis, Henoch-Schonlein purpura 2. Glomerular filtration rate (GFR) as estimated by the CKD-EPI equation <10ml/min/1.73m2 3. Participants with systemic diseases that can affect the kidneys like diabetes, systemic lupus erythematosus, presence of HIV, HbsAg, HCV infections, malignancies etc 4. Participants with a history of psychological illness or condition which interferes with their ability to understand or comply with the requirements of the study |
| Recruitment start date | 09/03/2015 |
| Recruitment end date | 31/12/2017 |
Locations
Countries of recruitment
- India
Study participating centre
Vellore, Tamil Nadu
632004
India
Sponsor information
Charity
Ida Scudder Road
Vellore, Tamil Nadu
632004
India
| Website | http://www.cmch-vellore.edu |
|---|---|
"ROR" |
https://ror.org/00c7kvd80 |
Funders
Funder type
University/education
Private sector organisation / Universities (academic only)
- Alternative name(s)
- CMC Vellore, CMC
- Location
- India
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- The Wellcome Trust DBT India Alliance, DBT/WT India Alliance, DBT-Wellcome Trust India Alliance, Wellcome Trust/DBT India Alliance, Wellcome Trust DBt India Alliance, India Alliance, DBT/Wellcome Trust India Alliance, WTDBT India Alliance
- Location
- India
Results and Publications
| Intention to publish date | 15/11/2017 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Protocol to be published by end of 2017 2. Incidence and presentation early 2018 3. Longitudinal follow-up in 2019 and 2021 4. Experimental and biomarker reporting as and when the results are available |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 26/07/2018 | 21/11/2023 | Yes | No | |
| Results article | Baseline clinical, biochemical, and histopathologic characteristics | 07/12/2020 | 21/11/2023 | Yes | No |
| Results article | Three-year clinical outcomes | 24/11/2021 | 21/11/2023 | Yes | No |
Editorial Notes
21/11/2023: Three publication references and total final enrolment added.
