Sodium/Glucose Cotransporter 2 Inhibitors and Magnesium Homeostasis: A Review.

Magnesium (Mg2+), also known as "the forgotten ion," is the second most abundant intracellular cation and is essential in a broad range of intracellular physiological and biochemical reactions. Its deficiency, hypomagnesemia (Mg2+<1.8mg/dL), is a prevalent condition and routinely poses challenges in its management in clinical practice. Sodium/glucose cotransporter 2 (SGLT2) inhibitors have emerged as a new class of drugs with treating hypomagnesemia as their unique extraglycemic benefit. The beneficial effect of SGLT2 inhibitors on magnesium balance in patients with diabetes with or without hypomagnesemia has been noted as a class effect in recent meta-analysis data from randomized clinical trials. Some reports have demonstrated their role in treating refractory hypomagnesemia in patients with or without diabetes. Moreover, studies on animal models have attempted to illustrate the effect of SGLT2 inhibitors on Mg2+homeostasis. In this review, we discuss the current evidence and possible pathophysiological mechanisms, and we provide directions for further research. We conclude by suggesting the effect of SGLT2 inhibitors on Mg2+homeostasis is a class effect, with certain patients gaining significant benefits. Further studies are needed to examine whether SGLT2 inhibitors can become a desperately needed novel class of medicines in treating hypomagnesemia.

Ageing-Related Alterations in Renal Epithelial Glucose Transport.

The kidney plays a crucial role in glucose homeostasis by regulating glucose transport. We aimed to investigate the impact of alterations in glucose transport on glucose metabolism during ageing. Adult male Sprague Dawley rats were divided into five groups: 3-month, 6-month, and 12-month control groups, and 6- and 12-month groups receiving the hydrogen sulfide donor molecule GYY4137. The study found that, as age increased, daily urinary uric acid and protein levels increased in the 12-month group. Blood sugar level and HOMA-IR index increased in the 12-month group, and were partially improved by GYY4137. The kidney tissue showed mild glomerulosclerosis in the 12-month group, which was diminished by GYY4137. Gene expression analysis showed decreased sirtuin and increased p21 expression in the aging groups. Increased SGLT1 and SGLT2 expression was observed in the 12-month group, which was reversed by GYY4137. Both GLUT1 and GLUT2 expression was increased in the 6- and 12-month groups, and reversed by GYY4137 in the 12-month group. The study concluded that aging was associated with increased blood sugar levels and the HOMA-IR index, and the abundance of renal glucose transporters increased as aging progressed. GYY4137 effectively reversed aging-related alterations in glucose homeostasis and renal epithelial transporters.

Perception and Mental Health Status Regarding COVID-19 Vaccination Among Taiwanese Adolescents and Their Caregivers.

Background: Vaccinating adolescents is a vital strategy to enhance population protection without imposing overly restrictive measures on our daily lives during the COVID-19 pandemic. As teenagers gain more independence, their willingness to get vaccinated may depend on their own understanding of the pandemic, vaccines, and mental well-being, as well as that of their caregivers. Our study aimed to examine how Taiwanese adolescents and their caregivers perceive COVID-19 vaccination and assess their mental health status. Methods: We invited a total of 138 vaccinated adolescents and their caregivers to complete several questionnaires, including the Drivers of COVID-19 Vaccination Acceptance Scale (DrVac-COVID19S), Impact of Event Scale (IES), and Chinese Health Questionnaire (CHQ). Results: Among the adolescents, 76.8% considered the BNT162b2 vaccine (Pfizer-BioNTech) as the ideal option for COVID-19 vaccination, while 27.5% of caregivers expressed acceptance of any available vaccine. Adolescents scored higher than caregivers in terms of vaccine value (p<0.001) and autonomy (p<0.001), but lower in knowledge (p<0.001), as assessed by the DrVac-COVID19S subscales. The adolescents' intention to get vaccinated against COVID-19 (DrVac-COVID19S total score) showed a positive correlation with their perception of the pandemic's impact (IES scores, r=0.214, p=0.012) and their caregivers' vaccination intention (r=0.371, p<0.001). Furthermore, adolescents' mental health demonstrated a positive association with the mental health of their caregiver (CHQ total scores, r=0.481, p<0.001). Conclusion: During the COVID-19 outbreak, caregivers have encountered heightened levels of mental stress, and this stress has been found to be positively correlated with the mental stress experienced by adolescents and their intentions regarding vaccination. These findings can serve as crucial references for healthcare providers and governments when formulating vaccination policies for adolescents in the future.

