Effects of osteoporosis medications on bone fracture in patients with chronic kidney disease.

PURPOSE OF THE STUDY: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. STUDY DESIGN: Patients with stage 3-5 CKD during 2011-2019 were enrolled. Patients were divided into two groups based on receiving osteoporosis medications (bisphosphonates, raloxifene, teriparatide or denosumab) or not. Two groups were matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors. Additional stratified analyses by cumulative dose, treatment length and menopause condition were performed. RESULTS AND CONCLUSIONS: 67 650 patients were included. After propensity score matching, 1654 patients were included in the study and control group, respectively. The mean age was 70.2±12.4 years, and 32.0% of patients were men. After a mean follow-up of 3.9 years, the incidence rates of bone fracture, CV events and all-cause mortality were 2.0, 1.7 and 6.5 per 1000 person-months, respectively. Multivariate analysis results showed that osteoporosis medications reduced the risk of CV events (HR, 0.35; 95% CI, 0.18 to 0.71; p = 0.004), but did not alleviate the risks of bone fracture (HR, 1.48; 95% CI, 0.73 to 2.98; p = 0.28) and all-cause mortality (HR, 0.93; 95% CI, 0.67 to 1.28; p = 0.65). Stratified analysis showed that bisphosphonates users have most benefits in the reduction of CV events (HR, 0.26; 95% CI, 0.11 to 0.64; p = 0.003). In conclusion, osteoporosis medications did not reduce the risk of bone fractures, or mortality, but improved CV outcomes in patients with CKD.

Development of an enrichment-free one-pot sample preparation and ultra-high performance liquid chromatography-tandem mass spectrometry method to identify Immunoglobulin A1 hinge region O-glycoforms for Immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is a highly prevalent autoimmune renal disease. Human IgA1 with galactose deficiency in the hinge region (HR) has been identified as an autoantigen for this disease. Therefore, analyzing IgA1 HR glycoforms in biofluids is important for biomarker discovery. Herein, an analytical method that includes one-pot sample preparation with unbiased plasma IgA purification, dual internal standard addition, and sensitive ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectroscopy (UHPLC-QqQ-MS/MS) was developed. Targeted O-glycopeptides detection was performed in pooled plasma with the validation of theoretical retention times, enzymatic treatment outcomes, product ion scans, and signal repeatability. A total of 42 IgA1 O-glycopeptides with N-acetylgalactosamines, galactoses, and sialic acids were determined from 8 µL of plasma. The newly developed method was applied to plasma samples from 16 non-IgAN controls and 19 IgAN patients. Comparing the 42 targets, 16 IgA1 HR O-glycopeptides were statistically different between the two groups (p<0.05). Decreased sialylation was identified in the IgA1 hinge region of IgAN patients, which was also correlated with the estimated glomerular filtration rate (eGFR). The developed method is sensitive and precise and can be used to identify plasma biomarkers for IgA nephropathy.

A Consistency Model for Identifying the Effects of n-3 and n-6 Fatty Acids on Lipoproteins in Dialysis Patients.

Numerous randomized controlled trials (RCTs) and meta-analyses have assessed the effects of supplemental dietary polyunsaturated fatty acids (PUFAs) on levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) and the LDL/HDL ratio in patients receiving renal replacement therapy (RRT). However, results are ambiguous due to mixed reports of various nutrients used in the intervention group. We performed a network meta-analysis of RCTs to assess the effects of PUFAs on lipid profiles in patients undergoing RRT. RCTs performed before November 2021 were gathered from three databases. The means, standard deviations and the number of cases for each arm were independently extracted by two authors to form a network meta-analysis of LDL and HDL levels and the LDL/HDL ratio in a random effects model. Twenty-eight RCTs (n = 2017 subjects) were included in this study. The pooled results revealed that the combination of omega-3 fatty acids (n-3) and omega-6 fatty acids (n-6) produced significantly lower LDL (standardized mean difference (SMD) = -1.43, 95% confidence interval: -2.28 to -0.57) than the placebo. Both n-3 fatty acids (SMD = 0.78) and the combination of n-3 + n-6 (SMD = 1.09) benefited HDL significantly compared with placebo. Moreover, n-3 alone also exhibited a significantly lower LDL/HDL ratio than placebo. Collectively, PUFAs seem to be adequate nutrients for controlling lipoproteins in patients undergoing RRT. Specifically, n-3 + n-6 supplementation improved LDL levels, while n-3 improved HDL levels and the LDL/HDL ratio. However, our data provide limited information on specific dosages of PUFAs to form a concrete recommendation.

Effects of osteoporosis medications on bone fracture in patients with chronic kidney disease.

