Dapagliflozin Reduces Urinary Kidney Injury Biomarkers in Chronic Kidney Disease Irrespective of Albuminuria Level.

The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD) with low albuminuria levels have not been established. This study aimed to compare the effects of dapagliflozin on kidney injury biomarkers in patients with CKD stratified by albuminuria level. We prospectively enrolled healthy volunteers (HVs; n = 20) and patients with CKD (n = 54) with and without diabetes mellitus. Patients with CKD were divided into two age-matched and sex-matched subgroups according to urinary albumin-creatinine ratio (uACR) levels (<300 mg/g and ≥300 mg/g). The CKD group received dapagliflozin (10 mg/day). Urine samples were collected before treatment and after 3 and 6 months of dapagliflozin. Urinary kidney injury molecule-1 (KIM-1), interleukin-1ß (IL-1ß), and mitochondrial DNA nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND1) copy number were measured. The estimated glomerular filtration rate (eGFR) of patients with CKD was lower than that of HVs (P < 0.001). During the study period, eGFR decreased and uACR did not change in the CKD group. Kidney injury markers were significantly elevated in patients with CKD compared with those in HVs. Dapagliflozin reduced urinary KIM-1, IL-1ß, and mtDNA copy number in patients with CKD after 6 months of treatment. In further, the levels of urinary KIM-1 and IL-1ß, patients with CKD decreased after 6 months of dapagliflozin treatment regardless of albuminuria level. Dapagliflozin reduced urinary kidney injury biomarkers in patients with CKD, regardless of albuminuria level. These findings suggest that SGLT2 inhibitors may also attenuate the progression of low albuminuric CKD.

MicroRNA-5010-5p ameliorates high-glucose induced inflammation in renal tubular epithelial cells by modulating the expression of PPP2R2D.

INTRODUCTION: We previously reported the significant upregulation of eight circulating exosomal microRNAs (miRNAs) in patients with diabetic kidney disease (DKD). However, their specific roles and molecular mechanisms in the kidney remain unknown. Among the eight miRNAs, we evaluated the effects of miR-5010-5p on renal tubular epithelial cells under diabetic conditions in this study. RESEARCH DESIGN AND METHODS: We transfected the renal tubular epithelial cell line, HK-2, with an miR-5010-5p mimic using recombinant plasmids. The target gene of hsa-miR-5010-5p was identified using a dual-luciferase assay. Cell viability was assessed via the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Moreover, mRNA and protein expression levels were determined via real-time PCR and western blotting, respectively. RESULTS: High glucose levels did not significantly affect the intracellular expression of miR-5010-5p in HK-2 cells. Transfection of the miR-5010-5p mimic caused no change in cell viability. However, miR-5010-5p-transfected HK-2 cells exhibited significantly decreased expression levels of inflammatory cytokines, such as the monocyte chemoattractant protein-1, interleukin-1ß, and tumor necrosis factor-ɑ, under high-glucose conditions. These changes were accompanied by the restored expression of phosphorylated AMP-activated protein kinase (AMPK) and decreased phosphorylation of nuclear factor-kappa B. Dual-luciferase assay revealed that miR-5010-5p targeted the gene, protein phosphatase 2 regulatory subunit B delta (PPP2R2D), a subunit of protein phosphatase 2A, which modulates AMPK phosphorylation. CONCLUSIONS: Our findings suggest that increased miR-5010-5p expression reduces high glucose-induced inflammatory responses in renal tubular epithelial cells via the regulation of the target gene, PPP2R2D, which modulates AMPK phosphorylation. Therefore, miR-5010-5p may be a promising therapeutic target for DKD.

Dietary cholesterol intake is not associated with the development of chronic kidney disease: Results from two Korean cohort studies.

