None listed
Conditions
Brief summary
Background: An understanding of the molecular pathways driving persistent renal inflammation is essential to decipher the pathogenesis of various forms of kidney diseases and to develop novel and more-efficient targeted therapeutics to prevent end stage kidney disease. Cell and molecular pathways will be tested for utility as a non-invasive precision diagnostic that is adjunct to traditional histopathology. Regulatory and switch points in the pathogenesis will be tested as targets for more specific therapeutic immunosuppression. Aim: We aim to define the lymphocyte subsets, explore novel hypoxia-inducible pathways and characterize proximal tubular epithelial cell (PTEC) derived urinary exosomes and their contribution to tubulointerstitial inflammation/fibrosis and thus, progression of FSGS. Methods: Clinical information, blood, urine and renal tissue will be collected in 50 consecutive patients who are clinically suspected to have FSGS. The samples will be processed in those whose histological diagnosis is in keeping with the clinical suspicion of FSGS. Patients with glomerulonephritis other than FSGS will be treated as disease controls and we will also recruit 20 healthy controls. The source of biosamples in these experiments will be the blood, urine and renal tissue collected from patients at the time of kidney biopsy performed for clinical indications. Results: We hope to describe patient, demography and clinical variables and map these to histopathology, steroid responsiveness and disease/ patient outcomes. The study will enumerate the localisation, activation state and cytokine profile of the lymphocyte subsets in the peripheral blood and renal tissue. We will describe the molecular profiling of pathways for hypoxia response, mitochondrial activity, apoptosis/necrosis and tissue remodelling/fibrosis in renal tissue and urine and establish both the source (location of renal injury) and molecular cargo of urinary exosomes in FSGS. Conclusions: The results of these experiments will define novel pathogenic pathways in FSGS about inflammation, hypoxia and fibrosis. These can in turn help us in developing novel therapeutic targets for treatment of FSGS.
Interventions
The exposure to be studied is primary focal segmental glomerulosclerosis (FSGS). At baseline, the demography, clinical features, investigations, renal biopsy and treatment details will be recorded in case report forms. The follow-up will be at least twice a year for 24 months. At follow-up the relevant clinical features, investigations and treatment details will be recorded in the case report forms. The duration of follow up for participants in the study is 24 months from the time of recruitment
The exposure to be studied is primary focal segmental glomerulosclerosis (FSGS). At baseline, the demography, clinical features, investigations, renal biopsy and treatment details will be recorded in case report forms. The follow-up will be at least twice a year for 24 months. At follow-up the relevant clinical features, investigations and treatment details will be recorded in the case report forms. The duration of follow up for participants in the study is 24 months from the time of recruitment.
Sponsors
Christian Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for the FSGS study group i. Adult patients (age greater than or equal to 18 years) ii. Diagnosed as primary FSGS by renal biopsy iii. Immunosuppressive treatment naïve for at least one month prior to renal biopsy iv. Baseline estimated GFR (glomerular filtration rate) between 15-60ml/min/1.73m2 v. Willingness to be included in the study Inclusion criteria for the Disease control group i. Adult patients (age greater than or equal to 18 years) ii. Diagnosed as primary glomerulonephritis other than FSGS by renal biopsy iii. Immunosuppressive treatment naïve for at least one month prior to renal biopsy iv. Baseline estimated GFR (glomerular filtration rate) between 15-60ml/min/1.73m2 v. Willingness to be included in the study Inclusion criteria for the Healthy control group i. Adults (age greater than or equal to 18 years) ii. No known illnesses iii. Willingness to be included in the study
Exclusion criteria
Exclusion criteria for the FSGS study group i. Secondary FSGS ii. Glomerular filtration rate (GFR) as estimated by the CKD-EPI equation <15ml/min/1.73m2 or >60ml/min/1.73m2 iii. Patients with systemic diseases that can affect the kidneys like diabetes, systemic lupus erythematosus, presence of HIV, HbsAg, HCV infections, malignancies etc. iv. Patients with a history of psychological illness or condition which interferes with their ability to understand or comply with the requirements of the study. Exclusion criteria for Disease control group i. Secondary glomerulonephritis ii. Glomerular filtration rate (GFR) as estimated by the CKD-EPI equation <15ml/min/1.73m2 or >60ml/min/1.73m2 iii. Patients with systemic diseases that can affect the kidneys like diabetes, systemic lupus erythematosus, presence of HIV, HbsAg, HCV infections, malignancies etc. iv. Patients with a history of psychological illness or condition which interferes with their ability to understand or comply with the requirements of the study. Exclusion criteria for Healthy control group i. Age greater than or equal to 18 years ii. Any known systemic illnesses
Outcome results
None listed