Secondary hyperparathyroidism is driven by pathological overproduction of parathyroid hormone. Surgery is invasive, drug therapy offers only transient control, and both carry substantial side effects. Previous efforts to deliver siRNA to the parathyroid glands achieved only marginal efficacy because the constructs lacked a targeting ligand to overcome the organ's limited vascular permeability and were rapidly cleared by renal filtration. This study provides a targeted RNA interference therapeutic strategy for treatment of secondary hyperparathyroidism by leveraging the angiogenic characteristics of parathyroid glands via systemic route. Particularly, we manufactured an Arg-Gyl-Asp (RGD)-conjugated siRNA delivery system that exploits the overexpression of integrins and increased vascular permeability in parathyroid glands to achieve preferential siRNA accumulation. The multifunctional cationic copolymers of RGD-poly(ethylene glycol) (PEG)-polylysine-azido [PLys(N3)] and PLys(ss-dibenzocyclooctyne: DBCO) were synthesized and characterized, demonstrating their ability to formulate robust nanocomplexes with small interference RNA [(siRNA): knockdown of parathyroid hormone (PTH)] by virtue of favorable reversible disulfide cross-linking (based on click reaction) post electrostatic complexation. These nanocomplexes exhibited prolonged systemic circulation, preferential accumulation in the angiogenic parathyroid glands, and active intracellular delivery, leading to significant suppression of PTH expression. In a parathyroid hyperplasia mouse model, the siPTH delivery construct from RGD-PEG-PLys(N3)&PLys(ss-DBCO) substantially reduced the serum PTH levels to near-normal values, highlighting the therapeutic potential of our siRNA delivery system. Hence, this RNAi approach outperforms conventional modalities by achieving rapid, potent, and sustained gene knockdown without surgical risk or chronic pharmacologic burden, establishing a paradigm for precision endocrine therapy.

Immunoglobulin A nephropathy (IgAN) stands as the most prevalent primary glomerulonephritis globally, almost half of patients progress to end-stage kidney disease (ESKD). However, the precise pathogenesis of IgAN remains elusive. Long non-coding RNAs (lncRNAs), non-protein-coding transcripts that regulate gene expression, have been found to exhibit distinct expression patterns in various disease states. Comprehensive bioinformatic analyses from IgAN patients have uncovered differential expression of lncRNAs such as HOTAIR, H19, and MALAT1. Furthermore, a single nucleotide polymorphism in MIR31HG has been linked to IgAN susceptibility and correlated with clinical markers like urinary red blood cells and hemoglobin levels. Lnc-TSI and lnc-CHAF1B-3, specifically expressed in the kidneys of IgAN patients, exhibit associations with renal fibrosis indices and the degree of kidney function deterioration, influencing the progression of renal fibrosis through distinct signaling pathways. Additionally, renal intercellular adhesion molecule 1 (ICAM-1) related long noncoding RNA (ICR) levels positively correlate with IgAN severity and contribute to renal fibrosis, whereas serum H19 serves as an independent protective factor against IgAN. Notably, experiments have validated the involvement of PTTG3P, lnc-CHAF1B-3, and CRNDE in the pathogenesis of IgAN. Nevertheless, data on the roles of lncRNAs in IgAN pathogenesis and their potential as biomarkers remain limited, and effective therapeutic options for IgAN are similarly rare. Therefore, there is an urgent need to bridge this knowledge gap. This article presents a review of current literature on lncRNAs related to IgAN, aiming to consolidate existing findings and identify future research avenues.

