Thioredoxin interacting protein expression in the urinary sediment associates with renal function decline in type 1 diabetes

ABSTRACT

Aims: Thioredoxin interacting protein (TXNIP), an inhibitor of antioxidant thioredoxin (Trx), is upregulated by hyperglycemia and implicated in pathogenesis of diabetes complications. We evaluated mRNA expressions of genes encoding TXNIP and Trx (TXN) in urinary sediment and peripheral blood mononuclear cells (PBMC) of type 1 diabetes (T1D) patients with different degrees of chronic complications. Methods: qPCR was employed to quantify target genes in urinary sediment (n = 55) and PBMC (n = 161) from patients sorted by presence or absence of diabetic nephropathy (DN), retinopathy, peripheral and cardiovascular neuropathy; 26 healthy controls and 13 patients presenting non-diabetic nephropathy (focal and segmental glomerulosclerosis, FSGS) were also included. Results: Regarding the urinary sediment, TXNIP (but not TXN) expression was higher in T1D (p = 0.0023) and FSGS (p = 0.0027) patients versus controls. Expressions of TXNIP and TXN were higher, respectively, in T1D patients with versus without DN (p = 0.032) and in those with estimated glomerular filtration rate (eGFR) < 60 versus ≥60 mL/min/1.73 m² (p = 0.008). eGFR negatively correlated with TXNIP (p = 0.04, r = −0.28) and TXN (p = 0.04, r = −0.30) expressions. T1D patients who lost ≥5 mL/min/1.73 m² yearly of eGFR presented higher basal TXNIP expression than those who lost <5 mL/min/1.73 m² yearly after median follow-up of 24 months. TXNIP (p < 0.0001) and TXN (p = 0.002) expressions in PBMC of T1D patients were significantly higher than in controls but no differences were observed between patients with or without chronic complications. Conclusions: TXNIP and TXN are upregulated in urinary sediment of T1D patients with diabetic kidney disease (DKD), but only TXNIP expression is associated with magnitude of eGFR decline.

KEYWORDS:

• Diabetic complications
• diabetic kidney disease
• oxidative stress
• PBMC
• urinary sediment

Declaration of interest

The authors have nothing to disclose. This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) to Maria Lúcia Corrêa-Giannella (12/05583-1 and 12/04831-1), Maria Beatriz Monteiro (12/02003-4), Daniele Santos-Bezerra (12/25490-8), Ubiratan Fabres Machado (12/04831-1) and Maria Oliveira-Souza (13/19569-3).