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Objectives Despite the preclinical evidence on protective effects of colchicine against kidney fibrosis, whether colchicine could delay the progression of chronic kidney disease (CKD) in humans remains unknown. This study examined the association between long-term colchicine use and risk of adverse kidney outcome in patients with CKD who were treated for hyperuricaemia or chronic gout. Methods We conducted a multicentre, nested, case-control study in three Korean hospitals. Patients were aged ≥19 years; had CKD G3–G4; and used drugs including colchicine, allopurinol and febuxostat for hyperuricaemia or chronic gout during the period from April 2000 to October 2020. Patients with CKD progression, which was defined as ≥40% decrease from the baseline estimated glomerular filtration rate or the onset of kidney failure with replacement therapy, were matched to controls based on follow-up time, age and sex. Results Overall, 3085 patients with CKD progression were matched to 11   715 control patients. Multivariate conditional logistic regression analysis showed that patients with ≥90 cumulative daily colchicine doses were associated with a lower risk of CKD progression [adjusted odds ratio (AOR), 0.77; 95% CI: 0.61, 0.96] than non-users. In the sensitivity analysis with matched CKD stages, the AOR was 0.77 (95% CI: 0.62, 0.97). This association was more pronounced in patients without diabetes or hypertension, and in patients with CKD G3. Conclusion Colchicine use is associated with a lower risk of adverse kidney outcomes in CKD patients with hyperuricaemia, or chronic gout. [ABSTRACT FROM AUTHOR]

High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT). We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1–199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT. During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02–2.87) and 2.55 (95 % CI, 1.07–6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis. CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression. [Display omitted] • Coronary artery calcification (CAC) is common in patients with chronic kidney disease (CKD). • CAC progression was more evident in patients with advanced CKD. • Greater CAC progression was associated with a higher risk for kidney failure with replacement therapy in patients with CKD. • CAC score assessment and follow-up could serve as a valuable tool for risk stratification in patients with CKD. [ABSTRACT FROM AUTHOR]

Among kidney disease patients ≥80 years progressing to end-stage renal disease, there is growing interest in conservative nondialytic management approaches. However, among those who have initiated hemodialysis, little is known about the impact of withdrawal from dialysis on mortality, nor the patient characteristics associated with withdrawal from dialysis. Historical cohort study. We examined 133,162 incident hemodialysis patients receiving care within a large national dialysis organization from 2007 to 2011. We identified patients who withdrew from dialysis, either as a listed cause of death or censor reason. Incidence rates and subdistribution hazard ratios for withdrawal from dialysis as well as 4 other censoring reasons were examined across age groups. In addition, demographic and clinical characteristics associated with withdrawal from dialysis therapy among patients ≥80 years old was assessed using logistic regression analysis. Among 17,296 patients aged ≥80 years, 10% of patients withdrew from dialysis. Duration from the last hemodialysis treatment to death was 10 [interquartile range 6-16] days in patients with available data. Withdrawal from dialysis was the second and third most common cause of death among patients aged ≥80 years and <80 years, respectively. Among patients ≥80 years, minorities were much less likely than non-Hispanic whites to stop dialysis. Other factors associated with higher odds of dialysis withdrawal included having a central venous catheter compared to an arteriovenous fistula at dialysis start, dementia, living in mid-west regions, and less favorable markers associated with malnutrition-inflammation-cachexia syndrome such as higher white blood cell counts and lower body mass index, albumin, and normalized protein catabolic rate. Among very-elderly incident hemodialysis patients, dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status. Further studies examining implications of withdrawal from dialysis in older patients are warranted [ABSTRACT FROM AUTHOR]

Background: Soluble CD89 (sCD89)-IgA complex plays a key role in the pathogenesis of IgA nephropathy (IgAN). However, there is a lack of evidence supporting this complex as a good biomarker for disease progression. This study aimed to evaluate the usefulness of sCD89-IgA complex for risk stratification of IgAN. Methods: A total of 326 patients with biopsy-proven IgAN were included. sCD89-IgA complex was measured by sandwich-enzyme-linked immunosorbent assay. The study endpoints were a 30% decline in estimated glomerular filtration rate (eGFR). Results: sCD89-IgA complex levels were inversely and weakly associated with eGFR at the time of biopsy (r = - 0.12, p = 0.03). However, the significance between the two factors was lost in the multivariate linear regression after adjustment of clinical factors (ß = 0.35, p = 0.75). In a multivariate Cox model, the highest (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.35-1.61; p = 0.45) and middle (HR, 0.93; 95% CI, 0.46-1.89; p = 0.84) tertiles of sCD89-IgA complex levels were not associated with an increased risk of developing a 30% decrease in eGFR. Furthermore, the decline rates in eGFR did not differ between groups and C-statistics revealed that the sCD89-IgA complex were not superior to clinical factors in predicting disease progression. Conclusions: This study found no association between sCD89-IgA complex levels and disease progression in IgAN. Although sCD89 can contribute to the formation of immune complexes, our findings suggest that the sCD89- IgA level is not a good predictor of adverse outcomes and has limited clinical utility as a biomarker for risk stratification in IgAN. [ABSTRACT FROM AUTHOR]

We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value. [ABSTRACT FROM AUTHOR]

Background: Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population.Methods: We analyzed 8717 subjects with normal renal function recruited from the Korean Genome and Epidemiology Study (KoGES) cohort. Based on a food frequency questionnaire, coffee consumption was categorized into 5 groups: 0 per week, <1 cup per week, 1-6 cups per week, 1 cup per day, and ≥2 cups per day. The primary outcome was incident chronic kidney disease, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2.Results: The mean age (standard deviation) of study subjects was 52.0 (8.8) years, and 47.8% were male. Among the subjects, 52.8% were daily coffee consumers. During a mean follow-up of 11.3 (range, 5.9-11.5) years, 9.5% of participants developed chronic kidney disease. The incident chronic kidney disease occurred less in daily coffee consumers. Unadjusted hazard ratios (HRs) was significantly lower in daily coffee consumers. In multivariable Cox model even after adjustment of blood pressure, hypertension, cardiovascular disease, diabetes, and amount of daily intake for caffeine-containing foods such as tea and chocolate, coffee consumers with 1 cup per day (HR, 0.76; 95% confidence interval, 0.63-0.92) and ≥2 cups per day (HR, 0.80; 95% confidence interval, 0.65-0.98) were associated with a lower risk of chronic kidney disease development than nondrinkers. Time-averaged and time-varying Cox models yielded similar results. The rates of decline in glomerular filtration were lower in daily coffee consumers.Conclusions: Our findings suggest that daily coffee intake is associated with decreased risk of the development of chronic kidney disease. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD., Methods: We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents., Results: Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32-6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents., Conclusion: The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy., (© 2024. The Author(s).)

