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Background and Objectives Research on racial and gender disparities in end-of-life care quality has burgeoned over the past few decades, but few studies have incorporated the theory of intersectionality, which posits that membership in 2 or more vulnerable groups may result in increased hardships across the life span. As such, this study aimed to examine the intersectional effect of race and gender on the quality of care received at the end of life among older adults. Research Design and Methods Data were derived from the combined Round 3 to Round 10 of the National Health and Aging Trends Study. For multivariate analyses, 2 logistic regression models were run; Model 1 included the main effects of race and gender and Model 2 included an interaction term for race and gender. Results Results revealed that White men were the most likely to have excellent or good care at the end of life, followed by White women, Black men, and Black women, who were the least likely to have excellent or good care at the end of life. Discussion and Implications These results point to a significant disadvantage for Black women, who had worse end-of-life care quality than their gender and racial peers. Practice interventions may include cultural humility training and a cultural match between patients and providers. From a policy standpoint, a universal health insurance plan would reduce the gap in end-of-life service access and quality for Black women, who are less likely to have supplemental health care coverage.

The purpose of this systematic review was to provide a comprehensive account of racial and ethnic differences in retrospective end-of-life outcomes. Studies were searched from the following databases: Abstracts in Social Gerontology, Academic Search Premier, CINAHL Plus with Full Text, ERIC, MEDLINE, PsycINFO, PubMED, and SocIndex. Studies were included if they were published in English, included people from groups who have been minoritized, included adults aged 18 and older, used retrospective data, and examined end-of-life outcomes. Results from most of the 29 included studies showed that people from groups who have been minoritized had more aggressive/intensive care, had less hospice care, were more likely to die in a hospital, less likely to engage in advance care planning, less likely to have good quality of care, and experienced more financial burden at the end of life. Implications for practice (timely referrals), policy (health insurance access), and research (intervention studies) are provided.

Prior research reported lower engagement in end-of-life discussions and planning among Korean American (KA) immigrants; however, there is a dearth of research investigating factors associated with their willingness to discuss their end-of-life care wishes. This study aimed to examine the willingness to have end-of-life discussions with family and doctors among KA immigrants and social determinants of health (SDH) associated with willingness. A self-administered, cross-sectional survey was conducted with a convenience sample of 259 KA immigrants recruited from two counties in Alabama. Demographic, health, acculturation and SDH information were collected. Logistic regression analyses were conducted to examine associations between SDH and willingness for end-of-life discussion with family and doctors, respectively. The majority of the sample was willing to discuss end-of-life care with family (94%) and doctors (82%). Those with hospice awareness were more likely to have willingness for discussion with family (OR = 27.70, p 0.001) and doctors (OR = 5.01, p 0.001). Those who could not see a doctor because of cost (OR = 0.03, p 0.01) and who had higher threats to interpersonal safety (OR = 0.74, p 0.05) were less likely to have willingness for discussion with family. Those who had more chronic conditions (OR = 0.60, p 0.05) and higher levels of social isolation (OR = 0.77, p 0.05) were less likely to have willingness for discussion with doctors. The SDH identified in this study should be considered in developing interventions to promote end-of-life discussions in the KA immigrant community. Future research should investigate the associations explored in this study in a larger and more representative sample.

Background Recently, a new international risk prediction model including the Oxford classification was published which was validated in a large multi‐ethnic cohort. Therefore, we aimed to validate this risk prediction model in Korean patients with IgA nephropathy. Methods This retrospective cohort study was conducted with 545 patients who diagnosed IgA nephropathy with renal biopsy in three medical centers. The primary outcome was defined as a reduction in estimated glomerular filtration rate (eGFR) of >50% or incident end‐stage renal disease (ESRD). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) were used to validate models. Results During the median 3.6 years of follow‐up period, 53 (9.7%) renal events occurred. In multivariable Cox regression model, M1 (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.02–4.82; p = .043), T1 (HR, 2.98; 95% CI, 1.39–6.39; p = .005) and T2 (HR, 4.80; 95% CI, 2.06–11.18; p, SUMMARY AT A GLANCE Prediction models for IgA nephropathy using clinical variables and the Oxford MEST scores were developed and may be utilised to individualise risk of progression. This study evaluates the performance of these prediction models in an external cohort of Korean patients.

