Fibrotic Burden in Patients With Hepatitis B Virus-Related Cirrhosis Is Independently Associated With Poorer Kidney Outcomes.

BACKGROUND: We investigated whether higher fibrotic burden was independently associated with poorer kidney outcomes in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: A total of 1691 patients with radiologically diagnosed HBV-related cirrhosis but without baseline chronic kidney disease (CKD) who underwent transient elastography (TE) between March 2012 and August 2018 were selected. The study outcome was the composite of development of incident CKD, defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 or proteinuria (≥1+ on dipstick test) on 2 consecutive measurements during follow-up, 50% decline in eGFR or onset of end-stage kidney disease (initiation of chronic dialysis), or all-cause mortality. RESULTS: The mean age was 53.4 years and 1030 (60.9%) patients were male. During 8379 person-years of follow-up (median 5.2 years), 60 (3.5%) patients experienced study outcomes. When stratified according to TE-defined fibrotic burden, multivariable Cox models revealed that risk of poorer kidney outcomes was 2.77-fold (95% confidence interval, 1.16-6.63; P < .001) higher in patients with liver stiffness range indicating cirrhosis (≥11.7 kPa), compared to those without significant liver fibrosis (<7.9 kPa). These associations remained significant even after adjusting for vigorous confounders. CONCLUSIONS: Higher fibrotic burden assessed using TE was independently associated with poorer kidney outcomes in patients with HBV-related cirrhosis.

Findings from the KNOW-CKD Study indicate that higher systolic blood pressure time in target range is associated with a lower risk of chronic kidney disease progression.

Time-in-target range (TTR) of systolic blood pressure (SBP) is determined by the proportion of time during which SBP remains within a defined optimal range. TTR has emerged as a useful metric for assessing SBP control over time. However, it is uncertain if SBP-TTR can predict the progression of chronic kidney disease (CKD). Here, we investigated the association between SBP-TTR during the first year of enrollment and CKD progression among 1758 participants from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). Baseline median estimated glomerular filtration rate (eGFR) was 51.7 ml/min per 1.73 m2. Participants were categorized into four SBP-TTR groups (0%, 1-50%, 51-99%, and 100%). The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of kidney replacement therapy. During the follow-up period (9212 person-years over a median 5.4 years), the composite outcome occurred in 710 participants. In the multivariate cause-specific hazard model, a one-standard deviation increase in SBP-TTR was associated with an 11% lower risk of the composite outcome with hazard ratio, 0.89 (95% confidence interval, 0.82-0.97). Additionally, compared to patients with SBP-TTR 0%, the respective hazard ratios for those with SBP-TTR 1-50%, 51-99%, and 100% were 0.85 (0.68-1.07), 0.76 (0.60-0.96), and 0.72 (0.55-0.94), and the respective corresponding slopes of eGFR decline were -3.17 (-3.66 to -2.69), -3.02 (-3.35 to -2.68), -2.62 (-2.89 to - 2.36), and -2.33 (-2.62 to -2.04) ml/min/1.73 m2. Thus, higher SBP-TTR was associated with a decreased risk of CKD progression in patients with CKD.

Difference Between Estimated GFR Based on Cystatin C Versus Creatinine and Incident Atrial Fibrillation: A Cohort Study of the UK Biobank.

