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 mechanis...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.展开更多
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-mi...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.展开更多
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...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.展开更多
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 treatment...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.展开更多
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...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.展开更多
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 ri...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 ost...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.展开更多
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 acquire...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.展开更多
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. Altho...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.展开更多
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...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.展开更多
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-ve...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.展开更多
To evaluate the operative characteristics and efficacy of retroperitoneoscopic resection of renal,ureter and partial bladder for the treatment of native renal pelvic and ureteral transitional cell cancer occurring at ...To evaluate the operative characteristics and efficacy of retroperitoneoscopic resection of renal,ureter and partial bladder for the treatment of native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.Methods In 5 cases of renal transplantation,there were 2 cases of right native renal pelvic cancer,1 case of right native renal pelvic and ureter cancer and 2 cases of right ureter cancer respectively.The transplanted kidney was in the same iliac fossa side of the tumor.All 5 patients were subjected to nephroureterectomy and bladder cuff excision by retroperitoneoscopic technique.Results Five operations were completed successfully.The operative time was 180 to 280 min,and the blood loss was 50 to 200 ml.The recovery of intestinal function after operation was 12 to 36 h.The urine output was 1 500 to 4 000 per day.Postoperative serum creatinine was still normal.The mean hospital stay after operation was 4.5 days.Conclusion Retroperitoneal laparoscopic nephroureterectomy and bladder cuff excision is a good method to treat the native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.The procedure is safe and less invasive,which provides a good protection of transplanted kidney.12 refs.展开更多
As a traditional concept of Chinese medicine(CM), the theory of "Shen(Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development ...As a traditional concept of Chinese medicine(CM), the theory of "Shen(Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal(HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue(osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.展开更多
Background:Mineral and bone disorder (MBD),especially hyperphosphatemia,is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD).However,CKD-MBD among Chinese population...Background:Mineral and bone disorder (MBD),especially hyperphosphatemia,is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD).However,CKD-MBD among Chinese population was poorly studied.This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD.Methods:Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is a prospective multicenter cohort study involving predialysis CKD patients in China.Markers of MBD,including serum phosphorus,calcium,and intact parathyroid hormone,were measured in baseline samples at the patients&#39; entry.The association between serum phosphorus and abdominal aortic calcification (AAC),left ventricular hypertrophy (LVH) were examined by logistic regression models.Results:Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml·min^- 1· 1.73 m^- 2 were included.The proportion of patients with hyperphosphatemia were 2.6%,2.9%,6.8%,and 27.1% in CKD Stages 3a,3b,4,and 5,respectively.Moreover,71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder (PB).Lateral abdominal X-rays were obtained in 2280 patients,9.8% of the patients were diagnosed as having AAC.Altogether 2219 patients had data of echocardiography,and 13.2% of them were diagnosed with LVH.Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH.Conclusions:In Chinese patients with CKD,the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal.The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population.展开更多
OBJECTIVE: To explore the effect of kidney-rein- forcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone mar- row mesenchymal stem cells (MSCs) from patients with chronic aplas...OBJECTIVE: To explore the effect of kidney-rein- forcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone mar- row mesenchymal stem cells (MSCs) from patients with chronic aplastic anemia (CAA). METHODS: We used three Traditional Chinese Medicine recipes, namely a kidney-reinforcing recipe (KRR), blood-activating and stasis-removing recipe (BASRR), and kidney-reinforcing, blood-activating and stasis-removing recipe (KRBASFIR), and a nor- mal saline control to prepare herbal medicine se- rum in Sprague Dawley rats. Thirty CAA patients were enrolled in the experimental group, including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients. Ten healthy individuals were included in the control group. MSCs were isolated from bone marrow samples, and the cell density was observed to measure their proliferation ability by microscopy on days 2, 7, and 14 after isolation. In addition, the expression of adhesion molecules of bone marrow MSCs (CD106, CD49d, CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medi- cine serums. RESULTS: The proliferation of MSCs from kid- ney-Yang deficient and kidney-Yin deficient pa- tients was weaker than that of MSCs from the con- trol group. The expression of all adhesion mole- cules of bone marrow MSCs from CAA patients was obviously lower than that in the control group (P〈 0.01). The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was low- er than in those with a kidney-yang deficiency (P〈 0.05 and P〈O.01, respectively). For kidney-Yang defi- cient patients, CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group (P〈O.01), while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈O.01). For kidney-Yin defi- cient patients, CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group (P〈0.05), while CD31 and CD44 ex- pression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈 0.05 and P〈0.01, respectively). CONCLUSION: The bone marrow microenviron- ment in CAA patients is abnormal. The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin de- ficient patients by improving the expression levels of MSC adhesion molecules.展开更多
基金financially supported by Shenzhen Agricultural Development Special Fund(Fishery)Agricultural High-Tech Project([2021]735)the Shenzhen Science and Technology Innovation Commission(KCXFZ20201221173207022)Youth Science Foundation Project(32101936)。
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by Grants-in-Aid for Young Scientists(B)(No.15K18454 to Tsujimura T)Scientific Research(B)(No.15H03001 to Hishikawa K)Scientific Research(C)(Nos.25461208 to Takase O,15K09244 to Yoshikawa M and 26462400 to Idei M)from the Japan Society for the Promotion of Science
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China (81371173)the Program for New Century Excellent Talents in University (NCET-12-0379)+1 种基金Sichuan Provincial Government Grant (2013JQ0017)supported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘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.
