Plain English Summary
Background and study aims [objectives and aims]
Despite the success of antiretroviral therapies, HIV-related kidney disease still carries a significant risk of kidney failure (end-stage renal disease). HIV-associated nephropathy (HIVAN) is a type of kidney disease that has a large risk for end-stage renal disease, and without antiretroviral therapy, it can rapidly progress to end-stage renal disease. Moreover, some patients still have worsening kidney function and disease progression, despite using the correct antiretroviral therapies. This can be explained by the kidneys acting as a reservoir for HIV, and the fact that antiretroviral therapy is unable to access the kidneys.
Kidney diseases can be treated with drugs called corticosteroids. Research has looked at the effectiveness and safety of using corticosteroids with antiretroviral therapy for the treatment of HIVAN; however, this research is incomplete and more studies are required. This study aims to look at the balance between an improvement in kidney function and side effects with the use of corticosteroids as an add-on to antiretroviral therapy in patients with HIVAN.
Who can participate?
HIV positive adults with unexplained kidney impairment, proteinuria and/or haematuria, who have undergone renal biopsy
What does the study involve?
All patients will be given antiretroviral therapy. They will then be randomly allocated to receive add-on corticosteroids or antiretroviral therapy only. Those allocated to receive corticosteroids had this treatment slowly reduced over a 6 month protein. All patients were offered additional medication to control proteinuria if their blood pressure meant they could tolerate this. Additionally, all patients were given medication to prevent other diseases such as tuberculosis. Patients were tested for improvements in kidney function every month for the 6 month study period and then every 3 months for 2 years after the study.
What are the possible benefits and risks of participating?
The possible benefits of participating include possible improvement in renal function and proteinuria with the addition of corticosteroids and regular patient review. All patients on the study remained as patients in the clinic after the trial finished. There is a possible risk of infection as a result of corticosteroid use; however, preventative medication will be given and patients will be monitored closely for any kind of infection.
Where is the study run from?
Groote Schuur Hospital Cape Town (South Africa)
When is the study starting and how long is it expected to run for?
May 2007 to May 2017
Who is funding the study?
This study is self-funded, as all aspects were part of routine clinical practice
Who is the main contact?
Associate Professor Nicola Wearne
nicola.wearne@uct.ac.za
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HREC:241/2007
Study information
Scientific title
The effects of add-on corticosteroids on renal outcomes in patients with biopsy-proven HIV-associated nephropathy: a single centre study from South Africa
Acronym
Study hypothesis
Corticosteroids will improve renal outcomes (i.e. eGFR and proteinuria) in HIV-associated nephropathy in patients also initiated on antiretroviral therapy.
Ethics approval
Human Research Ethics Committee of the University of Cape Town South Africa, 24/07/2007, HREC:241/2007
Study design
Interventional prospective open-label randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details (nicola.wearne@uct.ac.za) to request a participant information sheet
Condition
HIV associated nephropathy
Intervention
Participants were randomly allocated to 1 of 2 groups - either antiretroviral therapy (ART) and corticosteroids (1 mg/kg prednisone), or ART alone. Patients were assigned their treatment by randomly selecting a sealed opaque envelope with the treatment allocation. Both investigator and patients were not blinded during the study period as additional prophylactic treatment (i.e. cotrimoxazole, isoniazid) was required to prevent opportunistic infections in those receiving ART and corticosteroids.
The maximum dose of ART was 60 mg/day regardless of body weight. Prednisone was tapered over a 6 month period by 10 mg per month. All patients were given angiotensin converting enzyme inhibition (ACEi) or angiotensin receptor blockade (ARB), if their blood pressure and renal function could tolerate it (this is standard care for proteinuria). Isoniazid and cotrimoxazole was started in those patients offered corticosteroids for tuberculosis and pneumocystis jirovecii prophylaxis.
Patients were followed up monthly for 6 months and then every 3 months for 2 years. After the 2 year period the patients remain in the HIV renal clinic and are followed up as required clinically.
Intervention type
Drug
Phase
Not Specified
Drug names
Prednisone
Primary outcome measure
Improvement in the following renal outcomes in patients with glomerular or tubulointerstitial features of HIVAN as a result of corticosteroid therapy, from the at the baseline, then monthly for 6 months, then every 3 months for 2 years:
1. Improvement in estimated glomerular filtration rate (eGFR), assessed using the CKD EPI formula
2. Serum creatinine (mol/l), assessed using a blood test
3. Urine protein/creatinine ratio (uPCR) (g/mmol), assessed using a blood test
Secondary outcome measures
1. Adverse events, assessed using death certificates, patient folders, records from HIV clinics and family members at every 3 months during the 2 year follow-up period
2. Improvements in the following histologies, assessed using a renal biopsy at the baseline and after 6 months:
2.1. Podocytopathy
2.2. Interstitial fibrosis
2.3. Lymphocytic cell infiltration
2.4. Plasma cell infiltration
Overall trial start date
24/05/2007
Overall trial end date
18/05/2017
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically-proven HIV-associated nephropathy, defined as having the presence of chronic tubulointerstitial inflammation with plasma cells, lymphocytes and microcysts, along with any of the following:
1.1. Collapsing glomerulopathy
1.2. Focal segmental glomerulosclerosis
1.3. Podocyte hypertrophy and/or hyperplasia
2. Antiretroviral therapy naïve for at least 2 weeks prior to renal biopsy
3. Initiation of antiretroviral therapy within 1 month of the renal biopsy
3. Aged 18 years or older
4. Able to provide written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40 patients (20 in each arm)
Participant exclusion criteria
1. Any active infection
2. Kaposi sarcoma
3. Active cytomegalovirus
4. Inability to follow-up at study centre
Recruitment start date
01/04/2010
Recruitment end date
18/05/2015
Locations
Countries of recruitment
South Africa
Trial participating centre
Groote Schuur Hospital
Anzio road, Observatory
Cape Town
7708
South Africa
Funders
Funder type
Not defined
Funder name
SELF FUNDED
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
We intend to publish in BMC Nephrology in 2018.
IPD sharing statement:
Any data from this study is available on request. There is an Excel spreadsheet with STATA analysis. All information is stored in a password protected file. Patients have given consent to data distribution. All data will be made available by Prof Nicola Wearne [ Nicola.wearne@uct.ac.za]
Intention to publish date
01/09/2018
Participant level data
Available on request
Basic results (scientific)
See additional file (ISRCTN56112439 _BasicResults_05Sep2018)
Publication list
2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/30728003
Publication citations
Additional files
- ISRCTN56112439 _BasicResults_05Sep2018.pdf uploaded 24/04/2019