RATIONALE & OBJECTIVE: The difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFRdiff) has been suggested to reflect factors distinct from kidney function that are associated with cardiovascular risk. However, the association between eGFRdiff and atrial fibrillation (AF) risk has not been extensively evaluated. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Using data from the UK Biobank, this study included 363,494 participants with measured serum creatinine and cystatin C levels and without a prior diagnosis of AF or a history of related procedures. EXPOSURE: Estimated GFRdiff, calculated as cystatin C-based eGFR minus creatinine-based eGFR. Estimated GFRdiff was also categorized as negative (<-15mL/min/1.73m2), midrange (-15 to 15mL/min/1.73m2), or positive (≥15mL/min/1.73m2). OUTCOME: Incident AF. ANALYTICAL APPROACH: Subdistribution hazard models were fit, treating death that occurred before development of AF as a competing event. RESULTS: During the median follow-up period of 11.7 years, incident AF occurred in 18,994 (5.2%) participants. In the multivariable-adjusted model, participants with a negative eGFRdiff had a higher risk of incident AF (subdistribution HR [SHR], 1.25 [95% CI, 1.20-1.30]), whereas participants with a positive eGFRdiff had a lower risk of AF (SHR, 0.81 [95% CI, 0.77-0.87]) compared with those with a midrange eGFRdiff. When eGFRdiff was treated as a continuous variable in the adjusted model, every 10mL/min/1.73m2 higher eGFRdiff was associated with a 0.90-fold decrease in the risk of incident AF. LIMITATIONS: A single measurement of baseline serum creatinine and cystatin C levels. CONCLUSIONS: The difference between cystatin C- and creatinine-based eGFRs was associated with the risk of AF development. A higher eGFRdiff was associated with a lower risk of AF. These findings may have implications for the management of patients at risk of incident AF. PLAIN-LANGUAGE SUMMARY: The difference between cystatin C-based estimated glomerular filtration rate (eGFR) and creatinine-based eGFR has recently gained attention as a potential indicator of cardiovascular outcomes influenced by factors other than kidney function. This study investigated the association between the differences in 2 eGFRs (cystatin C-based eGFR minus creatinine-based eGFR) and incident atrial fibrillation (AF) among>340,000 participants from the UK Biobank Study. Compared with those with a near zero eGFR difference, participants with a negative eGFR difference had a higher risk of AF, while those with a positive eGFR difference had a lower risk. These findings suggest that measuring eGFR differences may help identify individuals at a higher risk of developing AF.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes.

RATIONALE & OBJECTIVE: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010. EXPOSURE: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. OUTCOME: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. ANALYTICAL APPROACH: Cox proportional hazards regression analyses, including a cause-specific competing risk model. RESULTS: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. LIMITATIONS: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. CONCLUSIONS: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. PLAIN-LANGUAGE SUMMARY: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.

New-onset atrial fibrillation in seropositive rheumatoid arthritis: association with disease-modifying anti-rheumatic drugs treatment.

OBJECTIVE: Atrial fibrillation (AF) is a potentially lethal complication that leads to increased hospitalization, disability and mortality. Furthermore, the risk of cardiovascular disease is increased in RA. We evaluated whether DMARD treatment is associated with incident AF in patients with seropositive RA (SPRA). METHODS: The South Korean Health Insurance Review and Assessment Service database was used to identify patients newly diagnosed with SPRA between 2010 and 2020. A nested case-control analysis was performed to match AF-affected patients to unaffected controls for age, sex, follow-up duration, and index year of SPRA diagnosis at a 1:4 ratio. Adjusted conditional logistic regression was used to identify the predictive factors for AF. RESULTS: Of the 108 085 patients with SPRA, 2,629 (2.4%) developed new-onset AF, and the proportion of females was ∼67%. In the matched population, pre-existing comorbidities of hypertension, chronic kidney disease, and heart failure were associated with increased risk of AF. Meanwhile, the use of methotrexate (MTX) decreased the risk of incident AF [adjusted odds ratio (aOR), 0.89], whereas the use of leflunomide (LEF) increased AF (aOR, 1.21). In a subgroup of patients aged ≥50 years, LEF and adalimumab increased the occurrence of AF, while MTX decreased AF in males and LEF increased this risk in females. CONCLUSION: Although the number of subjects developing new-onset AF was small, MTX decreased and LEF increased incident AF in patients with RA. Especially, a distinct pattern of AF risk with DMARDs usage was observed according to age and sex.

Outcomes of ABO-Incompatible Living Donor Kidney Transplantation Compared to Waiting or Deceased Donor Kidney Transplantation.