Recent studies have suggested that ferroptosis participates in various renal diseases. However, its effect on focal segmental glomerulosclerosis remains unclear. This study analyzed the GSE125779 and GSE121211 datasets to identify the differentially expressed genes (DEGs) in renal tubular samples with and without FSGS. The Cytoscape was used to construct the protein-protein interaction network. Moreover, the ferroptosis-related genes (FRGs) were obtained from the ferroptosis database, while ferroptosis-related DEGs were obtained by intersection with DEGs. The target genes were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The GSE108112 dataset was used to verify the expression of target FRGs. Besides, we built the mRNA-miRNA network regarding FRGs using the NetworkAnalyst database, and circRNAs corresponding to key miRNAs were predicted in the ENCORI database. In this study, 16 ferroptosis-related DEGs were identified between FSGS and healthy subjects, while five co-expressed genes were obtained by three topological algorithms in Cytoscape. These included the most concerned Hub genes JUN, HIF1A, ALB, DUSP1 and ATF3. The KEGG enrichment analysis indicated that FRGs were associated with mitophagy, renal cell carcinoma, and metabolic pathways. Simultaneously, the co-expressed hub genes were analyzed to construct the mRNA-miRNA interaction network and important miRNAs such as hsa-mir-155-5p, hsa-mir-1-3p, and hsa-mir-124-3p were obtained. Finally, 75 drugs targeting 54 important circRNAs and FRGs were predicted. This study identified the Hub FRGs and transcriptomic molecules from FSGS in renal tubules, thus providing novel diagnostic and therapeutic targets for FSGS.

The aim of this study was to investigate the effects of all-trans retinoic acid (atRA) on oxidative stress in renal tubular epithelial cells induced by high glucose (HG) and its potential mechanism. We investigated the effects of atRA in HG-induced renal epithelial cell line HK-2. Seven groups were designed for this experiment: negative control, mannitol, high-glucose (HG), HG combined with a low concentration of atRA, HG combined with a middle concentration of atRA, HG combined with a high concentration of atRA, and HG combined with captopril. After 48 h of incubation, oxidative stress factor expression in the supernatant was detected by enzyme-linked immunosorbent assay. Reactive oxygen species and cell apoptosis expression were assessed by flow cytometry. NADPH oxidase, fibrosis factor, and angiotensin-converting enzyme 2/angiotensin (1-7)/mas receptor (ACE2/Ang (1-7)/MasR) pathway-related protein expressions were determined by western blot analysis. The expressions of oxidative stress factors, NADPH oxidase components, and fibrosis factors were significantly higher after HG treatment. Apoptosis of HK2 cells in the HG group was also significantly higher. AtRA could reverse the above abnormal changes in a concentration-dependent manner. HG significantly promoted the expression of ACE, Ang II, and Ang II type 1 receptor (AT1R), whereas it inhibited the expression of ACE2, Ang (1-7), and MasR. With the elevation of concentration, atRA could gradually suppress the expression of ACE, Ang II, and AT1R, but facilitate ACE2, Ang (1-7), and MasR. These results were statistically significant. AtRA could significantly inhibit oxidative stress and apoptosis of renal tubular epithelial cells induced by HG. The mechanism may inhibit the ACE/Ang II/AT1R pathway and/or activate ACE2/Ang (1-7)/MasR pathway.

Immune dysregulation is not only a pathogenic mechanism in systemic lupus erythematosus (SLE) but also a potential cause of the link between SLE and cancer. The current understanding of SLE monocyte-associated biomarkers is limited, and the precise mechanism behind the link between SLE and cancer is uncertain. By using WGCNA and immune infiltration to analyze the GSE72326 dataset, we determined the most pertinent modules for monocytes and discovered eight candidate hub genes from them. The limma software was used to find genes that were differently expressed in SLE. The genes that overlapped between the two were chosen using a Venn diagram as the essential genes related to monocytes in SLE, and the essential genes were verified by several datasets. Correlation analysis and GSEA analysis were used to examine the probable immunological pathways connected to key genes. We examined the expression of hub genes in cancer and their interaction with monocytes using the GEPIA and TIMER databases to understand the significance of essential genes in tumorigenesis. In addition, we performed transcription factor identification. We discovered three biomarkers (IFI30, BLVRA, and RIN2) that are mostly involved in interferon-related signaling pathways and are associated with monocyte-mediated immune responses in SLE. The three important genes are also strongly expressed in a number of malignancies and have a relationship with monocytes. As a result, IFI30, BLVRA, and RIN2 may act as SLE-associated biomarkers of monocytes and as a bridge between SLE and tumors. We proposed that interferon-related signaling pathways might function as possible mediators of cancer risk in SLE.

