Wcn24-2186 Building the Rationale for Clinical Trial Equity Across the World: The Case of Apol1 Nephropathy in the Caribbean

Introduction: To assess the frequency of APOL1 gene high risk alleles using DNA extraction from kidney tissue, among biopsies with sufficient tissue performed over 10 years in two of Jamaica's leading tertiary care centers. Plan to obtain 200 Biopsy samples (100 with FSGS diagnosis, 50 with membranous nephropathy, and 50 with Lupus Nephritis) Design and Methods: A descriptive, retrospective study will be conducted of native kidney biopsy specimens received by the Department of Pathology, UWI, between July 1, 2013 to June 30, 2023, in the Department of Pathology, UWI. The Department of Pathology, UWI, is the only institution in the island which offers a nephropathology service and therefore the samples would be representative of the Jamaican population. The medical renal biopsy pathology reports and medical records will be reviewed sequentially and all native kidney biopsies retrieved. Clinical data such as age, sex, clinical diagnosis, indication for biopsy (proteinuria, worsening kidney function, urine albumin creatinine ratio or urine protein creatinine ratio, comorbidities e.g., hypertension and diabetes, creatinine and estimated glomerular filtration rate at the time of biopsy) will be obtained. The light and immunofluorescence microscopic findings will be recorded. If electron microscopic evaluation was performed, this data will also be included. Paraffin-fixed formalin embedded tissue blocks of the medical renal biopsies are stored in the Department of Pathology, UWI. Two hundred (200) tissue blocks from the study set will be selected randomly for electron microscopy and APOL-1 gene studies at Stanford University. The three main biopsy diagnoses will be Focal Segmental Glomerulosclerosis, Membranous Nephropathy, and Lupus Nephritis. The investigators performing the APOL-1 testing will be blinded to the biopsy findings and clinical data. Genomic DNA will be extracted from paraffin embedded blocks in Department of Pathology at Stanford University. Cases with sufficient DNA extracted will be deidentified and sent to Genewiz (GENEWIZ, South San Francisco, CA, USA) for APOL-1 gene analysis. Based on review of pathology reports so far, we have identified 63 patients with a FSGS diagnosis, 25 patients with a membranous nephropathy diagnosis, and 103 patients with a Lupus diagnosis. There a 9 path samples with unclear diagnoses. There are 73.5% females, and 26.5% males. The average age of patient's biopsied was 33. Once blocks are confirmed to have enough tissue for genotyping will be able to get more clinical information from the charts and ultimately have preliminary data while we wait for genotyping results. Preliminary conclusions will be available at the time of conference. We hypothesize that we will see a rate of the APOL1 HR genotype greater than 13% percent in this Jamaican population with kidney disease and biopsy results. We hope to use the final results to build the rationale for clinical trials in Jamaica among patients with APOL1 nephropathy and proteinuria.