Progression of Vascular Calcification and Clinical Outcomes in Patients Receiving Maintenance Dialysis.

Importance: Baseline findings from the China Dialysis Calcification Study (CDCS) revealed a high prevalence of vascular calcification (VC) among patients with end-stage kidney disease; however, data on VC progression were limited. Objectives: To understand the progression of VC at different anatomical sites, identify risk factors for VC progression, and assess the association of VC progression with the risk of cardiovascular events and death among patients receiving maintenance dialysis. Design, Setting, and Participants: This cohort study was a 4-year follow-up assessment of participants in the CDCS, a nationwide multicenter prospective cohort study involving patients aged 18 to 74 years who were undergoing hemodialysis or peritoneal dialysis. Participants were recruited from 24 centers across China between May 1, 2014, and April 30, 2015, and followed up for 4 years. A total of 1489 patients receiving maintenance dialysis were included in the current analysis. Data were analyzed from September 1 to December 31, 2021. Exposures: Patient demographic characteristics and medical history; high-sensitivity C-reactive protein laboratory values; serum calcium, phosphorus, and intact parathyroid hormone (iPTH) values; and previous or concomitant use of medications. Main Outcomes and Measures: The primary outcome was progression of VC at 3 different anatomical sites (coronary artery, abdominal aorta, and cardiac valves) and identification of risk factors for VC progression. Participants received assessments of coronary artery calcification (CAC), abdominal aortic calcification (AAC), and cardiac valve calcification (CVC) at baseline, 24 months, 36 months, and 48 months. Secondary outcomes included (1) the association between VC progression and the risk of all-cause death, cardiovascular (CV)-related death, and a composite of all-cause death and nonfatal CV events and (2) the association between achievement of serum calcium, phosphorus, and iPTH target levels and the risk of VC progression. Results: Among 1489 patients, the median (IQR) age was 51.0 (41.0-60.0) years; 59.5% of patients were male. By the end of 4-year follow-up, progression of total VC was observed in 86.5% of patients; 69.6% of patients had CAC progression, 72.4% had AAC progression, and 33.4% had CVC progression. Common risk factors for VC progression at the 3 different anatomical sites were older age and higher fibroblast growth factor 23 levels. Progression of CAC was associated with a higher risk of all-cause death (model 1 [adjusted for age, sex, and body mass index]: hazard ratio [HR], 1.97 [95% CI, 1.16-3.33]; model 2 [adjusted for all factors in model 1 plus smoking status, history of diabetes, and mean arterial pressure]: HR, 1.89 [95% CI, 1.11-3.21]; model 3 [adjusted for all factors in model 2 plus calcium, phosphorus, intact parathyroid hormone, and fibroblast growth factor 23 levels and calcium-based phosphate binder use]: HR, 1.92 [95% CI, 1.11-3.31]) and the composite of all-cause death and nonfatal CV events (model 1: HR, 1.98 [95% CI, 1.19-3.31]; model 2: HR, 1.91 [95% CI, 1.14-3.21]; model 3: HR, 1.95 [95% CI, 1.14-3.33]) after adjusting for all confounding factors except the presence of baseline calcification. Among the 3 targets of calcium, phosphorus, and iPTH, patients who achieved no target levels (model 1: odds ratio [OR], 4.75 [95% CI, 2.65-8.52]; model 2: OR, 4.81 [95% CI, 2.67-8.66]; model 3 [for this analysis, adjusted for all factors in model 2 plus fibroblast growth factor 23 level and calcium-based phosphate binder use]: OR, 2.76 [95% CI, 1.48-5.16]), 1 target level (model 1: OR, 3.71 [95% CI, 2.35-5.88]; model 2: OR, 3.62 [95% CI, 2.26-5.78]; model 3: OR, 2.19 [95% CI, 1.33-3.61]), or 2 target levels (model 1: OR, 2.73 [95% CI, 1.74-4.26]; model 2: OR, 2.69 [95% CI, 1.71-4.25]; model 3: OR, 1.72 [95% CI, 1.06-2.79]) had higher odds of CAC progression compared with patients who achieved all 3 target levels. Conclusions and Relevance: In this study, VC progressed rapidly in patients undergoing dialysis, with different VC types associated with different rates of prevalence and progression. Consistent achievement of serum calcium, phosphorus, and iPTH target levels was associated with a lower risk of CAC progression. These results may be useful for increasing patient awareness and developing appropriate strategies to improve the management of chronic kidney disease-mineral and bone disorder among patients undergoing dialysis.