Objectives: The purpose of this study was to examine racial differences in the discussion of advance care planning among older adults using Andersen’s behavioral model of health care utilization. Method: This cross-sectional study utilized data from the 2018 National Health and Aging Trends Study. Weighted multivariable logistic regressions were used to predict advance care planning discussion ( n = 1,326). Results: After accounting for predisposing, enabling, and need factors, Black older adults were less likely to discuss end-of-life care (odds ratio [OR] = .527) and medical power of attorney (OR = .531) compared with Whites. Hispanic older adults were also less likely to discuss end-of-life care (OR = .389) and power of attorney (OR = .384) compared with Whites. Discussion: These results point to significant racial disparities in advance care planning discussions among older adults and call for future examinations of cultural, historical, and systemic factors that could influence the discussion of advance care planning among this population.

Willingness for end-of-life discussion and related factors among rural Blacks/African Americans of the Alabama Black Belt have not been well-studied. This study aims to assess their willingness for the discussion and examine its relationship with social determinants of health (SDH) and demographic factors. A cross-sectional survey was conducted with a convenience sampling of 182 participants. Most participants were willing to discuss end-of-life wishes with family (77.1%) or doctors (72.1%). Controlling for demographics, results from binary logistic regressions showed those with hospice awareness were more likely to have willingness for discussion with family ( OR = 10.07, p < .01) and doctors ( OR = 7.23, p < .05). Those who were older (50+) were less likely to have willingness for discussion with doctors ( OR = 0.19, p < .05), whereas those who were more socially isolated were less likely to have willingness for discussion with family ( OR = 0.53, p < .05). Therefore, end-of-life discussion efforts should focus on older, socially isolated individuals and consider hospice awareness.

BACKGROUND AND AIMS Globally, the incidence and prevalence of CKD have been increased. Also, CKD DALYs and death due to CKD have been increased (DALYs: The disability-adjusted life-year).[1] CKD puts a lot of mental and economic burden on an individual’s life and lowers the quality of life.[2] As CKD progress, kidney-specific risk factor for cardiovascular events and disease are increased.[3] Dyslipidemia is generally known to be associated with the development and progression of chronic kidney disease.[4] However, it is unclear whether limiting cholesterol intake helps prevent CKD. Recent studies have reported that there is no association between cholesterol intake and cardiovascular disease.[5] The aim of our study is to analyze the relationship between cholesterol intake and the development of CKD in a general population. METHOD We included 9226 subjects without CKD from the Korean Genome and Epidemiology Study. The amount of daily cholesterol intake was assessed by food frequency questionnaire. The primary outcome was the development of CKD, which was defined as an estimated glomerular filtration rate (eGFR) of RESULTS The mean age was 55.7 ± 8.8 years and 39.6% of subjects were men. The cholesterol intake was only significantly correlated with serum HDL cholesterol but not with total and non-HDL cholesterol. Moreover, this significant relationship was disappeared after adjusting for daily fat intake. During median follow-up duration of 11.4 years, 778 (8.5%) CKD events occurred. In multivariable Cox analysis, serum total cholesterol was significantly associated with incident CKD (hazard ratio [HR] 1.005, 95% confidence interval [CI]: 1.003–1.007; P CONCLUSION Cholesterol intake was not correlated with serum cholesterol levels with considering fat intake. In addition, cholesterol intake was not associated with increased risk of CKD in the general population. Therefore, it may not be necessary to limit cholesterol intake to prevent CKD in this population.