Cardiorenal Outcomes with Finerenone in Asian Patients with Chronic Kidney Disease and Type 2 Diabetes: A FIDELIO-DKD post hoc Analysis.

INTRODUCTION: In FIDELIO-DKD, finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease and type 2 diabetes (T2D). This post hoc analysis explores finerenone in patients from the Asian region. METHODS: In FIDELIO-DKD, 5,674 patients with T2D and urine albumin-to-creatinine ratio (UACR) ≥30-<300 mg/g and estimated glomerular filtration rate (eGFR) ≥25-<60 mL/min/1.73 m2 or UACR ≥300-≤5,000 mg/g and eGFR ≥25-<75 mL/min/1.73 m2, treated with optimized renin-angiotensin system blockade, were randomized 1:1 to finerenone or placebo. Efficacy outcomes included a primary kidney composite (time to kidney failure, sustained decrease of ≥40% in eGFR from baseline, and death from renal causes) and secondary cardiovascular (CV) (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and kidney (time to kidney failure, sustained decrease of ≥57% in eGFR from baseline, and death from renal causes) composites. RESULTS: Of 1,327 patients in the Asian subgroup, 665 received finerenone. Finerenone reduced the ≥40% and ≥57% eGFR kidney and CV composite outcomes versus placebo in the Asian subgroup (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.56-0.87, HR: 0.73; 95% CI: 0.55-0.97, and HR: 0.85; 95% CI: 0.59-1.21, respectively), with no apparent differences versus patients from the rest of the world (HR: 0.88; 95% CI: 0.77-1.02; p interaction 0.09, HR: 0.78; 95% CI: 0.64-0.95; p interaction 0.71, and HR: 0.86; 95% CI: 0.74-1.00; p interaction 0.95, respectively). The safety profile of finerenone was similar across subgroups. CONCLUSION: Finerenone produces similar cardiorenal benefits in Asian and non-Asian patients.

Clinical effectiveness of molnupiravir in patients with COVID-19 undergoing haemodialysis.

BACKGROUND: Molnupiravir is an essential oral antiviral agent against coronavirus disease 2019 (COVID-19); however, its real-world effectiveness has not been evaluated in patients undergoing haemodialysis (HD). METHODS: This multi-centre retrospective study, involving 225 patients undergoing HD with initially mild or asymptomatic COVID-19, was conducted to compare the risks of 30-day COVID-19-related acute care visits between patients receiving and not receiving molnupiravir. Patients who received molnupiravir were stratified by rapid antigen detection (RAD) test results on day 7 after disease onset to assess whether rapid molnupiravir introduction accelerated viral clearance. RESULTS: Thirty-day COVID-19-related acute care visits were reported in 9.41% and 21.74% of the molnupiravir and control groups, respectively, and use of molnupiravir markedly reduced the risk of acute care visits after adjusting for baseline characteristics via propensity score weighting [hazard ratio 0.218, 95% confidence interval (CI) 0.074-0.642; P=0.006]. The tolerability of molnupiravir in the enrolled patients was generally acceptable, with only 11.88% of molnupiravir users reporting mild adverse events. Moreover, rapid initiation of molnupiravir within 1 day of COVID-19 onset was an independent predictor of conversion to a negative RAD test result on day 7 after disease onset (odds ratio 6.207, 95% CI 2.509-15.358; P<0.001). CONCLUSIONS: Molnupiravir is well tolerated and decreases the medical needs in patients with COVID-19 undergoing HD. Furthermore, the rapid initiation of molnupiravir accelerates viral clearance in patients with COVID-19 undergoing HD. These findings highlight the therapeutic role of molnupiravir for this vulnerable population.

Ultrasonography Measurement of Renal Dimension and Its Correlation with Age, Body Indices, and eGFR in Type 1 Diabetes Mellitus Patients: Real World Data in Taiwan.