Background: High-potassium intake is associated with a lower risk of cardiovascular disease. However, the association between potassium intake and the development of chronic kidney disease (CKD) remains unclear., Objective: The objective of this study was to investigate whether potassium intake is associated with outcomes of incident CKD., Methods: This is a population-based prospective observational cohort study from the UK Biobank cohort between 2006 and 2010. We included 317,162 participants without CKD from the UK Biobank cohort. The main predictor was spot urine potassium-to-creatinine ratio (KCR). The primary outcome was incident CKD, which was defined by the International Classification of Disease 10 codes or Operating Procedure Codes Supplement 4 codes., Results: At baseline, individuals with higher KCR had lower blood pressure, body mass index, and inflammation, and were less likely to have diabetes and hypertension. During a median follow-up of 11.9 y, primary outcome events occurred in 15,246 (4.8%) participants. In the cause-specific model, the adjusted hazard ratio (aHR) per 1-standard deviation increase in KCR for incident CKD was 0.90 [95% confidence interval (CI): 0.89, 0.92]. Compared with quartile 1 of KCR, the aHRs (95% CIs) for quartiles 2-4 were 0.98 (0.94, 1.02), 0.90 (0.86, 0.95), and 0.80 (0.76, 0.84), respectively. In sensitivity analysis with different definitions of CKD, the results were similar. In addition, further analysis with dietary potassium intake also showed a negatively graded association with the primary outcome., Conclusions: Higher urinary potassium excretion and intake were associated with a lower risk of incident CKD., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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 m 2 . 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 m 2 . Thus, higher SBP-TTR was associated with a decreased risk of CKD progression in patients with CKD., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Urolithiasis has been infrequently implicated to have a causal association with chronic kidney disease (CKD). Recently, several studies have demonstrated the relationship between urolithiasis and CKD. However, the generalizability of their results is limited. This study aimed to investigate the association between urolithiasis and the risk of incident CKD., Methods: This longitudinal cohort study used the National Health Insurance Service data, including 219 570 Korean adults with incident urolithiasis requiring procedural interventions and without prior kidney disease and 219 570 age- and sex-matched controls without urolithiasis between 1 January 2002 and 31 December 2020. Primary outcome was the development of CKD, defined by an estimated glomerular filtration rate <60 ml/min/1.73 m 2 for at least two consecutive measurements at least 90 days apart. The risk for incident CKD was further examined using the outcome defined by newly occurring diagnostic codes indicating CKD., Results: Over a mean follow-up of 6 years, 12 338 (2.8%) primary outcome events of CKD were observed (incidence rate 4.6/1000 person-years). Per multivariable Cox analysis, urolithiasis was associated with a higher risk of incident CKD [adjusted hazard ratio 1.41 (95% confidence interval 1.36-1.46)]. This association remained consistent across all clinically relevant subgroups and when the CKD outcome was defined based on the diagnostic codes in the sensitivity analysis., Conclusions: In this large national cohort study, patients with urolithiasis were associated with a higher risk of incident CKD than those without urolithiasis. Further studies are warranted to establish the benefits of preventing urolithiasis in reducing CKD development., Competing Interests: All authors declare no relevant conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

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/1.73m 2 , 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/1.73m 2 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., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to investigate the association between systolic blood pressure (SBP) and risk of incident chronic kidney disease (CKD) using marginal structural model (MSM) to reflect mutual effects of exposure and confounders on the outcome., Methods: A total of 195,970 adults with an estimated glomerular filtration rate (eGFR) of >60 mL/min/1.73 m2 and no proteinuria were included from a nationally representative sample cohort of Korean population. SBPs were measured through national health examinations. Primary outcome was incident CKD, defined as a composite of events of a decrease in eGFR to <60 mL/min/1.73 m2 or a newly developed proteinuria for at least two consecutive measurements. The association between SBP and risk of CKD was examined using Cox model, time-dependent Cox model, and MSM., Results: During a follow-up of 5 years, CKD occurred in 3,355 participants (1.7%). With SBP treated as a continuous variable, each 10-mmHg increment was associated with higher risk for incident CKD, regardless of analytical models used. Compared to SBP group of 120-129 mmHg, hazard ratios (95% confidence intervals) for incident CKD for SBP groups of <110, 110-119, 130-139, and ≥140 mmHg in MSM were 0.70 (0.62-0.80), 0.85 (0.77-0.95), 1.16 (1.05-1.27), and 1.63 (1.47-1.80), respectively., Conclusion: In this nationwide study, we found a significant relationship between higher SBP and higher risk of incident CKD. Further studies are warranted to verify the potential significance of high SBP as a preventable risk factor for the development of CKD in those with preserved renal function.

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., (© 2023 The Association for the Publication of the Journal of Internal Medicine.)