ObjectiveLack of palliative care knowledge among caregivers may pose an access barrier for cognitively impaired older adults, who may benefit from the specialized care. Therefore, this study aims to examine the effectiveness of an educational intervention in improving palliative care knowledge among informal caregivers of cognitively impaired older adults.MethodUsing a one-group, pre- and post-test intervention design, this study implemented an individual, face-to-face educational intervention with an informational brochure for 43 informal caregivers of chronically or seriously ill older adults (50+) with cognitive impairment, recruited from communities in West Alabama. Their level of knowledge about palliative care was assessed by the Palliative Care Knowledge Scale (PaCKS). The pre- and post-test scores were compared by the Wilcoxon signed-ranks test, and the racial subgroup (Whites vs. Blacks) comparison was made by the Mann–Whitney U test.ResultsThere was a statistically significant difference between the pre- and post-test scores (z = 5.38, p < 0.001), indicating a statistically significant effect of the educational intervention in improving palliative care knowledge among participants. There was a significant difference (U = 143, p < 0.05) between Whites and Blacks in the pre-test, which, however, disappeared in the post-test (U = 173.50, p > 0.05), suggesting that the amount of increased PaCKS scores were significantly greater for Blacks (Mdn = 9.50) than for Whites (Mdn = 4.00, U = 130.50, p < 0.05).Significance of resultsThis study demonstrated that a one-time educational intervention can improve the level of palliative care knowledge among informal caregivers of chronically or seriously ill older adults with cognitive impairment, particularly among Black caregivers. Therefore, further educational efforts can be made to promote palliative care knowledge and reduce racial disparities in palliative care knowledge and its use.

Background: Despite the need for hospice care as our society ages, adults in the U.S.’s southern rural region have limited awareness of hospice care. Objective: This study aims to assess the rate of awareness of hospice care among rural residents living in Alabama’s Black Belt region and examine social determinants of health (SDH) associated with the awareness. Methods: A cross-sectional survey was conducted among a convenience sample living in Alabama’s Black Belt region (N = 179, age = 18-91). Participants’ awareness of hospice care, demographic characteristics (ie, age and gender), and SDH (ie, financial resources strain, food insecurity, education and health literacy, social isolation, and interpersonal safety) were assessed. Lastly, a binary logistic regression was used to examine the association between SDH and hospice awareness among participants while controlling for demographic characteristics. Results: The majority of participants had heard of hospice care (n = 150, 82.1%), and older participants (50 years old or older) were more likely to report having heard of hospice care ( OR = 7.35, P < 0.05). Participants reporting worries about stable housing (OR = 0.05, P < 0.05) and higher social isolation were less likely to have heard of hospice care ( OR = 0.53, P < 0.05), while participants with higher health literacy had a higher likelihood to have heard of it ( OR = 2.60, P < 0.01). Conclusions: Our study is the first study assessing the status of hospice awareness among residents of Alabama’s Black Belt region. This study highlighted that factors including age and certain SDH (ie, housing status, health literacy, and social isolation) might be considered in the intervention to improve hospice awareness.

The radiodensity and volume of epicardial adipose tissue (EAT) on computed tomography angiography (CTA) may provide information regarding cardiovascular risk and long-term outcomes. EAT volume is associated with mortality in patients undergoing incident hemodialysis. However, the relationship between EAT radiodensity/volume and all-cause mortality in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis remains elusive. In this retrospective study, EAT radiodensity (in Hounsfield units) and volume (in cm3) on coronary CTA were quantified for patients with ESRD using automatic, quantitative measurement software between January 2012 and December 2018. All-cause mortality data (up to December 2019) were obtained from the Korean National Statistical Office. The prognostic values of EAT radiodensity and volume for predicting long-term mortality were assessed using multivariable Cox regression models, which were adjusted for potential confounders. A total of 221 patients (mean age: 64.88 ± 11.09 years; 114 women and 107 men) with ESRD were included. The median follow-up duration (interquartile range) after coronary CTA was 29.63 (range: 16.67–44.7) months. During follow-up, 82 (37.1%) deaths occurred. In the multivariable analysis, EAT radiodensity (hazard ratio [HR]: 1.055; 95% confidence interval [CI]: 1.015–1.095; p = 0.006) was an independent predictor of all-cause mortality in patients with ESRD. However, EAT volume was not associated with mortality. Higher EAT radiodensity on CTA is associated with higher long-term all-cause mortality in patients undergoing prevalent hemodialysis, highlighting its potential as a prognostic imaging biomarker in patients undergoing hemodialysis.

