Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Cemented vertebra and adjacent vertebra refractured in a chronic kidney disease-mineral and bone disorder patient: A case report

BACKGROUND Although percutaneous vertebral augmentation(PVA)is a commonly used procedure for treating vertebral compression fracture(VCF),the risk of vertebral refracture should be considered.Chronic kidney disease-mineral and bone disorder(CKD-MBD)is a systemic disease of mineral and bone metabolism.It is associated with an increased risk of fracture.Few studies have reported the use of PVA in patients with CKD-MBD.We herein report a rare case wherein the cemented vertebra and the adjacent vertebra refractured simultaneously in a CKD-MBD patient after PVA.CASE SUMMARY A 74-year-old man suffered from low back pain after taking a fall about 3 wk ago.According to physical examination,imaging and laboratory findings,diagnoses of T12 VCF,CKD-MBD,and chronic kidney disease stage 5 were established.He then received percutaneous vertebroplasty at T12 vertebra.Fourteen weeks later,he presented with T12 and L1 vertebral refractures caused by lumbar sprain.Once again,he was given PVA which was optimized for the refractured vertebrae.Although the short-term postoperative effect was satisfactory,he reported chronic low back pain again at the 3-month follow-up.CONCLUSION It is necessary that patients with CKD-MBD who have received PVA are aware of the adverse effects of CKD-MBD.It may increase the risk of vertebral refracture.Furthermore,the PVA surgical technique needs to be optimized according to the condition of the patient.The medium-and long-term effects of PVA remain uncertain in patients with CKD-MBD.

Impact of bisphosphonate treatment on bone mineral density after kidney transplant

BACKGROUND Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation.Immunosuppressive treatment contributes to the patho-genesis of this disease.Bisphosphonate treatments have shown positive but inde-finite results.AIM To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density(BMD).METHODS We included kidney transplant recipients(KTRs)whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later.We also evaluated the BMD of KTRs using two valid mea-surements after transplantation who received no treatment(control group).RESULTS Out of 254 KTRs,62(39 men)were included in the study.Bisphosphonates were initiated in 35 KTRs in total(20 men),1.1±2.4 years after operation and for a period of 3.9±2.3 years while 27(19 men)received no treatment.BMD improved significantly in KTRs who received bisphosphonate treatments(from-2.29±1.07 to-1.66±1.09,P<0.0001).The control group showed a non-significant decrease in BMD after 4.2±1.4 years of follow-up after surgery.Kidney function was not affected by bisphosphonate treatment.In KTRs with established osteoporosis,active treatment had a similar and significant effect on those with osteopenia or normal bone mass.CONCLUSION In this retrospective study of KTRs receiving bisphosphonate treatment,we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.

Roles and regulation of bone morphogenetic protein-7 in kidney development and diseases

The gene encoding bone morphogenetic protein-7(BMP7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of BMP7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways. Intriguingly, in the adult organ, BMP7 has been implicated in protection against and regeneration from injury. Exogenous administration of recombinant BMP7 to animal models of kidney diseases has shown promising effects in counteracting inflammation, apoptosis and fibrosis evoked upon injury. Although the expression pattern of BMP7 has been well described, the mechanisms by which it is regulated have remained elusive and the processes by which the secretion sites of BMP7 impinge upon its functions in kidney development and diseases have not yet been assessed. Understanding the regulatory mechanisms will pave the way towards gaining better insight into the roles of BMP7, and to achieving desired control of the gene expression as a therapeutic strategy for kidney diseases.

Vascular calcification,bone and mineral metabolism after kidney transplantation

The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article.

Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

Patients with chronic kidney disease （CKD） have an extremely poor cardiovascular outcome. Arterial stiff-ness, a strong independent predictor of survival in CKD, is connected to arterial media calcification. A huge number of different factors contribute to the increased arterial calcification and stiffening in CKD, a process which is in parallel with impaired bone metabolism. This coincidence was demonstrated to be part of the direct inhibition of calcifcation in the vessels, which is a counterbalancing effect but also leads to low bone turnover. Due to the growing evidence, the defnition of “CKD mineral bone disorder” was created recently, un-derlining the strong connection of the two phenomena. In this review, we aim to demonstrate the mechanisms leading to increased arterial stiffness and the up-to date data of the bone-vascular axis in CKD. We over-view a list of the different factors, including inhibitors of bone metabolism like osteoprotegerin, fetuin-A, pyro-phosphates, matrix Gla protein, osteopontin, fbroblast growth factor 23 and bone morphogenic protein, which seem to play role in the progression of vascular calcif-cation and we evaluate their connection to impaired ar-terial stiffness in the mirror of recent scientifc results.