Background: This study aimed to examine the association of serum uric acid levels with incident cardiovascular disease and mortality in Korean adults without gout., Methods: This large longitudinal cohort study included adults aged > 19 years who had serum uric acid levels measured at least once at the National Health Insurance Service Ilsan Hospital from January 1, 2006 to December 31, 2015. Longitudinal data on person-level cardiovascular disease and cardiovascular mortality were linked to the National Health Insurance Service claims database and National Death Index., Results: Among a total of 92,454 study participants with a median follow-up of 4.7 years, 7,670 (8.3%) composite events of cardiovascular disease or cardiovascular mortality were observed. Multivariable Cox proportional-hazards models revealed that each 1 mg/dL increment in uric acid level was associated with a 6% higher risk of composite outcomes. Compared with that for the uric acid level category of 4.0 to < 5.0 mg/dL, adjusted hazard ratios (95% confidence interval) for uric acid level categories of 5.0 to < 6.0, 6.0 to < 7.0, and ≥ 7.0 mg/dL were 1.10 (1.04-1.18), 1.20 (1.11-1.30), and 1.36 (1.25-1.47), respectively. In the secondary analyses for cardiovascular disease or cardiovascular mortality examined separately, a higher uric acid level was similarly associated with a higher risk of each adverse outcome. These associations were generally consistent across clinically relevant subgroups., Conclusion: A graded association was noted between serum uric acid levels and cardiovascular risk, suggesting that higher uric acid levels may adversely affect cardiovascular health and survival in individuals without gout., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: Elevated blood pressure and intrarenal renin-angiotensin system activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between blood pressure and intrarenal renin-angiotensin system activity on the risk of CKD progression is unknown., Methods: We analyzed 2076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic blood pressure (SBP). The urinary angiotensinogen-to-creatinine ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy., Results: During 10 550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and urinary angiotensinogen-to-creatinine ratio on the risk of the primary outcome ( P value for interaction=0.019). In patients with urinary angiotensinogen-to-creatinine <3.65 μg/gCr, the hazard ratios (95% CIs) for SBP 120 to 129, 130 to 139, and ≥140 mmHg were 1.46 (1.07-1.99), 1.71 (1.25-2.35), and 2.40 (1.73-3.32), respectively, compared with SBP <120 mmHg. However, these associations were not observed in patients with urinary angiotensinogen-to-creatinine ≥3.65 μg/gCr., Conclusions: In this prospective CKD cohort, higher SBP was associated with CKD progression when urinary angiotensinogen levels were low, while this association was not seen when urinary angiotensinogen levels were high. This finding suggests that intrarenal renin-angiotensin system activity may modify the relationship between SBP and adverse kidney outcome.

Background: Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition., Methods: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the number of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis., Results: The C3D-GN group exhibited higher serum creatinine (p ≤ 0.001), a greater prevalence of estimated glomerular filtration rate of &lt;60 mL/min/1.72 m2 (p ≤ 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p ≤ 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p &lt; 0.001), in parallel with increased subendothelial deposition (p ≤ 0.001)., Conclusion: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.

Objective: Studies on the mutual relationship between blood pressure (BP) variability and arterial stiffness using time-dependent changes in arterial stiffness are scarce., Methods: In this prospective cohort of Korean patients with chronic kidney disease (CKD) G1-G5 without kidney replacement therapy, we studied the bidirectional association between visit-to-visit SBP variability (VVSV) and arterial stiffness in 1036 participants who underwent brachial-ankle pulse wave velocity (baPWV) measurement at baseline and year four. We constructed multivariable logistic regression models using two analytical sets. First, we determined the VVSV [standard deviation (SD)] of all SBP readings over 4 years, and then calculated the odds ratios (ORs) for arterial stiffness progression according to tertiles of VVSV. Arterial stiffness progression was defined as at least 75th percentile of the difference in baPWV between baseline and year four. Second, we analysed the ORs for at least 75th percentile of the 4-year VVSV according to tertiles of baseline baPWV., Results: Compared with the lowest tertile of VVSV (SD), the ORs [95% confidence interval (95% CI)] for arterial stiffness progression were 1.42 (0.96-2.10) and 1.64 (1.11-2.43) for the middle and highest tertiles, respectively. In the second analysis based on tertiles of baseline baPWV, the ORs for at least 75th percentile of VVSV (SD) were 1.41 (95% CI, 0.95-2.10) and 1.64 (95% CI, 1.04-2.61) for the middle and highest tertiles, respectively. This association was similar in both analytical models when VVSV and baPWV were treated as continuous variables., Conclusion: There is a bidirectional relationship between BP variability and arterial stiffness in patients with CKD., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2022 by the American Society of Nephrology.)

Background Whether visit-to-visit systolic blood pressure (SBP) variability can predict major adverse cardiovascular events (MACE) in patients with chronic kidney disease is unclear. Methods and Results We investigated the relationship between SDs of visit-to-visit SBP variability during the first year of enrollment and MACE among 1575 participants from KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into 3 groups according to tertiles of visit-to-visit SBP variability (SD). The study end point was MACE, defined as a composite of nonfatal myocardial infarction, unstable angina, revascularization, nonfatal stroke, hospitalization for heart failure, or cardiac death. During 6748 patient-years of follow-up (median, 4.2 years), MACE occurred in 64 participants (4.1%). Compared with the lowest tertile of visit-to-visit SBP variability (SD), the hazard ratios (HRs) for the middle and the highest tertile were 1.64 (95% CI, 0.80-3.36) and 2.23 (95% CI, 1.12-4.44), respectively, in a multivariable cause-specific hazard model. In addition, the HR associated with each 5-mm Hg increase in visit-to-visit SBP variability (SD) was 1.21 (95% CI, 1.01-1.45). This association was consistent in sensitivity analyses with 2 additional definitions of SBP variability determined by the coefficient of variation and variation independent of the mean. The corresponding HRs for the middle and highest tertiles were 2.11 (95% CI, 1.03-4.35) and 2.28 (95% CI, 1.12-4.63), respectively, in the analysis with the coefficient of variation and 1.76 (95% CI, 0.87-3.57) and 2.04 (95% CI, 1.03-4.03), respectively, with the variation independent of the mean. Conclusions Higher visit-to-visit SBP variability is associated with an increased risk of MACE in patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

[Figure: see text].

Background The function of high-density lipoprotein can change from protective to proatherosclerotic under inflammatory conditions. Herein, we studied whether inflammation could modify the relationship between high-density lipoprotein level and risk of adverse outcomes in patients with chronic kidney disease . Methods and Results In total, 1864 patients from the prospective KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were enrolled. The main predictor was high-density lipoprotein cholesterol (HDL-C) level. Presence of inflammation was defined by hs-CRP (high-sensitivity C-reactive protein) level of ≥1.0 mg/L. The primary outcome was extended major adverse cardiovascular events. During 9231.2 person-years of follow-up, overall incidence of the primary outcome was 15.8 per 1000 person-years. In multivariable Cox analysis after adjusting for confounders, HDL-C level was not associated with the primary outcome. There was a significant interaction between the inflammatory status and HDL-C for risk of extended major adverse cardiovascular events ( P =0.003). In patients without inflammation, the hazard ratios (HRs) (95% CIs) for HDL-C levels <40, 50 to 59, and ≥60 mg/dL were 1.10 (0.50-1.82), 0.95 (0.50-1.82), and 0.42 (0.19-0.95), respectively, compared with HDL-C of 40 to 49 mg/dL. However, the significant association for HDL-C ≥60 mg/dL was not seen after Bonferroni correction. In patients with inflammation, we observed a trend toward increased risk of extended major adverse cardiovascular events in higher HDL-C groups (HRs [95% CIs], 0.73 [0.37-1.43], 1.24 [0.59-2.61], and 1.56 [0.71-3.45], respectively), but without statistical significance. Conclusions The association between HDL-C level and adverse cardiovascular outcomes showed reverse trends based on inflammation status in Korean patients with chronic kidney disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01630486.