BACKGROUND AND AIMS: Although dyslipidemia is a major risk factor for chronic kidney disease (CKD), the relationship between dietary cholesterol and CKD remains unknown. We investigated the association between cholesterol intake and CKD risk. METHODS AND RESULTS: The Korea National Health and Nutrition Examination Survey (KNHANES) 2019-2021 (n = 13,769) and the Korean Genome and Epidemiology Study (KoGES) (n = 9225) data were used for this study. Cholesterol intake was assessed using a 24-h recall food frequency questionnaire, and participants were categorized into three groups (T1, T2, and T3) based on cholesterol intake. Primary outcomes were prevalence and incidence of CKD. Higher cholesterol intake was modestly associated with increased serum levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol in the KNHANES. However, we found no significant association between cholesterol intake and CKD prevalence in the KNHANES, regardless of a history of hypercholesterolemia. In the KoGES, during a median follow-up of 11.4 years, cholesterol intake was not associated with incident CKD in participants without hypercholesterolemia (hazard ratio [HR] per 10 mg increase, 1.00; 95 % confidence interval [CI], 0.99-1.01) and in those with hypercholesterolemia (HR, 1.01; 95 % CI, 0.98-1.04). Egg consumption also showed no significant association with the risk of incident CKD. Additionally, cholesterol intake had no significant interaction on the relationships between serum cholesterol levels and incident CKD. CONCLUSION: Although cholesterol intake was associated with increased serum cholesterol levels, it was not associated with CKD prevalence and incidence. Our findings suggest that reducing cholesterol intake alone may not be sufficient to prevent CKD.

Evaluating anti-thymocyte globulin induction doses for better allograft and patient survival in Asian kidney transplant recipients.

Anti-thymocyte globulin (ATG) is currently the most widely prescribed induction regimen for preventing acute rejection after solid organ transplantation. However, the optimal dose of ATG induction regimen in Asian kidney recipients is unclear. Using the Korean Organ Transplantation Registry, we performed a retrospective cohort study of 4579 adult patients who received renal transplantation in South Korea and divided them into three groups according to the induction regimen: basiliximab group (n = 3655), low-dose ATG group (≤ 4.5 mg/kg; n = 467), and high-dose ATG group (> 4.5 mg/kg; n = 457). We applied the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) package to generate high-quality propensity score weights for intergroup comparisons. During four-year follow-ups, the high-dose ATG group had the highest biopsy-proven acute rejection rate (basiliximab 20.8% vs. low-dose ATG 22.4% vs. high-dose ATG 25.6%; P < 0.001). However, the rates of overall graft failure (4.0% vs. 5.0% vs. 2.6%; P < 0.001) and mortality (1.7% vs. 2.8% vs. 1.0%; P < 0.001) were the lowest in the high-dose ATG group. Our results show that high-dose ATG induction (> 4.5 mg/kg) was superior to basiliximab and low-dose ATG induction in terms of graft and patient survival in Asian patients undergoing kidney transplant.

Association between abdominal perivascular adipose tissue quantity and quality assessed by CT and cardiometabolic risk.

BACKGROUND & AIMS: Changes in the perivascular adipose tissue (PVAT) are associated with the risk of metabolic syndrome (MetS). We hypothesized that the quantity and quality of PVAT measured by computed tomography (CT) are associated with cardiometabolic risk. METHODS: This study analyzed the data of 505 participants (men, 72.7%) who underwent general health checkups, including abdominal and pelvic CT. We measured the volume and fat attenuation index (FAI) of the abdominal periaortic (APA) and renal sinus (RS) adipose tissues. Participants were categorized into three groups according to the number of MetS components they had based on the modified ATP III criteria (0, 1-2, and ≥3). RESULTS: Moving stepwise from the no MetS component group to the 1-2 components group to the ≥3 components group, all PVAT volumes increased and all PVAT FAIs decreased consistently. Greater PVAT volume was independently associated with greater prevalence of MetS components in the ≥3 components group (P = 0.002 for right RS, P = 0.027 for left RS, and P = 0.001 for APA), whereas lower FAI in all PVATs was associated with greater prevalence of MetS components in the 1-2 components group after adjusting for the corresponding adipose tissue volumes (P = 0.007 for right RS, P = 0.002 for left RS, and P = 0.001 for APA). CONCLUSION: Higher abdominal PVAT volume was independently associated with prevalent MetS. Moreover, lower abdominal PVAT FAI was associated with mild metabolic derangement. Image-based assessment of abdominal PVAT may be a potential biomarker for cardiometabolic risk.