Metabolic bone diseases in kidney transplant recipients

Metabolic bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a dif-ferent osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Each patient may have multiple risk factors of bone loss, such as steroids usage, hypo-gonadism, persistent hyperparathyroidism （HPT）, poor allograft function, metabolic acidosis, hypophosphate-mia, vitamin D defciency, aging, immobility and chronic disease. Clinical management requires a comprehen-sive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D, bisphosphonates, cal-citonin as well as treatment of hypogonadism and HPT. Novel approach to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fracture rate in kidney transplant recipients.

Potential efficacy and mechanism of medicinal plants on chronic kidney disease-associated vascular calcification:a review

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.

Fibroblast growth factor 23 and bone mineralisation

Fibroblast growth factor 23 （FGF23） is a hormone that is mainly secreted by osteocytes and osteoblasts in bone. The critical role of FGF23 in mineral ion homeostasis was first identified in human genetic and acquired rachitic diseases and has been further characterised in animal models. Recent studies have revealed that the levels of FGF23 increase significantly at the very early stages of chronic kidney disease （CKD） and may play a critical role in mineral ion disorders and bone metabolism in these patients. Our recent publications have also shown that FGF23 and its cofactor, Klotho, may play an independent role in directly regulating bone mineralisation instead of producing a systematic effect. In this review, we will discuss the new role of FGF23 in bone mineralisation and the pathophysiology of CKD-related bone disorders.

Type 2 diabetes and bone fragility in children and adults

Type 2 diabetes(T2D)is a global epidemic disease.The prevalence of T2D in adolescents and young adults is increasing alarmingly.The mechanisms leading to T2D in young people are similar to those in older patients.However,the severity of onset,reduced insulin sensitivity and defective insulin secretion can be different in subjects who develop the disease at a younger age.T2D is associated with different complications,including bone fragility with consequent susceptibility to fractures.The purpose of this systematic review was to describe T2D bone fragility together with all the possible involved pathways.Numerous studies have reported that patients with T2D show preserved,or even increased,bone mineral density compared with controls.This apparent paradox can be explained by the altered bone quality with increased cortical bone porosity and compromised mechanical properties.Furthermore,reduced bone turnover has been described in T2D with reduced markers of bone formation and resorption.These findings prompted different researchers to highlight the mechanisms leading to bone fragility,and numerous critical altered pathways have been identified and studied.In detail,we focused our attention on the role of microvascular disease,advanced glycation end products,the senescence pathway,the Wnt/β-catenin pathway,the osteoprotegerin/receptor-activator of nuclear factor kappa B ligand,osteonectin and fibroblast growth factor 23.The understanding of type 2 myeloid bone fragility is an important issue as it could suggest possible interventions for the prevention of poor bone quality in T2D and/or how to target these pathways when bone disease is clearly evident.

Receptor activator of nuclear factorκB ligand/osteoprotegerin axis and vascular calcifications in patients with chronic kidney disease

Vascular calcifications are commonly observed in patients with chronic kidney disease （CKD） and contri-bute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although the pathogenetic mechanisms are not yet fully elucidated, recent evidence suggests a link between bone metabolism and the development and progression of vascular calcifications. Moreover, accumulating data indicate that receptor activator of nuclear factor κB ligand/osteoprotegerin axis which plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation. Further studies are required to establish the prognostic significance of the above biomarkers as predictors of the presence and severity of vascular calcifications in CKD patients and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifcations.

Parathyroid ultrasonography and bone metabolic profile of patients on dialysis with hyperparathyroidism

AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure.METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics(etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory(calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ~2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables.RESULTS Fifty-three patients(66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product(P = 0.03 and P = 0.006, respectively). They also had lower mortality(32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events(27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg^2/dL^2 [RR 1.48(1.06, 2.08), P = 0.03], presence of vascular calcification [1.33(1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25(1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality.CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure.