A single-center experience of parathyroidectomy in 1500 cases for secondary hyperparathyroidism: a retrospective study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. With the deterioration of renal function, a certain proportion of CKD patients enter the uremic stage, and secondary hyperparathyroidism (SHPT) becomes a challenge. For refractory hyperparathyroidism, parathyroidectomy (PTX) plays a key role in reducing mortality and improving prognosis. Nevertheless, no consensus has been reached on the optimal surgical method. We aimed to provide evidence for the effectiveness of surgical treatment by summarizing the experience from our center. METHODS: Clinical data from 1500 patients undergoing parathyroidectomy were recorded, which included 1419 patients in a total parathyroidectomy without autotransplantation (tPTX) group, 54 patients in a total parathyroidectomy plus autotransplantation (tPTX + AT) group, and 27 patients in the other group. Perioperative basic data, intact parathyroid hormone (i-PTH) levels, serum calcium levels, serum phosphorus levels, pathological reports, coexisting thyroid diseases, short-term outcomes and complications were analyzed. Moreover, postoperative complications were compared between the tPTX and tPTX + AT groups. RESULTS: Parathyroid hormone, serum calcium and phosphorus levels decreased significantly post-surgery. Two patients died during the perioperative period. As the two most common complications, the incidences of severe hypocalcemia and hyperkalemia were 36.20% (543 cases) and 24.60% (369 cases), respectively. Pre-iPTH levels (OR = 1.001, 95% CI: 1.001-1.001, p < 0.01), serum alkaline phosphatase (ALP) levels (OR = 1.002, 95% CI: 1.001-1.002, p < 0.01) and the mass of excised parathyroid gland (OR = 3.06, 95% CI: 1.24-7.55, p = 0.02) were positively associated with postoperative severe hypocalcemia, while age and serum calcium were negatively associated with it. Pathological reports of resected parathyroid and thyroid glands indicated that 96.49% had parathyroid nodular hyperplasia, 13.45% had thyroid nodular hyperplasia, and 4.08% had thyroid papillary carcinoma. CONCLUSIONS: Parathyroidectomy is a safe and effective treatment for refractory secondary hyperparathyroidism. Severe hypocalcemia is the main complication, and coexistent thyroid diseases should never be neglected.

Comparison of mesophilic and thermophilic dark fermentation with nickel ferrite nanoparticles supplementation for biohydrogen production.

In this work, nickel ferrite nanoparticles (NiFe2O4 NPs) was prepared to improve hydrogen (H2) production by dark fermentation. Moderate amounts (50-200 mg/L) promoted H2 generation, while excess NiFe2O4 NPs (over 400 mg/L) lowered H2 productivity. The highest H2 yields of 222 and 130 mL/g glucose were obtained in the 100 mg/L (37 °C) and 200 mg/L NiFe2O4 NPs (55 °C) groups, respectively, and the values were 38.6% and 28.3% higher than those in the control groups (37 °C and 55 °C). Soluble metabolites showed that NiFe2O4 NPs enhanced the butyrate pathway, corresponding to the increased abundance of Clostridium butyricum in mesophilic fermentation. The endocytosis of NiFe2O4 NPs indicated that the released iron and nickel favored ferredoxin and hydrogenase synthesis and activity and that NiFe2O4 NPs could act as carriers in intracellular electron transfer. The NPs also optimized microbial community structure and increased the levels of extracellular polymeric substances, leading to increased H2 production.