Aims: Longitudinal studies of the association between sex and adverse clinical outcomes in patients with chronic kidney disease (CKD) are scarce. We assessed whether major outcomes may differ by sex among CKD patients., Methods: We analyzed a total of 1780 participants with non-dialysis CKD G1-5 from the KoreaN cohort study for Outcome in patients with Chronic Kidney Disease (KNOW-CKD). The primary outcome was a composite of non-fatal cardiovascular events or all-cause mortality. Secondary outcomes included fatal and non-fatal cardiovascular events, all-cause mortality, and a composite kidney outcome of ≥ 50% decline in estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease., Results: There were 1088 (61%) men and 692 (39%) women in the study cohort. The proportion of smokers was significantly higher in men (24% vs. 3%). During 8430 person-years of follow-up, 201 primary outcome events occurred: 144 (13%) in men and 57 (8%) in women, with corresponding incidence rates of 2.9 and 1.7 per 100 person-years, respectively. In multivariable Cox models, men were associated with a 1.58-fold (95% CI 1.06-2.35) higher risk of composite outcome. Propensity score matching analysis revealed similar findings (HR 1.81; 95% CI 1.14-2.91). Risk of all-cause mortality was significantly higher in men of the matched cohort. However, there was no difference in the risk of CKD progression. In the subgroup with coronary artery calcium (CAC) measurements, men had a higher likelihood of CAC progression., Conclusions: In Korean CKD patients, men were more likely to experience adverse cardiovascular events and death than women.

The transferrin receptor (CD71) is known as a receptor for IgA1 on mesangial cells, but the role of CD71 in IgA nephropathy (IgAN) is unknown. We studied clinical implication of mesangial CD71 in 282 patients with biopsy-proven IgAN (2005-2018). The transcript and protein expression of glomerular CD71 was determined by real-time polymerase chain reaction and immunohistochemistry. Ten subjects with microscopic hematuria only and no evidence of histologic abnormalities on kidney biopsy were considered as controls. Human mesangial cells (HMCs) were treated with sera from IgAN patients and expression levels of CD71 and inflammatory cytokine markers were compared according to disease status. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate from the baseline value. During a mean follow up of 53.5 (18.3-75.9) months, 80 (28.4%) patients developed disease progression. The mRNA expression of CD71 was significantly higher in progressors than in nonprogressors (P = 0.001). Among the Oxford classification scores, patients with M1 had significantly higher CD71 expression levels than those with M0. In a multivariable Cox model, elevated transcript levels of CD71 were significantly associated with 4.32-fold higher risk of disease progression (P = 0.009). Furthermore, CD71 expression levels independently predicted the increase in proteinuria of ≥50% from the baseline (P = 0.03). Finally, HMCs treated with sera from IgAN patients with the higher Oxford score (M1E1S1T0) more increased the mRNA expression of CD71 and inflammatory markers than those with sera from negative score (M0E0S0T0). However, silencing CD71 significantly reduced expression levels of the inflammatory cytokine genes. Our results show that mesangial CD71 is significantly associated with disease progression and may play a biologic role in IgAN., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Polypharmacy is a growing and major public health issue, particularly in the geriatric population. This study aimed to examine the association between polypharmacy and the risk of hospitalization and mortality. We included 3,007,620 elderly individuals aged ≥ 65 years who had at least one routinely-prescribed medication but had no prior hospitalization within a year. The primary exposures of interest were number of daily prescribed medications (1-2, 3-4, 5-6, 7-8, 9-10, and ≥ 11) and presence of polypharmacy (≥ 5 prescription drugs per day). The corresponding comparators were the lowest number of medications (1-2) and absence of polypharmacy. The study outcomes were hospitalization and all-cause death. The median age of participants was 72 years and 39.5% were men. Approximately, 46.6% of participants experienced polypharmacy. Over a median follow-up of 5.0 years, 2,028,062 (67.4%) hospitalizations and 459,076 (15.3%) all-cause deaths were observed. An incrementally higher number of daily prescribed medications was found to be associated with increasingly higher risk for hospitalization and mortality. These associations were consistent across subgroups of age, sex, residential area, and comorbidities. Furthermore, polypharmacy was associated with greater risk of hospitalization and death: adjusted HRs (95% CIs) were 1.18 (1.18-1.19) and 1.25 (1.24-1.25) in the overall and 1.16 (1.16-1.17) and 1.25 (1.24-1.25) in the matched cohorts, respectively. Hence, polypharmacy was associated with a higher risk of hospitalization and all-cause death among elderly individuals.