AbstractRecent studies have demonstrated the close relationship between parathyroid adenoma (PA) and thyroid follicular adenoma (FTA). However, the underlying pathogenesis remains unknown. This study focused on exploring common pathogenic genes, as well as the pathogenesis of these two diseases, through bioinformatics methods. This work obtained PA and FTA datasets from the Integrated Gene Expression Database to identify the common differentially expressed genes (DEGs) of two diseases. The functions of the genes were investigated by GO and KEGG enrichment. The program CytoHubba was used to select the hub genes, while receiver operating characteristic curves were plotted to evaluate the predictive significance of the hub genes. The DGIbd database was used to identify gene-targeted drugs. This work detected a total of 77 DEGs. Enrichment analysis demonstrated that DEGs had activities of 3′,5′-cyclic AMP, and nucleotide phosphodiesterases and were associated with cell proliferation. NOS1, VWF, TGFBR2, CAV1, and MAPK1 were identified as hub genes after verification. The area under the curve of PA and FTA was>0.7, and the hub genes participated in the Relaxin Signaling Pathway, focal adhesion, and other pathways. The construction of the mRNA-miRNA interaction network yielded 11 important miRNAs, while gene-targeting drug prediction identified four targeted drugs with possible effects. This bioinformatics study demonstrated that cell proliferation and tumor suppression and the hub genes co-occurring in PA and FTA, have important effects on the occurrence and progression of two diseases, which make them potential diagnostic biomarkers and therapeutic targets.

Purpose Acute kidney injury (AKI) has been reported to be one of the most common complications in patients receiving extracorporeal membrane oxygenation (ECMO), yet variations in AKI between different types of ECMO remain unclear. This meta-analysis systematically compares AKI/severe AKI in adult patients requiring different types of ECMO. Methods Two authors independently performed a literature search using PubMed, Web of Science, and Embase, encompassing publications up until April 20, 2020 (inclusive). The number of AKI patients, including patients who required/did not require renal replacement therapy (RRT), and deceased patients with AKI/severe AKI, who received different types of ECMO were collated and analyzed using STATA. Results The results indicated that there were no significant differences in the risk of AKI/severe AKI among different types of ECMO. However, the presence of AKI and severe AKI during veno-arterial (VA) ECMO was more strongly associated with mortality. Conclusions Although mortality rates related to AKI/severe AKI during VV ECMO are high, the occurrence of AKI/severe AKI during VA ECMO should be given greater attention, as these instances are considered strong indicators of patient deterioration and even death. Additional studies are needed to corroborate these findings.

To accomplish the transcellular transportation of the RNA interfering payloads, an attempt was made to electrostatically complex an anionic small interfering RNA (siRNA) with the cationic polylysine segments of both hydrophilic poly(ethylene glycol) (PEG) and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) containing block copolymers into nanoscaled delivery systems. Notably, the formulated PLys&siRNA complex was schemed for disulfide cross-linkages with the aim of preventing the premature release of the vulnerable siRNA payloads into the extracellular compartment. Moreover, the thermal-responsive hydrophilic-hydrophobic transition of PNIPAM segments enabled the precise fabrication of hydrophilic PEG and hydrophobic PNIPAM alternative double-layered surroundings along the formulated PLys&siRNA complex core. These unique double-layered surroundings have been validated as vital in protecting the internal vulnerable siRNA payloads, particularly those from enzymatic digestion by the environmental ribonucleases. Therefore, the proposed siRNA delivery constructs have prompted progressive endocytosis into the parathyroid cells due to their persistent retention in the biological environment. Also noteworthy was the fact that the proposed disulfide cross-linkages could be selectively cleaved in the intracellular environment due to the enriched glutathione in the cytosol (in stark contrast to the minimal presence of glutathione in the extracellular environment), thereby facilitating the selective intracellular liberation of the functional siRNA payloads in the RNA-iactive cytosol. Eventually, with our proposed siRNA delivery constructs, after encapsulation of the therapeutic siRNA [siPTH: knockdown of the mRNA of parathyroid hormone (PTH) for the potential treatment of hyperparathyroidism], the potent knockdown of parathyroid hormone mRNA and consequent suppressed expression of parathyroid hormone was accomplished. Therefore, the proposed hydrophilic-hydrophobic alternative double-layered nanocapsules can be highlighted in the fabrication of a variety of nanomaterials for the protection of vulnerable payloads in harsh environments.

