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

• Published in: Metabolism, clinical and experimental Vol. 65; no. 6; pp. 816 - 824
• Main Authors: Monteiro, Maria Beatriz, Thieme, Karina, Santos-Bezerra, Daniele Pereira, Queiroz, Márcia Silva, Woronik, Viktoria, Passarelli, Marisa, Machado, Ubiratan Fabres, Giannella-Neto, Daniel, Oliveira-Souza, Maria, Corrêa-Giannella, Maria Lúcia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2016
• Subjects: Adult; Albumins - pharmacology; Albuminuria - genetics; Albuminuria - urine; Beta-2-microglobulin; Biomarkers; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - urine; Diabetic kidney disease; Diabetic Nephropathies - genetics; Diabetic Nephropathies - urine; Diabetic nephropathy; Endocrinology & Metabolism; Female; Focal segmental glomerulosclerosis; Globulins - genetics; Globulins - urine; Glomerulosclerosis, Focal Segmental - genetics; Glomerulosclerosis, Focal Segmental - urine; Glucose - pharmacology; HEK293 Cells; Humans; Kidney - drug effects; Male; RNA, Messenger - genetics; RNA, Messenger - urine; Urinary sediment; TLR-4; Focal segmental glomerulosclerosis; MHC; DN; SLC2A5; sICAM-1; ACEI; FSGS; Diabetic nephropathy; TGF-β; DKD; B2M; CKD; Diabetic kidney disease; AGE; Urinary sediment; eGFR; IL; SGLT2; VEGF; ACR; ARB; ELF1; NPHS2; Beta-2-microglobulin; urinary sediment; estimated glomerular filtration rate; advanced glycation end products; albumin-to-creatinine ratio; beta-2-microglobulin; gene encoding SGLT2 protein; interleukin; diabetic kidney disease; type 1 diabetes mellitus; gene encoding podocin protein; angiotensin receptor blockers; angiotensin converting enzyme inhibitors; focal segmental glomerulosclerosis; focal and segmental glomerulosclerosis; transforming growth factor-β; vascular endothelial growth factor; E74-Like Factor 1; soluble intercellular adhesion molecule 1; toll-like receptor 4; diabetic nephropathy; sodium glucose cotransporter 2
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2016.02.012

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.