Beta-2-microglobulin (B2M) expression in the urinary sediment correlates with clinical markers of kidney disease in patients with type 1 diabetes

Author(s)

Monteiro, Maria Beatriz ^[1] ; Thieme, Karina ^[1] ; Santos-Bezerra, Daniele Pereira ^[1] ; Queiroz, Marcia Silva ^[2] ; Woronik, Viktoria ^[3] ; Passarelli, Marisa ^[4] ; Machado, Ubiratan Fabres ^[5] ; Giannella-Neto, Daniel ^[6] ; Oliveira-Souza, Maria ^[7] ; Correa-Giannella, Maria Lucia ^{[1, 8]}

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Cellular & Mol Endocrinol LIM 25, Au Dr Arnaldo 455 4305, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Hosp Clin, Div Endocrine, Sch Med, Av Dr Eneas de Carualho Aguiar 155, BR-05403000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Lab Renal Pathophysiol LIM 16, Av Dr Arnaldo 455 3345, BR-01246903 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Lipids Lab LIM 10, Av Dr Arnaldo 455 3305, BR-01246903 Sao Paulo - Brazil

^[5] Inst Biomed Sci, Lab Metab & Endocrinol, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524 126, BR-05508000 Sao Paulo - Brazil

^[6] Univ Nove Julho UNINOVE, Programa Posgrad Med, R Vergueiro 235-249, BR-01504001 Sao Paulo - Brazil

^[7] Inst Biomed Sci, Dept Physiol & Biophys, Lab Renal Physiol, Av Prof Lineu Prestes 1524 227, BR-05508000 Sao Paulo - Brazil

^[8] Univ Sao Paulo, Sch Med, Cell & Mol Therapy Ctr NUCEL, Lab Cellular & Mol Endocrinol LIM 25, BR-05360120 Sao Paulo - Brazil

• Document type: Journal article
• Source: METABOLISM-CLINICAL AND EXPERIMENTAL; v. 65, n. 6, p. 816-824, JUN 2016.
• Web of Science Citations: 8

Abstract

Purpose. 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. Methods. 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 25 mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu. Results. 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 25 mM glucose and to albumin. Conclusions. B2M 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. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives
• Grantee: Ubiratan Fabres Machado
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/05583-1 - Expression of mRNA of the TXNIP, SCL19A2 and SCL19A3 genes in the urinary sediment of patients with type 1 diabetes with and without diabetic nephropathy
• Grantee: Maria Lucia Cardillo Corrêa Giannella
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/02003-4 - Expression of mRNA of the TXNIP, SCL19A2 and SCL19A3 genes in the urinary sediment of patients with type 1 diabetes with and without diabetic nephropathy
• Grantee: Maria Beatriz Camargo Monteiro Caillaud
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/19569-3 - Effects of endothelin-3 and leptin in renal morphology and function in vivo: involvement of the intrarenal renin-angiotensin system
• Grantee: Maria Oliveira de Souza
• Support Opportunities: Regular Research Grants