RESUMEN
A dietary protein intake (DPI) of between 0.6 and 0.8 g protein per kilogram body weight per day (g/kg/day) is frequently recommended for adults with moderate-to-advanced chronic kidney disease (CKD). However, evidence on whether patients with diabetic kidney disease (DKD) actually benefit from a DPI of ≤ 0.8 g/kg/day and from a low-protein diet (LPD) at CKD stages 1-3 has not been consistent. We systematically searched MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, as well as the bibliographies of articles identified in the search, for eligible randomized controlled trials that had investigated the effects of LPD (prescribed DPI < 0.8 g/kg/day) versus control diet on the progression of DKD. Nine trials that included 506 participants and follow-up periods varying from 4.5 to 60 months were included in the subsequent systematic review and meta-analysis. The data showed that patients with DKD who consumed < 0.8 g protein/kg/day had a significantly reduced decline in glomerular filtration rate (GFR) (mean difference [MD] 22.31 mL/min/1.73 m2, 95% confidence interval [CI] 17.19, 27.42; P < 0.01) and a significant decrease in proteinuria (standard mean difference [SMD] - 2.26 units, 95% CI - 2.99, - 1.52; P < 0.001) versus those on the control diet. The benefits of LPD to patients with DKD at CKD stages 1-3 were a markedly decreased proteinuria (SMD - 0.96 units, 95% CI - 1.81, - 0.11; P = 0.03) and slight but significant decreases in glycated hemoglobin (- 0.42%) and cholesterol levels (- 0.22 mmol/L). Our meta-analysis indicated that a DPI of < 0.8 g/kg/day was strongly associated with a slow decline in GFR and decreased proteinuria in the patients with DKD. Patients with CKD stages CKD 1-3 benefited from LPD in terms of a marked decrease of proteinuria and slight but significant improvements in lipid and glucose control.
RESUMEN
Histone deacetylase 6 (HDAC6) is the specific subtype of HDACs which preferentially located in the cytoplasm, and is crucial in insulin signalling. However, the role of HDAC6 in type 2 diabetic nephropathy (DN) remains undefined. In current study, we observed that HDAC6 was markedly activated in the kidneys of type 2 diabetic patients and db/db mice with albuminuria, along with the advanced glycation end products (AGE)-treated podocytes. Selective inhibition of HDAC6 activity protected kidneys from hyperglycaemia in db/db mice. Notably, overexpressing HDAC6 inhibited autophagy and promoted motility aside from the apoptosis of podocytes exposed to AGE. We further determined that HDAC6 regulated the autophagy partially by decreasing the acetylation of α-tubulin at the residue of lysine 40. In contrast, we confirmed that there was no interaction of HDAC6 with α-tubulin at the sites of lysine 112 and lysine 352. Consistently, inhibiting HDAC6 by siRNA or the selective inhibitor, tubacin, restored the autophagy level and motility of podocytes and rescued podocytes from AGE stimulation. We provide strong evidence of an unexpected role of HDAC6 in the cascade that modulates podocytes autophagy and motility, enlightening that HDAC6 may be a promising therapeutic target for DN treatment.
