Thioredoxin interacting protein expression in the urinary sediment associates with renal function decline in type 1 diabetes.
OBJECTIVE
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 m(2) (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 m(2) yearly of eGFR presented higher basal TXNIP expression than those who lost <5 mL/min/1.73 m(2) 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.
a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ;
Maria Beatriz
MB
Monteiro
a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ;
Daniele Pereira
DP
Santos-Bezerra
a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ;
Karina
K
Thieme
a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ;
Sharon Nina
SN
Admoni
a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ;
Ricardo Vessoni
RV
Perez
b Divisão de Oftalmologia , Hospital das Clínicas, FMUSP , Brazil ;
Cleide Guimarães
CG
Machado
c Divisão de Endocrinologia , Hospital das Clínicas, FMUSP , Brazil ;
Marcia Silva
MS
Queiroz
c Divisão de Endocrinologia , Hospital das Clínicas, FMUSP , Brazil ;
Marcia
M
Nery
d Laboratório de Fisiologia Renal , Departamento de Fisiologia e Biofísica do Instituto de Ciências Biomédicas da Universidade de São Paulo (ICBUSP) , Brazil ;
Maria
M
Oliveira-Souza
e Divisão de Nefrologia , Hospital das Clínicas, FMUSP , Brazil ;
Viktoria
V
Woronik
f Laboratório de Lípides (LIM-10) , FMUSP , Brazil ;
Marisa
M
Passarelli
g Programa de Pós-Graduação em Medicina , Universidade Nove de Julho - UNINOVE , Brazil ;
Daniel
D
Giannella-Neto
h Laboratório de Metabolismo e Endocrinologia , Departamento de Fisiologia e Biofísica do ICBUSP , Brazil ;
Ubiratan Fabres
UF
Machado
a Laboratório de Endocrinologia Celular e Molecular (LIM-25) , Faculdade de Medicina da Universidade de São Paulo (FMUSP) , Brazil ;|i Núcleo de Terapia Celular e Molecular (NUCEL/NETCEM), FMUSP , Brazil.
Maria Lúcia
ML
Corrêa-Giannella
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000652:urine*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000503:physiopathology / Q000652:urine*; D005260:Female; D015870:Gene Expression; D005919:Glomerular Filtration Rate; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000652:urine; D013879:Thioredoxins / Q000235:genetics / Q000652:urine; D016482:Urinalysis
D002352:Carrier Proteins; D012333:RNA, Messenger; C491203:TXN protein, human; C486715:TXNIP protein, human; D013879:Thioredoxins
Diabetic complications; PBMC; diabetic kidney disease; oxidative stress; urinary sediment