Background Acute kidney injury (AKI) is one of the most common complications in patients with cancer, yet the specific reasons, mechanisms, and the influence of AKI are not clear in hepatocellular carcinoma (HCC) after treatment. This meta-analysis aimed to find out the risk factors and the impact on mortality of AKI in adult patients with HCC after treatment using available published data. Methods We performed a systemic literature search using PubMed, Web of Science, and Embase, encompassing publications up until November 30, 2021 (inclusive), with 17 cohort studies involving 11,865 patients that fulfilled the prespecified criteria for inclusion in the meta-analysis. The number of AKI/non-AKI patients identified by risk factors, the number of AKI/non-AKI-related deaths, the incidence rates, the mortality rates, and the irreversible rates of AKI were derived and analyzed using STATA. Results Age, diabetes mellitus (DM), and the number of transarterial chemoembolization (TACE) sessions are risk factors for AKI in patients with HCC after TACE. On the other hand, male gender, age, DM, major resection of the liver, and operation-related transfusion are risk factors for AKI in patients with HCC after hepatectomy. The risk of mortality in those with renal failure due to AKI was up to 4.74 times higher than in those without AKI in a short-term observation period after TACE treatment. Conclusions Attention should be paid to the risk of AKI in HCC patients with DM. The occurrence of AKI during TACE treatment is especially dangerous and should be considered a strong red flag, obviously with regard to the extremely high risk of death in a short period. Furthermore, studies are needed to detect more associations of AKI in patients with HCC.

Chronic kidney diseases (CKD) with complication of sepsis brings great clinical burden worldwide. Regulatory T cells (Tregs) can regulate key immune response during the progression of the diseases. The present study aims to investigate the role of HMGB1 in the regulation of Tregs and find out the potential mechanism. Jurkat cells were stimulated with 0.5 ng/ml TGF-β1 for 24 h to induce phenotypic alternation into Tregs, followed by stimulation with indoxyl sulfate (IS) and lipopolysac-charide (LPS) for 24 h. Then, Tregs were treated with recombinant human HMBG1 (rHMGB1) at different concentrations (10, 100 and 1000 ng/ml). Cell viability of Tregs was assayed by CCK-8. The gene expressions related to proliferation and autophagy were determined using RT-qPCR and western blotting. RAGE was inhibited by transfection with shRNA-RAGE in Tregs. The results showed that HMGB1 and RAGE were upregulated upon IS and LPS induction in Tregs. rHMGB1 significantly promoted the viability, proliferation and function of Tregs at a concentration-dependent way, which was partly reversed by RAGE knockdown. Besides, HMGB1-RAGE could regulate autophagy activity and AMPK-mTOR signaling pathway. In summary, our study concluded that the active autophagy mediated by enhanced HMGB1-RAGE axis through AMPK-mTOR signaling pathway was a potential mechanism to enhance Tregs viability and function in chronic kidney diseases with complication of sepsis.

Polymeric small interfering RNA (siRNA) conjugate was elaborated to sequentially circumvent the predefined biological barriers encountered in the journey of transcellular delivery of siRNA into cytosol. Herein, classic ring-opening polymerization was employed for synthesis of well-defined poly(amino acid) derivatives possessing an array of carboxyl groups in an attempt to resemble the structural characteristics of hyaluronan. Furthermore, the hyaluronan-like synthetic was conjugated with a multiple of siRNA through a glutathione (GSH)-responsive disulfide linkage. The siRNA conjugate appeared to utilize the hyaluronan-specific receptors of CD44 for cell internalization, indicating similar functionalities to our hyaluronan-mimicking synthetic. Furthermore, the carboxyl groups of hyaluronan-like synthetics were designed to be selectively detached in subcellular acidic endosomes/lysosomes and transform into the cytomembrane-disruptive flanking ethylenediamine moieties, which appeared to be crucial in facilitating translocation of siRNA payloads from entrapment and degradation in lysosomes toward the cytosol. Eventually, active siRNA could be smoothly released from the synthetic due to the GSH cleavage disulfide linkage (disulfide), consequently accounting for potent RNA knockdown activities (>90%) toward cancerous cells. In addition, appreciable knockdown of parathyroid hormone was also achieved from our proposed siRNA conjugates in parathyroid cells. Hence, the elaborated siRNA conjugate showed tremendous potential in treatment of hyperparathyroidism, and could be developed further for systemic RNA interference (RNAi) therapeutics. Moreover, this study could also be the first example of a synthetic mimic to hyaluronan acquiring its functionalities, which could have important implications for further development of biomimic materials in pursuit of biomedical applications.