Time-Varying Risk Factors for Incident Fractures in Kidney Transplant Recipients: A Nationwide Cohort Study in South Korea.

Little is known about the time-varying risk factors for fractures in kidney transplant recipients (KTRs). Using the Korea Organ Transplantation Registry, a nationwide cohort study of KTRs, the incidence, locations, and time-varying predictors of fractures were analyzed, including at baseline and post-transplant 6-month variables in KTRs who underwent KT between January 2014 and June 2019. Among 4134 KTRs, with a median follow-up of 2.94 years (12,441.04 person-years), 63 patients developed fractures. The cumulative 5-year incidence was 2.10%. The most frequent locations were leg (25.40%) and foot/ankle (22.22%). In multivariable analysis, older recipient age at baseline (hazard ratio [HR], 1.035; 95% confidence interval [CI], 1.007-1.064; p = 0.013) and higher tacrolimus trough level (HR, 1.112; 95% CI, 1.029-1.202; p = 0.029) were associated with higher risks for fractures. Pretransplant diabetes mellitus had a time-dependent impact on fractures, with increasing risk as time elapses (HR for diabetes mellitus 1.115; 95% CI, 0.439-2.832; HR for diabetes mellitus × time, 1.049; 95% CI, 1.007-1.094; p = 0.022). In conclusion, KTRs had a high risk of peripheral skeletal fractures in the first 5 years. At baseline recipient age, pretransplant diabetes mellitus and tacrolimus trough level after KT were responsible for the fractures in KTRs.

Association of glomerular hyperfiltration with carotid artery plaque in the general population.

BACKGROUND AND AIMS: Glomerular hyperfiltration (GHF) is a hemodynamic change of the kidney as an adaptive response to nephron loss. Although GHF is associated with metabolic risk factors and cardiovascular disease (CVD), the mechanisms that explain these relationships remain largely unknown. This is partially caused by a non-unified definition of GHF based on pathophysiologic vascular changes. Thus, the objective of this study was to evaluate the association between various definitions of GHF and carotid plaque in a health checkup cohort. METHODS: A total of 4493 individuals without history of CVD who had carotid ultrasonography (USG) results available between January 2016 and June 2018 were enrolled. GHF was defined as >90th percentile of eGFR residuals after adjusting for confounding factors. Carotid plaque score was calculated based on carotid USG results. RESULTS: Of 4493 individuals (mean age, 52.3 ± 10.1 years; 3224 [71.8%] males), 449 subjects were included in the GHF group (mean eGFR, 107.0 ± 7.1 ml/min/1.73 m2) and 4044 subjects were included in the non-GHF group (mean eGFR, 92.5 ± 12.3 ml/min/1.73 m2). When the GHF group was compared to the non-GHF group, GHF was associated with the presence of significant carotid plaque (carotid plaque score ≥2) (adjusted OR: 1.46; 95% CI: 1.16 to 1.83; p = 0.001). GHF defined in this study showed higher sensitivity to the presence of carotid plaque than other definitions of GHF. CONCLUSIONS: GHF status was associated with risk of carotid plaque in individuals without history of CVD. Presence of subclinical carotid plaque was associated with risk of future CVD. Therefore, GHF based on creatinine could be a useful surrogate marker for surveillance of CVD in asymptomatic individuals.

Changes in abdominal fat depots after bariatric surgery are associated with improved metabolic profile.