Co-transport of U(VI), humic acid and colloidal gibbsite in water-saturated porous media.

The release of uranyl from uranium tailing sites is a widely concerned environmental issue, with limited investigations on the effect of coexistence of various colloids. Gibbsite colloids extensively exist, together with ubiquitous humic substances, in uranium polluted waters at tailing sites, due to high concentration of dissolved Al in acid mine drainage. In this context, we investigated the co-transport of U(VI), gibbsite colloids and humic acid (HA) as a function of pH and ionic strength at a U(VI) concentration (5.0 × 10-5 M) relevant within mine tailings and related waste. It was found that, owing to electrostatic attraction, gibbsite colloids and HA associated with each other and transported simultaneously regardless of U(VI) presence. Besides the impact of pH and ionic strength, whether gibbsite colloids facilitated U(VI) transport depended on HA concentration. Gibbsite colloids impeded U(VI) transport at relatively low HA concentration (≤5 mg L-1), because associated colloids loaded with U(VI) were positively charged which favored colloid retention on negatively charged quartz sand in the column. U(VI) together with gibbsite colloids and low concentration HA was completely blocked at natural pH and/or high ionic strength. At relatively high HA concentration (20 mg L-1), however, the associated colloids showed negative zeta potential which facilitated U(VI) transport because of repulsion between negatively charged colloids and quartz sand. Meanwhile, high concentration of HA dramatically accelerated the transport of gibbsite colloids. These results implied that gibbsite colloids might imped U(VI) migration at uranium tailing sites unless the aquifers are enriched with abundant humic substances.

Co-transport of U(VI) and akaganéite colloids in water-saturated porous media: Role of U(VI) concentration, pH and ionic strength.

Remediating uranium contamination becomes a worldwide interest because of increasing uranium release from mining activities. Due to ubiquitous presence of pyrite and the application of iron-based technology, colloidal iron oxy-hydroxides such as akaganéite colloid (AKC) extensively exist in uranium polluted water at uranium tailing sites. In this context, we studied individual and co-transport of U(VI) and AKC in water-saturated sand columns at 50 mg/L AKC and environmentally relevant U(VI) concentrations (5.0 × 10-7 ∼ 5.0 × 10-5 M). It was found that, in addition to the impact of pH and ionic strength, whether AKC facilitated U(VI) transport depended on U(VI) concentration as well. The presence of AKC facilitated U(VI) transport at relatively low U(VI) concentration (5.0 × 10-7 ∼ 5.0 × 10-6 M), which was due to the strong adsorption of U(VI) on AKC and faster transport of AKC than that U(VI) as observed in their individual transport experiments. At relatively high U(VI) concentrations (5.0 × 10-5 M), however, AKC impeded U(VI) transport because U(VI) of high concentration decreased AKC colloidal stability and increased AKC aggregation and attachment. Thus, U(VI) and AKC co-transport was even blocked completely at relatively high pH and ionic strength. The mechanisms behind the co-transport of U(VI) and AKC were also confirmed by assessing the evolutions of aqueous pH and AKC zeta potential and particle size distribution in the column effluents. A two-site non-equilibrium model and a two-site kinetic attachment/detachment model well-described the breakthrough curves of U(VI) and AKC, respectively. Knowledge generated from this study provides a thorough understanding of uranium transport in the absence/presence of AKC, and brings new insights into the influence of contaminant concentration on co-transport in the presence of colloids.

Prevalence and risk factors for vascular calcification in Chinese patients receiving dialysis: baseline results from a prospective cohort study.

