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.

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.

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.

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.

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.

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.

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.

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.

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.

Changes in the Physico-Chemical Properties of Human Kidney Cell Membranes during the Cancer Transformation

Kidney tissue is particularly susceptible to reactive oxygen species attack which leads to development of cancer. During oxidative stress, membrane lipids and proteins are major targets of re-active oxygen species (ROS). This work is focused on changes of phospholipids, proteins content and electric charge that occur in cell membranes of kidney cancer of pT3 stage, grade G3 and with metastasis. Qualitative and quantitative phospholipid composition and the presence of integral membrane proteins were determined by high-performance liquid chromatography. Electrophoresis was used to determine the surface charge density of the human kidney cell membrane. It was shown that the process of cancer transformation was accompanied by an increase phospholipid levels and altered the level of integral proteins as determined by decrease phenylalanine, tyrosine, cysteine and arginine. Moreover, the process of cancer transformation significantly enhanced changes in the surface charge density of the human kidney cell membrane. Cell membrane structure and function are modified by neoplasm lesion.

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.

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.

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.

Effects of Houttuynia Cordata Thumb on Expression of BMP-7 and TGF-β_1 in the Renal Tissues of Diabetic Rats

Objective： To explore the effects of Houttuynia Cordata Thumb （HCT 鱼腥草 Yu Xing Cao） on expression of transforming growth factor-β1 （TGF-β1） and bone morphogenetic protein-7 （BMP-7） in the renal tissues of diabetic rats. Methods： The diabetic rats induced by intravenous injection of streptozotocin（STZ） were randomly divided into a model group, a HCT group and a lotensin group, with normal rats designated as the controls. 8 weeks later, the ratio of kidney weight to body weight, the glomerular area, the excretion of β 2-microglobin （β2-MG） in 24-hr urine, the albumin excretion in 24-hr urine, and creatinine clearance rate （CCR） were investigated. The expression of TGF- β 1, BMP-7 and collagen I in the renal tissues was observed with the immunohistochemical method and by the semi-quantitative assay. Results： The overgrowth of glomerulus, the excretion of β 2-MG in 24-hr urine, the albumin excretion rate in 24-hr urine and CCR in the HCT group significantly reduced （P〈0.05）, and the expression of TGF-β1 and collagen I significantly decreased （P〈0.05）, but BMP-7 significantly increased （P〈0.05） in the HCT group as compared with those in the model group, with no significant difference as compared with the lotensin group （P〉0.05）. Conclusion： HCT has a protective effect on the renal tissues in diabetic rats, which is probably correlated with the decrease of the expression of TGF-β1 and collagen I and with the increase of the expression of BMP-7 in the renal tissues.

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.

Electrospinning and Electrospun Nanofibers

Electro-spinning is a very modern process which can be used in various purposes. We did this experimental work at Swerea IVF in Sweden during M. Sc in Textile Technology programme at University of Bor?s. We should especially thank our supervisor—Anna Thorvaldsson and course teacher—Ioannis S. Chronakis. In this report, we have tried to explain the basic manufacturing techniques of the electrospun nanofiber by the electro-spinning, how one can characterize it by SEM (Scanning Electron Microscopy) and its various applications in the practical field, e.g wound healing, Tissue Engineering Scaffold. The experimental work helped us a lot to gather sufficient knowledge about the electro-spinning process which we wanted to share with all.

The Research Progression of Calcitonin for the Therapy of Renal Osteodystrophy

Calcitonin is a common medicine used in the treatment of osteoporosis,which could restrain the activity of osteoclasts,stop the loss of osteocalcin and reduce the transfer of osteocalcin.Calcitonin can also be used in the treatment of the pain-caused diseases which usually cause by hypercalcemia and others such like Paget's disease and bone tumors.As is approved by several clinic researches,calcitonin is powerful in adjusting the level of calcium,phosphorus and PTH during the treatment of renal osteodystrophy.In addition,it could improves the life quality of the patients who suffered from chronic kidney disease(CKD)and extending their life period.At present,several studies have shown us Calcitonin could be treated in renal osteodystrophy.However,the treatment experiences of Calcitonin are still lacking.Better understanding of the clinical evaluation for calcitonin in the treatment of renal osteodystrophy will hopefully help us to improve outcomes for these patients.

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.

探析“少阳主骨”学说与骨质疏松的联系

“少阳主骨”原初来自于《黄帝内经》,经过过去多代医家的不断深化和完善,现在已经成为了一种针对骨科疾病的全方位中医理论体系。骨质疏松症(osteoporosis,OP)是一种全身的慢性骨代谢疾病,其主要表现形式是全身骨量的减退和骨内微观结构的破坏,这一特征对应了“骨痿”“骨痹”等中医骨病。然而,现代医家很少从少阳角度出发去治疗此类疾病。本文对于“少阳主骨”的本质和少阳与OP的联系进行了明确梳理,并对从少阳视角出发治疗OP的方法进行了探讨,具有“少阳主骨”理论的实践意义,对于引导OP病人的中医药防疗方案具有重要价值。