BACKGROUND AND AIMS: Obesity associated with a change in the quantity and quality of fat depots. Using computed tomography (CT), we analyzed abdominal fat depots in patients with obesity after bariatric surgery according to their metabolic health status. METHODS AND RESULTS: We recruited 79 individuals with metabolically unhealthy obesity before bariatric surgery and compared them with age-sex matched healthy controls. The volume and fat attenuation index (FAI) of fat depots were measured using CT scans that were conducted prior to and a year after bariatric surgery. 'Metabolically healthy' was defined as having no hypertension, normal fasting glucose and a waist-to-hip ratio of <1.05 for men and <0.95 for women. Individuals who achieved a metabolic health status conversion (MHC) (n = 29, 37%)-from unhealthy to healthy-were younger (p < 0.001) as compared to individuals without MHC. Pre-surgery BMI and reduction of BMI did not differ between the two groups (p = 0.099, p = 0.5730). Bariatric surgery reduced the volume and increased the FAI of fat depots. Baseline lower abdominal periaortic adipose tissue (AT) volume (p = 0.014) and great percent reduction in renal sinus AT volume after surgery (p = 0.019) were associated with MHC after surgery. Increased intraperitoneal AT FAI (p = 0.031) was also associated with MHC. CONCLUSION: MHC was not associated with improvement in general obesity, based on indicators such as reduction of BMI after surgery. Weight reduction induced specific abdominal fat depot changes measured by CT are positively associated with MHC.

Empagliflozin suppresses urinary mitochondrial DNA copy numbers and interleukin-1ß in type 2 diabetes patients.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1ß (IL-1ß) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1ß levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in healthy volunteers. Empagliflozin induced marked reduction in both urinary and serum mtND-1 and mtCOX-3 copy numbers, as well as in urinary IL-1ß. Empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response in T2DM patients. This would explain the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes.

Circulating miRNAs in extracellular vesicles related to treatment response in patients with idiopathic membranous nephropathy.

BACKGROUND: Extracellular vesicle (EV)-microRNAs (miRNAs) are potential biomarkers for various renal diseases. This study attempted to identify the circulating EV-miRNA signature not only for discriminating idiopathic membranous nephropathy (IMN) from idiopathic nephrotic syndrome (INS), but also to predict the treatment response of patients with IMN. METHODS: We prospectively enrolled 60 participants, including those with IMN (n = 19) and INS (n = 21) and healthy volunteers (HVs; n = 20) in this study. Using RNA sequencing, we assessed the serum EV-miRNA profiles of all participants. To identify the EV-miRNAs predictive of treatment response in IMN, we also analyzed EV-miRNAs among patients with IMN with and without clinical remission. RESULTS: The expression levels of 3 miRNAs differed between IMN patients, INS patients and HVs. In addition, compared to HVs, RNA sequencing revealed differential expression of 77 and 44 EV-miRNAs in patients with IMN without and with remission, respectively. We also identified statistically significant (|fold change ≥ 2, p < 0.05) differences in the expression levels of 23 miRNAs in IMN without remission. Biological pathway analysis of miRNAs in IMN without remission indicated that they are likely involved in various pathways, including renal fibrosis. CONCLUSION: Our study identified EV-miRNAs associated with IMN as well as those associations with therapeutic response. Therefore, these circulating EV-miRNAs may be used as potential markers for the diagnosis and prediction of treatment response in patients with IMN.

Weight Change Alters the Small RNA Profile of Urinary Extracellular Vesicles in Obesity.

INTRODUCTION: Various kidney diseases reportedly show different urinary extracellular vesicle (EV) RNA profiles. Although obesity is one of the main causes of chronic kidney disease, the expression pattern of urinary EV RNA in obesity is uncertain. Our aim was to sequence the small RNA profiles of urinary EVs in obese patients before and after weight reduction and compare them to those of healthy volunteers (HVs). METHODS: We recruited age-sex-matched obese patients and HVs. The small RNA profiles of urinary EVs were analyzed using RNA sequencing. To evaluate the effect of weight reduction, small RNA profiles of urinary EVs 6 months after bariatric surgery were also analyzed. RESULTS: The proportion of urinary EVs transfer RNA and microRNA of obese patients differed from that of HVs. Obese patients showed differential expression of 1,343 small RNAs in urinary EVs compared to HVs (fold change ≥2 and p value <0.05). Among those, 61 small RNAs were upregulated in obese patients and downregulated after weight reduction, whereas 167 small RNAs were downregulated in obese patients and upregulated after weight reduction. RNA sequencing revealed the correlation between the specific urinary EV small RNAs and clinical parameters including body weight, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, serum glucose, estimated glomerular filtration rate, and albuminuria. CONCLUSION: Obese patients showed distinct urinary EV small RNA profiles compared to HVs. Weight reduction altered urinary EV small-RNA profiles in obese patients.