This study aimed to examine social determinants of health (SDH) associated with Korean American (KA) immigrants’ willingness for end-of-life discussions with family and doctors. A self-administered, cross-sectional survey was conducted with 259 KAs in Alabama. Demographic, health, acculturation, and SDH information were collected. Binary logistic regression analyses were conducted to examine associations between SDH and willingness for end-of-life discussion. Most participants were willing to discuss with family (94%) and doctors (82%). Those aware of hospice care were more likely to have willingness for discussion with family and doctors. Those who could not see a doctor because of cost and who had higher threats to interpersonal safety were less likely to have willingness for discussion with family. Those with more chronic conditions and higher social isolation were less likely to have willingness for discussion with doctors. Interventions aimed to promote KAs' end-of-life discussions should consider the SDH identified in this study.

Although pain control is an essential factor in promoting quality of life, pain is undertreated among certain sub-populations, such as older adults and rural residents. The purpose of this study was to explore pain experiences and its treatment among rural older adults. A qualitative research design was adopted to capture the common essence of participants’ experiences through a phenomenological method. Purposeful sampling was used, and the participant criteria was: age 55+, have good thinking skills, resident of Alabama, have chronic/serious health conditions, and experienced pain or discomfort in the last 3 months. Twenty-three participants were recruited from rural counties of West and South Alabama through the local Area Agency on Aging and health and senior service centers. Individual semi-structured interviews were conducted via phone and were recorded and transcribed verbatim. Thematic analysis was conducted to identify emerging themes and repeated patterns from the data. Our results revealed themes in four categories: 1) impact of pain: physical limitations and coping strategies, 2) Impact of Covid-19: physical health, social, and mental health impact, 3) challenges in pain treatment: transportation (driver/time/cost/Covid-19 exposure) and non-transportation related problems (lacking resources/mistrust/limited health insurance coverage), and 4) suggestions: transportation-related (more transportation options/financial assistance) and non-transportation-related support (improved insurance coverage/non-pharmacological care) . Findings of this study highlight rural older adults’ unique needs in access to pain treatment, further amplified during the Covid-19 pandemic. Increase in sustainable, funded transportation programs and the supply of local pain specialists is critical to meet such needs and improve their quality of life.

Family caregivers face various challenges in assisting older adults experiencing pain and difficult symptoms. Living in rural areas poses additional obstacles to their caregiving. The purpose of this study was to explore family caregivers’ lived experiences in caring for older adults with pain and discomfort in rural communities. A qualitative research design was adopted to capture the common essence of participants’ experiences through a phenomenological method. Purposeful sampling was used, and the participant criteria was: age 18+, have good thinking skills, resident of Alabama, provide unpaid assistance to a family/relative who has chronic/serious health conditions and experienced pain/discomfort in the last 3 months. Ten participants were recruited from rural counties of Alabama. Individual semi-structured interviews were conducted via phone and were recorded and transcribed verbatim. Inductive, thematic analysis of the data revealed themes in five categories: 1) impact of pain (physical and psychological/emotional toll), 2) coping strategies (faith/contentment with life/logistical adaptation), 3) impact of Covid-19 (physical health/social interaction/mental health/added caregiving), 4) challenges in pain treatment (transportation (time/distance/driver/cost) and non-transportation related problems (healthcare provider issues/health insurance/financial burden)), and 5) suggestions (transportation-related (more transportation options/tailored services) and non-transportation-related support (home-based services/better health insurance coverage)). Findings of this study highlight rural family caregivers’ unique experiences in assisting older adults’ access to pain treatment, particularly during the Covid-19 pandemic. Policy- and program-level intervention is called for to increase individualized transportation options, improve health insurance coverage, and expand financial support for rural older adults experiencing pain and their caregivers.