Rationale & Objective: Clinical practice guidelines recommend a target blood pressure (BP)<130/80 mm Hg to reduce cardiovascular risk. However, the optimal BP to prevent chronic kidney disease (CKD) is unknown., Study Design: Population-based retrospective cohort study., Setting & Participants: 10.5 million adults who participated in the National Health Insurance Service National Health Checkup Program in South Korea between 2009 and 2015 and had an estimated glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m 2 at the beginning of follow-up., Predictors: Baseline and time-updated systolic BP (SBP) as a continuous variable and categorized as<110, 110 to 119, 120 to 129, 130 to 139, or≥140 mm Hg., Outcome: Incident CKD GFR categories 3 to 5 (CKD G3-G5), defined as de novo development of estimated GFR<60 mL/min/1.73 m 2 for at least 2 consecutive assessments confirmed at least 90 days apart., Analytical Approach: Cox proportional hazards regression for baseline BP and marginal structural analysis for time-updated BP., Results: During 49,169,311 person-years of follow-up, incident CKD G3-G5 developed in 172,423 (1.64%) individuals with a crude event rate of 3.51 (95% CI, 3.49-3.52) per 1,000 person-years. Compared to a baseline SBP of 120 to 129 mm Hg, HRs for incident CKD G3-G5 for the<110, 110 to 119, 130 to 139, and≥140 mm Hg categories were 0.84 (95% CI, 0.82-0.85), 0.92 (95% CI, 0.91-0.94), 1.11 (95% CI, 1.09-1.12), and 1.30 (95% CI, 1.28-1.31), respectively. For time-updated SBPs, corresponding HRs were 0.57 (95% CI, 0.56-0.59), 0.79 (95% CI, 0.78-0.80), 1.58 (95% CI, 1.55-1.60), and 2.49 (95% CI, 2.45-2.53), respectively. Treated as a continuous exposure, each 10-mm Hg higher SBP was associated with 35% higher risk for incident CKD G3-G5 (95% CI, 1.35-1.36)., Limitations: Use of International Classification of Diseases codes to assess comorbid condition burden; residual confounding, and potential selection bias cannot be excluded., Conclusions: In this large national cohort study, higher SBPs were associated with higher risk for incident CKD G3-G5. These findings support evaluation of SBP-lowering strategies to reduce the development of CKD., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Arteriovenous fistulas (AVFs) are the preferred vascular access type in most hemodialysis patients. However, the optimal vascular access type in octogenarians and older (≥80 years) hemodialysis patients remains widely debated given their limited life expectancy and lower AVF maturation rates., Methods: Among incident hemodialysis patients receiving care in a large national dialysis organization during 2007-2011, we examined patterns of vascular access type conversion in 1 year following dialysis initiation in patients <80 versus ≥80 years of age. Among a subcohort of patients ≥80 years of age, we examined the association between vascular access type conversion and mortality using multivariable survival models., Results: In the overall cohort of 100 804 patients, the prevalence of AVF/arteriovenous graft (AVG) as the primary vascular access type increased during the first year of hemodialysis, but plateaued thereafter. Among 8356 patients ≥80 years of age and treated for >1 year, those with initial AVF/AVG use and placement of AVF from a central venous catheter (CVC) had lower mortality compared with patients with persistent CVC use. When the reference group was changed to patients who had AVF placement from a CVC in the first year of dialysis, those with initial AVF use had similar mortality. A longer duration of CVC use was associated with incrementally worse survival., Conclusions: Among incident hemodialysis patients ≥80 years of age, placement of an AVF from a CVC within the first year of dialysis had similar mortality compared with initial AVF use. Our data suggest that initial CVC use with later placement of an AVF may be an acceptable option among elderly hemodialysis patients., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Rationale & Objective: We aimed to elucidate whether a balanced salt solution decreases the occurrence of contrast-induced acute kidney injury (CI-AKI) after contrast-enhanced computed tomography (CE-CT) as compared to 0.9% saline solution., Study Design: A randomized clinical trial., Setting & Participants: The study was performed in 14 tertiary hospitals in South Korea. Patients with estimated glomerular filtration rates (eGFRs) < 45 or <60 mL/min/1.73 m 2 and additional risk factors (age ≥ 60 years or diabetes) who were undergoing scheduled CE-CT were included from December 2016 to December 2018., Intervention: An open-label intervention was performed. The study group received a balanced salt solution and the control group received 0.9% saline solution as prophylactic fluids for CE-CT., Outcomes: The primary outcome was CI-AKI, defined by creatinine level elevation ≥ 0.5 mg/dL or 25% from baseline within 48 to 72 hours after CE-CT. Secondary outcomes included AKI defined based on the KDIGO (Kidney Disease: Improving Global Outcomes) guideline, eGFR changes, death, or requiring dialysis within 6 months after CE-CT., Results: 493 patients received the study fluids. The control and study groups included 251 and 242 patients, respectively. The occurrence of CI-AKI in the study (10 [4.2%]) and control (17 [6.8%]) groups was not significantly different ( P  = 0.27). No significant difference was present for the secondary outcomes; AKI by the KDIGO definition (study: 19 [7.9%], control: 27 [10.8%]; P  = 0.33), death/dialysis (study: 11 [4.7%], control: 9 [3.7%]; P  = 0.74), and eGFR changes (study: 0.1 ± 0.2 mg/dL, control: 0.3 ± 2.8 mg/dL; P  = 0.69)., Limitations: This study failed to meet target enrollment., Conclusions: The risk for CI-AKI was similar after administration of a balanced salt solution and after use of 0.9% saline solution during CE-CT in higher-risk patients., Funding: This study was funded by CJ Healthcare (CS2015&#95;0046)., Trial Registration: Registered at ClinicalTrials.gov with study number NCT02799368., (© 2020 The Authors.)