Association between blood pressure and the risk of chronic kidney disease in treatment-naïve hypertensive patients.

BACKGROUND: Although hypertension is a well-known risk factor for chronic kidney disease (CKD), the blood pressure (BP) at which antihypertensive interventions should be initiated remains to be determined. Therefore, we investigated the association between BP and CKD in treatment-naïve individuals. METHODS: This prospective cohort study considered 7,343 individuals in the Korean Genome and Epidemiology Study who were not taking antihypertensive medications. Subjects were categorized into six groups according to their systolic BP (SBP) and five groups according to their diastolic BP (DBP). The primary outcome was incident CKD, which was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or the development of proteinuria. The secondary outcome was incident cardiovascular disease (CVD). RESULTS: In the time-varying Cox models, the hazard ratios (95% confidence interval [CI]) for CKD were 1.39 (1.10-1.77) with SBP 130-139 mmHg, 1.79 (1.40-2.28) with SBP 140-159 mmHg, and 3.22 (2.35-4.40) with SBP ≥ 160 mmHg, compared with SBP 100-119 mmHg. In addition, the hazard ratios (95% CI) for CKD were 1.88 (1.48-2.37) with DBP 90-99 mmHg and 4.30 (3.20-5.76) with DBP ≥ 100 mmHg, compared with DBP 70-79 mmHg. A significantly increased CVD risk was also observed in subjects with SBP ≥ 130 mmHg or DBP ≥ 90 mmHg. CONCLUSION: Our findings indicate that SBP ≥ 130 mmHg and DBP ≥ 90 mmHg are associated with an increased risk of CKD. Therefore, BP-lowering strategies should be considered starting at those thresholds to prevent CKD development.

Abdominal periaortic and renal sinus fat attenuation indices measured on computed tomography are associated with metabolic syndrome.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Both metabolic syndrome and obesity were associated with lower RS and APA adipose tissue FAI, and APA FAI performed best for predicting metabolic syndrome. KEY POINTS: • 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.

Pericoronary fat attenuation index in computed tomography angiography is associated with mortality in end-stage renal disease.

BACKGROUND: An increased pericoronary fat attenuation index (FAI) on computed tomography angiography (CTA) is associated with increased all-cause and cardiac mortality in the general population. However, the ability of pericoronary FAI to predict long-term outcomes in chronic kidney disease (CKD) patients is unknown. METHODS: In this single-center retrospective longitudinal cohort study, we assessed the utility of CTA-based pericoronary FAI measurement to predict mortality of CKD patients, including those with end-stage renal disease (ESRD). Mapping and analysis of pericoronary FAI involved three major proximal coronary arteries. The prognostic value of pericoronary FAI for long-term mortality was assessed with multivariable Cox regression models. RESULTS: Among 268 CKD participants who underwent coronary CTA, 209 participants with left anterior descending artery (LAD) FAI measurements were included. The pericoronary FAI measured at the LAD was not significantly associated with adjusted risk of allcause mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 0.94-3.51) in any CKD group. However, ESRD patients with elevated pericoronary FAI values had a greater adjusted risk of all-cause mortality compared with the low-FAI group (HR, 2.26; 95% CI, 1.11-4.61). CONCLUSION: The pericoronary FAI measured at the LAD predicted long-term mortality in patients with ESRD, which could provide an opportunity for early primary intervention in ESRD patients.

Metformin use and cardiovascular outcomes in patients with diabetes and chronic kidney disease: a nationwide cohort study.

