Prevalence and Risk Factors of Reduced Bone Mineral Density in Systemic Lupus Erythematosus Patients: A Meta-Analysis.

BACKGROUND: We aimed to conduct a meta-analysis concerning the frequency and risk factors of reduced bone mineral density (BMD) in systemic lupus erythematosus (SLE) with evidence from published studies. METHODS: A comprehensive literature search was conducted based on the EMBASE, Web of Science, PubMed, and Cochrane Library databases up to March 5th, 2017. Eligible studies reported any prevalence of reduced BMD in SLE patients. All risk factors with odds ratios or risk ratios associated with reduced BMD were extracted. RESULTS: 71 reports with 33527 SLE patients were included. Low BMD, osteopenia, and osteoporosis at any site were presented, respectively, in 45%, 38%, and 13% of the SLE patients. The prevalence of osteoporosis increased with the advancing of age, while U-shaped associations between age and the prevalence of low BMD and osteopenia were found. Lumbar spine was indicated to have higher prevalence of osteoporosis. Age, disease duration, drugs use, and many other factors were identified as predictors of reduced BMD. CONCLUSION: Low BMD, osteoporosis, and osteopenia appeared to be prevalent in patients with SLE. Risk factors of reduced BMD were various.

HMGB1-TLR4 signaling participates in renal ischemia reperfusion injury and could be attenuated by dexamethasone-mediated inhibition of the ERK/NF-κB pathway.

Studies have shown that the HMGB1-TLR4 (High-mobility group protein B1, toll-like receptor 4) pathway participates in renal ischemic reperfusion injury (IRI) and that dexamethasone (DEX) could protect the kidney against IRI. This study aims to examine the protective effects of DEX on renal IRI and further explore the possible mechanism of action. During mouse renal IRI, HMGB1-TLR4 signals changed markedly including HMGB1 translocation and TLR4 up-regulation, resulting in histological damage and an increase in MPO expression. Treatment with DEX markedly decreased the damage to renal function (serum Cr and BUN; kidney KIM-1 expression) and the histological pathology of the kidney after renal IRI. The activation of GR by DEX did not suppress p38 and JNK activity but inhibited ERK phosphorylation. Treatment with DEX also attenuated IκB-α phosphorylation and further reduced NF-κB expression in the nucleus by decreasing acetylation of the p65 subunit. Furthermore, the HMGB1-TLR4 inflammatory pathway was inhibited via the attenuated translocation of HMGB1 from the nucleus to the cytoplasm and the down-regulation of TLR4 expression through DEX treatment. The inhibition of HMGB1 translocation may interact with acetyltransferase and attenuate HMGB1 acetylation. As a result, the levels of cytokines (TNF-α, IL-6, and IL-1ß) were down-regulated and inflammatory cell infiltration after renal IRI was attenuated by treatment with DEX. This study demonstrated that the HMGB1-TLR4 pathway may play a critical role in renal IRI. DEX may attenuate renal IRI by suppressing ERK and NF-κB activation, followed by attenuating the HMGB1-TLR4 pathway through inhibiting acetyltransferases.

A more accurate method acquirement by a comparison of the prediction equations for estimating glomerular filtration rate in Chinese patients with obstructive nephropathy.

BACKGROUND: Researchers have developed several equations to predict glomerular filtration rate (GFR) in patients with chronic kidney diseases (CKD). However, there are scarcely any studies performed to discern the best equation to estimate GFR in patients with pure obstructive nephropathy. In present study, we assessed the suitability of six prediction equations and compared their performance in eGFR evaluation for Chinese patients with obstructive nephropathy. METHODS: A total of 245 adult patients with obstructive nephropathy were enrolled. We evaluated the performance of the 3 Modification of Diet in Renal Disease equations (MDRD) (the original MDRD7, 7MDRD; the abbreviated MDRD, aMDRD; and re-expressed abbreviated MDRD, re-aMDRD) and 3 Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI) (CKD-EPI equation based on creatinine alone, CKD-EPIcr; CKD-EPI equation based on cystatin C alone, CKD-EPIcys; CKD-EPI equation based on combined creatinine-cystatin, CKD-EPIcr-cys). The measured GFR (mGFR) by 99mTc-DTPA renal dynamic imaging method was used as the reference GFR. RESULTS: The mean age of the study population was 51.61 ± 14.17 and 131 were male (53.47 %). The mean measured GFR was 66.54 ± 23.99 ml/min/1.73 m2. Overall, the CKD-EPIcr-cys equation gave the best performance with the best correlation (R = 0.72) and agreement (-34.87, 40.83). CKD-EPIcr-cys equation also exhibited the highest accuracy (69.39 %, P < 0.01) and diagnostic efficacy (ROCAUC = 0.874) with the smallest bias (2.98, P < 0.01). In the subgroup of the lowest GFR, CKD-EPIcys equation exhibited the highest accuracy (52.69 %) and the smallest bias (0.27). In the youngest age subgroup, CKD-EPIcys equation had the highest accuracy (71.64 %) and the smallest bias (-1.24). In other subgroups stratified by GFR, age and gender, CKD-EPIcr-cys equation remained the best performance. CONCLUSION: The 3 CKD-EPI equations performed better than the 3 MDRD equations in estimating GFR in Chinese obstructive nephropathy patients; while the CKD-EPI equation based on combined creatinine-cystatin C provided the best estimation of GFR.

Downregulation of p38 MAPK involved in inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin.

Curcumin, as a main pharmacological component in the traditional Chinese medicine-turmeric, has shown anti-inflammatory, anti-oxidation, anti-tumor and anti-fibrotic effects. This study aimed to investigate the possible underlying signaling pathway which was involved in the inhibition of LDL-induced proliferation of mesangial cells and matrix by curcumin. Rat mesangial cells in vitro were incubated with low-density lipoprotein (LDL) and different concentrations of curcumin (0, 6.25, 12.5, 25.0 µmol/L) or p38 MAPK inhibitor, SB203580 (10 µmol/L). Under LDL incubation, mesangial cells proliferated, the expression of MMP-2 mRNA and protein was decreased, the expression of COX-2 mRNA and protein was increased, reactive oxygen species (ROS) generation was increased and p38 MAPK was activated significantly (P<0.05). When LDL-induced cells were treated with curcumin in the concentration of 12.5 or 25.0 µmol/L, LDL-induced proliferation of mesangial cells was suppressed, the expression of MMP-2 mRNA and protein increased, the expression of COX-2 mRNA and protein downregulated, the production of ROS inhibited and p38 MAPK inactivated (P<0.05). In conclusion, curcumin can inhibit the LDL-induced proliferation of mesangial cells and up-regulate the expression of MMP-2, which may be related with the inhibitory effect of curcumin on COX-2 expression, ROS production and p38 MAPK.