Currently Used Methods to Evaluate the Efficacy of Therapeutic Drugs and Kidney Safety.

Kidney diseases with kidney failure or damage, such as chronic kidney disease (CKD) and acute kidney injury (AKI), are common clinical problems worldwide and have rapidly increased in prevalence, affecting millions of people in recent decades. A series of novel diagnostic or predictive biomarkers have been discovered over the past decade, enhancing the investigation of renal dysfunction in preclinical studies and clinical risk assessment for humans. Since multiple causes lead to renal failure, animal studies have been extensively used to identify specific disease biomarkers for understanding the potential targets and nephropathy events in therapeutic insights into disease progression. Mice are the most commonly used model to investigate the mechanism of human nephropathy, and the current alternative methods, including in vitro and in silico models, can offer quicker, cheaper, and more effective methods to avoid or reduce the unethical procedures of animal usage. This review provides modern approaches, including animal and nonanimal assays, that can be applied to study chronic nonclinical safety. These specific situations could be utilized in nonclinical or clinical drug development to provide information on kidney disease.

Comparison of Humoral Antibody Responses and Seroconversion Rates between Two Homologous ChAdOx1 nCoV-19 and mRNA-1273 Vaccination in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND: Hemodialysis patients are at an increased risk of SARS-CoV-2 infection and are excluded from preauthorization COVID-19 vaccine trials; therefore, their immunogenicity is uncertain. METHODS: To compare the antibody responses to homologous ChAdOx1 and mRNA-1273 SARS-CoV-2 vaccination in hemodialysis patients, 103 age- and sex-matched hemodialysis patients with two homologous prime-boost vaccinations were recruited to detect anti-receptor-binding domain (RBD) IgG levels and seroconversion rates (SCRs) 14 days after a prime dose (PD14), before and 28 days after a boost dose (pre-BD0 and BD28). RESULTS: Both mRNA-1273 and ChAdOx1 vaccinations elicited immunogenicity in study subjects, and the former induced higher anti-RBD IgG levels than the latter. The SCRs of both groups increased over time and varied widely from 1.82% to 97.92%, and were significantly different at PD14 and pre-BD0 regardless of different thresholds. At BD28, the SCRs of the ChAdOx1 group and the mRNA-1273 group were comparable using a threshold ≥ 7.1 BAU/mL (93.96% vs. 97.92%) and a threshold ≥ 17 BAU/mL (92.73% vs. 97.92%), respectively, but they were significantly different using a threshold ≥ 20.2% of convalescent serum anti-RBD levels (52.73% vs. 95.83%). The seroconversion (≥20.2% of convalescent level) at BD28 was associated with mRNA-1273 vaccination after being adjusted for age, sex, body mass index, and the presence of solicited reactogenicity after a prime vaccination. CONCLUSION: Our prospective, observational cohort indicates that a full prime-boost mRNA-1273 vaccination is likely to provide higher immune protection in hemodialysis patients compared to ChAdOx1, and this population with a prime-boost ChAdOx1 vaccination should be prioritized for a third dose.

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.

Economic Analysis of a Ketoanalogue-Supplemented Very Low-Protein Diet in Patients With Chronic Kidney Disease in Taiwan and Thailand.

OBJECTIVE: A vegetarian very low-protein diet (VLPD) supplemented with ketoanalogues of essential amino acids Ketoanalogue-supplemented very low-protein diet (sVLPD) delays dialysis initiation in patients with chronic kidney disease (CKD). In this cost-effectiveness analysis, we compare an sVLPD with a conventional low-protein diet (LPD) in patients with CKD stage 4-5 using data from Taiwan and Thailand. DESIGN AND METHODS: A Markov model simulated health outcomes and care costs in patients receiving an sVLPD (0.3-0.4 g/kg-day, vegetarian diet) supplemented with ketoanalogues (1 tablet/5 kg-day) or an LPD (0.6 g/kg-day, mixed proteins). Health state transition probability and resource cost inputs were based on published literature and local sources, respectively. RESULTS: An sVLPD increased survival and quality-adjusted life years (QALYs) at a lower cost than an LPD. Total cost of care in Taiwan was 2,262,592.30 New Taiwan dollars (NTD) (68,059.35 EUR) with an LPD and 1,096,938.20 NTD (32,996.18 EUR) with an sVLPD (difference -1,165,654.10 NTD; -35,063.17 EUR). Total cost of care in Thailand was 500,731.09 Thai baht (THB) (14,584.12 EUR) with an LPD and 421,019.22 THB (12,262.46 EUR) with an sVLPD (difference -79,711.86 THB; -2,321.66 EUR). CONCLUSION: A ketoanalogue-supplemented vegetarian sVLPD increased QALYs and lowered lifetime care costs versus an LPD in patients with predialysis CKD in Taiwan and Thailand. These data, together with the new KDOQI Guidelines for nutrition in CKD, support dietary intervention using ketoanalogue-supplemented vegetarian sVLPDs to prevent CKD progression and postpone dialysis as a cost-effective approach, with beneficial effects for patients and health care providers.