PURPOSE OF THE STUDY: The risk of bone fracture is high in patients with chronic kidney disease (CKD), and aggressive treatment to reduce fragility fracture risk is the major strategy. However, the outcomes of osteoporosis medications in patients with CKD remain unclear. STUDY DESIGN: Patients with stage 3-5 CKD during 2011-2019 were enrolled. Patients were divided into two groups based on receiving osteoporosis medications (bisphosphonates, raloxifene, teriparatide or denosumab) or not. Two groups were matched at a 1:1 ratio by using propensity scores. The outcomes of interest were bone fractures, cardiovascular (CV) events and all-cause mortality. Cox proportional hazard regression models were applied to identify the risk factors. Additional stratified analyses by cumulative dose, treatment length and menopause condition were performed. RESULTS AND CONCLUSIONS: 67 650 patients were included. After propensity score matching, 1654 patients were included in the study and control group, respectively. The mean age was 70.2±12.4 years, and 32.0% of patients were men. After a mean follow-up of 3.9 years, the incidence rates of bone fracture, CV events and all-cause mortality were 2.0, 1.7 and 6.5 per 1000 person-months, respectively. Multivariate analysis results showed that osteoporosis medications reduced the risk of CV events (HR, 0.35; 95% CI, 0.18 to 0.71; p = 0.004), but did not alleviate the risks of bone fracture (HR, 1.48; 95% CI, 0.73 to 2.98; p = 0.28) and all-cause mortality (HR, 0.93; 95% CI, 0.67 to 1.28; p = 0.65). Stratified analysis showed that bisphosphonates users have most benefits in the reduction of CV events (HR, 0.26; 95% CI, 0.11 to 0.64; p = 0.003). In conclusion, osteoporosis medications did not reduce the risk of bone fractures, or mortality, but improved CV outcomes in patients with CKD.

Alterations of bone markers in obese patients with type 2 diabetes after bariatric surgery: A meta-analysis and systemic review of randomized controlled trials and cohorts.

BACKGROUND: The aim of this study is to evaluate the alterations in bone mineral density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control. METHODS: We searched 4 electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide level, and parathyroid hormone level. RESULTS: Three randomized clinical trials and 2 observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: -2.90, 95% CI: -2.99∼-2.81, P < .00001) and total hip BMD loss (mean difference: -5.81, 95% CI: -9.22∼-2.40, P = .0008). As to biochemical markers of bone metabolism, we found significantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57-13.75, P < .00001). However, higher C-terminal telopeptide level and parathyroid hormone level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11-0.48, P = .002; mean difference: 1.56, 95% CI: 0.84-2.27, P < .0001). CONCLUSIONS: RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of perioperative and postsurgical supplementation should be evaluated.

Efficacy of Polyunsaturated Fatty Acids on Inflammatory Markers in Patients Undergoing Dialysis: A Systematic Review with Network Meta-Analysis of Randomized Clinical Trials.

The effects of polyunsaturated fatty acids (PUFAs) on inflammatory markers among patients receiving dialysis have been discussed for a long time, but previous syntheses made controversial conclusion because of highly conceptual heterogeneity in their synthesis. Thus, to further understanding of this topic, we comprehensively gathered relevant randomized clinical trials (RCTs) before April 2019, and two authors independently extracted data of C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) for conducting network meta-analysis. Eighteen eligible RCTs with 962 patients undergoing dialysis were included in our study. The result showed that with placebo as the reference, PUFAs was the only treatment showing significantly lower CRP (weighted mean difference (WMD): -0.37, 95% confidence interval (CI): -0.07 to -0.68), but the CRP in PUFAs group was not significantly lower than vitamin E, PUFAs plus vitamin E, or medium-chain triglyceride. Although no significant changes were noted for hs-CRP and IL-6 levels, PUFAs showed the best ranking among treatments according to surface under the cumulative ranking. Therefore, PUFAs could be a protective option for patients receiving dialysis in clinical practice.

Different Effects of Iron Indices on Mortality in Patients With Autosomal Dominant Polycystic Kidney Disease After Long-Term Hemodialysis: A Nationwide Population-Based Study.

OBJECTIVE: Iron supplementation and erythropoietin stimulating agents (ESAs) are essential for maintaining hemoglobin levels in hemodialysis patients. However, patients with autosomal-dominant polycystic kidney disease (PKD) have higher endogenous erythropoietin levels, so their recommended iron indices for hemodialysis patients may differ. This study evaluated iron profiles, including ferritin levels and transferrin saturation (TSAT) to identify factors affecting mortality in patients on dialysis, and those associated with mortality in patients with and without PKD. DESIGN: This cohort study from the Taiwan Renal Registry Data System stratified mortality risk by the presence of PKD recorded as the underlying disease. SUBJECTS: We enrolled 1346 hemodialysis patients with PKD and 82,873 hemodialysis patients without PKD. MAIN OUTCOME MEASURE: The primary outcome was 3-year all-cause mortality. Predictors included time-averaged and baseline serum ferritin levels and TSAT. Multivariate Cox regression analysis adjusting for age, comorbidities, and relevant laboratory parameters was used to estimate the all-cause hazard ratios (HRs) for mortality. RESULTS: The mean ages of patients with and without PKD were 56.2±13.2 and 61.7±13.5 years and the median follow-up time was 37 (15-76) months. The adjusted mortality risks for time-averaged ferritin levels >800 ng/mL (HR=1.52; 95% confidence interval: 1.40-1.65) or TSAT levels >50% (HR=1.46; 95% confidence interval: 1.30-1.65) were significantly higher among patients without PKD than those for patients with normal iron indices. However, a U-shaped curve of mortality against ferritin/TSAT levels was not observed in patients with PKD. In the sensitivity test, there was no difference among PKD patients who underwent regular ESA therapy and those who did not. CONCLUSION: Iron indices have different effects on mortality among patients with and without PKD. Iron supplementation, recommended serum ferritin levels, or TSAT should be monitored in hemodialysis patients, especially those without PKD. Clinicians should consider treating anemia in hemodialysis patients individually, especially in PKD.