BACKGROUND: Assessment of renal size is clinically significant for the screening, diagnosis, and follow-up of renal diseases as the basis of clinical decisions. However, the relationship of renal dimension with age, body indices, and the estimated glomerular filtration rate (eGFR) has rarely been reported in the Chinese type 1 diabetes mellitus (T1DM) population. METHODS: A total of 220 T1DM patients were retrospectively analyzed from the Chang Gung Research Database in Taiwan. Demographic data, laboratory data, and ultrasonographic images from January 2001 to November 2018 were extracted. RESULTS: Eighty-five participants (38.6%) were male. The mean age was 34.2 years. The median eGFR was 60.0 mL/min/1.73 m2. The mean ultrasonographic left and right renal lengths (LL and RL) with S.D. were 10.9 ± 1.5 cm and 11.0 ± 1.1 cm, respectively. Renal lengths were longer with increasing body height and body weight but shorter with increasing age in patients with T1DM. In trajectory analysis, a linear mixed model revealed no significant trend in the changes in eGFR during the follow-up period. Moreover, renal length did not play a significant role in predicting KDIGO CKD stage 5 in the cohort. CONCLUSIONS: Renal length and its comparison to the reference ranges demonstrated very limited advantages in predicting renal function decline in T1DM patients.

Real-World Effectiveness of SARS-CoV-2 Vaccine Booster in Hemodialysis Patients with COVID-19 Receiving Molnupiravir.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine booster is one of the most essential strategies against coronavirus disease 2019 (COVID-19) in the era of emerging variants. However, the effectiveness of SARS-CoV-2 vaccine boosters has not much been investigated in hemodialysis (HD) patients receiving oral antiviral agents. In this retrospective study involving 258 HD patients with COVID-19 receiving molnupiravir, we stratified the study cohort according to vaccination status and compared the baseline characteristics and risks of 30-day composite events (COVID-19-related acute care visits, hospitalization, or mortality) among groups. Our analysis demonstrated that the SARS-CoV-2 vaccine boosters markedly decreased the risk of composite events in HD patients (hazard ratio (95% confidence interval), 0.163 (0.063-0.423) for three vs. ≤ two doses of vaccination, p < 0.001; 0.309 (0.115-0.830) for four vs. ≤ two doses of vaccination, p = 0.020). The benefits of vaccine boosters were similar between patients receiving mRNA-based and protein-based boosters and between those with post-booster intervals of ≤ 120 and > 120 days. In conclusion, for HD patients with initially mild or asymptomatic COVID-19 receiving molnupiravir, the benefits of SARS-CoV-2 vaccine boosters are prominent, irrespective of booster vaccine types.

Predictors of Self-Management Behaviors After Discharge Among Unplanned Dialysis Patients.

BACKGROUND: Patients with unplanned dialysis must perform self-management behaviors to maintain their health in the community after discharge. Understanding the factors that predict the postdischarge self-management behaviors of patients with unplanned dialysis can assist nurses to implement appropriate discharge plans for this population. PURPOSE: This study was designed to predict the effects of uncertainty in illness, self-care knowledge, and social-support-related needs during hospitalization on the self-management behaviors of patients with unplanned dialysis during their first 3 months after discharge from the hospital. METHODS: One hundred sixty-nine patients with unplanned dialysis from the nephrology department of a medical center in Taiwan were enrolled in this prospective study using convenience sampling. At hospital admission, demographic, uncertainty in illness, self-care knowledge, and social support information was collected using a structured questionnaire. Information on self-management behavior was collected at 3 months postdischarge when the patients visited outpatient clinics. RESULTS: Hierarchical multiple regression analyses showed that self-care knowledge, uncertainty in illness, and social support were important predictors of self-management behaviors at 3 months postdischarge, explaining 65.6% of the total variance in self-management behaviors. Social support increased the variance in self-management behaviors by 27.9%. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Comprehensive discharge planning to improve the postdischarge self-management behaviors of patients with unplanned dialysis should involve interventions to improve self-care knowledge, reduce uncertainty in illness, and increase social support. Building social support should be given priority attention.

Parental Attitudes, Intentions, Decisions, and Psychological Wellbeing Regarding COVID-19 Vaccination: Preschool, School-Age, and Adolescent Caregivers.