Factors Influencing Self-Management Behaviors among Hemodialysis Patients.

AIM: To investigate the factors affecting hemodialysis patients' self-management ability at a dialysis center in Taiwan. BACKGROUND: Taiwan has the highest incidence and prevalence of end-stage kidney disease (ESKD) in the world. Over 90% of patients with ESKD receiving hemodialysis (HD) and self-management behaviors are critical among these patients. Failure to adhere to self-managed care increases the cost of medical care and the risk of morbidity and mortality. METHODS: In this cross-sectional study, a total of 150 HD patients were observed for their self-management behaviors and the factors influencing these behaviors including education level, comorbid conditions, biochemical analysis, depression, and social support, etc., were analyzed. RESULTS: Self-management behaviors in HD patients were significantly impaired in the presence of diabetes mellitus, hypertension, anemia, hypoalbuminemia, and depression. The major predictor of patients' self-management was depression, explaining 14.8% of the total variance. Further addition of social support, hypertension, and diabetes mellitus into the regression model increased the total explained variance to 28.6%. Of the various domains of self-management, the partnership domain received the highest score, whereas emotional processing received the lowest score. CONCLUSIONS: This study found the important factors influencing self-management behaviors; through this acknowledgement and early correction of these factors, we hope to improve HD patients' individual life quality and further decrease their morbidity and mortality.

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.

Effect of Dialysis Modalities on All-Cause Mortality and Cardiovascular Mortality in End-Stage Kidney Disease: A Taiwan Renal Registry Data System (TWRDS) 2005-2012 Study.

Introduction: End-stage kidney disease (ESKD) patients who need renal replacement therapy need to face a dialysis modality decision: the choice between hemodialysis (HD) and peritoneal dialysis (PD). Although the global differences in HD/PD penetration are affected by health-care policies, these two modalities may exert different effects on survival in patients with ESKD. Although Taiwan did not implicate PD as first policy, we still need to compare patients' outcomes using two modalities in a nation-wise database to determine future patients' care and health policies. Methods: We used the nationwide Taiwan Renal Registry Data System (TWRDS) database from 2005 to 2012 and included 52,900 patients (48,371 on HD and 4529 on PD) to determine all-cause and cardiovascular mortality among ESKD patients. Results: Age-matched survival probability from all-cause mortality was significantly lower in patients on PD than in those on HD (p < 0.05). The adjusted hazard ratios of 3-year and 5-year all-cause and cardiovascular mortality were significantly higher in PD compared with HD. The presence of comorbid conditions including myocardial infarction, coronary artery disease (CAD), diabetes mellitus (DM), hypoalbuminemia, hyperferritinemia and hypophosphatemia was related with significantly higher all-cause and CV mortality in PD patients. No significant difference was noted among younger patients <45 years of age regardless of DM and/or comorbid conditions. Conclusion: Although PD did not have the survival advantage compared to HD in all dialysis populations, PD was related with superior survival in younger non-DM patients, regardless of the presence of comorbidities. Similarly, for younger ESKD patients without the risk of CV disease, both PD and HD would be suitable dialysis modalities.