Clinical observation of kidney tonifying and collateral tonifying acupuncture combined with thermosensitive moxibustion in the treatment of knee osteoarthritis and its effect on TRACP and CTX-I

Objective:To observe the clinical effect of kidney-tonifying and colllateral-tonifying acupuncture combined with thermosensitive moxibustion in the treatment of knee osteoarthritis and cold congealing syndrome and the effect on Tartrate-resistant Acid Phosphatase(TRACP)andⅠcollagen C-terminal foreign body peptide(CTX-I).Methods:Totally 90 patients with knee osteoarthritis were divided into three groups:acupuncture group,thermosensitive moxibustion group and routine group with 30 cases in each group.In the conventional group,sodium hyaluronate was injected into the joint cavity and diclofenac sustained release tablets were taken orally.Thermosensitive moxibustion group was given thermosensitive moxibustion on the basis of conventional treatment.Acupuncture and moxibustion group in the heat sensitive moxibustion group treatment was given kidney tonifying acupuncture.VAS score,JKOM score and Ly-Sholm knee score were observed before and after treatment and followed up for 2 weeks.The levels of TRACP and CTX-I in serum before and after treatment.Results:Before treatment,there were statistically significant differences in VAS score,JKOM score and Ly-Sholm knee score among all groups(P>0.05).After treatment,the VAS score and JKOM score decreased,and the decrease degree was the greatest in the acupuncture group(P<0.05).Ly-Sholm knee score increased,and the change degree was the greatest in acupuncture group(P<0.05).Before treatment,the levels of TRACP and CTX-I in serum of all groups were significantly different(P>0.05).After treatment,serum TRACP and CTX-I levels were decreased,and the decrease degree was the greatest in acupuncture group(P<0.05).The total effective rates of the acupuncture group,the thermal sensitive moxibustion group and the conventional group were 96.7%,80%and 66.7%,respectively,and the difference between each group was statistically significant(P<0.05).Conclusion:Kidney-tonifying and collature-tonifying acupuncture combined with thermosensitive moxibustion can significantly relieve knee pain and other symptoms of knee osteoarthritis in patients and cold congealing syndrome,which is worthy of clinical promotion.

Beyond kidney stones:Why pediatricians should worry about hypercalciuria

The incidence of urolithiasis(UL)is increasing,and it has become more common in children and adolescents over the past few decades.Hypercalciuria is the leading metabolic risk factor of pediatric UL,and it has high morbidity,with or without lithiasis as hematuria and impairment of bone mass.The reduction in bone mineral density has already been described in pediatric idiopathic hypercalciuria(IH),and the precise mechanisms of bone loss or failure to achieve adequate bone mass gain remain unknown.A current understanding is that hypercalciuria throughout life can be considered a risk of change in bone structure and low bone mass throughout life.However,it is still not entirely known whether hypercalciuria throughout life can compromise the quality of the mass.The peak bone mass is achieved by late adolescence,peaking at the end of the second decade of life.This accumulation should occur without interference in order to achieve the peak of optimal bone mass.The bone mass acquired during childhood and adolescence is a major determinant of adult bone health,and its accumulation should occur without interference.This raises the critical question of whether adult osteoporosis and the risk of fractures are initiated during childhood.Pediatricians should be aware of this pediatric problem and investigate their patients.They should have the knowledge and ability to diagnose and initially manage patients with IH,with or without UL.

Anemia in ESKD Patient (End-Stage Kidney Disease): The Rare Cause Is in the Forefront

We reported a case of severe anemia in a patient with end-stage kidney disease (ESKD) on dialysis. The anemia developed when the patient is switched from hemodialysis (HD) to peritoneal dialysis (PD) when the intra-venous erythropoietin stimulating agent (ESA, Epogen) was changed into subcutaneous injection of darbepoetin. The patient’s hemoglobin dropped 2 grams in about two months during this period. Extensive work-up including, bleeding disorders, hemolysis, iron deficiency, infections including CMV, Epstein-Bar virus, parvo-19 virus infection were unrevealing The anti-Epogen neutralizing antibodies were not measured due to unavailability. Bone marrow biopsy and aspirate were negative for infiltrations or myelodysplastic syndrome (MDS). The leukocyte and platelet counts were normal. Even though anti-ESA antibodies were not measured in this case, all tentative causes of his anemia were excluded by laboratory investigations. The patient’s anemia was treated symptomatically with blood transfusion and discontinuation of the ESA treatment. He made a remarkable recovery.