INTRODUCTION: ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) is considered only for patients who do not have an ABO-compatible (ABOc) LD. Therefore, a clinically practical question is whether to proceed with ABOi LDKT or remain on dialysis while waiting for ABOc deceased donor kidney transplantation (DDKT). However, this issue has not been addressed in Asian countries, where ABOi LDKT programs are more active than DDKT programs. METHODS: A total of 426 patients underwent ABOi-LDKT between 2010 and 2020 at Seoul National University Hospital and Severance Hospital, Korea. We compared outcomes between the ABOi-LDKT and the propensity-matched control groups (waiting-list-only group, n = 1,278; waiting-list-or-ABOc-DDKT group, n = 1,278). RESULTS: The ABOi-LDKT group showed a significantly better patient survival rate than the waiting-list-only group (p = 0.001) and the waiting-list-or-ABOc-DDKT group (p = 0.048). When the ABOi-LDKT group was categorized into a high-titer group (peak anti-ABO titer ≥1:128) and a low-titer group (peak anti-ABO titer ≤1:64), the low-titer group showed better patient survival rates than those of the waiting-list-or-ABOc-DDKT group (p = 0.046) or the waiting-list-only group (p = 0.004). In contrast, the high-titer ABOi-LDKT group showed no significant benefit in patient survival compared to the waiting-list-or-ABOc-DDKT group. Death-censored graft survival in the ABOi-LDKT group was not significantly different from that in the ABOc-DDKT group (p = 0.563). CONCLUSION: The ABOi-LDKT group has better outcomes than the waiting-list-or-ABOc-DDKT group in a country with a long waiting time.

Clinical relevance of the living kidney donor profile index in Korean kidney transplant recipients.

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. METHODS: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1-19.9, and ≥20. RESULTS: During a median follow-up of 119 months, 232 recipients (12.5%) experienced death-censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death-censored graft loss independent of recipient characteristics (LKDPI 1-19.9: HR 1.389, 95% CI 1.036-1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50-2.998). High LKDPI score was also significantly associated with increased risk of biopsy-proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. CONCLUSION: High LKDPI scores were associated with an increased risk of death-censored graft loss, biopsy-proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort.

Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

BACKGROUND: With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. METHODS: Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. RESULTS: Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). CONCLUSION: Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

Low skeletal muscle mass is associated with mortality in kidney transplant recipients.

Muscle wasting in chronic kidney disease is associated with increased cardiovascular events, morbidity, and mortality. However, whether pretransplantation skeletal muscle mass affects kidney transplantation (KT) outcomes has not been established. We analyzed 623 patients who underwent KT between 2004 and 2019. We measured the cross-sectional area of total skeletal muscle at the third lumbar vertebra level on pretransplantation computed tomography scan. The patients were grouped into low and normal skeletal muscle mass groups based on the sex-specific skeletal muscle mass index lowest quartile. During the entire follow-up period, 45 patients (7.2%) died and 56 patients (9.0%) experienced death-censored graft loss. Pretransplantation low skeletal muscle mass was independently associated with all-cause mortality (adjusted hazard ratio, 2.269; 95% confidence interval, 1.232-4.182). Low muscle mass was also associated with an increased risk of hospital readmission within 1 year after transplantation. Death-censored graft survival rates were comparable between the 2 groups. The low muscle group showed higher creatinine-based estimated glomerular filtration rates (eGFRs) than the normal muscle group. Although cystatin C-based eGFRs were measured in only one-third of patients, cystatin C-based eGFRs were comparable between the 2 groups. Pretransplantation low skeletal muscle mass index is associated with an increased risk of mortality and hospital readmission after KT.

The 2021 KDIGO blood pressure target and the progression of chronic kidney disease: Findings from KNOW-CKD.

BACKGROUND: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes. METHODS: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow-up period. RESULTS: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person-years of follow-up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person-years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause-specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60-0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13-1.64) for BP above both targets, compared with BP controlled within 2012 target only. CONCLUSION: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline.

