Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts
Introduction: Kidney tubular biomarker trends may provide insight into tubulointerstitial pathology that is not evident through measurement of glomerular filtration rate (GFR) and albumin excretion rate (AER). Methods: We examined longitudinal changes in tubular biomarkers in 2 type 1 diabetes (T1D)...
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Elsevier
2025-07-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024925002827 |
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| author | Christine P. Limonte David K. Prince Andrew N. Hoofnagle Irl B. Hirsch Sushrut S. Waikar Alessandro Doria Michael Mauer Bryan R. Kestenbaum Ian H. de Boer |
| author_facet | Christine P. Limonte David K. Prince Andrew N. Hoofnagle Irl B. Hirsch Sushrut S. Waikar Alessandro Doria Michael Mauer Bryan R. Kestenbaum Ian H. de Boer |
| author_sort | Christine P. Limonte |
| collection | DOAJ |
| description | Introduction: Kidney tubular biomarker trends may provide insight into tubulointerstitial pathology that is not evident through measurement of glomerular filtration rate (GFR) and albumin excretion rate (AER). Methods: We examined longitudinal changes in tubular biomarkers in 2 type 1 diabetes (T1D) cohorts, namely the Renin-Angiotensin System Study (RASS, n = 283), including adults with normal GFR and AER and the Preventing Early Renal Loss in Diabetes Study (PERL, n = 530), including adults with albuminuria and/or rapid loss of estimated GFR (eGFR). The measurements included plasma kidney injury molecule-1 (KIM-1), soluble tumor necrosis factor receptor 1 (sTNFR1), arginine-citrulline ratio, urine epidermal growth factor (EGF), uromodulin (UMOD), and a tubular secretion score reflecting urinary clearances of 8 proximal tubular secreted molecules. Results: At baseline, RASS participants’ mean age was 30 years and 47% were male, with mean diabetes duration of 11 years, hemoglobin A1c (HbA1c) of 8.6%, iohexol-based measured GFR (iGFR) of 128 ml/min per 1.73 m2, and AER of 6 μg/min. PERL participants’ mean age was 51 years and 66% were male, with mean diabetes duration of 35 years, HbA1c of 8.2%, iGFR of 68 ml/min per 1.73 m2, and AER of 285 μg/min. Tubular biomarkers changed significantly over time as follows: KIM-1 of +5.7 pg/ml/yr, sTNFR1 of +14.2 pg/ml/yr, arginine-citrulline ratio of −0.03 units/yr, and EGF of −0.30 μg/d/yr in RASS; KIM-1 of +7.5 pg/ml/yr, sTNFR1 of +75.0 pg/ml/yr, UMOD of −3.4 mg/d/yr, and tubular secretion score of −0.53 units/yr in PERL. Higher baseline HbA1c and AER were associated with more rapid worsening of select tubular biomarkers in both RASS and PERL. Conclusion: Tubular biomarkers significantly worsen over time in T1D, potentially reflecting progression of tubulointerstitial pathology. |
| format | Article |
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| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-09eb10371c1a4650b73bde8bb91e31ea2025-08-20T03:24:16ZengElsevierKidney International Reports2468-02492025-07-011072311232210.1016/j.ekir.2025.04.057Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 CohortsChristine P. Limonte0David K. Prince1Andrew N. Hoofnagle2Irl B. Hirsch3Sushrut S. Waikar4Alessandro Doria5Michael Mauer6Bryan R. Kestenbaum7Ian H. de Boer8Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA; Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington, USA; Correspondence: Christine P. Limonte, Kidney Research Institute, Box 359606, 325 9th Ave., Seattle, Washington 98104, USA.Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA; Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington, USADepartment of Laboratory Medicine and Pathology, Department of Medicine, University of Washington, Seattle, Washington, USADivision of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle, Washington, USASection of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USAResearch Division, Joslin Diabetes Center, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USADepartment of Pediatrics and Medicine, University of Minnesota, Minneapolis, Minnesota, USADivision of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA; Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington, USADivision of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA; Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington, USAIntroduction: Kidney tubular biomarker trends may provide insight into tubulointerstitial pathology that is not evident through measurement of glomerular filtration rate (GFR) and albumin excretion rate (AER). Methods: We examined longitudinal changes in tubular biomarkers in 2 type 1 diabetes (T1D) cohorts, namely the Renin-Angiotensin System Study (RASS, n = 283), including adults with normal GFR and AER and the Preventing Early Renal Loss in Diabetes Study (PERL, n = 530), including adults with albuminuria and/or rapid loss of estimated GFR (eGFR). The measurements included plasma kidney injury molecule-1 (KIM-1), soluble tumor necrosis factor receptor 1 (sTNFR1), arginine-citrulline ratio, urine epidermal growth factor (EGF), uromodulin (UMOD), and a tubular secretion score reflecting urinary clearances of 8 proximal tubular secreted molecules. Results: At baseline, RASS participants’ mean age was 30 years and 47% were male, with mean diabetes duration of 11 years, hemoglobin A1c (HbA1c) of 8.6%, iohexol-based measured GFR (iGFR) of 128 ml/min per 1.73 m2, and AER of 6 μg/min. PERL participants’ mean age was 51 years and 66% were male, with mean diabetes duration of 35 years, HbA1c of 8.2%, iGFR of 68 ml/min per 1.73 m2, and AER of 285 μg/min. Tubular biomarkers changed significantly over time as follows: KIM-1 of +5.7 pg/ml/yr, sTNFR1 of +14.2 pg/ml/yr, arginine-citrulline ratio of −0.03 units/yr, and EGF of −0.30 μg/d/yr in RASS; KIM-1 of +7.5 pg/ml/yr, sTNFR1 of +75.0 pg/ml/yr, UMOD of −3.4 mg/d/yr, and tubular secretion score of −0.53 units/yr in PERL. Higher baseline HbA1c and AER were associated with more rapid worsening of select tubular biomarkers in both RASS and PERL. Conclusion: Tubular biomarkers significantly worsen over time in T1D, potentially reflecting progression of tubulointerstitial pathology.http://www.sciencedirect.com/science/article/pii/S2468024925002827diabetic kidney diseasetubular biomarkerstype 1 diabetes |
| spellingShingle | Christine P. Limonte David K. Prince Andrew N. Hoofnagle Irl B. Hirsch Sushrut S. Waikar Alessandro Doria Michael Mauer Bryan R. Kestenbaum Ian H. de Boer Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts Kidney International Reports diabetic kidney disease tubular biomarkers type 1 diabetes |
| title | Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts |
| title_full | Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts |
| title_fullStr | Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts |
| title_full_unstemmed | Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts |
| title_short | Kidney Tubular Biomarkers in Type 1 Diabetes - Longitudinal Analysis of 2 Cohorts |
| title_sort | kidney tubular biomarkers in type 1 diabetes longitudinal analysis of 2 cohorts |
| topic | diabetic kidney disease tubular biomarkers type 1 diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S2468024925002827 |
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