Yue XD, et al. J Korean Med Sci. 2017 Apr;32(4):621-627. https://doi.org/10.3346/jkms.2017.32.4.621

Aim. Patients with diabetic ketosis often exhibit albuminuria. We previously found that acute hyperglycaemia can cause nephrotoxic injury. Here, we explored whether an excessive ketone body level causes kidney injury and the potential underlying mechanism. Methods. Fifty-six type 2 diabetes without ketosis (NDK group), 81 type 2 diabetes with ketosis (DK group), and 38 healthy controls (NC group) were enrolled. Clinical data were collected before and after controlling diabetic ketosis. Beta-hydroxybutyric acid (BOHB), an AKT activator, an AKT inhibitor, or plasmids encoding DAB2 were transformed into human renal proximal tubule epithelial cells (HK-2 cells). Results. The urinary albumin-to-creatinine ratio (ACR), transferrin (TF), immunoglobulin G (IgG), Beta2-microglobulin (β2-MG), retinol-binding protein (RBP), N-acetyl-beta-glucosaminidase (NAG), and Beta-galactosidase (GAL) were higher in the DK than NC and NDK groups. The proportion of patients with an increased urinary level of TF, IgG, β2-MG, RBP, NAG, or GAL was higher in the DK group too. After controlling ketosis, urinary microalbumin, TF, IgG, β2-MG, and RBP decreased significantly. In HK-2 cells, albumin endocytosis and megalin expression decreased with increasing BOHB concentration. Compared with BOHB treatment, BOHB with AKT activator significantly increased the DAB2, megalin levels and albumin endocytosis; the AKT inhibitor treatment exhibited the opposite effects. Compared with BOHB treatment, megalin expression and albumin endocytosis were significantly increased after BOHB with DAB2 overexpression treatment. Conclusions. Patients with diabetic ketosis may suffer from glomerular and tubular injuries that recover after ketosis control. High concentrations of BOHB downregulate megalin expression by inhibiting the AKT/DAB2/megalin signalling pathway and albumin endocytosis in proximal renal tubules.

Aim: To further assess the correlation between urine immunoglobin G (IgG) greater than 2.45 mg/L and the onset and progression of diabetic kidney disease (DKD). Methods: One thousand and thirty-five patients with type 2 diabetes mellitus (T2DM) were divided into two groups based on the baseline levels of 24 h urinary albumin excretion (24 h UAE): one group with 24 h UAE < 30 mg/24 h and one with 24 h UAE ≥ 30 mg/24 h. The groups were subdivided using baseline levels of urine IgG (≤2.45 mg/L and >2.45 mg/L; hereafter, the Low and High groups, respectively). We used logistic regression to assess the risk of urine IgG and it exceeding 2.45 mg/L. Kaplan–Meier curves were used to compare the onset and progression time of DKD. The receiver operating characteristic curve was used to test the predictive value of urine IgG exceeding 2.45 mg/L. Results: Urine IgG was an independent risk factor for the onset and progression of DKD. The rate and risk of DKD onset and progression at the end of follow-up increased significantly in the High group. The onset and progression time of DKD was earlier in the High group. Urine IgG exceeding 2.45 mg/L has a certain predictive value for DKD onset. Conclusions: Urine IgG exceeding 2.45 mg/L has a correlation with the onset and progression of DKD, and it also has a certain predictive value for DKD onset.