Christina L Tamargo, Steven G Coca, Heather Thiessen Philbrook, David G Hu, Joachim H Ix, Michael G Shlipak, Linda F Fried, Orlando M Gutierrez, Sushrut S Waikar, Sarah J Schrauben, Jeffrey R Schelling, Peter Ganz, Paul L Kimmel, Jason H Greenberg, Rajat Deo, Ayumi Takakura, Ramachandran S Vasan, Joseph V Bonventre, Chirag R Parikh
{"title":"远端肾元生物标志物与糖尿病肾病进展相关。","authors":"Christina L Tamargo, Steven G Coca, Heather Thiessen Philbrook, David G Hu, Joachim H Ix, Michael G Shlipak, Linda F Fried, Orlando M Gutierrez, Sushrut S Waikar, Sarah J Schrauben, Jeffrey R Schelling, Peter Ganz, Paul L Kimmel, Jason H Greenberg, Rajat Deo, Ayumi Takakura, Ramachandran S Vasan, Joseph V Bonventre, Chirag R Parikh","doi":"10.1172/jci.insight.186836","DOIUrl":null,"url":null,"abstract":"<p><p>BACKGROUNDWhile urinary biomarkers show promise in predicting diabetic kidney disease (DKD) progression, distal tubular markers remain understudied. We investigated the association of distal tubule markers, epidermal growth factor (EGF) and uromodulin (UMOD), with DKD progression in the Veterans Affairs Diabetes in Nephropathy (VA NEPHRON-D) clinical trial.</p><p><strong>Methods: </strong>We used Cox regression models to evaluate the association between each biomarker and DKD progression and the relationship between change over time in biomarker and DKD progression. We used mixed models to investigate biomarker levels at baseline, 12 months, and over time and their relationships with longitudinal eGFR change.</p><p><strong>Results: </strong>Participants (n = 1,116) had type 2 diabetes, urine albumin-to-creatinine ratio (UACR) ≥ 300 mg/g, and eGFR 30-89.9 mL/min/1.73 m2. Mean age was 65 years, mean eGFR was 56 (SD 19) mL/min/1.73 m2, and median UACR was 840 (IQR 424-1,780) mg/g. One hundred forty-four participants (13%) had DKD progression over a median follow-up of 2.2 (1.3-3.1) years. Higher baseline EGF and UMOD were independently associated with a lower risk of DKD progression (adjusted HR 0.68, 95% CI 0.47, 0.99 and 0.85, [0.75, 0.98] per 2-fold higher concentration of EGF and UMOD, respectively). Serial biomarker measurements were performed at baseline and 12 months, and a slower decline in biomarkers was associated with a lower risk of DKD progression when adjusted for baseline biomarker levels.</p><p><strong>Conclusion: </strong>Urinary EGF and UMOD may serve as valuable prognostic biomarkers in DKD.</p><p><strong>Trial registration: </strong></p><p><strong>Clinicaltrials: </strong>gov NCT00555217.</p><p><strong>Funding: </strong>NIH U01DK102730, U01DK103225, K23 DK118198, R01DK137087, U01DK103225, R37DK039773, U01DK114866, U01DK106962, U01DK129984, and R01DK093770; National Institute of Diabetes and Digestive and Kidney Diseases contract U01DK106965.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":"10 12","pages":""},"PeriodicalIF":6.3000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220953/pdf/","citationCount":"0","resultStr":"{\"title\":\"The distal nephron biomarkers associate with diabetic kidney disease progression.\",\"authors\":\"Christina L Tamargo, Steven G Coca, Heather Thiessen Philbrook, David G Hu, Joachim H Ix, Michael G Shlipak, Linda F Fried, Orlando M Gutierrez, Sushrut S Waikar, Sarah J Schrauben, Jeffrey R Schelling, Peter Ganz, Paul L Kimmel, Jason H Greenberg, Rajat Deo, Ayumi Takakura, Ramachandran S Vasan, Joseph V Bonventre, Chirag R Parikh\",\"doi\":\"10.1172/jci.insight.186836\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BACKGROUNDWhile urinary biomarkers show promise in predicting diabetic kidney disease (DKD) progression, distal tubular markers remain understudied. We investigated the association of distal tubule markers, epidermal growth factor (EGF) and uromodulin (UMOD), with DKD progression in the Veterans Affairs Diabetes in Nephropathy (VA NEPHRON-D) clinical trial.</p><p><strong>Methods: </strong>We used Cox regression models to evaluate the association between each biomarker and DKD progression and the relationship between change over time in biomarker and DKD progression. We used mixed models to investigate biomarker levels at baseline, 12 months, and over time and their relationships with longitudinal eGFR change.</p><p><strong>Results: </strong>Participants (n = 1,116) had type 2 diabetes, urine albumin-to-creatinine ratio (UACR) ≥ 300 mg/g, and eGFR 30-89.9 mL/min/1.73 m2. Mean age was 65 years, mean eGFR was 56 (SD 19) mL/min/1.73 m2, and median UACR was 840 (IQR 424-1,780) mg/g. One hundred forty-four participants (13%) had DKD progression over a median follow-up of 2.2 (1.3-3.1) years. Higher baseline EGF and UMOD were independently associated with a lower risk of DKD progression (adjusted HR 0.68, 95% CI 0.47, 0.99 and 0.85, [0.75, 0.98] per 2-fold higher concentration of EGF and UMOD, respectively). 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The distal nephron biomarkers associate with diabetic kidney disease progression.
BACKGROUNDWhile urinary biomarkers show promise in predicting diabetic kidney disease (DKD) progression, distal tubular markers remain understudied. We investigated the association of distal tubule markers, epidermal growth factor (EGF) and uromodulin (UMOD), with DKD progression in the Veterans Affairs Diabetes in Nephropathy (VA NEPHRON-D) clinical trial.
Methods: We used Cox regression models to evaluate the association between each biomarker and DKD progression and the relationship between change over time in biomarker and DKD progression. We used mixed models to investigate biomarker levels at baseline, 12 months, and over time and their relationships with longitudinal eGFR change.
Results: Participants (n = 1,116) had type 2 diabetes, urine albumin-to-creatinine ratio (UACR) ≥ 300 mg/g, and eGFR 30-89.9 mL/min/1.73 m2. Mean age was 65 years, mean eGFR was 56 (SD 19) mL/min/1.73 m2, and median UACR was 840 (IQR 424-1,780) mg/g. One hundred forty-four participants (13%) had DKD progression over a median follow-up of 2.2 (1.3-3.1) years. Higher baseline EGF and UMOD were independently associated with a lower risk of DKD progression (adjusted HR 0.68, 95% CI 0.47, 0.99 and 0.85, [0.75, 0.98] per 2-fold higher concentration of EGF and UMOD, respectively). Serial biomarker measurements were performed at baseline and 12 months, and a slower decline in biomarkers was associated with a lower risk of DKD progression when adjusted for baseline biomarker levels.
Conclusion: Urinary EGF and UMOD may serve as valuable prognostic biomarkers in DKD.
Trial registration:
Clinicaltrials: gov NCT00555217.
Funding: NIH U01DK102730, U01DK103225, K23 DK118198, R01DK137087, U01DK103225, R37DK039773, U01DK114866, U01DK106962, U01DK129984, and R01DK093770; National Institute of Diabetes and Digestive and Kidney Diseases contract U01DK106965.
期刊介绍：
JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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