title: Beta-2-microglobulin (B2M) expression in the urinary sediment correlates with clinical markers of kidney disease in patients with type 1 diabetes.
abstract: After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD.
  
  
  
  qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0-39.7] years old, with diabetes duration of 21.0 [15.0-28.0] years and HbA1c of 8.2% [7.3-8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in human embryonic kidney epithelium-like (HEK-293) cells exposed to 25mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu.
  
  
  
  No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls (P=0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN (P=0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r=0.43; P=0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r=- 0.57; P=0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25mM glucose and to albumin.
  
  
  
  Β2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy.
authors.affiliation: Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #4305, 01246-903, São Paulo. Electronic address: maria.monteiro@usp.br.
authors.forename: Maria Beatriz
authors.initials: MB
authors.lastname: Monteiro
authors.affiliation: Endocrine Division, Hospital das Clínicas, University of São Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar 155, 05403-000, São Paulo. Electronic address: karina.thieme@usp.br.
authors.forename: Karina
authors.initials: K
authors.lastname: Thieme
authors.affiliation: Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #4305, 01246-903, São Paulo. Electronic address: dps.daniele@usp.br.
authors.forename: Daniele Pereira
authors.initials: DP
authors.lastname: Santos-Bezerra
authors.affiliation: Lipids Laboratory (LIM-10), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #3305, 01246-903, São Paulo. Electronic address: marciasqz@gmail.com.
authors.forename: Márcia Silva
authors.initials: MS
authors.lastname: Queiroz
authors.affiliation: Laboratory of Renal Pathophysiology (LIM-16), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #3345, 01246-903, São Paulo. Electronic address: viktoriaw@usp.br.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Woronik
authors.affiliation: Lipids Laboratory (LIM-10), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #3305, 01246-903, São Paulo. Electronic address: mpassere@usp.br.
authors.forename: Marisa
authors.initials: M
authors.lastname: Passarelli
authors.affiliation: Laboratory of Metabolism and Endocrinology, Department of Physiology and Biophysics, Biomedical Sciences Institute, Av. Prof. Lineu Prestes 1524 #126, 05508-000, São Paulo. Electronic address: ubiratan@icb.usp.br.
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
authors.affiliation: Programa de Pós-Graduação em Medicina, Universidade Nove de Julho - UNINOVE, R. Vergueiro, 235/249, 01504-001, São Paulo. Electronic address: dgiannella@terra.com.br.
authors.forename: Daniel
authors.initials: D
authors.lastname: Giannella-Neto
authors.affiliation: Laboratory of Renal Physiology, Department of Physiology and Biophysics, Biomedical Sciences Institute, Av. Prof. Lineu Prestes 1524 #227, 05508-000, São Paulo. Electronic address: souza@icb.usp.br.
authors.forename: Maria
authors.initials: M
authors.lastname: Oliveira-Souza
authors.affiliation: Laboratory of Cellular and Molecular Endocrinology (LIM-25), University of São Paulo Medical School, Av. Dr. Arnaldo 455 #4305, 01246-903, São Paulo; Laboratory of Cellular and Molecular Endocrinology (LIM-25), Cell and Molecular Therapy Center (NUCEL), University of São Paulo Medical School, R. Pangaré, 05360-120, São Paulo. Electronic address: malugia@lim25.fm.usp.br.
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Corrêa-Giannella
mesh_terms: D000328:Adult; D000418:Albumins / Q000494:pharmacology; D000419:Albuminuria / Q000235:genetics / Q000652:urine; D015415:Biomarkers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000652:urine*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000652:urine*; D005260:Female; D005916:Globulins / Q000235:genetics / Q000652:urine*; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics / Q000652:urine*; D005947:Glucose / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000652:urine
chemical_list: D000418:Albumins; D015415:Biomarkers; D005916:Globulins; D012333:RNA, Messenger; D005947:Glucose
keywords: Beta-2-microglobulin; Diabetic kidney disease; Diabetic nephropathy; Focal segmental glomerulosclerosis; Urinary sediment