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.

Identification of differentially expressed miRNAs associated with chronic kidney disease-mineral bone disorder

The purpose of this study is to characterize a meta-signature of differentially expressed mRNA in chronic kidney disease （CKD） to predict putative microRNA （miRNA） in CKD-mineral bone disorder （CKD- MBD） and confirm the changes in these genes and miRNA expression under uremic conditions by using a cell culture system. PubMed searches using MeSH terms and keywords related to CKD, uremia, and mRNA arrays were conducted. Through a computational analysis, a meta-signature that characterizes the significant intersection of differentially expressed mRNA and expected miRNAs associated with CKD-MBD was determined. Additionally, changes in gene and miRNA expressions under uremic conditions were confirmed with human Saos-2 osteoblast-like cells. A statistically significant mRNA meta-signature of upregulated and downregulated mRNA levels was identified. Furthermore, miRNA expression profiles were inferred, and computational anaIyses were performed with the imputed mieroRNA regulation based on weighted ranked expression and putative microRNA targets （IMRE） method to identify miRNAs associated with CKD occurrence. TLR4 and miR-146b levels were significantly associated with CKD-MBD. TLR4 levels were significantly downregulated, whereas pri- miR-146b and miR-146b were upregulated in the presence of uremic toxins in human Saos-2 osteoblast-like cells. Differentially expressed miRNAs associated with CKD-MBD were identified through a computational analysis, and changes in gene and miRNA expressions were confirmed with an in vitro cell culture system.

Mineral and Bone Disorder and Its Association with Cardiovascular Parameters in Chinese Patients with Chronic Kidney Disease

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.

Central blood pressure and chronic kidney disease

In this review, we focused on the relationship between central blood pressure and chronic kidney diseases(CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular(CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders(MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD.

Correlation between Vascular Calcification and Serum Sclerostin in MHD Patients

Objective Investigate the correlation between serum sclerostinlevel and chronic kidney disease-mineral and bone disorder(CKD-MBD),especially vascular calcification,in maintenance hemodialysis(MHD)patients.Methods This is across-sectional study,a total of 72 MHD patients were included from the first affiliated hospital of Jinan university.Measure the biochemical indicators of mineral metabolism,renal function,and serum sclerostin level by ELISA.The abdominal aorta calcification score(AACS)was assessed according to Kauppila method on lateral spine imaging using DEXA.Patients were distributed into two groups according to the level of serum sclerostin:low sclerostingroup(≤125 pg/ml)and high sclerostingroup(>125 pg/ml).Analyze the association of serum sclerostin level with the indicators of CKD-MBD.Results There was significant difference in i PTH level between high sclerost in group and low sclerost in group.Multivariate Logistic regression analysis demonstrated that dialysis duration,male and anuria were independent risk factor of high sclerostin level,and i PTH and Kt/V were protective factors.Conclusion Dialysis duration,man,anuria was independent risk factors and i PTH,Kt/V were protective factors of high serum sclerostin level in MHD patients.There was no correlation between abdominal aorta calcification and serum sclerostin level.