OBJECTIVE:To explore the genetic basis for a pedigree affected with Alport syndrome.METHODS:Next generation sequencing and Sanger sequencing was applied to detect potential variants of the COL4A3, COL4A4 and COL4A5 genes among members from the pedigree and 100 unrelated healthy controls.RESULTS:The proband and his twin brother were found to carry two novel variants, namely c.4953G>A and c.4623C>A, of the COL4A4 gene, which were respectively inherited from her father and mother. The same variants were not detected among the 100 healthy controls and medical literature. Based on the guidelines of the American College of Medical Genetics and Genomics, both the c.4953G>A and c.4623C>A variants were predicted to be pathogenic (PVS1+PM2_supporting+PP1).CONCLUSION:The c.4953G>A and c.4623C>A variants of the COLA4A gene probably underlay the Alport syndrome in this pedigree. Above finding has enriched the spectrum of COLA4A gene variants.

PURPOSE:Acute kidney injury (AKI) is one of the most common complications in patients receiving extracorporeal membrane oxygenation (ECMO), but there is no systematic analysis regarding its risk factors. This meta-analysis aims to determine the risk factors of AKI in adult patients with ECMO treatment. METHODS:Two authors independently carried out a systemic literature search using PubMed, Web of Science, and Embase until April 20, 2020 (inclusive) to enroll 12 studies reporting the necessary clinical characteristics. The Gender (male), age, APACHE II score, SOFA score, cancer, diabetes mellitus (DM), intra-aortic balloon pump (IABP), postcardiotomy, and ECMO supporting duration were pooled for further analysis by STATA. RESULTS:Adult patients receiving ECMO who develop AKI and severe AKI incidents are usually older or have a higher APACHE II scores; in addition, severe AKI is related to higher SOFA scores, DM, and longer duration of ECMO support. CONCLUSIONS:Patients with these clinical characteristics should be paid more attention during ECMO. There remains a need for additional studies to validate these conclusions and to detect additional AKI risk factors for ECMO patients.

: Objectives: The coronavirus strain first reported in December 2019 (COVID-19) has spread rapidly worldwide, posing a seriously risk to human health. This meta-analysis aims to shed much-needed light on the relationship between COVID-19 and AKI, and provide a stronger evidence base to support both further research and clinical application. Methods: Two authors independently performed a literature search using PubMed, Web of Science, Embase, and Cochrane Library. Then the incidence of AKI, incidence of RRT required, the mortality rate with AKI and the risk of death with AKI during a COVID-19 infection were statistically analyzed using Open Meta-Analyst software, from which conclusions are derived. Results: The incidence of AKI in hospitalized patients with the COVID-19 infection remains low, only about 3.8%; the in-hospital mortality rate with AKI in COVID-19 infected patients reaches up to 86.8%; the odds of death with AKI in COVID-19 infected patients is about 24.2 times higher than those without AKI. Conclusions: The occurrence of AKI during a COVID-19 infection should be considered a strong red flag with regards to the patient’s risk of death. Additional studies are still required to support the conclusions derived herein and to explore the AKI mechanism during a COVID-19 infection. and control of critical cases with AKI; the renal function of asymptomatic and mild cases should be frequently monitored, carried out blood purification treatment if necessary; (2) Conduct in-depth research on mechanisms of renal injury during COVID-19 attack (various signal pathways/virus proteins) for designing of blocking drugs; (3) Explore the combined application of antiviral and anti-inflammatory drugs in the design of clinical trials for COVID-19, further study is needed on the standard application, the evaluation for the curative effect, and the integration of them together. Finally to ameliorate the effectiveness of treatment, as well as to achieve the goal of reducing mortality patients infected with COVID-19.