OBJECTIVE: With limited data available on calcification prevalence in chronic kidney disease (CKD) patients on dialysis, the China Dialysis Calcification Study (CDCS) determined the prevalence of vascular/valvular calcification (VC) and association of risk factors in Chinese patients with prevalent hemodialysis (HD) or peritoneal dialysis (PD). METHODS: CKD patients undergoing HD/PD for ≥6 months were enrolled. Prevalence data for calcification and medical history were documented at baseline. Coronary artery calcification (CAC) was assessed by electron beam or multi-slice computed tomography (EBCT/MSCT), abdominal aortic calcification (AAC) by lateral lumbar radiography, and cardiac valvular calcification (ValvC) by echocardiography. Serum phosphorus, calcium, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D and FGF-23 were evaluated. A logistic regression model was used to evaluate the association between risk factors and VC. RESULTS: Of 1,497 patients, 1,493 (78.3% HD, 21.7% PD) had ≥1 baseline calcification image (final analysis cohort, FAC) and 1,423 (78.8% HD, 21.2% PD) had baseline calcification data complete (BCDC). Prevalence of VC was 77.4% in FAC (80.8% HD, 65.1% PD, p < .001) and 77.5% in BCDC (80.7% HD, 65.8% PD). The proportion of BCDC patients with single-site calcification were 20% for CAC, 4.3% for AAC, and 4.3% for cardiac valvular calcification (ValvC), respectively. Double site calcifications were 23.4% for CAC and AAC, 6.5% for CAC and ValvC, and 1.1% for AAC and ValvC, respectively. In total, 17.9% patients had calcification at all three sites. CONCLUSIONS: High prevalence of total VC in Chinese CKD patients will supplement current knowledge, which is mostly limited, contributing in creating awareness and optimizing VC management.

Genipin inhibits mitochondrial uncoupling protein 2 expression and ameliorates podocyte injury in diabetic mice.

Diabetic nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) in China, which requires renal replacement therapy. Recent investigations have suggested an essential role of podocyte injury in the initial stage of DN. This study investigated the potential therapeutic role of genipin, an active extract from a traditional Chinese medicine, on progression of DN in diabetic mice induced by intraperitoneally injection of streptozocin (STZ). In diabetic mice, orally administration of genipin postponed the progression of DN, as demonstrated by ameliorating body weight loss and urine albumin leakage, attenuating glomerular basement membrane thickness, restoring the podocyte expression of podocin and WT1 in diabetic mice. The protective role of genipin on DN is probably through suppressing the up-regulation of mitochondrial uncoupling protein 2 (UCP2) in diabetic kidneys. Meanwhile, through inhibiting the up-regulation of UCP2, genipin restores podocin and WT1 expression in cultured podocytes and attenuates glucose-induced albumin leakage through podocytes monolayer. Therefore, these results revealed that genipin inhibited UCP2 expression and ameliorated podocyte injury in DN mice.

Preventive effects and mechanisms of rhein on renal interstitial fibrosis in obstructive nephropathy.

Renal interstitial fibrosis is a common outcome of a variety of chronic renal diseases. Here we evaluated the therapeutic efficacy of rhein on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) and investigated the potential mechanisms. Mice underwent UUO, followed by orally administrated rhein (150 mg/kg/d) or control vehicle. Renal interstitial injury and the degree of fibrosis were evaluated by pathological staining and Western blot. The possible mechanisms were studied by Western blot, indirect immune-fluorescence and enzyme-linked immunosorbent assay. Our results showed that rhein therapy markedly ameliorated renal interstitial fibrotic lesions, reduced α-smooth muscle actin (α-SMA) expression, attenuated deposition of fibronectin (FN). Rhein also suppressed transforming growth factor-ß1 (TGF-ß1) and its type I receptor expression in obstructed kidneys. In vitro, rhein abolished the α-SMA and fibronectin expression of rat kidney interstitial fibroblasts cells (NRK-49F) induced by TGF-ß1. These observations strongly suggest that rhein is a potent inhibitor of renal interstitial fibrosis, and its therapeutic mechanism is, at least in part, blocking interstitial fibroblasts cells activation.