The vaccination of all children may be one of the most important public health measures for preventing a wider spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community. Therefore, the purpose of this study was to investigate the attitude, intention, decision making, and psychological well-being among the caregivers of children who received SARS-CoV-2 vaccination in Taiwan. The caregivers of children (98 preschool children, 191 school-age children, and 154 adolescents) who received COVID-19 vaccination were invited to fill in the following questionnaires: Adopting Self-Protective Behavior Scale, Drivers of COVID-19 Vaccination Acceptance Scale, Impact of Event Scale, Chinese Health Questionnaire, and Parental Bonding Instrument. Compared to the caregivers of adolescents, the caregivers of preschool children exhibited more protective behaviors toward the COVID-19 pandemic. The caregivers of preschool children also displayed a higher emotional impact than those of adolescents and took a greater interest in the family's opinion about vaccination. Finally, we found that COVID-19 ideological invasion and protective parenting style were significantly related to the prevalence of mental illness among caregivers. The results of this study can be used as an important reference for vaccination health care and policy formulation for adolescents with regard to COVID-19.

The associations between renal disease severity and exposure to organophosphate flame retardants in patients with chronic kidney disease.

Organophosphate flame retardants (OPFRs) are emerging and widespread environmental pollutants with potential health hazards, including nephrotoxicity. However, the exposure patterns and nephrotoxic potential of OPFRs are yet to be investigated in patients with chronic kidney disease (CKD). We conducted a cross-sectional study involving 166 patients with CKD stratified by estimated glomerular filtration rate (eGFR) and severity of proteinuria. The urinary concentrations of 10 OPFR compounds were measured to evaluate the exposure patterns. Clinical and urinary OPFR profiles were compared among subgroups to identify whether the OPFR compounds were independently correlated with eGFR and proteinuria. Additionally, lifestyle factors were compared among subgroups stratified by median concentrations of urinary OPFR compounds associated with renal disease severity. This study revealed universal exposure to OPFRs in the CKD population, with an overall urinary detection rate of 98.80 %. Furthermore, after adjusting for covariates, the urinary concentration of bis(2-chloroethyl) phosphate (BCEP) was identified as an independent predictor of lower eGFR (low vs high eGFR, odds ratio (OR) (95 % confidence interval (CI)), 1.761 (1.032-3.005) per log µg/g creatinine, p = 0.038), and the urinary concentration of bis(2-butoxyethyl) phosphate (BBOEP) was independently correlated with overt proteinuria in CKD patients (with vs without overt proteinuria, OR (95 % CI), 1.813 (1.065-3.086) per log µg/g creatinine, p = 0.028). Moreover, frequent seafood consumption was negatively correlated with urinary BCEP concentration (high vs low BCEP, OR (95 % CI), 0.455 (0.228-0.908), p = 0.025), and age was inversely associated with urinary BBOEP concentration (high vs low BBOEP, OR (95 % CI), 0.968 (0.937-0.999) per year, p = 0.048). In conclusion, our investigation highlights the extensive exposure to OPFRs and the independent association between renal disease severity and urinary BCEP/BBOEP concentrations in the CKD population, indicating the nephrotoxic potential of these pollutants.

The Waxing, Waning, and Predictors of Humoral Responses to Vector-Based SARS-CoV-2 Vaccine in Hemodialysis Patients.

Hemodialysis (HD) patients are vulnerable to coronavirus disease 2019 (COVID-19) and have a high mortality rate. We evaluated the anti-SARS-CoV-2 spike protein antibody (ACOV2S) levels in 385 HD patients before and 4 and 8 weeks after the second dose of vector-based ChAdOx1 nCoV-19 vaccine. For study control, week 4 ACOV2S levels after the second vaccination dose were measured in 66 healthcare workers (HCWs). The seroconversion rate of HD patients was 98.96% 4 weeks after the second vaccination. Despite low antibody levels before the second dose (week 0), week 4 ACOV2S levels after the second vaccine dose in HD patients increased prominently and were compatible with those in HCWs (p = 0.814 for HCWs vs. HD patients). The ACOV2S levels in HD patients waned significantly 8 weeks after the second vaccination dose (p < 0.001 at week 8 vs. 4). Older age and immunosuppressant use were negative predictors, while higher C-reactive protein (CRP) levels were positive predictors of ACOV2S waxing after the second vaccine dose in HD patients. Higher CRP levels and platelet counts were independently associated with decreased ACOV2S waning. The ChAdOx1 nCoV-19 vaccine is effective and safe for primary vaccination in HD patients and a booster dose is necessary.

Exogenous BMP7 administration attenuated vascular calcification and improved bone disorders in chronic uremic rats.