The efficacy of corticosteroids in the treatment of patients with severe COVID-19 remains unknown. We evaluated the impact of corticosteroids on clinical improvement among severe COVID-19 patients. In this retrospective, two-centered, cohort study, we enrolled 101 patients with severe COVID-19: with 39 patients in the steroid group and 63 patients in the non-steroid group. The primary endpoint was Time to Clinical Improvement (TTCI) by up to 28 days after the treatment. Secondary endpoints included the rate of CAT scan improvement, the percentage of negative SARS-Cov-2 RT-PCR tests by Day 28, and the time to discharge. We found that patients in the steroid group did not have significant differences of TTCI from patients in the non-steroid group by 28 days after the treatment (median, 19 days vs. 20 days; hazard ratio, 1.07; p=0.797). The CAT scan improvement rate was not statistically different between the two groups by Day 28 (87.2% vs. 79.0%, p=0.170). The negative test of SARS-CoV2 RT-PCR by Day 28 was 68.4% in the steroid group, 87.1% in the non-steroid group (p= 0.060). Time to discharge was significantly longer in the steroid group than the non-steroid group (35 days vs 21 days, p=0.005). Our findings indicated the short-term corticosteroid at a low to moderate dose did not improve the clinical outcomes for patients with severe COVID-19. Further randomized clinical trials are needed to confirm the findings.

目的 观察维持性血液透析(hemodialysis,HD)患者肾性贫血治疗达标后,不同补铁方式对血红蛋白变异度(hemoglobin variation,Hb-Var)的影响.方法 选择2015年1-12月厦门大学附属中山医院行HD的患者160例,按照随机数字表法分入静脉补铁组(蔗糖铁注射液100 mg,每周1次,静脉滴注)与口服补铁组(多糖铁复合物100 mg,每天1次,口服)并随访1年,观察2种维持性补铁方式对Hb-Var的影响.结果 采用4种方法对Hb-Vat进行评估:①静脉组患者剩余标准差明显低于口服组[(8.04 ±4.58)g/L vs.(12.25±6.85) g/L,P=0.042].②静脉组患者血红蛋白(hemoglobin,Hb)振幅低于口服组[(15.88±8.07) g/L vs.(27.00±15.88) g/L,P=0.015].③连续测量相邻时间点Hb变化绝对值,静脉组患者Hb的个体变化值及其标准差均较口服组明显降低[分别为(8.64±4.91)g/Lvs.(13.69±7.60) g/L及(6.25±3.76) g/L vs.(11.23±8.49) g/L,均P＜0.05].④观察期内4次检测血红蛋白高于、处于及低于靶目标(Hb:110 ～ 130 g/L)的比例分别为:静脉组12.85％、71.14％及16.01％;口服组6.90％、55.17％及37.93％(x2=7.164,P=0.028).静脉组转铁蛋白饱和度及铁蛋白在治疗后均增高[分别为(29.29±11.80)％vs.(39.36±12.32)％,P=0.025;(375.39±223.77) ng/ml vs.(463.05±303.26)ng/ml,P=0.005].结论 不同的维持性补铁方式对Hb-Var的影响程度不同,静脉补铁较口服补铁更有助于血液透析患者Hb的持续达标,其原因可能与铁储备的稳定性及铁离子利用率的提高有关.

Background: This study investigated the therapeutic effect of intensive phosphorus-lowering therapy on intact-parathyroid hormone (iPTH) levels in hemodialysis patients. Methods: Ninety-five hemodialysis patients with serum phosphorus ≥1.78 mmol/L and iPTH ≥300 pg/dL were apportioned to either the treatment or control group (n = 43 and 52, respectively) based on patient commitment to treatment. The treatment group was given phosphorus-lowering therapies with phosphate binders (lanthanum, sevelamer or/and calcium reagent) combined with dietary phosphate restriction and intensified hemodialysis. The control individuals were given low doses of calcium agents, if serum calcium was <2.54 mmol/L. Percent changes in serum phosphorus and iPTH levels were compared between the two groups. In addition, based on the time required to achieve >20% decrease in serum phosphorus, the patients in the treatment group were further stratified as rapid responders (≤2 months; 27 patients) or slow responders (>2 months; 16 patients) and percent changes in iPTH were compared. Results: Serum phosphorus and iPTH levels decreased from baseline in the treatment group (−24.08 ± 1.93% and −9.92 ± 3.70%, respectively) but increased in the control group (22.00 ± 3.63% and 104.21 ± 23.89%; both p < .001). In the rapid responders subgroup, the iPTH decreased (−16.93 ± 3.49%), but in the slow responders subgroup the iPTH increased slightly (0.68 ± 7.37%, p < .05). Conclusions: For these patients on maintenance hemodialysis, intensive treatment of hyperphosphatemia was associated with a decrease in iPTH levels, especially for those who had achieved substantial reduction in serum phosphorus within 2 months.