Objective: To examine the association between income level and incident chronic kidney disease (CKD) in adults with normal baseline kidney function., Patient and Methods: We studied the association between income level categorized into deciles and incident CKD in a national cohort comprised of 7,405,715 adults who underwent National Health Insurance Service health examinations during January 1, 2009, to December 31, 2015, with baseline estimated glomerular filtration rates (eGFRs) ≥60 mL/min/1.73 m 2 . Incident CKD was defined as de novo development of eGFR <60 mL/min/1.73 m 2 (model 1) or ≥25% decline in eGFR from baseline values accompanied by eGFR <60 mL/min/1.73 m 2 (model 2)., Results: During a median follow-up of 4.8 years, there were 122,032 of 7,405,715 (1.65%) and 55,779 of 7,405,715 (0.75%) incident CKD events based on model 1 and 2 definitions, respectively. Compared with income levels in the sixth decile, there was an inverse association between lower income level and higher risk for CKD up to the fourth decile, above which no additional reduction (model 1) or slightly higher risk for CKD (model 2) was observed at higher income levels. The multivariable-adjusted hazard ratios from the lowest to fourth deciles were 1.30 (95% CI, 1.26-1.33), 1.16 (95% CI, 1.13-1.19), 1.07 (95% CI, 1.05-1.10), and 1.06 (95% CI, 1.03-1.09) in model 1 and 1.32 (95% CI, 1.27-1.37), 1.18 (95% CI, 1.14-1.22), 1.08 (95% CI, 1.04-1.13), and 1.05 (95% CI, 1.01-1.09) in model 2, respectively. These associations persisted across various subgroups of age, sex, and comorbidity status., Conclusion: In this large nationwide cohort, lower income levels were associated with higher risk for incident CKD., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background High-density lipoprotein cholesterol ( HDL -C) levels are generally decreased in patients with chronic kidney disease ( CKD ). However, studies on the relationship between HDL -C and CKD progression are scarce. Methods and Results We studied the association between serum HDL -C levels and the risk of CKD progression in 2168 participants of the KNOW - CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease). The primary outcome was the composite of a 50% decline in estimated glomerular filtration rate from baseline or end-stage renal disease. The secondary outcome was the onset of end-stage renal disease. During a median follow-up of 3.1 (interquartile range, 1.6-4.5) years, the primary outcome occurred in 335 patients (15.5%). In a fully adjusted Cox model, the lowest category with HDL -C of <30 mg/dL (hazard ratio, 2.21; 95% CI, 1.30-3.77) and the highest category with HDL -C of ≥60 mg/dL (hazard ratio, 2.05; 95% CI , 1.35-3.10) were associated with a significantly higher risk of the composite renal outcome, compared with the reference category with HDL -C of 50 to 59 mg/dL. This association remained unaltered in a time-varying Cox analysis. In addition, a fully adjusted cubic spline model with HDL -C being treated as a continuous variable yielded similar results. Furthermore, consistent findings were obtained in a secondary outcome analysis for the development of end-stage renal disease. Conclusions A U-shaped association was observed between serum HDL -C levels and adverse renal outcomes in this large cohort of patients with CKD . Our findings suggest that both low and high serum HDL -C levels may be detrimental to patients with nondialysis CKD .

Background: There is accumulating evidence that serum levels of non-high-density lipoprotein cholesterol (non-HDL-C) are a more accurate predictor of cardiovascular outcomes when compared with low-density lipoprotein cholesterol. However, we recently found that higher serum concentrations of triglycerides are associated with better outcomes in patients undergoing hemodialysis. Therefore, we hypothesized that the association of serum levels of non-HDL-C (which includes triglyceride-rich lipoproteins) with outcomes may also be different in patients undergoing hemodialysis when compared with other patient populations., Methods and Results: We studied the association of baseline and time-dependent serum levels of non-HDL-C with all-cause and cardiovascular mortality using Cox proportional hazard regression models in a nationally representative cohort of 50 118 patients undergoing incident hemodialysis from January 1, 2007, to December 31, 2011. In time-dependent models adjusted for case mix and surrogates of malnutrition and inflammation, a graded inverse association between non-HDL-C level and mortality was demonstrated with hazard ratios (95% confidence intervals) of the lowest (<60 mg/dL) and highest (≥160 mg/dL) categories: 1.88 (1.72-2.06) and 0.73 (0.64-0.83) for all-cause mortality and 2.07 (1.78-2.41) and 0.75 (0.60-0.93) for cardiovascular mortality, respectively (reference, 100-115 mg/dL). In analyses using baseline values, non-HDL-C levels <100 mg/dL were also associated with significantly higher mortality risk across all levels of adjustment. Similar associations were found when evaluating non-HDL/HDL cholesterol ratio and mortality, with the highest all-cause and cardiovascular mortality being observed in patients with decreased non-HDL/HDL-C ratio (<2.5)., Conclusions: Contrary to the general population, decrements in non-HDL-C and non-HDL/HDL cholesterol ratio were paradoxically associated with increased all-cause and cardiovascular mortality in patients undergoing incident hemodialysis. The underlying mechanisms responsible for these associations await further investigation., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Elevated serum high-density lipoprotein cholesterol (HDL-C) has not been associated with better cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the association between change in HDL over time and mortality has not been fully examined., Objective: In a nationally representative cohort of incident hemodialysis patients who had available HDL data at baseline and 6 months after dialysis initiation, we studied the association of change in HDL-C during the first 6 months of dialysis with all-cause and CV mortality., Methods: Associations between HDL-C change and mortality were determined in Cox proportional hazard regression models with adjustment for multiple variables., Results: In case-mix models, there was a J-shaped association between change in HDL-C and mortality, such that quartiles 1 (<-5 mg/dL) and 4 (≥7 mg/dL) were each associated with higher all-cause (hazard ratio, 1.32 [95% confidence interval, 1.21-1.45] and 1.09 [1.01-1.18]) and CV (1.28 [1.06-1.55] and 1.23 [1.04-1.45]) death risk, respectively. In fully adjusted models that included indices of malnutrition and inflammation, the higher death risk observed in the lowest quartile was attenuated, whereas the highest quartile continued to demonstrate significantly higher all-cause (1.11 [1.02-1.20]) and CV mortality (1.15 [1.00-1.32]). These associations persisted across various subgroups., Conclusions: Although malnutrition and inflammation may explain the increased risk for mortality in patients with decreasing serum HDL-C concentrations over time, these indices do not mitigate the elevated risk in patients with rising serum HDL-C. We found that increasing serum HDL-C over time is paradoxically associated with worse outcomes in incident hemodialysis patients., (Published by Elsevier Inc.)

Background: The population of elderly end-stage renal disease patients initiating dialysis is rapidly growing. Although longer treatment is supposed to benefit for hemodialysis (HD) patients through more solute clearance and slower fluid removal, it is not yet clear how treatment session length affects mortality risk in octogenarians and nonagenarians., Methods: In a cohort of 112,026 incident HD patients between 2007 and 2011, we examined the association of treatment session length with all-cause mortality, adjusting for demographics and comorbid conditions. We also used restricted spline functions for age to evaluate continuous changes in the association of short (< 210 min) and extended (≥240 min) HD treatment (vs. 210 to < 240 min) with all-cause mortality over continuous age., Results: During the first 91 days of dialysis, patients aged ≥80 years tended to have the lowest treatment session length (median [interquartile range] 211 [193-230] min, r > 0.5). Longer treatment was associated with better survival in patients < 65 and 65 to < 80 years but not in octogenarians/nonagenarians. The association of extended treatment (≥240 min) with better survival was attenuated across age and not significant among patients aged ≥80 years with a hazard ratio of 1.10 (95% CI 0.99-1.20). Shorter treatment sessions (< 210 min) was associated with higher mortality across all age groups., Conclusion: Extended HD was not associated with lower mortality among octogenarians and nonagenarians, while it was associated with better survival among younger patients. Further studies are needed to determine the optimal treatment session length in elderly incident HD patients., (© 2018 S. Karger AG, Basel.)