The Effect of Statin on Anemia in Patients with Chronic Kidney Disease and End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Although erythropoietin-stimulating agents are effective in treating anemia in patients with end-stage kidney disease (ESKD) undergoing hemodialysis, some ESKD patients, especially those with inflammation, continue to suffer from anemia. Statin, an inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase with lipid-lowering effects, may have a pleiotropic effect in reducing inflammation, and thus increase hemoglobin (Hb) level. We searched the PubMed, Embase, and Cochrane databases for relevant studies. The population of interest comprised advanced chronic kidney disease (CKD) patients and ESKD patients receiving hemodialysis with statin treatment. The included study designs were randomized control trial/cohort study/pre-post observational study, and outcomes of interest were Hb, erythropoietin resistance index (ERI) and ferritin. PRISMA 2020 guidelines were followed, and risk of bias (RoB) was assessed using the RoB 2.0 tool in randomized controlled trials, and the Newcastle-Ottawa scale (NOS) in cohort studies. We eventually included ten studies (5258 participants), comprising three randomized controlled trials and seven cohort studies. Overall, Hb increased by 0.84 g/dL (95% confidence interval [CI]: -0.02 to 1.70) in all groups using statins, including single-arm cohorts, and by 0.72 g/dL (95% CI: -0.02 to 1.46) in studies with placebo control. Hb levels were higher in the study group than in the control group, with a mean difference of 0.18 g/dL (95% CI: 0.04-0.32) at baseline and 1.0 g/dL (95% CI: 0.13-1.87) at the endpoint. Ferritin increased by 9.97 ng/mL (95% CI: -5.36 to 25.29) in the study group and decreased by 34.01 ng/mL (95% CI: -148.16 to 80.14) in the control group; ferritin fluctuation was higher in the control group. In conclusion, statin may improve renal anemia in ESKD patients receiving hemodialysis and regular erythropoietin-stimulating agents. Future studies with more rigorous methodology and larger sample size study should be performed to confirm this beneficial effect.

The Humoral Immune Response of the ChAdOx1 nCoV-19 Vaccine in Maintenance Dialysis Patients without Prior COVID-19 Infection.

BACKGROUND: Chronic kidney disease (CKD) patients tend to have a reduced immune response to infection and vaccination. The efficacy of current available COVID-19 vaccines in CKD patients has not been widely evaluated. METHODS: In the present study, three hundred and eight chronic dialysis patients received ChAdOx1 nCoV-19 (Oxford-AstraZeneca, AZ). Blood tests using an antibody against the receptor-binding domain (RBD) of the S1 subunit of the SARS-CoV-2 spike protein had performed at four designed time points before and after the first and second vaccine. RESULTS: The mean age of patients was 65.5 ± 12.38 years, and the male/female ratio was 61.4%:38.6% (189/119). Two weeks after the first vaccination, only 37.66% of patients had a positive antibody response (>50 AU/mL). However, 65.58% of the participants showed a delayed antibody response ten weeks after the first vaccine. Four weeks after the second vaccine, 94.16% of participants had positive antibody levels. Age was the most significant factor associated with antibody response. Flow cytometry analysis revealed that immune-naïve patients had significantly lower early active B cells and proliferative B cells than the age- and sex-matched immune responders. CONCLUSION: Despite a delayed response, 94.16% of chronic dialysis patients achieved a positive antibody response after two doses of the AZ vaccine. Age is the most significant factor associated with antibody response.

Endoloop-Assisted Polypectomy for a Symptomatic Giant Colonic Polyp in a Pediatric Patient.

Colonic polyps are a common cause of persistent bloody stools in pediatric patients. Such polyps are easily diagnosed by a barium study of the lower gastrointestinal tract or by colonoscopy. Polypectomies utilizing electric ligators are generally performed on pediatric patients, and such patients can be easily operated on. However, giant colonic polyps have been reported in pediatric patients. In the past, a laparotomy or laparoscopy would have been performed in some pediatric patients diagnosed with a giant colonic polyp; however, the large size, location, or position of the polyp would sometimes be too large or the location or position of the polyp would make successful operation difficult. In general, larger stumps with large feeding arteries are associated with larger colonic polyps. Therefore, if such a polyp is removed via electric polypectomy alone, there may be a higher risk of post-polypectomy bleeding from its stump. We report a case of a 14-year-old male patient who presented with a 2-month history of bloody stools. A giant juvenile colonic polyp was detected by colonoscopy in the transverse colon. Finally, we successfully removed the giant polyp by using endoloop-assisted polypectomy.

