Crosstalk of Hyperglycemia and Dyslipidemia in Diabetic Kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) is defined by the functional, structural, and clinical abnormalities of the kidney that are caused by diabetes. SUMMARY: One-third of both type 1 diabetes and type 2 diabetes patients suffer from DKD, which is the leading cause of end-stage renal disease, and is also associated with cardiovascular disease and high public health care costs. Serum glucose level and lipid level are key factors in the pathogenesis of DKD and are modifiable. The goal of this review is to provide an update on the roles of glucose and lipid metabolism in DKD and their crosstalk at the molecular level. We will further discuss the recent advances regarding metabolic nuclear receptors in glucose-lipid crosstalk, which may provide new potential therapeutic targets for DKD. KEY MESSAGE: AMPK, SREBP-1, and some metabolic hormone receptors including liver X receptors, farnesoid X receptors, and peroxisome proliferator-activated receptors mediate the crosstalk of hyperglycemia and dyslipidemia in diabetic kidney disease and might be potential treatment candidates.

Tacrolimus combined with low-dose corticosteroids is an effective and safe therapeutic option for refractory IgA nephropathy.

Tacrolimus (TAC) has been shown to improve remission from proteinuria in patients with refractory IgA nephropathy (IgAN); however, the efficacy and safety of TAC in such patients have not been fully explored. Therefore, the present study was conducted to evaluate the tolerance to and efficacy of TAC combined with low-dose corticosteroids in patients with refractory IgAN. This was a single-center retrospective study. A total of 28 patients with refractory IgAN were randomly included and received TAC plus corticosteroid; 26 patients received TAC and prednisone, and 2 patients received TAC and methylprednisolone. In addition, all patients were treated with an angiotensin inhibitor. Total urinary protein excretion, serum albumin, blood glucose, complete remission (CR), partial remission (PR), cholesterol, low-density lipoprotein (LDL), serum creatinine (Scr) and estimated GFR (eGFR) were tested at baseline and at 3, 6 and 12 months after the initiation of treatment in all patients. The primary endpoints were CR and PR. Secondary endpoints included changes of Scr, eGFR, clinical data and adverse events. After 12 months, CR was achieved in 40.1% of patients and PR in 43.4%, yielding a total response rate of 83.5%, and the total urinary protein excretion, serum albumin, cholesterol and LDL results were improved significantly compared with those at baseline. Proteinuria and serum albumin results were significantly improved by month 3 of treatment. Two patients relapsed during months 3-6 of follow-up. At the 12-month follow-up, renal function was improved compared with the baseline level as evidenced by eGFR and Scr, respectively. The blood glucose level was stable. One case of pneumococcal pneumonia developed in a patient treated with TAC plus low-dose methylprednisolone and one case of upper gastrointestinal hemorrhage was found in a patient treated with TAC plus low-dose prednisone; both cases completely recovered after treatment. In conclusion, TAC combined with low-dose corticosteroids may be an effective and safe therapeutic option for the treatment of refractory IgAN. However, given the small number of patients in this study, further prospective randomized controlled trials are required with a larger sample of participants and longer follow-up period.

Severe pneumonia in mycophenolate mofetil combined with low-dose corticosteroids-treated patients with immunoglobulin A nephropathy.

The tolerance of mycophenolate mofetil (MMF; Shanghai Roche, China) in Lee Classes III, IV, and V immunoglobulin A nephropathy (IgAN) remains unclear. This article reports nine cases of severe pneumonia (SP), including pneumocystis pneumonia (PCP) and cytomegalovirus (CMV) pneumonia, and its risk factors in MMF plus low-dose corticosteroid-treated patients with Lee Classes III, IV, and V IgAN. Fifty-three patients with IgAN were included in this single-center study. The treatment regimen was MMF (1-1.5 g/d) plus low-dose corticosteroids (0.5 mg/kg/d). SP was defined as diffuse bilateral lung infiltrate with respiratory failure. PCP was diagnosed by detecting the organisms in the sputum and bronchoalveolar lavage. CMV infection was diagnosed through serum screening for CMV-IgG and IgM antibodies and CMV-DNA testing by a real-time polymerase chain reaction assay. The risk factors of SP were analyzed. Nine cases (16.9%) of SP occurred in this study. All SP developed at approximately the 10(th)-14(th) week after the initiation of the regimen: PCP was diagnosed in four cases and CMV infection in two cases. Renal function impairing was more serious in patients with SP than in those without SP, as evidenced by estimated glomerular filtration rate (p = 0.019) and serum creatinine level (p = 0.016). Six of the nine SPs occurred in MMP plus low-dose methylprednisolone group, which was statistically higher than that in the MMF plus low-dose prednisone group (p = 0.000). The incidence of SP in this study was 16.9%. Chronically impaired renal function and the use of methylprednisolone may be the risk factors for SP.

[The effects of TCM Yishen Decoction on the expression of MMP-9 and TIMP-1 in kidney of mouse with IgA nephropathy].

AIM: To explore effects of Yishen Decoction on the expression of MMP-9 and TIMP-1 in kidney of mice with IgA nephropathy (IgAN). METHODS: The IgAN model was established by oral administration of bovine serum albumin (BSA) together with the injection of Staphylococcus enterotoxin B (SEB) through caudal vein. The mRNA and protein expression of MMP-9 and TIMP-1 were measured by fluorescent quantitative RT-PCR and immunohistochemistry respectively. RESULTS: No significant differences of mRNA and protein expression of MMP-9 and TIMP-1 were found between the low and high concentration Yishen Decoction treated group. But the expression of TIMP-1 in the Yishen Decoction treated group was lower than that in the IgAN group, while that of MMP-9 was higher than that in the control group. CONCLUSION: The TCM Yishen Decoction can inhibit the abnormal expression of TIMP-1, and strengthen the expression of MMP-9 in kidney of mouse with IgA nephropathy.