Association of Plant Protein Intake With Risk of Incident CKD: A UK Biobank Study.

RATIONALE & OBJECTIVE: Data suggest that various dietary interventions slow kidney disease progression and improve clinical outcomes for those with chronic kidney disease (CKD). However, the association between plant protein intake and incident CKD has been uncertain. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 117,809 participants who completed at least 1 dietary questionnaire and had an estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m2, a urinary albumin-creatinine ratio (UACR)<30mg/g, and no history of CKD. EXPOSURE: Daily plant protein intake in g/kg/day. OUTCOME: Incident CKD based on the International Classification of Diseases, 10th Revision (ICD-10) or the Office of Population Censuses and Surveys Classification of Interventions and Procedures, version 4 (OPCS-4) codes. ANALYTICAL APPROACH: A cause-specific proportional hazards analysis incorporating competing risks that treated death occurring before incident CKD as a competing event. RESULTS: During a median follow-up period of 9.9 years, incident CKD occurred in 3,745 participants (3.2%; incidence rate, 3.2 per 1,000 person-years). In a multivariable model, the adjusted hazard ratio (AHR) for the second, third, and highest quartiles of plant protein intake was 0.90 (95% CI, 0.82-0.99), 0.83 (95% CI, 0.75-0.92), and 0.82 (95% CI, 0.73-0.93), respectively, compared with the lowest quartile. Modeled as a continuous variable, the AHR per 0.1g/kg/day plant protein intake increase was 0.96 (95% CI, 0.93-0.99). This beneficial association was also consistent in secondary analyses for which CKD was defined based on codes or 2 consecutive measures of eGFR<60mL/min/1.73m2 or UACR>30mg/g. Various sensitivity analyses demonstrated consistent findings. LIMITATIONS: Potential incomplete dietary assessments; limited generalizability due to the characteristics of participants in the UK Biobank Study. CONCLUSIONS: In this large, prospective cohort study, greater dietary plant protein intake was associated with a lower risk of incident CKD. Further interventional studies demonstrating the kidney-protective benefits of plant protein intake are warranted. PLAIN-LANGUAGE SUMMARY: Plant-based diets confer various health benefits, including lowering the risk of cardiovascular disease and certain cancers. However, the relationship between plant protein intake and the risk of chronic kidney disease (CKD) remains unclear. Our study investigated the association between plant protein intake and the development of CKD. Using the UK Biobank Study data, we found that participants with a higher plant protein intake had a lower risk of developing CKD. Our finding suggests that a higher dietary intake of plant-based protein may be beneficial for kidney health and provides insight into dietary interventions to prevent CKD in primary care settings.

Incidence of septic arthritis in patients with ankylosing spondylitis and seropositive rheumatoid arthritis following TNF inhibitor therapy.

OBJECTIVES: Septic arthritis (SA) is a serious complication occurring in the joints, and its risk increases with immunosuppressive therapy. This study investigated whether TNF inhibitors increase the risk of SA in patients with AS and seropositive RA (SPRA). METHODS: We searched the South Korean Health Insurance Review and Assessment Service database for incident cases of AS and SPRA between 2010 and 2020. SA was defined using the diagnostic code M00 and hospital admission. Cox-proportional hazards analysis was conducted to compare the incidence of SA according to TNF inhibitor (infliximab, etanercept, adalimumab/golimumab) use during follow-up. RESULTS: Of the 145 129 patients analysed, 1170 (0.8%) developed SA during the follow-up period. Older age; male sex; SPRA diagnosis; comorbidities of hypertension (HTN), diabetes mellitus (DM) and chronic pulmonary disease (CPD); and infliximab and etanercept use increased the incidence of SA in the overall population. However, in patients with AS, only age and renal disease were predictors of SA, and TNF inhibitors did not increase the incidence of SA. Meanwhile, patients with SPRA treated with TNF inhibitors were prone to SA regardless of TNF inhibitor type, and age, HTN, DM and CPD were associated with SA. The incidence of SA was prominent after the first year of commencing TNF inhibitor therapy, for both AS and SPRA. CONCLUSION: TNF inhibitors increase the incidence of SA, specifically in patients with SPRA, but not AS. Importantly, age, comorbidities and the early time period after starting TNF inhibitors were associated with SA, which should be considered simultaneously when initiating TNF inhibitor therapy.