Background/aims: Ultrafiltration rate (UFR) appears to be associated with mortality in prevalent hemodialysis (HD) patients. However, the association of UFR with mortality in incident HD patients remains unknown., Methods: We examined a US cohort of 110,880 patients who initiated HD from 2007 to 2011. Baseline UFR was divided into 5 groups (<4, 4 to <6, 6 to <8, 8 to <10, and ≥10 mL/h/kg body weight [BW]). We examined predictors of higher baseline UFR using logistic regression and the association of baseline UFR and all-cause and cardiovascular (CV) mortality using Cox proportional hazard models with adjustments for demographics, comorbidities, and markers of malnutrition-inflammation-cachexia syndrome., Results: Patients were 63 ± 15 years, with 43% women, 32% African Americans, and had a mean baseline UFR of 7.5 ± 3.1 mL/h/kg BW. In the fully adjusted logistic regression models, factors associated with higher UFR (≥7.5 mL/h/kg BW) included Hispanic ethnicity, diabetes, and higher dietary protein intake. There was a linear association between UFR and all-cause and CV mortality, where UFR ≥10 mL/h/kg BW (reference UFR 6-<8 mL/h/kg BW) conferred the highest risk in both unadjusted (HR 1.15 [95% CI 1.10-1.19]) and adjusted models (HR 1.23 [95% CI 1.16-1.31]). The linear association with all-cause mortality remained consistent across strata of age, urine volume, and treatment time., Conclusions: Higher UFR is independently associated with higher all-cause and CV mortality in incident HD patients. Clinical trials are warranted to examine the effects of lowering UFR on outcomes., (© 2018 S. Karger AG, Basel.)

Proteinuria is a major determinant of adverse renal outcome, and its reduction slows renal progression in glomerular diseases. However, the optimal target of proteinuria in glomerular diseases is unclear, and discrepancies in the definition of proteinuria produce ambiguous findings. Here we investigated the optimal target of proteinuria by using different definitions of proteinuria. We analyzed 574 IgA nephropathy (IgAN), 175 membranous nephropathy (MGN), and 177 focal segmental glomerulosclerosis (FSGS) cases from 3 Korean kidney centers. We evaluated the impact of proteinuria on renal outcome with 2 definitions: time-average proteinuria (TAP) and time-varying proteinuria (TVP). The endpoint was renal progression, defined as a 50% decline in glomerular filtration rate or end-stage renal disease. During a median follow-up of 57.3 months, the primary outcome occurred in 54 patients with IgAN, 26 with MGN, and 30 with FSGS. Multivariate Cox regression using TAP indicated that there was a linear association between proteinuria and risk of renal progression in IgAN. However, moderate proteinuria was not associated with an increased risk of renal progression in MGN and FSGS. In contrast, the analysis by TVP showed that the risk significantly increased in proportion to proteinuria during follow-up in all 3 diseases. Our findings suggest that TVP-based model can delineate association between proteinuria and risk of renal progression better than TAP-based model, considering that TVP reflects the dynamic change of proteinuria over time. Thus, proteinuria reduction to the lowest possible level is required to improve renal outcomes in patients with glomerular diseases.

Background: Incident hemodialysis patients may experience rapid weight loss in the first few months of starting dialysis. However, trends in weight changes over time and their associations with survival have not yet been characterized in this population., Methods: In a large contemporary US cohort of 58 106 patients who initiated hemodialysis during 1 January 2007-31 December 2011 and survived the first year of dialysis, we observed trends in weight changes during the first year of treatment and then examined the association of post-dialysis weight changes with all-cause mortality., Results: Patients' post-dialysis weights rapidly decreased and reached a nadir at the 5th month of dialysis with an average decline of 2% from baseline, whereas obese patients (body mass index ≥30 kg/m 2 ) did not reach a nadir and lost ∼3.8% of their weight by the 12th month. Compared with the reference group (-2 to 2% changes in weight), the death hazard ratios (HRs) of patients with -6 to -2% and greater than or equal to -6% weight loss during the first 5 months were 1.08 (95% confidence interval, 1.02-1.14) and 1.14 (1.07-1.22), respectively. Moreover, the death HRs with 2-6% and ≥6% weight gain during the 5th to 12th months were 0.91 (0.85-0.97) and 0.92 (0.86-0.99), respectively., Conclusions: In patients who survive the first year of hemodialysis, a decline in post-dialysis weight is observed and reaches a nadir at the 5th month. An incrementally larger weight loss during the first 12 months is associated with higher death risk, whereas weight gain is associated with greater survival during the 5th to 12th month but not in the first 5 months of dialysis therapy., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background and Purpose: The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry., Methods: Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models., Results: Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P =0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P =0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P =0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P =0.470)., Conclusions: Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications., (© 2017 American Heart Association, Inc.)