Network Meta-analysis of the clinical efficacy and safety of kidney-tonifying and bone-strengthening therapies for the treatment of rheumatoid arthritis with kidney deficiency type

OBJECTIVE: To compare the efficacy and safety of different Traditional Chinese Medicine(TCM)-based kidney-tonifying and bone-strengthening therapies for rheumatoid arthritis(RA). METHODS: The current Bayesian network Meta-analysis compared different TCM-based kidney-tonifying and bone-strengthening therapies for RA. Eight electronic databases and two trial registration platforms were searched. Rev Man 5.4 and Stata 16 software were employed. RESULTS: A total of 42 studies involving 3779 cases were included. The results showed that the most effective intervention for improving efficacy was Wanbi decoction(顽痹汤);Bushen Quhan Zhiwang decoction(补肾祛寒治尪汤) was superior in reducing the incidence of adverse reactions;and Qiwei Tongbi oral liquid(七味通痹口服液) effectively reduced C-reactive protein and erythrocyte sedimentation rate levels.CONCLUSION: Combining TCMs with conventional Western Medicine can improve the clinical efficacy of RA treatments, reduce inflammatory indexes, and result in a higher safety profile. However, this conclusion needs to be verified by more high-quality randomized controlled trials.

The mechanism by which exosomes derived from bone marrow mesenchymal stem cells promote the regeneration of renal tubules in acute kidney injury through the regulation of the PTEN signaling pathway by miR-21

Acute kidney injury(AKI)is a significant global health issue with limited current treatment options.This study focused on the mechanism by which exosomes derived from bone marrow mesenchymal stem cells(BMSCs)promote renal tubule regeneration in AKI through the regulation of the PTEN signaling pathway by miR-21.BMSCs were isolated and characterized,and their exosomes were purified.In vitro,renal tubular epithelial cell injury models were established,and the co-culture of exosomes and cells demonstrated enhanced cell proliferation and reduced apoptosis.In vivo,AKI animal models showed improved renal function and histopathological changes after exosome treatment.miR-21 was found to be upregulated in exosomes and recipient cells,targeting PTEN and activating the PI3K/AKT pathway.The signaling network also interacted with other pathways related to renal tubule regeneration.The study highlights the potential of exosome therapy for AKI and provides insights into the underlying molecular mechanisms,although further research is needed to address remaining challenges and translate these findings into clinical applications.

王祥麒教授基于“肾主骨”理论妙治乳腺癌骨转移

目的:探讨乳腺癌骨转移机理与治疗,学习王祥麒教授从"肾主骨"论乳腺癌骨转移的治疗经验。方法:通过跟师,学习并整理王祥麒教授治疗乳腺癌骨转移的经验。结果:王祥麒教授秉承中医"肾主骨"经典理论思想,治疗乳腺癌骨转移,将该病症归因于癌病日久,肾精亏虚,骨失所养,癌毒入骨,骨蚀髓空,气机闭乱,痰瘀互结,阻滞经络所致。据此提出"益肾填精壮骨为主,兼化痰散结、化瘀止痛"之法,拟定滋肾化痰破瘀方内服,配合佛手金贴外敷治疗本病。结论:王祥麒教授治疗乳腺癌骨转移疗效显著。

商代乐器补说

商代社会音乐歌舞甚盛,乐器品类众多,就甲骨金文及石器刻铭中所见,有20多种乐器名。传世和考古出土的商代乐器,已知的有铜鼓、木鼓、石磬、玉磬、编铙、钟、镛、镈、铎、铜铃、陶铃、埙等,大抵为打击乐器、摇乐器或吹奏乐器,弹拨类弦乐器殆地下难存,考古发掘尚未见。《礼记·郊特牲》所谓“殷人尚声”,信而有征。