Vascular calcification is commonly observed in chronic kidney disease (CKD) and is associated with increased morbidity and mortality. This study examined whether exogenous BMP7 administration can modulate disturbed CKD-MBD in adenine-induced chronic uremic rats. After an adenine diet for 4 weeks, the animals were injected with BMP7 for 2 weeks. Biochemical data, kidney tissue, bony structure, and vascular calcification of the thoracic aorta were examined and compared. Reduced renal function, hyperphosphatemia, and hyperparathyroidism with low 1,25(OH)2 vitamin D levels were observed in the adenine group. MicroCT revealed reduced bone mineral density (BMD), decreased bone and tissue volume ratio (BV/TV), and decreased trabecular number with increased separation. Marked vascular calcification was observed in adenine-fed animals, and immunohistochemical analysis showed increased expression of BMP2, RUNX2, vitamin D receptor (VDR), and Pit1 in aortic tissue. Treatment with BMP7 was associated with reduced serum phosphate, intact parathyroid hormone, FGF23, sclerostin, and DKK1 levels. BMP7 administration was accompanied with improvements in BMD and BV/TV. The increase in BMP2, RUNX2, VDR, and Pit1 was reversed by BMP7. In conclusion, exogenous BMP7 administration improved hyperphosphatemia and hyperparathyroidism in adenine-induced CKD. This treatment also attenuated vascular calcification and modulated structural abnormalities in the skeletal system.

Predictors of Acute Kidney Disease Severity in Hospitalized Patients with Acute Kidney Injury.

Acute kidney disease (AKD) forms part of the continuum of acute kidney injury (AKI) and worsens clinical outcomes. Currently, the predictors of AKD severity have yet to be established. We conducted a retrospective investigation involving 310 hospitalized patients with AKI and stratified them based on the AKD stages defined by the Acute Dialysis Quality Initiative criteria. Demographic, clinical, hematologic, and biochemical profiles, as well as 30-day outcomes, were compared between subgroups. In the analysis, the use of offending drugs (odds ratio, OR (95% confidence interval, CI), AKD stage 3 vs. non-AKD, 3.132 (1.304−7.526), p = 0.011, AKD stage 2 vs. non-AKD, 2.314 (1.049−5.107), p = 0.038), high AKI severity (OR (95% CI), AKD stage 3 vs. non-AKD, 6.214 (2.658−14.526), p < 0.001), and early dialysis requirement (OR (95% CI), AKD stage 3 vs. non-AKD, 3.366 (1.008−11.242), p = 0.049) were identified as independent predictors of AKD severity. Moreover, a higher AKD severity was associated with higher 30-day mortality and lower dialysis-independent survival rates. In conclusion, our study demonstrated that offending drug use, AKI severity, and early dialysis requirement were independent predictors of AKD severity, and high AKD severity had negative impact on post-AKI outcomes.

A Pilot Study of the Effects on an Inpatient Geriatric Consultation Team on Geriatric Syndrome Patients.

Purpose: To evaluate the effect of comprehensive geriatric assessment performed by an inpatient aging consultation team on older patients with geriatric syndromes. Methods: Fifty-nine patients with ≧65 years, Barthel Index score ≦60, at least one geriatric syndrome, and admitted to non-geriatric wards were enrolled. By their preference, 16 were in the intervention group with comprehensive geriatric assessment and instructions from the consultation team. And 43 were in the control group, receiving standard care from non-geriatric-specialist physicians. Outcomes were readmission and mortality within one year after discharge. Results: The mean age of the intervention and control groups was 78.35 (8.54) and 80.23 (6.36) years (p = 0.36), with female of 62.5% and 60.5%, respectively. Compared to control, intervention is not significantly associated with attenuated risk for readmission (adjusted hazard ratio (aHR): 0.256, 95% confidence interval (CI): 0.12-1.78, p = 0.256) and mortality (aHR: 2.13, 95% CI: 0.29-15.7, p = 0.457) within one year after discharge. Multivariate analysis showed that patients with a fall history ≧1 in the past one year had a lower risk of readmission (aHR: 0.28, 0.07-0.6, p = 0.004) or mortality (aHR: 0.11, 95% CI: 0.01-0.97, p = 0.047), and disability is associated with mortality (aHR: 5.37, 95% CI: 0.87-33.12, p = 0.07). Conclusion: Intervention is not significantly associated with outcomes in our pilot study. But fall history ≧1 in the recent one year is associated with a lower risk of readmission and mortality among all included patients. More participants and longer follow-up are needed for better elucidation.

