Background: Secondary hyperparathyroidism is characterized by parathyroid gland (PG) hyperplasia, and excessive synthesis and secretion of parathyroid hormone (PTH). Reduced vitamin D receptor (VDR) density has shown to play an essential role in PG hyperplasia progression; nevertheless, its exact mechanism remains unclear. VDR has shown to suppress the inflammation mediator NF-κB-mediated gene transcription. The aim of this study is to examine whether NF-κB is involved in the pathogenesis of parathyroid hyperplasia. Methods: 35 PGs was obtained from 10 maintenance hemodialysis patients who underwent parathyroidectomy surgery. 5/6-nephrectomized rats fed with a high-phosphate diet were divided into four groups: (1) Nx + vehicle group, treated with vehicle; (2) Nx + PDTC prevention group, treated with NF-κB inhibitor PDTC for 2 months; (3) Nx + PDTC therapy group, treated with PDTC for 1 month; (4) Nx + calcitriol group, treated with activated vitamin D calcitriol for 1 month. Ten sham-operated rats fed with normal-phosphate diet were used as a control group. Serum calcium, phosphorus, creatinine, Blood urea nitrogen (BUN), intact PTH and PG size in rats were measured. Proliferating cell nuclear antigen (PCNA), VDR, NF-κB of PGs were examined using immunohistochemistry and western blot. Results: The activation of NF-κB pathway in the nodular hyperplasia gland was significantly increased compared with the diffuse hyperplasia gland found in hemodialysis patients. Markedly higher serum creatinine, BUN, phosphorus levels, serum iPTH levels and larger PGs were found in Nx rats fed with a high-phosphate diet compared to sham-operated rats. Also, PCNA levels and activation of NF-κB pathway in PGs were higher compared with the sham group, meanwhile the VDR levels decreased. Contrary, treating rats with PDTC and calcitriol notably reduced serum iPTH, expression of PCNA and activation of NF-κB pathway, and decreased the enlargement of PGs in those animals. Conclusions: NF-κB plays an important role in PG hyperplasia progression. VDR deficiency may be involved in the parathyroid gland hyperplasia through the activation of NF-κB pathway.

Objective. There is a high prevalence of sarcopenia in maintenance hemodialysis (MHD) patients, which is known to be associated with increased mortality. This study is aimed at analyzing the risk factors affecting muscle mass decline in MHD patients. Methods. This retrospective study included MHD patients who underwent two body composition assessments in October 2013 and November 2017. Depending on whether there was muscle loss or not, the patients were divided into a normal muscle mass (NMM) group and a muscle mass decline (MMD) group. According to the muscle mass decline rate, patients in the MMD group were further classified into a low‐rate group and a high‐rate group. Biochemical variables, serum vitamin concentrations, anthropometric data, SGA, muscle mass, handgrip, and daily steps were assessed. Risk factors for muscle mass decline were screened by multivariate logistic analysis and linear regression analysis. Results. Of the 72 MHD patients included in this study, 33 were male and 39 were female with a mean age of 56.80 ± 10.86 years and a mean dialysis duration of 7.50 ± 5.20 years. Age (P = .014) and serum 25(OH)D (P = .040) were found to be associated with a higher risk of muscle mass decline after adjusting for gender, dialysis vintage, albumin, and hs‐CRP (P = .040). Further analysis found that dialysis vintage (β = 0.285, P = .030), 25(OH)D (β = −0.351, P = .007), and log NT‐proBNP (β = 0.312, P = .020) were risk factors associated with the muscle mass decline rate in MHD patients. Conclusion. Age and serum 25(OH)D were associated with a higher risk of muscle mass decline, while 25(OH)D, dialysis vintage, and NT‐proBNP were associated with the muscle mass decline rate in MHD patients.

Secondary hyperparathyroidism (SHPT) in patients with end-stage renal disease (ESRD) is characterized by hyperplasia of the parathyroid glands (PTGs), while the underlying mechanism is not completely understood. Previously we demonstrated a relationship between cyclooxygenase 2 (COX2) overexpression and parathyroid hyperplasia and here we investigate the role of COX2 downstream metabolic product prostaglandin E2 (PGE2) and its receptor EP2 in the pathogenesis of SHPT. PTGs isolated from ESRD patients with advanced SHPT were used to test the expression of COX2-microsomal prostaglandin E synthase-1 (mPGES-1)-EP2 pathway. A diffuse proliferative section of the PTGs was used for tissue culture and treated with high phosphate (HPi) medium, COX2-PGE2-EP2 pathway inhibitors or agonists. EP2 short hairpin RNA (shRNA) lentivirus was locally applied to treat an SHPT rat model. In PTGs isolated from ESRD patients, enhanced immunoactivities of COX2, mPGES-1 and EP2 were observed. In primary cultured PTG tissues, HPi induced intact parathyroid hormone (iPTH) secretion, proliferating cell nuclear antigen (PCNA) expression and COX2 activity, while COX2 and EP2 inhibitors attenuated hyperparathyroidism promoted by HPi. Furthermore, PGE2 or EP2 agonist (butaprost) directly stimulated hyperparathyroidism, whereas EP2 receptor antagonist or cyclic adenosine monophosphate inhibitor attenuated the hyperparathyroidism promoted by PGE2 or butaprost. EP2 shRNA treatment significantly reduced excessive expressions of EP2 and PCNA in the PTGs of nephrectomy rats fed an HPi diet, diminished the size of PTGs and downregulated serum iPTH levels. The COX2 downstream PGE2 and its receptor EP2 may play an important role in HPi-induced parathyroid hyperplasia and may serve as a potential therapeutic target for SHPT in ESRD.