It is well-known that high protein intake is associated with renal hyperfiltration and faster renal function decline, but the association of other macronutrients, carbohydrate and fat, with development of chronic kidney disease (CKD) is still inconclusive. Therefore, we aimed to examine the relationship between fat-to-carbohydrate intake ratio (F/C ratio) and incident CKD.We included 9226 subjects from the Korean Genome and Epidemiology Study. The subjects were divided into two groups depending on 1 g protein intake per ideal body weight per day. Primary exposure was the F/C ratio defined as calorie intake of fat/calorie intake of fat and carbohydrate. The primary outcome was the development of CKD, which was defined as an estimated glomerular filtration rate (eGFR) of60 mL/min/1.73 mDuring a median follow-up duration of 11.4 years, 778 (8.4%) CKD events occurred. Subjects in the lowest F/C ratio tertile had faster eGFR decline rate than other tertiles. In multivariable Cox analysis, a significantly higher CKD risk was observed in the lowest tertile when protein intake1 g/kg/day (hazard ratio [HR] for T1 (16.1%) vs. T3 (21.5%), 1.38; 95% confidence interval [CI], 1.03-1.84; P = 0.031). In sensitivity analysis, subjects maintained low F/C ratio diet (16.1%) during 4 years showed higher risk of subsequent CKD development than those maintained high F/C ratio diet (≥16.1%; HR, 1.70; 95% CI, 1.10-2.63; P = 0.018). In cubic spline analysis, CKD risk was sharply increased in F/C ratio16.1%, but the risk was nearly constant in F/C ratio ≥16.1%.A diet with a low F/C ratio was associated with increased risk of CKD in the general population. Therefore, it is necessary to limit excessive high carbohydrate and low fat intake to prevent CKD development in this population.

Mesenchymal stem cells (MSCs) are promising source of cell‐based regenerative therapy. In consideration of the risk of allosensitization, autologous MSC‐based therapy is preferred over allogenic transplantation in patients with chronic kidney disease (CKD). However, it remains uncertain whether adequate cell functionality is maintained under uremic conditions. As chronic inflammation and oxidative stress in CKD may lead to the accumulation of senescent cells, we investigated cellular senescence of CKD MSCs and determined the effects of metformin on CKD‐associated cellular senescence in bone marrow MSCs from sham‐operated and subtotal nephrectomized mice and further explored in adipose tissue‐derived MSCs from healthy kidney donors and patients with CKD. CKD MSCs showed reduced proliferation, accelerated senescence, and increased DNA damage as compared to control MSCs. These changes were significantly attenuated following metformin treatment. Lipopolysaccharide and transforming growth factor β1‐treated HK2 cells showed lower tubular expression of proinflammatory and fibrogenesis markers upon co‐culture with metformin‐treated CKD MSCs than with untreated CKD MSCs, suggestive of enhanced paracrine action of CKD MSCs mediated by metformin. In unilateral ureteral obstruction kidneys, metformin‐treated CKD MSCs more effectively attenuated inflammation and fibrosis as compared to untreated CKD MSCs. Thus, metformin preconditioning may exhibit a therapeutic benefit by targeting accelerated senescence of CKD MSCs., Increased senescence of CKD MSCs may contribute to poor regenerative potential. Metformin decreased CKD‐induced prelamin A accumulation and DNA damage signaling, which may lead to cellular senescence. We suggest metformin preconditioning as an effective strategy to overcome the senescence‐associated barrier to autologous patient‐derived MSC therapy in CKD.