Background: The association of dyslipidemia with mortality has not been fully evaluated in patients on peritoneal dialysis (PD). Moreover, changes in lipids levels over time and associated death risk have not yet been studied in this population., Objective: We studied the association of time-updated serum lipid concentrations with all-cause and cardiovascular (CV) mortalities in a 10-year cohort of 749 incident PD patients., Methods: Association was assessed using time-varying Cox proportional hazard regression models with adjustment for multiple variables including statin therapy., Results: During a median follow-up of 36 (interquartile range, 21-61) months, 273 all-cause and 107 CV deaths occurred. Compared with those with total cholesterol (TC) of 180 to <210 or low-density lipoprotein cholesterol (LDL-C) of 100 to <130 mg/dL, hazard ratios (95% confidence interval) of the lowest TC (<150 mg/dL) and LDL-C (<70 mg/dL) were 2.32 (1.61-3.35) and 2.02 (1.45-2.83) for all-cause mortality and 1.87 (1.04-3.37) and 1.92 (1.13-3.26) for CV mortality, respectively. Lower triglyceride (<100 mg/dL) and high-density lipoprotein cholesterol (<30 mg/dL) levels were associated with higher all-cause mortality (1.66 [1.11-2.47] and 1.57 [1.08-2.29]) but not with CV mortality., Conclusions: Contrary to the general population, lower TC and LDL-C levels over time were significantly associated with both worse survival and increased CV mortality in incident PD patients. Although lower triglyceride and high-density lipoprotein cholesterol concentrations were associated with significantly higher all-cause mortality, they failed to show any clear association with CV mortality. The underlying mechanisms responsible for this apparent paradox await further investigations., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Elevated serum triglyceride/HDL cholesterol (TG/HDL-C) ratio has been identified as a risk factor for cardiovascular (CV) disease and mortality in the general population. However, the association of this important clinical index with mortality has not been fully evaluated in patients with ESRD on maintenance hemodialysis (MHD). We hypothesized that the association of serum TG/HDL-C ratio with all-cause and CV mortality in patients with ESRD on MHD is different from the general population., Design, Setting, Participants, & Measurements: We studied the association of serum TG/HDL-C ratio with all-cause and CV mortality in a nationally representative cohort of 50,673 patients on incident hemodialysis between January 1, 2007 and December 31, 2011. Association of baseline and time-varying TG/HDL-C ratios with mortality was assessed using Cox proportional hazard regression models, with adjustment for multiple variables, including statin therapy., Results: During the median follow-up of 19 months (interquartile range, 11-32 months), 12,778 all-cause deaths and 4541 CV deaths occurred, respectively. We found that the 10th decile group (reference: sixth deciles of TG/HDL-C ratios) had significantly lower risk of all-cause mortality (hazard ratio, 0.91 [95% confidence interval, 0.83 to 0.99] in baseline and 0.86 [95% confidence interval, 0.79 to 0.94] in time-varying models) and CV mortality (hazard ratio, 0.83 [95% confidence interval, 0.72 to 0.96] in baseline and 0.77 [95% confidence interval, 0.66 to 0.90] in time-varying models). These associations remained consistent and significant across various subgroups., Conclusions: Contrary to the general population, elevated TG/HDL-C ratio was associated with better CV and overall survival in patients on hemodialysis. Our findings provide further support that the nature of CV disease and mortality in patients with ESRD is unique and distinct from other patient populations. Hence, it is vital that future studies focus on identifying risk factors unique to patients on MHD and decipher the underlying mechanisms responsible for poor outcomes in patients with ESRD., (Copyright © 2017 by the American Society of Nephrology.)

Background: Higher serum ferritin levels may be influenced by iron use and inflammation, and are associated with higher mortality in hemodialysis (HD) patients. We hypothesized that a major rise in serum ferritin is associated with a higher risk of mortality, irrespective of baseline serum ferritin in incident HD patients., Methods: In a cohort of 93,979 incident HD patients between 2007 and 2011, we examined the association of change in serum ferritin from the baseline patient quarter (first 91 days from dialysis start) to the subsequent quarter with mortality. Multivariable adjustments were done for case-mix and markers of the malnutrition, and inflammation complex and intravenous iron dose. Change in serum ferritin was stratified into 5 groups: <-400, -400 to <-100, -100 to <100, 100 to <400, and ≥400 ng/mL/quarter., Results: The median change in serum ferritin was 89 ng/mL/quarter (interquartile range -55 to 266 ng/mL/quarter). Compared to stable serum ferritin (-100 to <100 ng/mL/quarter), a major rise (≥400 ng/mL/quarter) was associated with higher all-cause mortality (hazard ratio [95% CI] 1.07 [0.99-1.15], 1.17 [1.09-1.24], 1.26 [1.12-1.41], and 1.49 [1.27-1.76] according to baseline serum ferritin: <200, 200 to <500, 500 to <800, and ≥800 ng/mL in adjusted models, respectively. The mortality risk associated with a rise in serum ferritin was robust, irrespective of intravenous iron use., Conclusions: During the first 6-months after HD initiation, a major rise in serum ferritin in those with a baseline ferritin ≥200 ng/mL and even a slight rise in serum ferritin in those with a baseline ferritin ≥800 ng/mL are associated with higher mortality., (© 2017 S. Karger AG, Basel.)

Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy.

Background: Fungal peritonitis (FP) is an uncommon but serious complication of peritoneal dialysis (PD) and is associated with high morbidity and mortality. Although previous studies have demonstrated that abdominal pain and catheter in situ are associated with mortality in FP patients, the effect of early catheter removal on mortality remains largely unexplored. In this study, therefore, we not only determine the risk factors for mortality but also investigate the effect of immediate catheter removal on mortality in PD patients with FP., Patients and Methods: This retrospective study was conducted on 94 episodes of FP in 1926 patients that underwent PD at Yonsei University Health System from January 1992 to December 2008. Data including demographic characteristics, laboratory and clinical findings, management, and outcome were collected from medical records., Results: Among a total of 2361 episodes of peritonitis, there were 94 episodes of FP in 92 patients, which accounted for 4.0% of all peritonitis episodes and occurred in 4.8% of patients. Mean age of patients was 52.1 years and mean duration of PD before contracting FP was 46.1 months. The presenting symptoms included turbid dialysate (93.6%), abdominal pain (84.0%), and fever (66.0%). Intestinal obstruction was complicated in 39 episodes (41.5%). 75% of FP was caused by Candida species, among which Candida albicans was the most common pathogen, accounting for 41.5% of all episodes of FP. The PD catheter was removed within 24 hours in 39 patients (41.5%), whereas catheter removal was performed between 2 and 9 days after the diagnosis of FP in 42 patients (44.7%). 27 patients (28.7%) died as a result of FP, 59 patients (62.8%) required a change to hemodialysis, and PD was resumed in 8 episodes (8.5%). In addition, the mortality rate was significantly higher in patients with delayed catheter removal (13/41, 31.7%) compared to patients with catheter removal within 24 hours (5/39, 12.8%) (p < 0.01). Multivariate logistic regression analysis revealed that delayed catheter removal, the presence of intestinal obstruction, and higher white blood cell counts in the blood and in the PD effluent were independently associated with mortality in FP patients., Conclusion: These results suggest that immediate catheter removal (i.e., within 24 hours after the diagnosis of FP) is mandatory in PD patients with FP.