Urinary Sediment Transcriptomic and Longitudinal Data to Investigate Renal Function Decline in Type 1 Diabetes

Author(s)

Monteiro, Maria Beatriz ^[1] ; Pelaes, Tatiana S. ^[1] ; Santos-Bezerra, Daniele P. ^[1] ; Thieme, Karina ^[2] ; Lerario, Antonio M. ^[3] ; Oba-Shinjo, Sueli M. ^[4] ; Machado, Ubiratan F. ^[2] ; Passarelli, Marisa ^{[5, 6]} ; Marie, Suely K. N. ^[4] ; Correa-Giannella, Maria Lucia ^{[5, 1]}

Affiliation

^[1] Univ Sao Paulo, Facu Med, Hosp Clin HCFMUSP, Lab Carboidratos & Radioimunoensaio LIM 18, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo - Brazil

^[3] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA

^[4] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Lab Mol & Cellular Biol LIM 15, Sao Paulo - Brazil

^[5] Univ Nove Julho Uninove, Programa Posgrad Med, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Lab Lipides LIM 10, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN ENDOCRINOLOGY; v. 11, APR 30 2020.
• Web of Science Citations: 0

Abstract

Introduction: Using a discovery/validation approach we investigated associations between a panel of genes selected from a transcriptomic study and the estimated glomerular filtration rate (eGFR) decline across time in a cohort of type 1 diabetes (T1D) patients. Experimental: Urinary sediment transcriptomic was performed to select highly modulated genes in T1D patients with rapid eGFR decline (decliners) vs. patients with stable eGFR (non-decliners). The selected genes were validated in samples from a T1D cohort (n = 54, mean diabetes duration of 21 years, 61% women) followed longitudinally for a median of 12 years in a Diabetes Outpatient Clinic. Results: In the discovery phase, the transcriptomic study revealed 158 genes significantly different between decliners and non-decliners. Ten genes increasingly up or down-regulated according to renal function worsening were selected for validation by qRT-PCR; the genes CYP4F22, and PMP22 were confirmed as differentially expressed comparing decliners vs. non-decliners after adjustment for potential confounders. CYP4F22, LYPD3, PMP22, MAP1LC3C, HS3ST2, GPNMB, CDH6, and PKD2L1 significantly modified the slope of eGFR in T1D patients across time. Conclusions: Eight genes identified as differentially expressed in the urinary sediment of T1D patients presenting different eGFR decline rates significantly increased the accuracy of predicted renal function across time in the studied cohort. These genes may be a promising way of unveiling novel mechanisms associated with diabetic kidney disease progression. (AU)

• FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
• Grantee: Ubiratan Fabres Machado
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/19000-6 - Study of sediment and microRNAs in the urine of patients with Type 1 diabetes to identify pathways associated to the progression of diabetic kidney disease
• Grantee: Maria Beatriz Camargo Monteiro Caillaud
• Support Opportunities: Scholarships in Brazil - Post-Doctoral