To investigate the association between abdominal periaortic (APA) and renal sinus (RS) fat attenuation index (FAI) measured on MDCT and metabolic syndrome in non-obese and obese individuals. Visceral, subcutaneous, RS, and APA adipose tissue were measured in preoperative abdominal CT scans of individuals who underwent donor nephrectomy (n = 84) or bariatric surgery (n = 155). FAI was defined as the mean attenuation of measured fat volume. Participants were categorized into four groups: non-obese without metabolic syndrome (n = 64), non-obese with metabolic syndrome (n = 25), obese without metabolic syndrome (n = 21), and obese with metabolic syndrome (n = 129). The volume and FAI of each fat segment were compared among the groups. Receiver operator characteristics curve analysis was used to assess the association between the FAIs and metabolic syndrome. FAIs of all abdominal fat segments were significantly lower in the obese group than in the non-obese group (p < 0.001). RS, APA, and the visceral adipose tissue FAIs were significantly lower in participants with metabolic syndrome than in those without metabolic syndrome in the non-obese group (p < 0.001, p = 0.006, and p < 0.001, respectively). The area under the curve for predicting metabolic syndrome was significantly higher for APA FAI (0.790) than subcutaneous, visceral, and RS FAI in all groups (0.649, 0.647, and 0.655, respectively). Both metabolic syndrome and obesity were associated with lower RS and APA adipose tissue FAI, and APA FAI performed best for predicting metabolic syndrome. • The volume and FAI of RS, APA, and visceral adipose tissue showed opposite trends with regard to metabolic syndrome or obesity. • Both metabolic syndrome and obesity were associated with lower RS FAI and APA FAI. • APA FAI performed best for predicting metabolic syndrome among FAIs of abdominal fat segments.

Background: Pain and symptom management is critical in ensuring quality of life for chronically ill older adults. However, while pain management and palliative care have steadily expanded in recent years, many underserved populations, such as rural older adults, experience barriers in accessing such specialty services, in part due to transportation issues. The purpose of this systematic review is to examine the specific types of transportation-related barriers experienced by rural older adults in accessing pain and palliative care. Methods: Studies were searched through the following 10 databases: Abstracts in Social Gerontology, Academic Search Premier, CINAHL, MEDLINE, PsycINFO, SocINDEX with Full Text, Cochrane Database of Systematic Reviews, Nursing & Allied Health Database, Sociological Abstracts, and PubMED. Studies were chosen for initial review if they were written in English, full text, included older adults in the sample, and examined pain/palliative care/hospice, rural areas, and transportation. A total of 174 abstracts were initially screened, 15 articles received full-text reviews and 8 met the inclusion criteria. Results: Findings of the 8 studies identified transportation-related issues as major access barrier to pain and palliative care among rural older adults: specifically, lack of public transportation; lack of wheelchair accessible vehicles; lack of reliable drivers; high cost of transportation services; poor road conditions; and remoteness to the closest pain and palliative care service providers. Conclusion: Results suggest that rural older adults have unique transportation needs due to the urban-centric location of pain and palliative care services. Implications for practice, policy and research with older adults are discussed.

Background and Aims Mesenchymal stem cells (MSC) are promising source of cell-based regenerative therapy; however, adequate cell functionality is a critical factor for the success of autotransplantation. Method We investigated the effects of metformin on chronic kidney disease (CKD)-associated cellular senescence using MSC isolated from sham operated and subtotal nephrectomized mice and further explored the protective role of metformin-treated CKD MSC in renal progression. Results When compared to normal MSC, MSC isolated from CKD mice displayed reduced proliferation and early senescence as determined by enlarged cell morphology, increased oxidative stress, accumulation of DNA damage response marker p53 binding protein 1 (53BP1), phospho p53, p16INK4a, and β-gal expression, and decreased cyclin-dependent kinase 4 (CDK4) and cyclin D. CKD MSC exhibited activation of NFκB resulting in expression of senescence-associated secretory phenotype (SASP) factors compared to normal MSC. All of these changes were significantly prevented by metformin treatment. In vivo, metformin-treated CKD MSC attenuated inflammation and fibrosis in UUO kidney as compared to CKD MSC. Co-culture of LPS or TGF-β1-treated HK2 cells with metformin-treated CKD MSC markedly decreased LPS or TGF-β-induced tubular expression of proinflammatory markers and fibrogenesis when compared to CKD MSC suggesting paracrine action of CKD MSC enhanced by metformin treatment. Conclusion Our data suggest that metformin inhibits cellular senescence of CKD MSC and improves their renoprotective effects.