Long-term safety and efficacy of ferric citrate in phosphate-lowering and iron-repletion effects among patients with on hemodialysis: A multicenter, open-label, Phase IV trial.

BACKGROUND: We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups. METHODS: This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients' clinical condition and further adjusted to maintain serum phosphorus at 3.5-5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus. RESULTS: A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend<0.001), and the increase started to slow down after 3-6 months of treatment. In addition, the increase trend was found only in patients with lower baseline level of ferritin (≤500 ng/mL) and TSAT (<30%). CONCLUSIONS: Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

Effect of a Pay-for-Performance Program on Renal Outcomes Among Patients With Early-Stage Chronic Kidney Disease in Taiwan.

BACKGROUND: With the promising outcomes of the pre-ESRD (end-stage renal disease) pay-for-performance (P4P) program, the National Health Insurance Administration (NHIA) of Taiwan launched a P4P program for patients with early chronic kidney disease (CKD) in 2011, targeting CKD patients at stages 1, 2, and 3a. This study aimed to examine the long-term effect of the early-CKD P4P program on CKD progression. METHODS: We conducted a matched cohort study using electronic medical records from a large healthcare delivery system in Taiwan. The outcome of interest was CKD progression to estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 between P4P program enrolees and non-enrolees. The difference in the cumulative incidence of CKD progression between the P4P and non-P4P groups was tested using Gray's test. We adopted a cause-specific (CS) hazard model to estimate the hazard in the P4P group as compared to non-P4P group, adjusting for age, sex, baseline renal function, and comorbidities. A subgroup analysis was further performed in CKD patients with diabetes to evaluate the interactive effects between the early-CKD P4P and diabetes P4P programs. RESULTS: The incidence per 100 person-months of disease progression was significantly lower in the P4P group than in the non-P4P group (0.44 vs. 0.69, P<.0001), and the CS hazard ratio (CS-HR) for P4P program enrolees compared with non-enrolees was 0.61 (95% CI: 0.58-0.64, P<.0001). The results of the subgroup analysis further revealed an additive effect of the diabetes P4P program on CKD progression; compared to none of both P4P enrolees, the CS-HR for CKD disease progression was 0.60 (95% CI: 0.54-0.67, P<.0001) for patients who were enrolled in both early-CKD P4P and diabetes P4P programs. CONCLUSION: The present study results suggest that the early-CKD P4P program is superior to usual care to decelerate CKD progression in patients with early-stage CKD.

The Risk Factors of Blood Cadmium Elevation in Chronic Kidney Disease.

Low-level cadmium exposure has adverse effects on chronic kidney disease (CKD); however, the risk factors for elevated blood cadmium levels (BCLs) have not been studied in CKD. We conducted a cross-sectional investigation in 200 CKD patients and stratified them by the tertiles of BCL to compare their demographic, environmental, and biochemical data. The factors associated with BCL were identified, and their effects were examined in subgroups. In the analyses, female sex, smoking, and CKD stage 5D were associated with high BCL, and statin was inversely correlated with BCL (odds ratio [95% confidence interval, CI], 6.858 [2.381-19.746], p < 0.001, 11.719 [2.843-48.296], p = 0.001, 30.333 [2.252-408.520], p = 0.010, and 0.326 [0.122-0.873], p = 0.026; deviations of BCL [nmol/L, 95% CI], 2.66 [1.33-4.00], p < 0.001, 3.68 [1.81-5.56], p < 0.001, 3.38 [0.95-5.82], p = 0.007, and -2.07 [-3.35--0.78], p = 0.002). These factors were also independently correlated with BCL in subgroups, including non-dialysis CKD, hypertensive patients, non-smokers, and male patients. In conclusion, female sex, smoking, and CKD stage 5D were the major risk factors for elevated BCL; additionally, statins were negatively associated with BCL in CKD.

Impact on Mental Well-Being and Resilience of Patients with Multiple Chronic Conditions in Different Periods during the Coronavirus Disease 2019 Outbreak in Taiwan.