Insomnia in patients on incident maintenance dialysis and the risk of major acute cardio-cerebrovascular events and all-cause mortality.

BACKGROUND AND HYPOTHESIS: Insomnia is a known risk factor for cardio-cerebrovascular disease in the general population; however, its effect on cardio-cerebrovascular outcomes in end-stage kidney disease patients is unclear. Therefore, this study aimed to investigate the association between cardio-cerebrovascular outcomes and insomnia in patients who initiated maintenance dialysis. METHODS: This study used nationwide Korean health insurance claims data to analyze 79 420 patients who initiated maintenance dialysis from January 2009 to December 2017. Insomnia was defined using claim codes and sleep medication prescription data. Patients were categorized according to the presence of insomnia before and after dialysis initiation: a) no insomnia, b) insomnia before dialysis only (improved insomnia), c) insomnia after dialysis only (developed insomnia), and d) insomnia in both periods (persistent insomnia). The primary and secondary outcomes were major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality, respectively. The outcome risks were estimated by Cox regression models with inverse probability of treatment weighting. RESULTS: The mean age was 61.4 ± 13.4 years, and 39.7% were women. During the transition period from pre-dialysis to maintenance dialysis, 13.2% experienced insomnia. The insomnia groups showed significantly higher risks for MACCE (weighted hazard ratios [95% confidence intervals]: developed insomnia, 1.26 [1.25-1.28]; improved insomnia, 1.31 [1.29-1.33]; persistent insomnia, 1.39 [1.37-1.41]) and higher all-cause mortality risks than the no insomnia group. The insomnia related cardio-cerebrovascular disease risk elevation was more prominent in younger and male patients. CONCLUSIONS: Insomnia may increase cardio-cerebrovascular disease and all-cause mortality risk among end-stage kidney disease patients who initiate maintenance dialysis.

Association of coronary artery calcium with adverse cardiovascular outcomes and death in patients with chronic kidney disease: results from the KNOW-CKD.

BACKGROUND: In East Asian countries, patients with chronic kidney disease (CKD) have lower cardiovascular risk profiles and experience fewer cardiovascular events (CVEs) than those in Western countries. Thus the clinical predictive performance of well-known risk factors warrants further testing in this population. METHODS: The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) is a multicenter, prospective observational study. We included 1579 participants with CKD G1-G5 without kidney replacement therapy between 2011 and 2016. The main predictor was the coronary artery calcium score (CACS). The primary outcome was a composite of nonfatal CVEs or all-cause mortality. Secondary outcomes included 3-point major adverse cardiovascular events (MACEs; the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), all CVEs and all-cause mortality. RESULTS: During a median follow-up of 5.1 years, a total of 123 primary outcome events occurred (incidence rate 1.6/100 person-years). In the multivariable Cox model, a 1-standard deviation log increase in the CACS was associated with a 1.67-fold [95% confidence interval (CI), 1.37-2.04] higher risk of the primary outcome. Compared with a CACS of 0, the hazard ratio associated with a CACS >400 was 4.89 (95% CI 2.68-8.93) for the primary outcome. This association was consistent for secondary outcomes. Moreover, inclusion of the CACS led to modest improvements in prediction indices of the primary outcome compared with well-known conventional risk factors. CONCLUSIONS: In Korean patients with CKD, the CACS was independently associated with adverse cardiovascular outcomes and all-cause death. The CACS also showed modest improvements in prediction performance over conventional cardiovascular risk factors.