BACKGROUND: Metformin has recently been shown not to increase the risk of lactic acidosis in patients with chronic kidney disease (CKD). Thus, the criteria for metformin use in this population has expanded. However, the relationship between metformin use and clinical outcomes in CKD remains controversial. METHODS: This study considered data from 97,713 diabetes patients with an estimated glomerular filtration rate of <60 mL/min/1.73 m2. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcomes were all-cause mortality and incident end-stage renal disease (ESRD). RESULTS: Metformin users had a significantly higher risk of MACCE than non-users (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.14-1.26; p < 0.001). However, metformin users had a lower risk of all-cause mortality (HR, 0.78; 95% CI, 0.74-0.81; p < 0.001) and ESRD (HR, 0.44; 95% CI, 0.42-0.47; p < 0.001) during follow-up than non-users did. The relationships between metformin use and clinical outcomes remained consistent in propensity score matching analyses and subgroup analyses of patients with adequate adherence to anti-diabetes medication. CONCLUSION: Treatment with metformin was associated with an increased risk of MACCE in patients with diabetes and CKD. However, metformin users had a lower risk of all-cause mortality and ESRD during follow-up than non-users did. Therefore, metformin needs to be carefully used in patients with CKD.

A multicentre, multi-national, double-blind, randomised, active-controlled, parallel-group clinical study to assess the safety and efficacy of PDA10 (Epoetin-alpha) vs. Eprex® in patients with anaemia of chronic renal failure.

BACKGROUND: Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management. OBJECTIVE: To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®. METHODS: A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase. RESULTS: The PDA10 and Eprex® were shown to be therapeutically equivalent (p < 0.0001) with mean absolute change in haemoglobin from baseline of - 0.176 (± 0.91) g/dl and - 0.118 (± 1.114) g/dl, respectively. Weekly dose change was 10.01 IU/kg/week in PDA10 group and 10.30 IU/kg/week in Eprex® group, which has no significant difference. There were no significant differences in the safety profile between PDA10 and Eprex® groups. CONCLUSION: This study has confirmed the therapeutic equivalence between PDA10 and Eprex® in terms of efficacy, dosage requirement and safety profile in haemodialysis patients with renal anaemia. TRIAL REGISTRATION: The study was registered with the National Medical Research Register ( NMRR-13-400-16313 ). This study has been registered retrospectively with Clinical Research Information Service ( CRiS ), Republic of Korea on 25 March 2021.

Epicardial adipose tissue radiodensity is associated with all-cause mortality in patients undergoing hemodialysis.

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.

Relationship between carbohydrate-to-fat intake ratio and the development of chronic kidney disease: A community-based prospective cohort study.

BACKGROUND & AIMS: 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. METHODS: 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) of <60 mL/min/1.73 m2 and/or proteinuria (≥1+). RESULTS: During 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 intake > 1 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 ratio <16.1%, but the risk was nearly constant in F/C ratio ≥16.1%. CONCLUSIONS: 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.

Eculizumab therapy on a patient with co-existent lupus nephritis and C3 mutation-related atypical haemolytic uremic syndrome: a case report.

BACKGROUND: Thrombotic microangiopathy (TMA), a rare but serious complication of systemic lupus erythematosus (SLE), is associated with poor outcomes to conventional immunosuppressive therapy. Recently, eculizumab, a humanised monoclonal antibody that blocks the complement factor 5, has been known to effectively treat atypical haemolytic uremic syndrome (aHUS). Here, we report a case of aHUS co-existing with lupus nephritis that was successfully treated with eculizumab. CASE PRESENTATION: A 23-year-old man presented with abdominal pain and diarrhoea. Initial laboratory tests have shown thrombocytopaenia, microangiopathic haemolytic anaemia, and acute kidney injury. Immunologic tests were consistent with SLE. Kidney biopsy have revealed lupus nephritis class IV-G with TMA. Genetic analysis have shown complement C3 gene mutations, which hints the co-existence of lupus nephritis with aHUS, a form of complement-mediated TMA. Although initial treatment with haemodialysis, plasma exchange, and conventional immunosuppressive therapy (steroid and cyclophosphamide) did not appreciably improve kidney function and thrombocytopaenia, the patient was able to respond to eculizumab therapy. CONCLUSIONS: Due to the similar features of TMA and SLE, clinical suspicion of aHUS in patients with lupus nephritis is important for early diagnosis and prompt management. Timely administration of eculizumab should be considered as a treatment option for aHUS in lupus nephritis patients to yield optimal therapeutic outcomes.