Background and Aims Recent evidences has shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes of type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve clinical outcomes are unclear. Mitochondrial dysfunction plays a principal role in the pathophysiology of T2DM and its complications. We hypothesized empagliflozin, an SGLT2 inhibitor improves mitochondrial dysfunction in T2DM patients. Method We prospectively recruited healthy volunteers (n = 22) and SGLT2 naïve T2DM patients (n = 21). Copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) were measured using quantitative polymerase chain reaction in healthy volunteers and T2DM patients at baseline and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Results Patients with T2DM were older than healthy volunteers and had higher body mass index and systolic blood pressure, but lower estimated glomerular filtration rate. Urinary mtND-1 and mtCOX-3 copy numbers were significantly higher in the T2DM group than in healthy volunteers. Urinary mtDNA copy numbers were correlated with diabetes duration (8.74 ± 7.60 years, r = 0.54, P = 0.01 for mtND-1, r = 0.50, P = 0.02 for mtCOX-3). Urinary copy numbers of mtND-1 and mtCOX-3 decreased after empagliflozin treatment. The amount of reduction of urinary mtDNA copy number did not differ according to empagliflozin dose (P = 0.897 for mtND-1, P = 0.462 for mtCOX-3). Conclusion In this study, we found that T2DM is associated with elevated urinary mtND-1 and mtCOX-3 copy numbers. Empagliflozin reduces the elevated urinary mtND-1 and mtCOX-3 copy numbers in patients with T2DM. Our results suggest that empagliflozin could attenuate mitochondrial damage in the kidney cells of T2DM patients.

Background and Aims Diabetes mellitus is a risk factor of chronic kidney disease (CKD); however, the relationship between fasting glucose and CKD remains controversial in non-diabetic population. Method This study included 6,354 participants without diabetes and CKD from the KoreanGenome Epidemiology Study. The genetic risk score (GRS9) was calculated using nine genetic variants associated with fasting glucose in previous genome wide association studies. Incident CKD was defined as estimated glomerular filtration rate (eGFR) Results The GRS9 was strongly associated with fasting glucose (β, 1.01; P < 0.001). During a median follow-up of 11.6 years, 531 (8.4%) CKD events occurred. After adjusting for confounding factors, fasting glucose was not associated with incident CKD (odds ratio [OR], 0.991; 95% confidence interval [CI], 0.980–1.003; P =0.139). In the MR analysis, GRS9 was not associated with CKD development (OR per 1 standard deviation increase, 1.179; 95% CI, 0.819–1.696; P = 0.376). Further evaluation with various other MR methods using inverse-variance weighted, MR-Egger, and weighted median methods for multiple genetic variants and strict CKD criteria (decrease in the eGFR of ≥ 30% to a value of < 60 mL/min/1.73m2) found no significant relationship between GRS9 and incident CKD. Conclusion Impaired fasting glucose was not causally associated with CKD development in nondiabetic population.

Tubular injury and fibrosis are associated with progressive kidney dysfunction in advanced glomerular disease. Glomerulotubular crosstalk is thought to contribute to tubular injury. microRNAs (miRNAs) in extracellular vesicles (EVs) can modulate distant cells. We hypothesized that miRNAs in EVs derived from injured podocytes lead to tubular epithelial cell damage. As proof of this concept, tubular epithelial (HK2) cells were cultured with exosomes from puromycin-treated or healthy human podocytes, and damage was assessed. Sequencing analysis revealed the miRNA repertoire of podocyte EVs. RNA sequencing identified 63 upregulated miRNAs in EVs from puromycin-treated podocytes. Among them, five miRNAs (miR-149, -424, -542, -582, and -874) were selected as candidates for inducing tubular apoptosis according to a literature-based search. To validate the effect of the miRNAs, HK2 cells were treated with miRNA mimics. EVs from injured podocytes induced apoptosis and p38 phosphorylation of HK2 cells. The miRNA-424 and 149 mimics led to apoptosis of HK2 cells. These results show that miRNAs in EVs from injured podocytes lead to damage to tubular epithelial cells, which may contribute to the development of tubular injury in glomerular disease.