Background: Novel aptamer-based technologies can identify over 7000 analytes per sample, offering a high-throughput alternative to traditional immunoassays in biomarker discovery. However, their specificity for distinct proteins has not been thoroughly studied in the context of chronic kidney disease (CKD). Methods: We aimed to validate the use of SOMAscan, an aptamer-based technology, for the quantification of 8 immune activation biomarkers and cystatin C in 498 participants from the African American Study of Kidney Disease and Hypertension (AASK), using immunoassays as the gold standard. We evaluated correlations of serum proteins as measured by SOMAscan vs. immunoassays and correlations of proteins (measured by each method) with iothalamate-measured glomerular filtration rate (mGFR). Using Cox models, we compared associations between proteins measured by SOMAscan vs. immunoassays with risks of incident end-stage kidney disease (ESKD) and all-cause mortality. Results: Six biomarkers (IL-8, TNFRSF1B, cystatin C, TNFRSF1A, IL-6, suPAR) had moderate-to-high correlations (Pearson r=0.22 to 0.94, Spearman rs=0.30 to 0.98,) between SOMAscan and immunoassay measurements and three (TNF-?, IFN-g, IL-10) were uncorrelated (r=-0.03 to 0.10, rs=-0.03 to 0.06). Of those with moderate-to-high correlations, TNFRSF1B, cystatin C, TNFRSF1A, and suPAR were negatively correlated with mGFR and associated with higher risk of ESKD. All 6 biomarkers with moderate-to-high correlations were associated with increased risk of mortality. On average, immunoassay measurements were more strongly associated with adverse outcomes than their SOMAscan counterparts. Conclusions: SOMAscan is an efficient and relatively reliable technique for the quantification of biomarkers in the setting of CKD and for the detection of potential associations with clinical outcomes. Targeted immunoassays of candidate proteins may provide additional prognostic information.