Background Renal fibrosis is a common pathological symptom of chronic kidney disease (CKD). Many studies support that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are implicated in the pathogenesis of CKD. In our study, we investigated the benefits and underlying mechanisms of Mito-TEMPO on renal fibrosis in 5/6 nephrectomy mice. Methods Mice were randomly divided into five groups as follows: control group, CKD group, CKD + Mito-TEMPO (1 mg·kg−1·day−1) group, CKD + Mito-TEMPO (3 mg·kg−1·day−1) group, and Mito-TEMPO group (3 mg·kg−1·day−1). Renal fibrosis was evaluated by PAS, Masson staining, immunohistochemistry, and real-time PCR. Oxidative stress markers such as SOD2 activity and MDA level in serum and isolated mitochondria from renal tissue were measured by assay kits. Mitochondrial superoxide production was evaluated by MitoSOX staining and Western blot. Mitochondrial dysfunction was assessed by electron microscopy and real-time PCR. ER stress-associated protein was measured by Western blot. Results Impaired renal function and renal fibrosis were significantly improved by Mito-TEMPO treatment. Furthermore, inflammation cytokines, profibrotic factors, oxidative stress markers, mitochondrial dysfunction, and ER stress were all increased in the CKD group. However, these effects were significantly ameliorated in the Mito-TEMPO treatment group. Conclusions Mito-TEMPO ameliorates renal fibrosis by alleviating mitochondrial dysfunction and endoplasmic reticulum stress possibly through the Sirt3-SOD2 pathway, which sheds new light on prevention of renal fibrosis in chronic kidney disease.
BackgroundThere are few data on the prevalence of low T3 (triiodothyronine) syndrome in patients with non-dialysis chronic kidney disease (CKD) and it is unclear whether low T3 can be used to predict the progression of CKD.Material/MethodsWe retrospectively studied 279 patients who had been definitively diagnosed with CKD, without needing maintenance dialysis. Thyroid function was analyzed in all enrolled subjects and the incidence of thyroid dysfunction (low T3 syndrome, low T4 syndrome, and subclinical hypothyroidism) in patients at different stages of CKD was determined.ResultsGlomerular filtration rate (GFR) of CKD patients was estimated as follows: 145 subjects (52%) had GFR <60 ml/min per 1.73 m2; 47 subjects (16.8%) had GFR between 30 and 59 ml/min per 1.73 m2, and 98 subjects (35.1%) had GFR <30 ml/min per 1.73 m2. Among all enrolled subjects, 4.7% (n=13) had subclinical hypothyroidism, 5.4% (n=15) had low T4 syndrome, and 47% (n=131) had low T3 syndrome. In 114 CKD patients in stages 3–5, serum T3 was positively related to protein metabolism (STP, PA, and ALB) and anemia indicators (Hb and RBC), and negatively related to inflammatory status (CRP and IL-6).ConclusionsA high prevalence of low T3 syndrome was observed in CKD patients without dialysis, even in early stages (1 and 2). The increasing prevalence of low T3 as CKD progresses indicates its value as a predictor of worsening CKD. Furthermore, low T3 syndrome is closely associated with both malnutrition-inflammation complex syndrome (MICS) and anemia.
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