{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:49:03Z","timestamp":1789202943778,"version":"build-2803163510"},"reference-count":97,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":34,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,9]]},"abstract":"<jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Maladaptive hypertrophy, podocyte stress, and depletion contribute to kidney function decline. Although insulin-like growth factor 1 (IGF-1) plays a key role in early hypertrophic responses in the single kidney state, its impact on kidney transplant (KTx) outcomes remains uncertain. This report tests the hypothesis that early IGF-1 exposure reduces KTx survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Population datasets compared incident death-censored graft failure (DCGF) rates by age at KTx (\n                      <jats:italic>n<\/jats:italic>\n                      = 366,404) with IGF-1 levels by age (\n                      <jats:italic>n<\/jats:italic>\n                      = 15,014). A clinical study of 216 KTx recipients evaluated the association of IGF-1 exposure with DCGF and secondary outcomes of proteinuria and biopsy-proven acute rejection. IGF-1 exposure was modeled using pre-KTx IGF-1 levels and donor kidney dose estimated from the donor\/recipient body surface area ratio reflecting allograft hyperfiltration. The association of DCGF with an\n                      <jats:italic>IGF1<\/jats:italic>\n                      SNP linked to high IGF-1 levels was assessed in 724 genotyped allograft recipients. Single-cell transcriptomic data from first-year post-KTx patients and binephric donors were compared to assess intrarenal cellular expression of\n                      <jats:italic>IGF1<\/jats:italic>\n                      ,\n                      <jats:italic>IGF1R<\/jats:italic>\n                      , and growth hormone receptor (\n                      <jats:italic>GHR<\/jats:italic>\n                      ) transcripts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      DCGF risk by age at KTx paralleled IGF-1 levels by age. Higher IGF-1 exposure was associated with significantly increased risks of DCGF, proteinuria, and T cell\u2013mediated rejection. Genotypic analysis showed a 50% increase in DCGF risk per risk allele at\n                      <jats:italic>IGF1<\/jats:italic>\n                      expression quantitative trait locus\n                      <jats:italic>rs35767<\/jats:italic>\n                      . First-year biopsy results revealed no increase in intrarenal\n                      <jats:italic>IGF1<\/jats:italic>\n                      transcripts, while\n                      <jats:italic>GHR<\/jats:italic>\n                      and\n                      <jats:italic>IGF1R<\/jats:italic>\n                      transcripts were suppressed, consistent with circulating IGF-1 (vs. graft-derived IGF-1) being the primary source of IGF-1 exposure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>We identify a role for the growth hormone\/IGF-1 axis in reducing KTx survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.188485","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T12:00:13Z","timestamp":1746532813000},"source":"Crossref","is-referenced-by-count":8,"title":["The growth hormone\/IGF-1 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