Lowering Expectations with Niacin Treatment for CKD-MBD.
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ABSTRACT:
SUBMITTER: Drueke TB
PROVIDER: S-EPMC5753325 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
Lowering Expectations with Niacin Treatment for CKD-MBD.
Drüeke Tilman B TB Massy Ziad A ZA
Clinical journal of the American Society of Nephrology : CJASN 20171205 1
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Project description:BackgroundElevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT.MethodsUsing the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure.ResultsOf 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk.ConclusionReceiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.
| S-EPMC9585471 | biostudies-literature
Project description:Disturbances in mineral and bone metabolism have a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). The term 'renal osteodystrophy' has recently been replaced by 'CKD-mineral and bone disorder (CKD-MBD)', which includes abnormalities in bone and mineral metabolism and vascular calcification. The Japanese Society for Dialysis Therapy clinical practice guideline for the management of secondary hyperparathyroidism in chronic dialysis patients was originally published in Japanese in 2006, then in English in 2008. During the past 5 years, this first guideline has contributed to a considerably better understanding and control of secondary hyperparathyroidism in CKD patients by physicians, other medical professionals, and the patients themselves. However, since its publication several new therapeutic modalities have become available for Japanese dialysis patients, which added more evidence to this area. Thus, we revised the guideline to include several new policies, and the new guideline was published in Japanese in 2012. This article contains the new guideline text, and clinical significance of CKD-MBD in Japan.
| S-EPMC4089741 | biostudies-other
Project description:Purpose of reviewWe describe the mechanism of action of vitamin K, and its implication in cardiovascular disease, bone fractures, and inflammation to underline its protective role, especially in chronic kidney disease (CKD).Recent findingsVitamin K acts as a coenzyme of y-glutamyl carboxylase, transforming undercarboxylated in carboxylated vitamin K-dependent proteins. Furthermore, through the binding of the nuclear steroid and xenobiotic receptor, it activates the expression of genes that encode proteins involved in the maintenance of bone quality and bone remodeling. There are three main types of K vitamers: phylloquinone, menaquinones, and menadione. CKD patients, for several conditions typical of the disease, are characterized by lower levels of vitamin K than the general populations, with a resulting higher prevalence of bone fractures, vascular calcifications, and mortality. Therefore, the definition of vitamin K dosage is an important issue, potentially leading to reduced bone fractures and improved vascular calcifications in the general population and CKD patients.
| S-EPMC8821802 | biostudies-literature
Project description:Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early stages far exceeds the risk of progression to dialysis. The presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality. As a non-atheromatous process, it could be partially explained why standard CV disease-modifying drugs do not provide such an impact on CV mortality in CKD as observed in the general population. We summarize the potential association of CV comorbidities with the older (parathyroid hormone, phosphate) and newer (FGF23, Klotho, sclerostin) CKD-MBD biomarkers.
| S-EPMC7150959 | biostudies-literature
Project description:Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic disorder that affects blood measures of bone and mineral homeostasis, vascular calcification, and bone. We hypothesized that the accumulation of advanced glycation end-products (AGEs) in CKD may be responsible for the vascular and bone pathologies via alteration of collagen. We treated a naturally occurring model of CKD-MBD, the Cy/+ rat, with a normal and high dose of the AGE crosslink breaker alagebrium (ALT-711), or with calcium in the drinking water to mimic calcium phosphate binders for 10 weeks. These animals were compared to normal (NL) untreated animals. The results showed that CKD animals, compared to normal animals, had elevated blood urea nitrogen (BUN), PTH, FGF23 and phosphorus. Treatment with ALT-711 had no effect on kidney function or PTH, but 3 mg/kg lowered FGF23 whereas calcium lowered PTH. Vascular calcification of the aorta assessed biochemically was increased in CKD animals compared to NL, and decreased by the normal, but not high dose of ALT-711, with parallel decreases in left ventricular hypertrophy. ALT-711 (3 mg/kg) did not alter aorta AGE content, but reduced aorta expression of receptor for advanced glycation end products (RAGE) and NADPH oxidase 2 (NOX2), suggesting effects related to decreased oxidative stress at the cellular level. The elevated total bone AGE was decreased by 3 mg/kg ALT-711 and both bone AGE and cortical porosity were decreased by calcium treatment, but only calcium improved bone properties. In summary, treatment of CKD-MBD with an AGE breaker ALT-711, decreased FGF23, reduced aorta calcification, and reduced total bone AGE without improvement of bone mechanics. These results suggest little effect of ALT-711 on collagen, but potential cellular effects. The data also highlights the need to better measure specific types of AGE proteins at the tissue level in order to fully elucidate the impact of AGEs on CKD-MBD. © 2019 American Society for Bone and Mineral Research.
| S-EPMC9030558 | biostudies-literature
Project description:BackgroundChronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD.MethodsThis is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants.FindingsAllopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase.ConclusionThese data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.