Clinical characteristics and outcomes of patients requiring incident dialysis in Taiwan.

BACKGROUND: Despite having a well-established pre-end-stage kidney disease (pre-ESKD) care program, Taiwan has a high incidence of ESKD. Unrecovered incident dialysis may lead to the maintenance of dialysis. Contrast medium (CM) or general anesthesia (GA) may also induce dialysis. We aimed to examine the trends for incident dialysis, use of CM or GA, and its long-term trajectory outcomes. METHODS: Patients who received at least one dialysis intervention between 2010 and 2017 were identified using the National Health Insurance Research Database. We collected information on age, sex, comorbidities, causes of dialysis in outpatient or inpatient settings, use of CM or GA or pre-ESKD program enrolment before incident dialysis, and trajectory outcomes. RESULTS: Incident dialysis occurred more frequently in elderly inpatients with infectious diseases or previous chronic kidney disease (CKD). The number of patients who had a pre-ESKD care plan before incident dialysis increased from 25% in 2010 to 41% in 2017 (P < 0.001). In general, CM or GA exposure related with a higher mortality rate. Over the five-year longitudinal follow-up, patients without a history of CKD had a higher mortality rate than those with a history of CKD. CONCLUSION: Enrolment in the pre-ESKD care program increased, and inpatient incident dialysis decreased. The long-term survival of patients with CKD was higher than that of non-CKD patients after incident dialysis. CM or GA exposure appears to be related to dialysis-induced mortality, and further investigations are warranted.

Effect of dialyzer membranes on mortality in uremic patients undergoing long-term hemodialysis: A Nationwide population-based study using the Taiwan Dialysis Registry Data System 2005-2012.

The characteristics in dialyzer are associated with mortality in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This study is to investigate the effects of dialyzer membranes on 3-year mortality in ESRD patients. From the long-term nationwide population database. Prevalent HD patients during 2005-2012 were enrolled. Our main analysis to calculate the effect was cox regression multivariate model. Overall, the mean age of all population (N = 73 565) was 61.0 ± 13.6 years, the observation period is 2.46 years ±0.98 within 3 years and 64.6% used polysulfone (PS), polymethyl methacrylate (PMMA) (11.6%), polyethersulfone (11.4%), and cellulose triacetate (CTA) (10.7%), ethylene vinyl alcohol (EVAL) (hazard ratio [HR] 2.72, 95% confidence interval [CI] 1.71-4.33) and CTA (HR 1.35, 95% CI 1.12-1.64) were associated with higher mortality than PS, but PMMA was not. EVAL and CTA adversely affected mortality and PMMA had no protective role. Further investigations on membrane characters on HD patients are warranted. Taipei Medical University (TMU) (TMU-JIRB (No. N201804051).

Label-Free, Portable, and Color-Indicating Cholesteric Liquid Crystal Test Kit for Acute Myocardial Infarction by Spectral Analysis and Naked-Eye Observation.

The early diagnosis of acute myocardial infarction is difficult in patients with nondiagnostic characteristics. Acute myocardial infarction with chest pain is associated with increased mortality. This study developed a portable test kit based on cholesteric liquid crystals (CLCs) for the rapid detection of AMI through eye observation at home. The test kit was established on dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride-coated substrates covered by a CLC-binding antibody. Cardiac troponin I (cTnI) is a major biomarker of myocardial cellular injury in human blood. The data showed that the concentration of cTnI was related to light transmittance in a positive way. The proposed CLC test kit can be operated with a smartphone; therefore, it has high potential for use as a point-of-care device for home testing. Moreover, the CLC test kit is an effective and innovative device for the rapid testing of acute myocardial infarction-related diseases through eye observation, spectrometer, or even smartphone applications.

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.

Effect of profit status in facilities on the mortality of patients on long-term haemodialysis: a nationwide cohort study.