Background: Serum N-terminal probrain natriuretic peptide (NT-proBNP) level is known to be strongly associated with fluid overload, and serves as a guide for fluid management in patients on hemodialysis (HD). This study aimed at investigating the relationship between NT-proBNP level and blood pressure (BP), ultrafiltration/dry weight ratio as well as hemoglobin, and to explore the optimal cutoff point of NT-proBNP level in Chinese patients on HD.Methods: A total of 306 patients on maintained HD for stage 5 chronic kidney disease (CKD) were included in this prospective study. Their average ultrafiltration/dry weight ratio and BP before dialysis were recorded. The serum NT-proBNP, hemoglobin, serum calcium, and phosphorus were detected. The cutoff value for NT-proBNP level was calculated using receiver operating characteristic (ROC) analysis.Results: The high NT-proBNP level was associated with high BP and ultrafiltration/dry weight ratio, and low hemoglobin level. The optimal cutoff point of NT-proBNP level for patients on maintained HD was 5666 pg/mL, with a sensitivity of 78.5%, specificity of 43.9%, and area under the curve (AUC) of 0.703 (<0.001).Conclusions: NT-proBNP level ≤5666 pg/mL was recommended to achieve the target BP, hemoglobin level, and ultrafiltration/dry weight ratio in patients on maintained HD with an ejection fraction (EF) >50%.

目的 观察补铁治疗对维持性血液透析患者贫血指标和促红细胞生成素类药物(ESAs)用量的影响.方法 前瞻性入组2015年1-7月我科维持性血液透析患者169例,根据患者铁指标情况采用静脉补充铁剂或口服补充铁剂治疗,比较患者治疗前后的血红蛋白(Hb)、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)和ESAs治疗剂量.结果 与治疗前相比,静脉补充铁剂治疗后患者的Hb、SF和TSAT水平均显著增加(P＜0.05),ESAs使用剂量明显下降(P＜0.01).口服补充铁剂治疗后患者的Hb、SF、TSAT和ESAs使用剂量与治疗前相比,差异均不具有统计学意义(P＞0.05).结论 针对铁储备明显低下的透析患者,通过静脉补充铁剂后可提高血透患者贫血指标,减少ESAs使用剂量;铁储备在理想范围的透析患者通过补充口服铁剂可稳定患者的Hb和铁指标,为患者的后续治疗提供了指导和帮助.

Objective Anemia and secondary hyperparathyroidism are the two most common complications associated with chronic kidney disease. Erythropoiesis-stimulating agents (ESAs) are widely used in the management of anemia in hemodialysis patients. A reverse correlation has been established between hyperparathyroidism and hemoglobin levels. The aim of this retrospective study is to evaluate the relationship of high-dose ESAs and hyperparathyroidism in hemodialysis patients with anemia. Methods A total of 240 uremic patients maintained on regular hemodialysis were enrolled in this study. Among them, 142 patients were treated with Epiao® (epoetin-alfa) and 98 patients were treated with Recormon® (epoetin-beta). The target hemoglobin concentration was 110–130 g/L. Laboratory measurements including hemoglobin, calcium, phosphorus, albumin, intact-parathyroid hormone (iPTH), serum ferritin, and transferrin saturation were collected. Results Hemoglobin concentration increased as iPTH level decreased by stratification. However, no significant association between anemia and calcium or phosphorus level was found. Patients with iPTH levels within 150–300 pg/mL had the highest levels of hemoglobin, serum ferritin, and transferrin saturation. Patients treated with Recormon and Epiao had similar hemoglobin concentrations. However, the dose of Recormon for anemia treatment was significantly less than that the dose of Epiao (P < 0.05). The level of iPTH in the Recormon group was significantly lower than in the Epiao group. In patients with hemoglobin levels between 110 and 130 g/L (P < 0.05), iPTH level was found to be significantly lower in patients treated with lower doses of ESAs than in patients treated with higher doses of ESAs, no matter which ESA was used (Recormon or Epiao, P < 0.05). Conclusion The dose of ESAs might be positively associated with iPTH level, suggesting that a reasonable hemoglobin target can be achieved by using the lowest possible ESA dose.