Risk of cancer, tuberculosis and serious infections in patients with ankylosing spondylitis, psoriatic arthritis and psoriasis treated with IL-17 and TNF-α inhibitors: a nationwide nested case-control analysis.

OBJECTIVES: Targeting interleukin (IL)-17 and tumour necrosis factor (TNF)-α is recommended for the management of severe/refractory ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (PsO); however, safety data comparing these agents, especially in a large Asian population are unavailable. METHODS: Patients with AS, PsA and PsO were searched using the Health Insurance Review and Assessment Service database, defined according to the International Classification of Diseases-10 and unique insurance codes for rare diseases. By including patients newly diagnosed with AS, PsA, and PsO between 2010-2020, the outcomes of cancer, tuberculosis (TB) and serious infections following IL-17 and TNF-α inhibitor usage were evaluated. To investigate the association between treatments and outcomes, nested case-control analyses matching patients to controls (maximum of 1:10 ratio) according to index age, sex, index year, and follow-up duration were performed. RESULTS: Among 40322, 4953, and 5347 patients with AS, PsA, and PsO, respectively, three different datasets were generated to evaluate incidence of outcomes. Conditional logistic regression analysis revealed that cyclosporine use (odds ratio [OR] 2.286, p=0.0176) increased cancer, and a higher Charlson Comorbidity Index (CCI) score (OR 1.085, p=0.0406) and IL-17 inhibitor use only (OR 0.126, p=0.0457) showed a positive and negative association with TB, respectively. Serious infections increased in patients with high CCI scores (OR 1.117, p<0.0001), cyclosporine users (OR 1.445, p=0.0098), and medical-aided individuals (OR 1.667, p<0.0001). CONCLUSIONS: In this nationwide cohort of IL-17 and TNF-α inhibitor users, both treatments conferred comparable risk of cancer and serious infections, while IL-17 inhibitors may be advantageous for TB.

Cancers and cardiovascular diseases in patients with seropositive rheumatoid arthritis treated with JAK inhibitors, biologics and conventional synthetic DMARDs.

OBJECTIVES: Janus kinase inhibitors and biologics (JAKi/biologics) are cornerstone treatments for rheumatoid arthritis (RA). We evaluated the risks of cancers and cardiovascular diseases (CVDs) in patients with seropositive RA (SPRA) treated with JAKi/biologics. METHODS: Patients with new-onset SPRA during 2010-2020 in the national healthcare database were identified. Events of overall and site-specific cancers, as well as CVD outcomes, including deep vein thrombosis, pulmonary embolism, and composite cardiovascular events, were investigated. The relative risk of cancers and CVDs compared to conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) users was compared by evaluating the incidence rate ratios (IRRs). Time-dependent Cox analyses were performed to evaluate the relationship between JAKi/biologics usage and patient outcomes. RESULTS: A total of 101,816 and 96,220 patients with SPRA were analysed for cancers and CVD outcomes, respectively. Compared with patients treated only with csDMARDs, the IRRs of overall cancers and CVDs in patients administered JAKi/biologics were 0.88 (95% confidence interval [CI] 0.86-0.89) and 0.91 (95% CI 0.90-0.92), respectively. Site-specific lung, liver, prostate, and skin cancers were more frequent in JAKi/biologics users; JAKi did not confer a greater risk of overall CVDs and cancers compared with other biologics and csDMARDs. JAKi/biologics usage was not accounted for overall cancers and CVDs in adjusted Cox analyses. CONCLUSIONS: The incidence of overall cancer and CVD were not increased in patients with SPRA treated with JAKi/biologics and was relatively lower than csDMARD only users, underscoring optimal disease control for risk mitigation. The higher incidence of several site-specific cancers requires further investigation.

Coronary Artery Calcification Score and the Progression of Chronic Kidney Disease.

