{"doi":"10.2337/dc21-2196","title":"Advanced Glycation End Products Predict Loss of Renal Function and High-Risk Chronic Kidney Disease in Type 2 Diabetes","abstract":"OBJECTIVE: To evaluate the association of a multicomponent advanced glycation end product (AGE) panel with decline in kidney function and its utility in predicting renal function loss (RFL) when added to routine clinical measures in type 2 diabetes. RESEARCH DESIGN AND METHODS: Carboxymethyl and carboxyethyl lysine and methylglyoxal, 3-deoxyglucosone, and glyoxal hydroimidazolones were measured in baseline serum and plasma samples, respectively, from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (n = 1,150) and Veterans Affairs Diabetes Trial (VADT) (n = 447) participants. A composite AGE score was calculated from individual AGE z scores. The primary outcome was a sustained 30% decline in estimated glomerular filtration rate (eGFR) (30% RFL in both cohorts). Secondary outcomes (in ACCORD) were 40% RFL, macroalbuminuria, and high-risk chronic kidney disease (hrCKD). RESULTS: After adjustment for baseline and follow-up HbA1c and other risk factors in ACCORD, the AGE score was associated with reduction in eGFR (β-estimate -0.66 mL/min ⋅ 1.73 m2 per year; P = 0.001), 30% RFL (hazard ratio 1.42 [95% CI 1.13-1.78]; P = 0.003), 40% RFL (1.40 [1.13-1.74]; P = 0.003), macroalbuminuria (1.53 [1.13-2.06]; P = 0.006), and hrCKD (1.88 [1.37-2.57]; P < 0.0001). AGE score improved net reclassification (NRI) and relative integrated discrimination (IDI) for 30% RFL (NRI 23%; P = 0.02) (relative IDI 7%; P = 0.009). In VADT, the AGE score calculated by the ACCORD-derived coefficients was associated with 30% RFL (1.37 [1.03-1.82); P = 0.03) and improved NRI (24%; P = 0.03) but not IDI (P = 0.18). CONCLUSIONS: These data provide further support for a causal role of AGEs in diabetic nephropathy independently of glycemic control and suggest utility of the composite AGE panel in predicting long-term decline in renal function.","journal":"Diabetes Care","year":2022,"id":235552,"datarank":2.4590475488126655,"base_score":4.3694478524670215,"endowment":4.3694478524670215,"self_citation_contribution":0.6554171778700533,"citation_network_contribution":1.803630370942612,"self_endowment_contribution":0.6554171778700533,"citer_contribution":1.803630370942612,"corpus_percentile":null,"corpus_rank":null,"citation_count":78,"citer_count":71,"citers_with_citation_signal":57,"citers_with_endowment":57,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9665,"is_data_producer":true,"deposit_databanks":{"figshare":["10.2337/figshare.17372309"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":63109,"name":"Hertzel C. Gerstein","orcid":"0000-0001-8072-2836","position":1,"is_corresponding":false},{"id":743247,"name":"Paul J. Beisswenger","orcid":"0000-0002-6594-6978","position":2,"is_corresponding":false},{"id":329776,"name":"Peter D. Reaven","orcid":"0000-0001-8923-6690","position":3,"is_corresponding":false},{"id":329775,"name":"Juraj Koska","orcid":"0000-0002-6671-6250","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T00:21:53.333008Z","pmid":"35051276","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}