{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:43:57Z","timestamp":1776231837752,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the association between serum complement component 3 (C3) levels and renal pathological injury across different estimated glomerular filtration rate (eGFR) strata in patients with diabetic kidney disease (DKD) and evaluate its potential as an early-warning biomarker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study enrolled 187 DKD patients. Serum C3 levels were measured, and renal biopsies were evaluated by two independent pathologists using a standardized scoring system. Patients were stratified by eGFR (low: &amp;lt;90; high: \u226590 ml\/min\/1.73m\u00b2). The association between serum C3 levels and renal injury was evaluated using multivariable linear regression and binary logistic regression analyses, after adjusting for age, sex, TC, duration of diabetes, HbA1c, albumin and 24-h (24-hour) proteinuria. Restricted cubic spline analysis explored nonlinear relationships in the low eGFR subgroup. Exploratory longitudinal analysis was performed to compare changes in 24-h proteinuria over 1 year of follow-up between patients stratified by serum C3 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum C3 levels were negatively correlated with renal C3 deposition and eGFR (\u03c1 = \u22120.167,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.022; \u03c1 = 0.238,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001). In patients with low eGFR, lower C3 levels were consistently associated with higher renal pathology (RP) scoring. After full adjustment, this association remained significant (\u03b2 = \u22122.640,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.047). Interstitial fibrosis and tubular atrophy and C3 (OR\u00a0=\u00a00.09,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.037), showed significant inverse associations. Restricted cubic spline analysis demonstrated a linear relationship (\n                      <jats:italic>P<\/jats:italic>\n                      for overall = 0.031,\n                      <jats:italic>P<\/jats:italic>\n                      for nonlinear = 0.079). At 1-year follow-up, exploratory longitudinal analysis showed that patients with lower C3 (&amp;lt;1.10 g\/L) showed significantly greater 24-h proteinuria progression (-2869.27 vs. 250.46 mg\/24h,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.040).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In DKD patients with eGFR &amp;lt;90 ml\/min\/1.73m\u00b2, reduced serum C3 levels are associated with specific renal pathological injuries and may serve as a biomarker of disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1806382","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:44:53Z","timestamp":1776228293000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum C3 as an early-warning biomarker for renal pathological progression in DKD"],"prefix":"10.3389","volume":"17","author":[{"given":"Donghong","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]},{"name":"Xinxiang Key Laboratory of Precise Therapy for Diabetic Kidney Disease, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senle","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]},{"name":"Xinxiang Key Laboratory of Precise Therapy for Diabetic Kidney Disease, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tongtong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]},{"name":"Xinxiang Key Laboratory of Precise Therapy for Diabetic Kidney Disease, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]},{"name":"Xinxiang Key Laboratory of Precise Therapy for Diabetic Kidney Disease, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Renal Pathology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]},{"name":"Department of Renal Pathology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Renal Pathology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenchao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]},{"name":"Xinxiang Key Laboratory of Precise Therapy for Diabetic Kidney Disease, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First Affiliated Hospital of Henan Medical University","place":["Weihui, Henan, 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