文摘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.
文摘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.
文摘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.
文摘To evaluate the operative characteristics and efficacy of retroperitoneoscopic resection of renal,ureter and partial bladder for the treatment of native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.Methods In 5 cases of renal transplantation,there were 2 cases of right native renal pelvic cancer,1 case of right native renal pelvic and ureter cancer and 2 cases of right ureter cancer respectively.The transplanted kidney was in the same iliac fossa side of the tumor.All 5 patients were subjected to nephroureterectomy and bladder cuff excision by retroperitoneoscopic technique.Results Five operations were completed successfully.The operative time was 180 to 280 min,and the blood loss was 50 to 200 ml.The recovery of intestinal function after operation was 12 to 36 h.The urine output was 1 500 to 4 000 per day.Postoperative serum creatinine was still normal.The mean hospital stay after operation was 4.5 days.Conclusion Retroperitoneal laparoscopic nephroureterectomy and bladder cuff excision is a good method to treat the native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.The procedure is safe and less invasive,which provides a good protection of transplanted kidney.12 refs.
基金Supported by the Major Science and Technology Special Project of Zhejiang Province to TONG Pei-jian(No.2014C03035)the Zhejiang Provincial Major Science and Technology Project of Medical and Health of China to TONG Pei-jian(No.201487674)Cultivation Program for Innovative Talent Graduate Students to XU Tao-tao(No.311100G00901)from Zhejiang Chinese Medical University
文摘As a traditional concept of Chinese medicine(CM), the theory of "Shen(Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen deficiency as a pathological condition has a negative effect on the skeleton of body, specifically the disorder of bone homeostasis. Present studies indicate that Shen deficiency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal(HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue(osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.
文摘Background:Mineral and bone disorder (MBD),especially hyperphosphatemia,is an independently risk factor for adverse prognosis in patients with chronic kidney disease (CKD).However,CKD-MBD among Chinese population was poorly studied.This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD.Methods:Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) is a prospective multicenter cohort study involving predialysis CKD patients in China.Markers of MBD,including serum phosphorus,calcium,and intact parathyroid hormone,were measured in baseline samples at the patients&#39; entry.The association between serum phosphorus and abdominal aortic calcification (AAC),left ventricular hypertrophy (LVH) were examined by logistic regression models.Results:Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml·min^- 1· 1.73 m^- 2 were included.The proportion of patients with hyperphosphatemia were 2.6%,2.9%,6.8%,and 27.1% in CKD Stages 3a,3b,4,and 5,respectively.Moreover,71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder (PB).Lateral abdominal X-rays were obtained in 2280 patients,9.8% of the patients were diagnosed as having AAC.Altogether 2219 patients had data of echocardiography,and 13.2% of them were diagnosed with LVH.Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH.Conclusions:In Chinese patients with CKD,the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal.The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population.
基金Supported by 2011 Zhejiang province key science and technology innovation team(No.2011R09042-02)Special Item of Important Disease of Zhejiang Province TCM Sci-Tech Innovation Platform(No.2009ZDJB01,2009ZDJB01-08)
文摘OBJECTIVE: To explore the effect of kidney-rein- forcing, blood-activating and stasis-removing recipes on adhesion molecule expression of bone mar- row mesenchymal stem cells (MSCs) from patients with chronic aplastic anemia (CAA). METHODS: We used three Traditional Chinese Medicine recipes, namely a kidney-reinforcing recipe (KRR), blood-activating and stasis-removing recipe (BASRR), and kidney-reinforcing, blood-activating and stasis-removing recipe (KRBASFIR), and a nor- mal saline control to prepare herbal medicine se- rum in Sprague Dawley rats. Thirty CAA patients were enrolled in the experimental group, including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients. Ten healthy individuals were included in the control group. MSCs were isolated from bone marrow samples, and the cell density was observed to measure their proliferation ability by microscopy on days 2, 7, and 14 after isolation. In addition, the expression of adhesion molecules of bone marrow MSCs (CD106, CD49d, CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medi- cine serums. RESULTS: The proliferation of MSCs from kid- ney-Yang deficient and kidney-Yin deficient pa- tients was weaker than that of MSCs from the con- trol group. The expression of all adhesion mole- cules of bone marrow MSCs from CAA patients was obviously lower than that in the control group (P〈 0.01). The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was low- er than in those with a kidney-yang deficiency (P〈 0.05 and P〈O.01, respectively). For kidney-Yang defi- cient patients, CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group (P〈O.01), while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈O.01). For kidney-Yin defi- cient patients, CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group (P〈0.05), while CD31 and CD44 ex- pression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups (P〈 0.05 and P〈0.01, respectively). CONCLUSION: The bone marrow microenviron- ment in CAA patients is abnormal. The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin de- ficient patients by improving the expression levels of MSC adhesion molecules.