OBJECTIVES: Over the past two decades, debates on whether the profit status of dialysis facilities influences patient prognosis have been popular in the USA. Taiwan is one of the regions with the highest rate per capita of kidney replacement therapy worldwide, but no similar research has been conducted to date. This is the first study to address this issue. DESIGN: This was a nationwide retrospective cohort study based on the Taiwan Renal Registry Data System. SETTING: Patients were categorised into two groups based on the profit status (for-profit, not-for-profit (NFP)) of dialysis facilities, with 31 350 patients in each group. The patients were followed up from 2005 to 2012. PARTICIPANTS: Patients with uraemia who underwent long-term haemodialysis in private dialysis facilities and public facilities were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Survival analyses were performed to compare prognosis between the two groups. Adjustments to patients' basic profile, and facilities' geographical distribution, level, and length of ownership were carried out to minimise possible confounding effects. RESULTS: Analysis revealed that NFP dialysis facilities had better outcomes (HR=0.91, 95% CI (0.89 to 0.93)). A favourable effect remains with the adjustment of the facilities' level, geographical distribution (HR=0.89, 95% CI (0.86 to 0.93)) or length of ownership (HR=0.95, 95% CI (0.89 to 0.95)). Survival analysis based on the geographical distribution and level of facilities was also conducted, which showed better prognosis in medical centres in the six municipalities, whereas worse prognosis was found in local hospitals not located in these municipalities. CONCLUSION: Our findings suggest that in contemporary settings in Taiwan, treatment at NFP dialysis facilities was associated with a better prognosis. The results should be interpreted with caution since the possibility of residual confounding effects and uncertainty of casual relations exist due to the nature of observational studies.

Galectin-3 as a Biomarker for Stratifying Abdominal Aortic Aneurysm Size in a Taiwanese Population.

Abdominal aortic aneurysm (AAA) ruptures are unpredictable and lethal. A biomarker predicting AAA rupture risk could help identify patients with small, screen-detected AAAs. Galectin-3 (Gal-3), a ß-galactosidase-binding lectin, is involved in inflammatory processes and may be associated with AAA incidence. We investigated whether Gal-3 can be used as a biomarker of AAA size. Plasma Gal-3 protein concentrations were examined in patients with AAA (n = 151) and control patients (n = 195) using Human ProcartaPlex multiplex and simplex kits. Circulating Gal-3 levels were significantly higher in patients with AAA than in control patients. The area under the receiver operating characteristic curve for Gal-3 was 0.91. Multivariate logistic regression analysis revealed a significant association between Gal-3 level and the presence of AAA. Circulating Gal-3 levels were significantly correlated with aortic diameter in a concentration-dependent manner. In conclusion, higher plasma Gal-3 concentrations may be a useful biomarker of AAA progression.

Efficacy and Safety of Mineralocorticoid Receptor Antagonists in Kidney Failure Patients Treated with Dialysis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Patients with kidney failure have a high risk of cardiovascular disease due to cardiac remodeling, left ventricular fibrosis, and hyperaldosteronism, all of which can be potentially mitigated by mineralocorticoid receptor antagonists. However, because of the fear of hyperkalemia, the use of mineralocorticoid receptor antagonists in patients with kidney failure is limited in current clinical practice, and few studies have investigated the efficacy and safety. Thus, we aimed to determine the benefits and side effects of mineralocorticoid receptor antagonists in patients with kidney failure treated with dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a systematic review and meta-analysis of randomized controlled trials published from 2005 to 2020 that compared the effect of mineralocorticoid receptor antagonists with either placebo or no treatment in patients with kidney failure. Two reviewers independently searched the PubMed, EMBASE, and Cochrane databases for all published studies, extracted data, assessed the risk of bias, and rated the quality of evidence. A meta-analysis was conducted on 14 eligible randomized controlled trials, and a total of 1309 patients were included. RESULTS: High-quality evidence suggested that mineralocorticoid receptor antagonists are associated with lower cardiovascular mortality (relative risk, 0.41; 95% confidence interval, 0.24 to 0.70; P=0.001) and all-cause mortality (relative risk, 0.44; 95% confidence interval, 0.30 to 0.66; P<0.001), and the risk of hyperkalemia was comparable with that of control group (relative risk, 1.12; 95% confidence interval, 0.91 to 1.36; P=0.29). However, no significant decrease in nonfatal cardiovascular events and stroke was observed, and there was no significant improvement in BP or cardiac performance parameters, including left ventricular ejection fraction and left ventricular mass index. CONCLUSIONS: Our meta-analysis suggests that mineralocorticoid receptor antagonists might improve clinical outcomes of patients with kidney failure without significant increase in the risk of hyperkalemia.

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.