{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:11:24Z","timestamp":1792782684071,"version":"4.5.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"PROADI \/ SUS","award":["25000.180613\/2011-11"],"award-info":[{"award-number":["25000.180613\/2011-11"]}]},{"name":"Universidade De S\u00e3o Paulo","id":[{"id":"https:\/\/ror.org\/036rp1748","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertension and proteinuria are established risk factors for chronic kidney disease (CKD) progression in children. Given their pathophysiological interrelationship, whether their coexistence produces a multiplicative interaction remains uncertain. We evaluated this interaction in a Brazilian pediatric cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter prospective cohort (SP-CKD-Kids) included 254 children and adolescents aged 1\u201317\u00a0years at study entry with CKD stages 3\u20134, followed for a median of 3.2\u00a0years. The composite outcome comprised death, initiation of kidney replacement therapy, or\u2009&gt;\u200950% decline in estimated glomerular filtration rate (eGFR). Cox models were adjusted for age, sex, baseline eGFR, and CKD etiology. Multiplicative interaction was assessed using a hypertension \u00d7 proteinuria product term, and statistical power was evaluated by simulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Hypertension was present in 67.3% of participants and proteinuria in 77.1%; 98 participants (38.6%) experienced the composite outcome. After adjustment, hypertension (hazard ratio [HR] 1.7; 95% confidence interval [CI] 1.0\u20132.8) and proteinuria (HR 3.5; 95% CI 1.7\u20137.0) remained independently associated with CKD progression. Participants with both conditions had the highest risk compared with those with neither condition (HR 8.4; 95% CI 2.1\u201334.2). The multiplicative interaction was not statistically significant (HR 0.6; 95% CI 0.1\u20133.0;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.507), and simulation indicated limited power to detect interaction effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Hypertension and proteinuria were independent predictors of CKD progression in children. Although no statistically significant multiplicative interaction was detected, the wide confidence interval around the interaction term indicates that a clinically relevant interaction cannot be excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                    <jats:p>A higher resolution version of the Graphical abstract is available as Supplementary information.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00467-026-07542-w","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:16:27Z","timestamp":1790064987000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is there an interaction between hypertension and proteinuria in pediatric chronic kidney disease progression? 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All authors have approved the submission, and all necessary permissions have been obtained.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki and was approved by the Research Ethics Committees of all participating centers. Written informed consent was obtained from parents or legal guardians, with assent from children when appropriate.","order":2,"name":"Ethics","label":"<b>Ethics approval<\/b>","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Dr. Ivan Coelho Machado and Dr. Andreia Watanabe report serving as principal investigators in a clinical trial evaluating finerenone sponsored by Bayer since 2025. The other authors declare no conflicts of interest.","order":3,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}