BACKGROUND: An elevated coronary artery calcification score (CACS) is associated with increased cardiovascular disease risk in patients with CKD. However, the relationship between CACS and CKD progression has not been elucidated. METHODS: We studied 1936 participants with CKD (stages G1-G5 without kidney replacement therapy) enrolled in the KoreaN Cohort Study for Outcome in Patients With CKD. The main predictor was Agatston CACS categories at baseline (0 AU, 1-100 AU, and >100 AU). The primary outcome was CKD progression, defined as a ≥50% decline in eGFR or the onset of kidney failure with replacement therapy. RESULTS: During 8130 person-years of follow-up, the primary outcome occurred in 584 (30.2%) patients. In the adjusted cause-specific hazard model, CACS of 1-100 AU (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.04 to 1.61) and CACS >100 AU (HR, 1.42; 95% CI, 1.10 to 1.82) were associated with a significantly higher risk of the primary outcome. The HR associated with per 1-SD log of CACS was 1.13 (95% CI, 1.03 to 1.24). When nonfatal cardiovascular events were treated as a time-varying covariate, CACS of 1-100 AU (HR, 1.31; 95% CI, 1.07 to 1.60) and CACS >100 AU (HR, 1.46; 95% CI, 1.16 to 1.85) were also associated with a higher risk of CKD progression. The association was stronger in older patients, in those with type 2 diabetes, and in those not using antiplatelet drugs. Furthermore, patients with higher CACS had a significantly larger eGFR decline rate. CONCLUSION: Our findings suggest that a high CACS is associated with significantly increased risk of adverse kidney outcomes and CKD progression.

Advanced liver fibrosis measured by transient elastography predicts chronic kidney disease development in individuals with non-alcoholic fatty liver disease.

AIMS/HYPOTHESIS: Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are progressive chronic conditions that share important cardiometabolic risk factors and pathogenic mechanisms. We investigated the association between liver fibrosis measured by transient elastography (TE) and the risk of incident CKD in individuals with NAFLD. METHODS: A total of 5983 participants with NAFLD (defined as controlled attenuation parameter >222 dB/m) but without CKD who underwent TE between March 2012 and August 2018 were selected. The primary outcome was incident CKD, defined as the occurrence of eGFR <60 ml min-1 [1.73 m]-2 or proteinuria (≥1+ on dipstick test) on two consecutive measurements during follow-up. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits. RESULTS: The mean age was 51.8 years and 3756 (62.8%) participants were male. During 17,801 person-years of follow-up (mean follow-up of 3.0 years), 62 participants (1.0%) developed incident CKD. When stratified into TE-defined fibrosis stages (F0-F4), multivariable Cox models revealed that risk of incident CKD was 5.40-fold (95% CI 2.46, 11.84; p < 0.001) higher in the F3/F4 group (≥9.5 kPa) than in the F0 group (<5.5 kPa). During 17,577 person-years of follow-up (mean follow-up of 3.0 years), 201 participants (3.4%) experienced the secondary outcome, for which the F3/F4 group had a 3.22-fold higher risk (95% CI 1.96, 5.28; p < 0.001) than the F0 group. CONCLUSIONS/INTERPRETATION: In this large cohort of individuals with NAFLD but without baseline CKD, advanced liver fibrosis measured by TE was significantly associated with a higher risk of incident CKD.

Tenofovir is Associated With Higher Risk of Kidney Function Decline Than Entecavir in Patients With Chronic Hepatitis B.

Of the antiviral agents currently available to patients with chronic hepatitis B (CHB), entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are 2 of 3 first-line agents.1-3 Given the well-known renal and bone toxicity associated with TDF,4 major international hepatitis B virus treatment guidelines recommend ETV over TDF in patients with predisposing factors to kidney function decline.1-3 However, as evidenced by recent studies, nephrotoxicity of antiviral agents is still an issue under debate.5-7 Therefore, we investigated the differences in the risk of kidney function decline in patients with treatment-naive CHB who were treated with ETV or TDF.