Concerns over the coronavirus disease 2019 (COVID-19) pandemic and control measures have affected the routine outpatient visits of individuals with comorbidities and their mental well-being. From October 2019 to August 2020, this cross-sectional study enrolled 135 patients who sought medical attention at a medical center in Taiwan. This period covered the early (October to December 2019), peak (January to April 2020), and late (May to August 2020) periods of the COVID-19 outbreak in Taiwan. The demographic data, social support data, activities of daily living (ADL), resilience scale scores, and mental well-being scale scores of the participants were compared. There were no statistically significant differences in the participation rate, demographic data, and social support data between the three periods. The correlation analysis confirmed significant negative relationships between the number of COVID-19 cases and outpatient department visits per month (r = -0.764, p < 0.001), emergency department visits per month (r = -0.023, p < 0.001), ADL (r = -0.257, p = 0.03), resilience scale (r = -0.390, p < 0.001), and mental well-being scale (r = -0.475, p < 0.001). In conclusion, the severity of the COVID-19 outbreak in Taiwan was associated with declines in the ADL, mental well-being, and resilience of patients who sought medical attention.

Effect of Dapagliflozin and Magnesium Supplementation on Renal Magnesium Handling and Magnesium Homeostasis in Metabolic Syndrome.

The prevalence of metabolic syndrome (MetS) is increasing, and patients with MetS are at an increased risk of cardiovascular disease and diabetes. There is a close link between hypomagnesemia and MetS. Administration of sodium-glucose transporter 2 (SGLT2) inhibitors has been reported to increase serum magnesium levels in patients with diabetes. We investigated the alterations in renal magnesium handling in an animal model of MetS and analyzed the effects of SGLT2 inhibitors. Adult rats were fed a fructose-rich diet to induce MetS in the first 3 months and were then treated with either dapagliflozin or magnesium sulfate-containing drinking water for another 3 months. Fructose-fed animals had increased insulin resistance, hypomagnesemia, and decreased urinary magnesium excretion. Dapagliflozin treatment improved insulin resistance by decreasing glucose and insulin levels, increased serum magnesium levels, and reduced urinary magnesium excretion. Serum vitamin D and parathyroid hormone levels were decreased in fructose-fed animals, and the levels remained low despite dapagliflozin and magnesium supplementation. In the kidney, claudin-16, TRPM6/7, and FXDY expression was increased in fructose-fed animals. Dapagliflozin increased intracellular magnesium concentration, and this effect was inhibited by TRPM6 blockade and the EGFR antagonist. We concluded that high fructose intake combined with a low-magnesium diet induced MetS and hypomagnesemia. Both dapagliflozin and magnesium sulfate supplementation improved the features of MetS and increased serum magnesium levels. Expression levels of magnesium transporters such as claudin-16, TRPM6/7, and FXYD2 were increased in fructose-fed animals and in those administered dapagliflozin and magnesium sulfate. Dapagliflozin enhances TRPM6-mediated trans-epithelial magnesium transport in renal tubule cells.

Empagliflozin Ameliorates Free Fatty Acid Induced-Lipotoxicity in Renal Proximal Tubular Cells via the PPARγ/CD36 Pathway in Obese Mice.

High serum levels of free fatty acids (FFAs) could contribute to obesity-induced nephropathy. CD36, a class B scavenger receptor, is a major receptor mediating FFA uptake in renal proximal tubular cells. Empagliflozin, a new anti-diabetic agent, is a specific inhibitor of sodium-glucose co-transporter 2 channels presented on renal proximal tubular cells and inhibits glucose reabsorption. In addition, empagliflozin has shown renoprotective effects. However, the mechanism through which empagliflozin regulates CD36 expression and attenuates FFA-induced lipotoxicity remains unclear. Herein, we aimed to elucidate the crosstalk between empagliflozin and CD36 in FFA-induced renal injury. C57BL/6 mice fed a high-fat diet (HFD) and palmitic acid-treated HK-2 renal tubular cells were used for in vivo and in vitro assessments. Empagliflozin attenuated HFD-induced body weight gain, insulin resistance, and inflammation in mice. In HFD-fed mice, CD36 was upregulated in the tubular area of the kidney, whereas empagliflozin attenuated CD36 expression. Furthermore, empagliflozin downregulated the expression of peroxisome proliferator-activated receptor (PPAR)-γ. Treatment with a PPARγ inhibitor (GW9662) did not further decrease PPARγ expression, whereas a PPARγ antagonist reversed this effect; this suggested that empagliflozin may, at least partly, decrease CD36 by modulating PPARγ. In conclusion, empagliflozin can ameliorate FFA-induced renal tubular injury via the PPARγ/CD36 pathway.