| S-EPMC6200237 | biostudies-literature
Project description:IntroductionPatterns of testing, treatment, and retesting following treatment for disorders of chronic kidney disease mineral bone disorder (CKD-MBD) have not been explored using a large electronic database.MethodsTo determine concordance with CKD-MBD management guidelines, we used 2010 to 2019 data from an electronic health record (>50 million patients) to create cohorts of incident CKD stage 3, 4, and 5 patients using diagnosis codes and estimated glomerular filtration rates. The CKD-MBD test ordering and relevant drug prescribing were assessed during follow-up. We estimated cumulative incidence of posttreatment retesting (death as competing risk). We used multivariable Cox regression to examine baseline characteristics and pretreatment test results as predictors of retesting.ResultsFor 215,553 stage 3, 43,576 stage 4, and 11,407 stage 5 CKD patients, the mean follow-up was 2.3, 1.7, and 0.6 years, respectively. Only 46% of stage 4 and 41% of stage 5 patients underwent parathyroid hormone (PTH) testing, 74% and 73% had phosphorus testing, and 38% and 25% had 25D testing. By 1 year after vitamin D sterol treatment, only 50%, 53%, and 60% of stage 3, 4, and 5 patients had been retested for PTH. By 1 year after treatment with ergocalciferol or cholecalciferol, only 46%, 49%, and 55% had 25D reassessed. Pretreatment levels of PTH and 25D were not associated in a graded fashion with likelihood of retesting after treatment. Rates of retesting were not highest for patients with the highest and lowest pre-treatment PTH and 25D levels, respectively.ConclusionFrequency of testing for CKD-MBD abnormalities and posttreatment retesting appears to be suboptimal.
| S-EPMC8071625 | biostudies-literature
Project description:BackgroundThe longitudinal changes in hip-bone microstructures and estimated bone strength in dialysis patients, and the impact of chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers on these changes, remain insufficiently explored.MethodsThis retrospective study examined changes in cortical and trabecular bone compartments and estimated bone-strength indices, obtained by using 3D-SHAPER software, in the hip regions of 276 dialysis patients over up to 2.5 years. We used multivariate mixed models to investigate the associations between time-dependent CKD-MBD biomarkers and bone health metrics.ResultsThere was a significant decrease in areal bone mineral density (aBMD), integral volumetric BMD (vBMD), trabecular vBMD, cortical thickness and cortical surface BMD (sBMD). Similar deteriorations were found in estimated bone-strength indices [cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (SM) and buckling ratio]. Neither serum calcium nor phosphate levels were significantly associated with changes in three-dimensional parameters or estimated bone-strength indices. In contrast, serum alkaline phosphatase levels showed a significant inverse correlation with aBMD and CSA. The intact-parathyroid hormone (i-PTH) was significantly inversely correlated with aBMD, integral vBMD, trabecular vBMD, cortical thickness, cortical vBMD, CSA, CSMI and SM. When applying the KDIGO criteria as a sensitivity analysis, the higher PTH group had significant negative associations with aBMD, integral vBMD, cortical vBMD, cortical thickness and cortical sBMD. Notably, the lower PTH group showed a positive significant correlation with integral vBMD and trabecular vBMD.ConclusionsElevated PTH, not low PTH, was associated with deterioration of hip-bone microstructures. Better management of PTH levels may play a crucial role in the hip-bone microstructure in dialysis patients.
| S-EPMC11345638 | biostudies-literature
Project description:BackgroundChronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis patients remains mostly unknown. We investigated the associations between parathyroid hormone (PTH), phosphate and calcium (and their interactions), and all-cause, cardiovascular (CV) and non-CV mortality in older non-dialysis patients with advanced CKD.MethodsWe used data from the European Quality study, which includes patients aged ≥65 years with estimated glomerular filtration rate ≤20 mL/min/1.73 m2 from six European countries. Sequentially adjusted Cox models were used to assess the association between baseline and time-dependent CKD-MBD biomarkers and all-cause, CV and non-CV mortality. Effect modification between biomarkers was also assessed.ResultsIn 1294 patients, the prevalence of CKD-MBD at baseline was 94%. Both PTH [adjusted hazard ratio (aHR) 1.12, 95% confidence interval (CI) 1.03-1.23, P = .01] and phosphate (aHR 1.35, 95% CI 1.00-1.84, P = .05), but not calcium (aHR 1.11, 95% CI 0.57-2.17, P = .76), were associated with all-cause mortality. Calcium was not independently associated with mortality, but modified the effect of phosphate, with the highest mortality risk found in patients with both hypercalcemia and hyperphosphatemia. PTH level was associated with CV mortality, but not with non-CV mortality, whereas phosphate was associated with both CV and non-CV mortality in most models.ConclusionsCKD-MBD is very common in older non-dialysis patients with advanced CKD. PTH and phosphate are independently associated with all-cause mortality in this population. While PTH level is only associated with CV mortality, phosphate seems to be associated with both CV and non-CV mortality.
| S-EPMC10615632 | biostudies-literature
Project description:Chronic kidney disease (CKD) is a modern day epidemic and has significant morbidity and mortality implications. Mineral and bone disorders are common in CKD and are now collectively referred to as CKD- mineral and bone disorder (MBD). These abnormalities begin to appear even in early stages of CKD and contribute to the pathogenesis of renal osteodystrophy. Alteration in vitamin D metabolism is one of the key features of CKD-MBD that has major clinical and research implications. This review focuses on biology, epidemiology and management aspects of these alterations in vitamin D metabolism as they relate to skeletal aspects of CKD-MBD in adult humans.
| S-EPMC3944129 | biostudies-other